LECTURE NOTES

ON
CLINICAL PHARMACY
(Subject Code: 14T00403)

2018 – 2019

IV PHARM.D (JNTUA-R17)

KRISHNA TEJA PHARMACY COLLEGE(AF)

Chadalawada Nagar, Renigunta Road, Tirupati – 517 506
 PHARM D-IV YEAR

CLINICAL PHARMACY

UNIT-I:DEFINITIONS,DEVOLOPMENT AND SCOPE OF CLINICAL PHARMACY

DEFINITION:

Clinical pharmacy is defined as the branch of pharmaceutical science dealing with

utilization of pharmacist knowledge, skills and judgments related to biomedical and pharmaceutical
sciences, to prove the safety, the cost and the precision of the drug usage in the patient care.

DEVELOPMENT OF CLINICAL PHARMACY:

In developed countries like United States of America. Canada etc.

 Clinical Pharmacy has already taken good shape. In India, it is in the infancy stage.
 The role of the retail pharmacist is viewed by many people as simply transferring pills from a
large bottle to a small one - counting tablets, typing labels and calculating the price.
 Much of his time is seen as devoted to routine merchandising of cosmetics, shaving supplies,
stationery and other commodities which have little or no relation to health care.
 India stands among top fifteen in the world in pharmaceutical market with respect to
pharmaceutical production, exports, imports etc.
 There is still a need to develop the concept of clinical pharmacy.
 Today there is 'drug-explosion' and 'information explosion' in relation to the drugs.
 On one hand there is development of newer and more-effective drugs and on other hand their
potential hazards of side effects are on rise.

SCOPE OF CLINICAL PHARMACY:

Clinical pharmacy has emerged as one of the latest branches of pharmacy in 21 st Century.[1] It is
where pharmacists deal with various aspects of patient care, dispensing of drugs and advising patients
on the safe and rational use of drugs. It can also be explained as a part of pharmacy in which the
clinical pharmacist provides patient care that optimizes the use of medication and promotes health,
wellness, and disease prevention. To elaborate the story we can say that clinical pharmacy is to use
drug control and the effective application of the knowledge. Professional skills and ethics assure the
optimal safety in the distribution and use of medicine. The purpose of the Professional Education in
Clinical Pharmacy and Public Health is to qualify each pharmaconomist (expert in pharmaceuticals)
to practice clinical pharmacy at a higher and more professional level. [2,3]
Hence, ensures the patient’s
maximum well-being during the drug therapy.

Clinical pharmacy describes the new role of the 21st Century’s pharmacists. It doesn’t restrict the role
of a pharmacist merely to good manufacture practices, easy procurement, proper preparation,
distribution and control of drug products. In addition, it also comprises functions necessary to
discharge a particular set of social responsibilities related to proper therapeutic use of drugs in the
aspects like prescribing, dispensing and administrating drugs, documenting professional services,
direct patient involvement, Reviewing drug use, Education, Consultation and Counseling. The aim of
clinical pharmacy practice is to ensure the patient’s maximum well-being and to play a meaningful
role in the safe and rational use of the drugs. These goals are to enable the physician do a better job of
prescribing and monitor the drug therapy for patient. Further, to help the medical and para-medical
staff to enable effective drug therapy. Clinical pharmacy practice also deals with proper maintenance
of the documentation regarding the medication incidents effectively to maximize the patient’s
compliance in drug use process.

Building up a Clinical Pharmacist

Internationally, particularly in the countries like the US, Canada, Australia etc clinical pharmacists
have extensive education in the biomedical, pharmaceutical, socio-behavioural and clinical
sciences.[4] Most clinical pharmacists have a Doctor of Pharmacy (Pharm.D.) degree and many have
completed one or more years of post-graduate training (e.g. a general and/or specialty pharmacy
residency). Many clinical pharmacists also choose to become Board Certified through the Board of
Pharmacy Specialties (BPS) which was organized in 1976 as an independent certification agency of
APhA (American Pharmacists Association). A pharmacist may become a Board Certified
Pharmacotherapy Specialist (BCPS), a Board Certified Oncology Pharmacist (BCOP), Board
Certified Nuclear Pharmacist (BCNP), Board Certified Nutrition Support Pharmacist (BCNSP), or a
Board Certified Infectious Disease. [5] It is denoted as an "Added Qualification" or AQ. In order to
obtain one of these specialties you must first be a Board Certified Pharmacotherapy Specialist and
then submit a portfolio to the Board of Pharmacy Specialties for review to determine if they will grant
you the added qualifications.
In India, M.Pharm (Clinical Pharmacy) is a two-year post graduate Psychiatric Pharmacist (BCPP)
through the Board of Pharmacy Specialties (BPS). There are also sub specialties within the
Pharmacotherapy specialty: Cardiology and degree course, after B.Pharm. In this course, the
Graduates of Pharmacy are provided with the opportunity to acquire knowledge about all the tasks
performed by a pharmacist in hospitals, nursing homes, clinics or any other such places. The course
focuses on the study of the patterns of use and effects of drugs on patients and deal with the correct
and appropriate use of medicinal products and devices. In order to seek admission into the course,
one has to appear for GATE/GPAT Entrance examination or any other State or University entrance
examination.

Qualities of clinical pharmacist

Clinical pharmacists care for patients in all health care settings but the clinical pharmacy movement
initially began inside hospitals and clinics. Often collaborate with physicians and other healthcare
professionals. Pharmacists should be well-versed with the common language used by the people in
order to communicate with the patient and co-professionals easily and effectively. Pharmacists are
also expected to have thorough knowledge of the etiology of the disease, its signs, symptoms,
pathophysiology, diagnostic tests, pharmacokinetics, etc. Proper clinical training should be given to
the clinical pharmacist to provide information regarding rational drug use, drug therapy and drug
doses. [6]

Condition for a clinical pharmacy -A clinical pharmacy professional should appreciate the role of
medical and para-medical staff. There should be enough bondage between the physician and the
pharmacist to visit the patients together. All of the medical staff should develop an inter-professional
relationship to enhance the quality of patient care. Further, there should be a deep sense of
responsibility in the clinical pharmacist with respect to medical care. It helps in maintaining proper
patient history and gaining confidence. As drug therapy is an ongoing process it needs to be checked
by the clinical pharmacist timely. It may be changed according to the patient’s condition and
requirement.

Health care team and a clinical pharmacist

There are certain laid roles and responsibilities of a clinical pharmacist in a health care team that
consists of several medical and para-medical professionals. These responsibilities should be executed
by the clinical pharmacist with immense care. The clinical pharmacist should interact with the
patients and maintain their complete and exhaustible medical history. The clinical pharmacist should
also do proper documentation of the hypersensitivities or allergy to certain drugs, food habits, drug
dependence or intoxications to certain chemical substances, side effects of some drugs, incorrect drug
administration, etc about the patient. [7] The prescribed drugs may interact with certain OTC drugs;
therefore, after receiving the prescription the clinical pharmacist should check the patient’s medical
history for drug related interactions and patient’s habits. This helps in effective and accurate medical
therapy.

In the selection of a proper drug product/generic formulation (depending on the bio-availability and
equivalence of such products) the clinical pharmacist can help the physician. Clinical pharmacist can
help in monitoring of drug therapy to ensure safety and efficacy. Monitoring of the drug therapy is
very important particularly for those drugs that have narrow therapeutic index or administered
chronically.[8]Various pharmacokinetic parameters can also be checked by the clinical pharmacist
based on: plasma concentration of drug, enzymes and measurement of glucose quantity in blood, etc.

Patients with kidney impairment or hepatic disorders are more prone to adverse drug reactions.
Clinical pharmacist can help in detection, prevention and reporting of adverse drug reactions. He may
advice the physician for alternate drug therapy for the concerned patients. Clinical pharmacists may
play a major role in designing health and drug policies, and assist as a source of information for the
health care professionals and to the public. The drug management greatly relies on the clinical
pharmacist to check the selection, requirement, procurement, distribution and use of the drugs. Also,
Research and development in the field of biological availability of active ingredients requires active
participation by the clinical pharmacists. The clinical pharmacist can help in executing clinical trials
and based on standard principles and bio-statistical evaluation. A clinical pharmacist is an expert to
provide detailed information to the health professionals and the general public. Effective selection,
utilization and retrieval of drug literature by the clinical pharmacist can enable in the proper
understanding of the facts by the medical team. He can also abstract information from periodic
bulletins, newsletters or other pharmacy literature.

Scope of clinical pharmacy in India

In hospitals the services regarding clinical pharmacy are of considerable value because the concerned
clinical pharmacist serves as a guide to the physician for safe and rational use of drugs. [9] He also
assists to achieve economy in the hospital by planning safe drug policies, suggestive means of
reduction of waste, by preventing misuse or pilferage of drugs. In addition to it the preparation of
preventing forecasting future drug requirements of the hospital, based upon their drug utilization
patterns. Therefore, scope of clinical pharmacy covers areas to foster innovation, improve public
health and provide a knowledge exchange. Clinical pharmacist enables rational drug use by providing
correct drug information including the proper utilization of the drugs utilized as drug therapy, along
[10]
with all the precautions to be taken as indicated or asked by the pharmacist or the physician. It
discourages any irrational or reckless use of drugs and also, concerns with the procurement of the
drugs into the market from the industry and their channelization to the patient for use. Clinical
pharmacy also deals with ensuring safety and efficacy of the drugs after marketing. Safety can be
evaluated by means of non-experimental research, whereas evaluation of efficacy in a variety of
settings representing normal medical practice generally requires experiments, randomized and
blinded. National or International markets are flooded with tens of drug combinations, low
therapeutic value products or duplicate brand names[11]. Thus, under this study it is clarified how to
choose the correct drug for administration or treatment.

INTRODUCTION TO DAILY ACTIVITIES OF A CLINICAL PHARMACIST

a.DRUG THERAPY MONITERING:

Drug therapy monitoring is an ongoing process in which pharmacists actively review patients’
records, identify and resolve drug therapy problems such as adverse drug events (ADEs), and
communicate with prescribers when problems occur. Pharmacists educate patients and their
caregivers about potential adverse effects and work with patients to ensure adherence to therapy and
attainment of therapeutic goals.
Drug therapy monitoring should be routine but is not always done consistently or systematically. In a
recent paper, researchers discussed the importance of medication monitoring, the deficiencies of our
current system, and three steps to take when monitoring drug therapy to improve patient outcomes. 1

Key points:

In reducing problems with drug therapy, appropriate prescribing has received more attention than
ongoing monitoring. Appropriate prescribing—selecting the most appropriate medication for a
particular patient—is an important aspect of patient care; monitoring therapy to detect and mitigate
medication-related problems is just as important.

Patients’ responses to medications are complex. With multiple medications, the complexity increases.
Even if the right medication was prescribed, the patient may still suffer from an adverse drug event.
Drug therapy monitoring uncovers problems as they occur. In turn, health care providers take actions
that resolve the problems.

Medication monitoring is optimized by a team approach that includes pharmacists. Following are the
three steps of monitoring:

1. Educate patients about their therapy, potential adverse effects, and actions to take if problems
occur. Make patients active partners in their medication management and their own health
decisions.
2. Regularly assess patients’ drug therapy. Ensure that patients take their medications as
prescribed, proactively identify and resolve ADEs as they occur, and assess therapeutic
effectiveness. Ensure that appropriate labs are done and assessed.
3. Adjust drug therapy as needed based on information from the monitoring process.

The authors provided compelling statistics demonstrating that inadequate monitoring of drug therapy
leads to increased ADEs and hospital admissions. They also indicated that many such ADEs could be
identified and resolved at an early stage with appropriate patient assessment.

The authors noted that a number of factors make drug therapy monitoring challenging, including
fragmentation of the health care system, lack of a team-based approach, health information
technology that is less than ideal and not integrated among members of the health care team, and
conflicting evidence in the literature on appropriate monitoring of medications.

b. ward round participation:

It is very difficult to generalise about a ward round as their nature and purpose are generally
determined by the consultant involved. Common to all ward rounds is that it is conducted in a
multidisciplinary setting generally with the user present. Ward rounds are generally conducted once a
week with the progress of the user for the previous week reviewed and the various inputs of the
professionals concerned put into the meeting. Anticipated contributions from all those concerned with
the users care for the next week are then discussed and agreed upon. A ward round can vary from the
involvement of the nurse, consultant and user to a large group of people. The grouping of
professionals involved in a ward round varies from consultant to consultant. If a user is anxious about
a ward round they are sometimes invited in after most of the professionals have left, or the nurse may
act as their advocate / representative and sometimes, especially if the user has been unable to attend
the ward round, the consultant and nurse will meet with the user to debrief them on what has
happened on a ward round on the same day. Sometimes a consultant will see the user outside of the
ward round on a one to one basis to discuss the user`s concerns. Although on other occasions (a
situation that occurred more frequently in the past) the only contact some consultants have with 2 the
user is during ward rounds. This is sometimes attributed to their activities in the community taking
away from the time they could spend in the hospital. It is widely acknowledged that users can
experience distress through experiencing ward rounds although ways of making them more user
friendly have not been established with exception of the suggestion from some nursing staff that all
consultants do make an effort to see a user individually outside a ward round at a specified time.

The great majority of people involved in the HUG discussion described ward rounds as a negative
experience. Once people are told that they are going onto a ward round it is easy to become anxious.
During the often considerable wait to be asked in, they go over and over their feelings and the
possible questions you may be asked. This can make them feel more ill.

The words people used to describe their experience ranged from –

* overwhelming,
* you feel a fool when asked a question you weren’t expecting which you can’t answer

* its painful

* it can make people more ill

* in anticipation of it, during it and reflecting on it afterwards, it can be terrifying

* it feels totally uncomfortable

* it can be overpowering

* there is no empathy for the sufferer

* it is intimidating

* it is embarrassing

* you are put under pressure in a group

* there is too little information (although other people said that there is too much information to take
in especially if you are feeling ill.)

Some people had never experienced a ward round or even heard of one. Many people were very
unclear as to the reason for holding a ward round.

People`s perceptions of the purpose of ward rounds included:

* to assess someone’s mental health.

* to discuss your case and assess you

* to find out what progress you are making and whether your medication is working.

C.ADVERSE DRUG REACTION MANAGEMENT:

Adverse drug reactions (ADRs) are a leading cause of morbidity and mortality, accounting for up to
30% of hospital admissions in the United States,1 and costing approximately $170 billion
annually.2 Elderly patients are at highest risk of experiencing ADRs, many of which are
preventable.1 The most commonly-implicated medications include antibiotics, anticoagulants,
digoxin, diuretics, hypoglycemics, antineoplastics, and nonsteroidal antiinflammatory drugs, which
are responsible for about 60% of hospital admissions. 1

Actual, perceived, or even fear of ADRs increases the likelihood for medication nonadherence,
leading to suboptimal treatment efficacy and adding to the burden of disease. 1-3 Actual ADRs can
result from medication pharmacology, whereas perceived or fear of ADRs are influenced by
psychological factors such as predetermined medication views, lack of belief in treatment necessity,
anticipation of ADRs, conditioning based on past experiences, and misattributing symptoms as
ADRs.1-3Clinician awareness of these factors will help to reduce risk for ADRs and optimize
management, ultimately allowing patients to benefit from intended treatment.

The American Society of Health-Systems Pharmacists (ASHP) provides guidelines and emphasizes
the role of pharmacists in comprehensive ADR management. 4 Here are some tips:4-6

Risk Minimization

 Understand patient views about medication therapy.

 Educate about the benefits of treatment.
 Inform patients about potential ADRs and management strategies should any occur.
 Ensure an updated and accurate medication list.
 Utilize decision support software to help prevent ADRs.
 Start with low doses and frequencies and slowly titrate as tolerated.
 Initiate less-potent agents, agents with direct mechanisms of action, or alternatives with lower
adverse event incidence.
 Avoid or reduce the use of interacting medications.
 Prescribe dosage forms with minimal systemic exposure (eg creams, patches).

Recognition, Detection

 Be familiar with known ADRs of the medication as well as the patient’s pre-existing
symptoms.
  Evaluate new symptoms as possible ADRs, looking into health conditions, labs, or other
factors which may explain the symptoms.
 Consider the temporal relationship between medication initiation and symptom onset.
 Challenge concepts like stopping the medication to see if the symptom subsides in absence of
the medication, and restarting to see if symptoms return.
 Utilize lab tests for more evidence to identify an ADR.
 Apply probability tools7-9 such as the Naranjo Adverse Drug Reaction Probability Scale or
4Ts for heparin induced thrombocytopenia. 10
 Express empathy and maintain a trusting relationship with the patient.
 Reduce dosing or discontinue the offending medication.
 Switch to another agent or dosage form less likely to cause ADRs.
 Treat side effects when necessary (beware of prescribing cascades).
 Document the ADR in the patient’s medical record.
 If working from a care setting separate from pharmacy, notify the patient’s pharmacy to
document the ADR in the pharmacy records.
 Report ADRs through appropriate channels such as your organization’s reporting system, the
drug manufacturer, FDA MedWatch11 or Vaccine Adverse Event Reporting System.12
 Track and trend ADRs for ongoing process improvement.

D.DRUG INFORMATION AND POISONS INFORMATION:

DRUG INFORMATION:

 ™ Drug information means providing clinically relevant information on any aspect of drug
use relating to individual patients, or general information on how best to use drugs for
populations.
 ™ Drug information service can be applied to any activity where information about drug use
is transferred, and includes patientrelated aspects of pharmaceutical care.
 ™ A Drug information center is an area where pharmacists(or other health care professionals)
specialise in providing information to health professionals or public.
  ™ The drug information centre provides authenticate, unbiased information to healthcare
professionals, provide tailor-made counselling and health information to patients/consumer as
well as monitor and document adverse drug reactions.

INTRODUCTION DRUG INFORMATION:

 The first drug information centre was opened in 1962 at the university of Kentucky medical
centre and was intended to be utilised as a source of selected, comprehensive drug
information.
 A drug information centre can also contribute to pharmacovigilance( adverse drug reaction
reporting), drug use reviews, health education programmes and clinical research.

POISON INFORMATION:

Poison information is a specialised area of drug information which includes information about the
toxic effects of chemicals and pesticides, hazardous material spills , household products ,
overdose, of therapeutic medicines including mushrooms, animal toxins from bites of snakes ,
spiders and other venomous creature and stings.

The objectives of DIC are:

• To provide an organized database of specialized information on medicines and therapeutics to

meet the drug information needs of practitioners.

• To educate pharmacy students to serve as effective providers of medicines information.

• To provide accurate and unbiased medicines information service to the pharmacists, physicians
and other health care professionals in the hospital and community.

• To promote patient care through rational use of medicines.

DRUG INFORMATION RESOURCES:

• Textbooks, newsletters, journals,

• Newsletters, microfiche reader,

• Optical discs,
• Computer systems

• Tertiary resources >>>Secondary resources >>>Primary resources

Primary resources:

• Primary literature describes unique experiences which change the world in terms of available
knowledge.

• They are the foundation on which all other drug information is based. These include journal
publications on drug-related subjects, such as reports of clinical drug trials, case reports, and
pharmacological research. Evaluating primary literature is difficult.

• The most reliable evidence comes from reports on randomized controlled trials. Proper
evaluation of these trials requires considerable experience, and systematic reviews of combined
trials (meta-analyses) may be necessary.

• Sources: ¾ Medical and therapeutics Journal:

*annals of internal medicine.

* british medical journal.

*journal of the medical association.

* New England Journal of Medicine.

Pharmacy journals:

* American Journal of Hospital Pharmacy.

* Clinical Pharmacy.

* DICP-Annals of pharmacotherapy.

* Journal of Clinical and Hospital Pharmacy. ¾ Drug and Toxicology Information and
Pharmacology Journal.

* British Journal of Clinical Pharmacology.

 * Human and Experimental Toxicology.

Secondary sources:

secondary sources consists of reviews of primary reports. These provide a personal perspective of
the literature and can include cooments on how the author might apply the information in
practice.

•Medline

•International PharamaceuticalAbstracts

•Chemical Abstracts

•IOWA drug Information Service

•DRUGDEX

•Martindale

•POISINDEX

Tertiary resources:

Tertiary resources are summaries of the primary and secondar published literatre. Printed
textbooks are the main example and these ar characterised by a slow rate of revision compared to
secondary sources.

•AHFS-Drug information Book;AustralianMedicine Handbookook; Meylersside effect of drugs

• Avery’s Drug Treatment

•Basic skills in interpreting Lab data

•Drug information handbook

•Drug interactions Stockley/ Facts and comparison

•Handbook of injectables
•HarrisonsPrinciples of Internal Medicine

•Martindale, Pharmacopoeias, Physicians desk ref

•Merck index, Merck manual,

•BNF, USP, Australian formulary

E.MEDICATION HISTORY:

Taking medication histories can be difficult. Many patients don’t manage their own medications,
and many of those who do struggle with drug names, doses, and indications.

Using a standardized method for taking medication histories is vital to minimizing errors. Here
are 10 steps to do so:

Step 1: Introduce yourself to patients and ask for permission to discuss their home
medications.
If there are guests in the room, offer to come back later instead of asking whether it’s ok to speak
in front of others. This takes the burden off of patients and gives them an easy avenue to decline
discussing their medications in front of guests.

Step 2: Check each patient’s name and date of birth.

Step 3: Ask whether they came to the hospital from their home or a facility, if you’re
uncertain.
Oftentimes, patients coming from a nursing home or other care facility will have a W-10 form
that can be used to obtain their current medications.

Step 4: Ask whether they manage their own medications or if someone helps them.
Before spending a significant amount of time trying to obtain a medication history from patients
unfamiliar with their medications, ask if someone assists them. For example, many patients have
family members who set up their medication box. It may also be a good idea to inquire about a
visiting nurse who assists with their medications.
Step 5: Ask about the name, strength, dose, route, and frequency of their medications.
This question may be overwhelming for patients on many different medications, so encourage
them to start anywhere they remember. Although it may be tempting to read their current
medication list and ask whether it’s correct, there’s a lot of room for error in this method. Instead,
try prompting the patient by asking, “Do you take any medications to lower your cholesterol?”

Step 6: Ask about OTC products, vitamins, and any medications taken less often.
Aspirin is an important medication that patients might forget to mention.

Step 7: Ask about inhalers, injectables, creams/ointments, eye drops, ear drops, nasal
sprays, patches, and medication samples.
Patients often associate the word “medication” with pills, so prompting them with other dosage
forms can remind them of medications they might have missed.

Step 8: Ask which pharmacy/pharmacies they use and inquire about allergies.

Step 9: Thank them and ask whether they have any questions.
Using the phrase “I have the time” has been proven to increase a patient’s willingness to ask
questions.

Step 10: Evaluate the medication history obtained against at least one additional source.
The sources should contain the same medication names, strengths, dosages, routes, and
frequencies. Any discrepancies should be further investigated. Some examples of secondary
sources are previous medication list, prescription bottles, pharmacy records, and insurance
records.

F.PATIENT COUNSELLING:

1 Ensure prescription has been screened by pharmacist. Obtain

handover information from pharmacist
 2* Name and type of drug

3* Dosage schedule eg, dose, frequency, quantity, duration, how to

take it and additional warning

4* Compliance chart/ steroid card/ warfarin booklet

5* Technique

6 Patient information leaflet/ side effects

7† Special precautions/ storage conditions

G.DRUG 8† Missed a dose

9* Ancillary equipment

Any other question should be referred to a pharmacist

* To mention in a counselling session

† To mention if appropriate or if patient asks this question

UTILISATION EVALUATION(DUE) AND REVIEW(DUR):

Drug use studies using aggregate data or health facility indicators may indicate that there is over- or
under-consumption of medicines, and qualitative studies may indicate why certain health staff and
patients behave the way they do. However, such studies do not provide detail about the exact nature
of the irrational use. Such details may concern incorrect medicine choices, incorrect dose, prescribing
drugs that cause ADRs or drug interactions, and the use of expensive drugs when cheaper ones would
do.

Drug use evaluation (DUE) is a system of ongoing, systematic, criteria-based evaluation of drug use
that will help ensure that medicines are used appropriately (at the individual patient level). If therapy
is deemed to be inappropriate, interventions with providers or patients will be necessary to optimize
drug therapy. A DUE is drug- or disease-specific and can be structured so that it will assess the actual
process of prescribing, dispensing or administering a drug (indications, dose, drug interactions, etc.).
DUE is the same as drug utilization review (DUR) and terms are used synonymously.

Medication use evaluation (MUE) is similar to DUE but emphasizes improving patient outcomes
and individual quality of life; it is, therefore, highly dependent on a multidisciplinary approach
involving all professionals dealing with drug therapy. An MUE will assess clinical outcomes (cured
infections, decreased lipid levels, etc.).

The goal of a DUE or MUE is to promote optimal medication therapy and ensure that drug therapy
meets current standards of care. Additional objectives may include:

• creating guidelines (criteria) for appropriate drug utilization

• evaluating the effectiveness of medication therapy

• enhancing responsibility/accountability in the medicine use process

• controlling medicine cost

• preventing medication related problems, for example adverse drug reactions, treatment failures,
over-use, under-use, incorrect doses and non-formulary medicine use

• identifying areas in which further information and education may be needed by health-care
providers.

Once the main problem areas have been identified, (from aggregate data, health facility indicators,
qualitative studies, other DUE studies, or even recommendations from DTC members), a DUE
system can be established relatively quickly.

6.5.1 The steps of a DUE

The steps of a DUE are as follows. An example is shown in box 6.7.

 STEP 1 Establish responsibility

It is the responsibility of the DTC to establish procedures for the implementation of a DUE
programme; this includes appointing a responsible member of the DTC or a subcommittee to monitor
and supervise the DUE process in the hospital or clinics. Ideally the DTC should establish annual
plans, outlining which medicines or clinical conditions will be a part of the DUE process.

STEP 2 Develop the scope of activities and define the objectives

The DTC should decide upon the objectives of the DUE and the scope of the activities necessary. The
scope can be very extensive or it can focus on a single aspect of drug therapy and will depend upon
the type of problem identified, for example:

• overuse of a more expensive medicine when a cheaper equivalent is available, as revealed in

aggregate data

• incorrect use (indication, dosage, administration) of a particular drug, as revealed in patient charts,
medication error reports, ADR reports

• inappropriate choices of antibiotic, as revealed in antibiotic sensitivity reports

• a poor dispensing process, as revealed by patient complaints or feedback.

Due to the large number of medicines available at a hospital or clinic, the DTC must concentrate on
those medicines with the highest potential for problems in order to get the most return on the work
involved. These high-priority areas include:

• high-volume drugs

• expensive drugs

• drugs with a narrow therapeutic index

• drugs with a high incidence of ADRs

• critically important therapeutic categories, for example cardiovascular, emergency, toxicology,

intravenous drugs, chemotherapy and narcotic analgesics

• antimicrobial drugs, prophylactic and therapeutic

• drugs undergoing evaluation for addition to the formulary

• drugs used for non-labelled indications

• drugs used in high-risk patients

• common clinical conditions often poorly treated.

STEP 3 Establish criteria for review of the medicine

Establishing DUE criteria is extremely important, and is the responsibility of the DTC. DUE criteria
are statements that define correct drug usage with regard to various components, as shown in box 6.6.
Criteria for the use of any medicine should be established using the hospital’s STGs (assuming that
they have been correctly developed). In the absence of hospital STGs, criteria may be based on
recommendations from national or other locally available satisfactory drug use protocols, other
relevant literature sources, and/or recognized international and local experts. Credibility, and staff
acceptance, of the DUE relies on using criteria that have been developed from reading established
evidence-based medicine information from reputable sources and that have been discussed with
prescribers.

BOX 6.6 COMPONENTS OF DRUG USE FOR DUE CRITERIA

• uses: appropriate indication for drug, absence of contraindications

• selection: appropriate drug for clinical condition
• dosing: indication-specific dosing, intervals and duration of treatment
• interactions: absence of interactions - drug-drug, drug-food, drug-laboratory
• preparation: steps involved with preparing a drug for administration
• administration: steps involved in administration, quantity dispensed
• patient education: drug and disease-specific instructions given to patients
• monitoring: clinical and laboratory
• outcome, for example: decreased blood pressure, blood glucose, asthma attacks

Reviewing many criteria will make the DUE process more difficult, and may impair successful
completion of the review. Therefore the number of criteria established for each medicine is often
between 3 and 5. Once the criteria are established, thresholds or benchmarks are decided for each
criterion in order to define the expectations or goals for compliance with the criteria. Ideally one
would like 100% of all cases to comply with the criteria, but in reality this may not be possible, and a
DTC might decide to set a threshold of 90-95% compliance below which they would instigate
corrective action.

STEP 4 Data collection

Data may be collected retrospectively, from patient charts and other records, or prospectively, at the
time a medicine is prepared or dispensed. Retrospective data collection may be quicker and is best
accomplished away from the patient care areas and distractions. The advantage of a prospective
review is that the reviewer can intervene at the time the medicine is dispensed to prevent errors in
dosage, indications, interactions or other mistakes. A particular example of this is the computerized
systems used in some pharmacies; here the computer warns the pharmacist if patient data being
entered into the computer fails to meet established criteria and requires them to correct the problem(s)
noted. Such a system can also provide a large database for use retrospectively.

Data must be collected from a suitable random sample of charts or prescription records from the
health-care facility, usually selected by pharmacy personnel, but also by nurses or medical records
personnel. The treatment of at least 30 patients, or 100 patients for common clinical conditions,
should be reviewed per health facility or hospital. The larger the facility and the more practitioners,
the larger the number of records needed for review and analysis. Data collection forms based on the
criteria can be configured into simple ‘yes/no’ questions or may involve the filling in of open
questions (see annex 6.2). Sources of data include patient charts, dispensing records, medication
administration records, laboratory reports, ADR reports, medication error reports, antimicrobial
sensitivity reports, and documented staff and patient complaints.

STEP 5 Data analysis

Data are tabulated in a form that corresponds to the criteria chosen for the DUE. The percentages of
cases that meet the threshold for each criteria should be calculated and summarized for presentation
to the DTC. A report of all DUE programmes that are being conducted should be prepared on a
quarterly basis.

STEP 6 Feedback to the prescribers and making a plan of action

After information is presented (for example on inappropriate drug use or unacceptable patient
outcome), the DTC should develop conclusions about the differences between actual and desired
results. In other words, how do the actual results vary from the desired benchmark or threshold
levels? The DTC should then decide what follow-up action is necessary and whether to continue,
discontinue or expand the functions of the DUE in question. Recommendations should include
specific steps to correct any drug use problem that is evident from performing the DUE. For example,
if a specific medicine is being prescribed at too high a dose, the recommendations need to specify in
detail how the dosing of this medicine can be improved. Interventions to improve drug use would
include feedback to the prescribers and may also include:

• education, for example letters, in-service education, workshops, newsletters, face-to-face

discussions

• institution of drug order forms

• institution of prescribing restrictions

• changing the formulary list and/or manual

• changing the standard treatment guidelines

• using another DUE or continuing the present one.

STEP 7 Follow-up

In every DUE, follow-up is critical to ensure appropriate resolution of any problems. Did an
intervention achieve its objective? If an intervention is not evaluated, or drug use problems are not
resolved, then the DUE will have been of no use. As a part of a follow-up plan the DTC must assess
the need to continue, modify or discontinue the DUE. Thus, DUE activities should be evaluated
regularly (at least annually) and those that do not have a significant impact on drug use should be
redesigned in order to provide measurable improvements. Common problems associated with DUEs
include unclear responsibilities for different activities, poor prioritization of problems, lack of
documentation, lack of personnel and inadequate follow-up. If follow-up is adequate, prescribers are
likely to improve their performance in all areas knowing that they may be reviewed in the future!

H.QUALITY ASSURANCE OF CLINICAL SERVICES:

Quality assurance is a management technique used to ensure the quality of practice and its outcome.

 PATIENT COUNSELLING
 ADR reporting
 Ward round participation
 Drug information services
 Patient interview
 Case note review
 Medication chart review
 Therapeutic consultation
 Drug interactions pharmacoeconomics
 Poison management
 News letter initiation & conducting pharmaceutical research & development
 Hospital formulary
 Dosage adjustment calculations
  Therapeutic drug monitoring
 Therapeutic guideline preparation.

Assuring the quality through ‘customers’ who may be฀

 Patients
 Carers
 Clients or
 Other health care professionals.

PATIENT DATA ANALYSIS:

Providers have to watch over different dimensions simultaneously, balancing quality care delivery
with moderate costs while tracking workforce and financials. Keeping all these dimensions effective
is impossible without custom analytics, since only tailored, agile tools can accommodate both
established processes and changing conditions (such as the transition to a value-based care
environment).

The analytics that helps to improve value, keep up with the competition and evolve care quality is
based on 5 interconnected dimensions: outcomes, costs, patient-generated health data (PGHD),
financial management and internal processes.

THE PATIENT’S CASE HISTORY:

Practice Goals

It is the privilege of any physician to set his own practice goals. Such goals usually take one of two
major directions: comprehensive care or specific care. Comprehensive care implies the discovery of
all the patient's problems, forming a plan of action for each problem, putting that plan of action into
effect, and monitoring the progress results and revising the plan as necessary. On the otherhand,
specific care is restrictive care in which a doctor of specialized skill and interest concentrates on only
a part of the patient's problem or problems. Family practice is an example of comprehensive care;
chiropractic orthopedics is an example of specific care.
The point to be made here is that both comprehensive care and specific care require an accurate
diagnosis. Comprehensive care requires the discovery of all the patient's problems to direct problem-
oriented therapy. Specific care also requires the discovery of all the patient's problems so that all
problems can be considered in relation to the specific area of interest. Obviously, one cannot be
specific unless he has an appreciation for the whole. To do so would be like the story of the blind men
examining the elephant: all describing the animal according to the parts (ears, tail, tusk, legs, etc) they
were near without understanding the relationship of the parts to the whole.

Clinical Records

Good decisions are the result of accurate, complete facts being at hand from which a logical course of
action can be planned. This means that the health of the practice is determined to a great extent by the
quality of the doctor's data gathering and retrieval systems. Every office requires certain basic
information on every new patient.

To be aware of the patient's problems is the first step in logical health care. The second step is to have
systematically developed complete records of the patient's problems and the care administered to
monitor progress. More is needed besides a comprehension of the problems for it is extremely
doubtful if all the problems could be remembered without a written record. Total recall from visit to
visit of existing problems and their ramifications over a period of weeks or months is incredible.
Quality health care is the result of accurate observation, analysis and synthesis of information, and
appropriate action. Good records safeguard the quality of these functions.

Clinical records concern the health-care aspects of the practice. Examples are the entering patient data
form, the patient history form, the case history and examination form, case progress records, clinical
laboratory reports, and x-ray reports. Administration records concern the business side of the
practice.

Entering Patient Data

When new patients enter the typical chiropractic office, they are greeted, seated comfortably, handed
a clip board to which has been attached a card or slip, and requested to fill out the necessary
information. Much of this information is for administrative purposes such as the patient's address and
telephone number, employer's name and address, referral and insurance data. However, some of the
information is of a clinical nature and will be transferred to other records such as date of birth, chief
complaint, number and ages of children, and occupation.

Patient History Form

After the entering data are obtained, the next step is to obtain a record of the patient's health history.
A chiropractic assistant may be responsible for the initial gathering of this information which records
when symptoms first appeared, how long the disorder has existed, what the patient has previously
done about the condition, and other facts helpful in case evaluation.

Such information may be gathered by an assistant, and is usually restricted to that concerning the
patient's chief and minor complaints;

the patient's medical, surgical, obstetrical histories;

family, social, and accident histories.

Other points covered are:

record of past patient illnesses,

operations,

miscarriages,

births,
drug or food sensitivities,

congenital difficulties,

past medical and chiropractic care and the results obtained.

Family history will concern:

the health status of siblings and parents, offering possible clues to hereditary influences.

The patient's social history relates to where the patient lives, marital status, number and ages of
children, type of work and work environment, smoking and drinking habits, activity excesses and
inhibitions. The history of accidents and their effects are recorded. The doctor will later go over each
point in detail with the patient during the interview.

Questionnaires

Programmed questionnaires and direct questioning comprise the two most common methods used in
gathering a case history. A screening device such as a preprinted form does not minimize the doctor's
role in taking the history. It is just an efficiency means of supplying non-critical data and serving as
reference points from which the doctor will investigate further. The time saved in asking routine
questions can be used in more personal aspects of the case.

To save patient and office time, many doctors utilize a type of personal history form which requires
only a simple "Yes" or "No" answer which can be checked or encircled by the patient. These forms
are usually designed so that a group of questions refers to a particular body system.

A questionnaire gives the doctor an opportunity to review the data prior to seeing the patient so that
he may formulate some of the basic questions in his mind prior to contact. The person whose duty it
is to instruct the patient in how to fill out a questionnaire must be sure to stress the importance of the
information to the patient so that the form will be completed with sincerity. The patient should be
assured that all information will remain in confidence. If a question is not clear to a patient, there
should be someone available to help.

Obviously, a patient that is severely ill should not be asked to fill out a multi-page questionnaire. An
acutely ill patient is far too disturbed to be confronted with a printed form.

Many doctors feel that a questionnaire should be presented to the patient only after the initial history
has been obtained and a positive rapport has been established between doctor and patient. The
approach must be designed to the patient and problem at hand as well as to office philosophy.

Case History and Examination Form

The doctor's actual examination has begun with a review of the initial data. During the interview, the
doctor will further investigate this information, probing deeper and wider, and arrive at a judgment as
to what type examination procedures would be best suited for the particular patient and complaints
involved.

At the completion of the patient interview, the doctor will propose the type of examination necessary;
and upon patient agreement, the examination will proceed. After examination, the doctor will record
or dictate the results of his physical examination, spinal analysis, laboratory findings, and other data
necessary to profile the patient's condition.

In a simple acute case, this whole process may be completed in a matter of minutes. In a severe
chronic condition of an obscure nature, the process may take from several days to several weeks
before a working diagnosis and prognosis is arrived at. Regardless, after the examination and
evaluation of the patient's history and examination findings, the doctor will meet with the patient to
discuss his opinions and recommendation for treatment or referral.

Although professional printing houses have a large selection of case history forms to choose from,
many doctors prefer to design their own to meet personal goals and specifications. Still other doctors
do not desire a restricted format and prefer to develop clinical records on an open basis through
dictation which is later typed.

Case Progress Records

Once a patient enters therapy, his condition is recorded, together with changes in treatment or to
previously given instructions. Progress notations constitute a permanent record of what was done and
offer a chronological patient status. While the patient's history indicates the patient's status at the time
of the initial visit, the progress records indicate the patient's state of health at subsequent points in
time.

Elements in the Diagnostic Process

In the broad sense, the word symptom is used to label any manifestation of disease. In the diagnostic
sense, however, symptoms are thought of as being only subjective, appreciated only by the affected
person. Pain and itching are pure symptoms. Signs are detectable by another person and sometimes
by the patient himself. Faint cardiac murmurs and pulmonary rales are pure signs. Some features are
symptoms and signs as the same time such as fever and swelling. Conditions vary in classification.
Alcoholism, for instance, may be a diagnosis or it may be a symptom and/or sign of a severe
neurosis.

There is one basic reason for studying signs, symptoms, and, for that matter, the case history: to
determine the pathophysiological processes involved. Memorizing specific symptoms of specific
disease entities has little clinical value unless the processes involved are understood. Knowing "why"
a certain sign or symptom is present is vital for comprehension and competent therapy.

A sign or a symptom is never an isolated phenomenon but has multiple interrelationships, some
physiological and some psychological, which can be of a major or minor importance. The patient's
problems can only be interpreted and a diagnosis made possible when the clinical significance of the
patient's signs and symptoms are understood.
The structure of the diagnostic process in the typical chiropractor's office consists of:

(1) developing a patient profile,

(2) recording the history,
(3) conducting the physical examination and spinal analysis, and
(4) interpreting necessary laboratory reports and x-ray films.

These procedures may be directed either to specific problems such as low back pain, hypertension,
asthma, or they may be directed in a comprehensive manner which identifies all the patient's
problems even if some are not a concern to the patient at the time. Thus, the direction that these
procedures will take will be determined by both patient and practice goals. It is these first two
elements, patient profile and history, that are the major subject of discussion in this chapter. These
two elements are the components of the patient's initial interview with the doctor.

The Art of Clinical Inquiry

Several years ago, Dr. David C. Pamer offered a description of the need for the case history in an
article which appeared in "The Chiropractic Internist":

"An accurate, complete, usable, and at times laborious and exhausting case history is the essential
foundation that all practitioners must first obtain before they can build piece by piece the true
diagnosis. And only after a diagnosis has been reached should therapy be initiated. The case history
must be accurate and complete, thus warning the physician of conditions and protecting the patient
from possible detrimental diagnostic procedures which may be encountered within the realm of a
diagnostic 'work-up'. A complete case history will protect the fetus of a young 'surprised' female with
'low back pain' from x-ray irradiation. An accurate case history will protect the traumatized patient
from possible further injury or aggravation of injury during physical examination. A 'good' case
history of patient data must regulate and mandate diagnostic studies and aid in the interpretation of
the same. McBryde and Blacklow (SIGNS & SYMPTOMS, Lippincott, 1970) state that 50% of the
diagnoses made are possible solely on the data obtained from a complete case history. Another 25%
of the diagnoses are based on the physical examination alone. Laboratory, x-ray, and other procedures
contribute 20%, with 5% of the cases nondeterminable."

An understanding of the goals of the interview, how to handle the presenting symptom and present
illness during the interview, how to develop communications leadership and control, how to cope
with patient anxiety, what notes to take, and recognition of the pitfalls in interviewing are
prerequisites to developing the art of clinical inquiry.

Goals of the Interview

The patient's first interview is the first part, as well as the foundation, of the doctor-patient
relationship. This vital interview can be considered to have three basic content objectives: an
emotional substance, a factual substance, and a therapeutic substance. Thus, feelings, facts, and
direction are the primary goals of the interview.

The emotional substance is that atmosphere of developing good human relations. Interest, courtesy,
understanding, the development of rapport, and all the other social manners and arts of interpersonnel
communications will be tested here as they are in any meaningful social contact. Shewd assessment
of various personalities and the ability to adapt to a wide variety of personalities offer an optimal
climate for the doctor to gain knowledge of the individual and the person's full cooperation. This is
the time when first impressions and most lasting impressions are made. This is the period when
doctor and patient "size up" one another. The emotional substance is human reality. However,
balance is the key. One can show not enough interest in the emotional substance, or show too much.

The factual substance is that information about the patient's problem and its history. Here, the doctor's
knowledge of the basic and clinical sciences help the examiner to direct his questions with skill,
correlating the patient's symptoms with his clinical knowledge and experience. If backache is the
chief complaint, for instance, what is its possible pathophysiology and etiology? If the complaint is
chronic in nature, the doctor will reflect on what he has learned of the natural progression of such a
syndrome in a similar situation. The factual substance is one of data gathering, sifting, correlation,
and evaluation --without prejudgment that could cloud objectivity.
In the text CLINICAL METHODS, H.K. Walker, MD, states: "Therapy begins when the patient and
physican first set eyes on one another." There can be little therapy if there is little desire to cooperate.
Thus it is important that the examiner establish and cultivate a climate which informs the patient that
the doctor is interested in the person first as a human being, and second as a patient; and the patient is
instilled with the conviction that the doctor knows what he is doing. These factors are the product of
the emotional and factual substance of the interview.

The value of this first interview and the patient's history cannot be overestimated. It is the point in
which doctor and patient first have contact and attempt to construct a bond. It elicits valuable
information about the person as an individual and establishes the first steps toward the later diagnosis.
It designs the physical examination which is to follow and makes certain signs to be found more
meaningful. It provides an index to the seriousness of the illness. It indicates probable laboratory
tests, and it begins to direct the role of future therapy. In the majority of instances, following physical
and laboratory examinations will:

(1) confirm an accurate case history, or

(2) indicate case history inadequacy.

The value of a case history is directly proportional to its completeness and accuracy. Thus, in
questioning a patient, the doctor must accomplish two tasks:

(1) convince the patient of the importance of the interview and questioning, and
(2) establish the complete sequence and relationship of events up to the present illness. Unless the
first task is accomplished, the second can never be achieved. As the history-taking develops, the
doctor must begin to formulate tentative ideas about the pending diagnosis.

The Presenting Symptom

The presenting symptom is the chief complaint or major problem for which the patient is seeking
help. It is the response to such questions as "What seems to be the matter?" or "How can I help you?"

Deep probing into the patient's chief complaint will frequently uncover diseases and disorders that
were predestined in years past and could have been avoided or minimized if an efficient case history
had been obtained at that time. The doctor's role should be as much preventive as it is therapeutic.

Once the chief problem has been defined, the patient should be encouraged to offer more details of
the situation. Most patients will do this spontaneously. After the patient has "told his story", the
doctor is in a position to direct specific questions to profile the patient's problem in greater detail.

Remember that the patient's symptoms represent what the patient feels to be wrong and what the
patient is concerned with. The doctor may find a very severe problem that is asymptomatic, but this
should not be an excuse to minimize the patient's concern.

If the patient is in pain, then the doctor will limit his questions at this time by asking something to the
effect, "What's bothering you the most?" In most instances of pain, it is practical to concentrate on the
acute condition during the first visit.

The Present Illness

If the patient is not in pain, then the doctor should proceed to ask, "What else has been troubling you
lately?" Your goal is to encourage the patient to relate all his problems so that you can arrive at a
description of the present illness. It is also good to have the patient describe his symptoms on
following visits. The re-telling will invariably add new facts not previously revealed or recently
remembered. It takes time to build trust --and almost impossible to obtain a thorough case history in
the first visit. If the patient has been involved in trauma, shock, or a crisis, it is not unusual for a
degree of amnesia or faulty recall to be present.

At the end of the interview, you should feel confident that the emotional and factual substance of the
interview was to your liking and confident that the patient has been open and truthful with you. If not,
the data are most likely incomplete or misleading.
You now have a list of the patient's problems--some possibly related to the chief complaint and others
that are probably not. Clinical judgment will determine their priority consideration. The quality of
this judgment is determined to a great extent in how thoroughly you understand the beginning and
course of the problem, where the problem is located and its radiation, the problem's quantity and
quality, what circumstances aggravate or aid the problem, and what manifestations are associated.
Answers to these questions should be at hand for each complaint.

Leadership in Communicating

After the doctor is introduced to the patient and before the formal interview begins, it is always good
practice to start the conversation with a few social comments not related to health or sickness to put
the patient at ease. Don't be in a hurry to begin the actual interview. Let the person first understand
that you recognize him as an individual. Inquire into the patient's comfort, then explain your
professional role: family practitioner, specialist, practice goals.

Good answers come from tactful questions that are asked in a manner the patient understands. If you
ask most lay people, "Have you ever had jaundice?", most will respond, "No". If you then ask them,
"Do you understand what jaundice is?", most will reply, "Not exactly". And of those who say they do
understand, most will have an erroneous understanding. Thus, be sure to speak in terms that are
understandable and descriptive, and watch the responding body language as well as listen to the
words. Use similes and analogies whenever you think you might be misunderstood otherwise.

Time will be saved and continuity will be maintained by avoiding hopping between unrelated areas.
Poor transitions result in a disorganized picture.

Try to avoid Yes-No patient answers to your questions. They relate little information. Spontaneous
paragraphs are what you are seeking for they will most likely be closer to the relevant truth you seek.

A good rule of thumb is that three-fourths of the talking should be done by the patient. You can keep
the patient talking by:
(1) keeping silent when the patient pauses,
(2) ask, "Go on!" or nod in agreement,
(3) have the patient reaffirm his own words such as asking "It hurts only in the right leg, right?" or
(4) have the patient clarify something he said earlier.

Your job is to lead the patient so that he will not leave anything important out of his story. Such
control usually necessitates privacy and enough quiet so that both patient and doctor can concentrate.
Relatives and friends should not be present except in situations such as a pre-adolescent, mental
retardation, or when language interpretation is necessary.

You can lead the patient in several ways and maintain control of the situation; for example, by
frequent eye contact, offering undivided attention, changing the subject when the patient wanders,
and in the manner in which you frame your questions. Non-threatening questions as "Tell me more
about your...." or "Would you say your pain is sharp or burning?" elicit more information than simple
direct questions that require a mere yes or no response. A simple "Anything else?" or "What do you
mean by ...? often brings forth important information.

The facts you gain during the interview will become your basis for making a therapy decision when
they are correlated with physical and laboratory findings. And of all these procedures, most
diagnosticians feel that the history during the initial interview is the most important. It should never
be rushed.

Science and humanity are not incompatible. There is no substitute for a physician's interest,
acceptance, recognition, and empathy, from the patient's viewpoint. Studies have shown that these
qualities are more important to the patient in selecting a doctor than the physician's technical and
scientific ability. Galen told us centuries ago: "He heals the best in whom the most people have the
greatest confidence."

To understand why a patient thinks and acts as he does, the doctor must first learn why he thinks and
acts as he does. Each physician has a unique "anatomy and physiology" in his decision process, and
each has its own strengths and weaknesses.
The interview is not complete unless you are confident that you understand:

(1) the beginning and course that the patient's problem has followed,
(2) where the problem is located and its nature,
(3) the quality and quantity of the problem,
(4) under what circumstances the problem is aggravated and relieved, and
(5) the problem's associated manifestations.

Patient Anxiety

Every illness has an emotional component. Sometimes this component is slight, and sometimes it
may amount to an emotional crisis. Health and well being cannot become complete unless there is
both physical and emotional recovery. Young and inexperienced physicians have a tendency to
negate, minimize, and sometimes even ridicule psychological manifestations. This is probably the
result of academic over-emphasis upon objective technical data rather than upon the patient as a
whole. It is also much easier to interpret laboratory data than it is to evaluate subjective responses
during the diagnostic work up.

The technical and scientific aspects of health science can be learned through books and courses;
however, the art of clinical practice can only be learned in the doctor-patient relationship of heath
"care". For this reason, the diagnostic process can never become fully computerized. To diagnose
means to thoroughly understand, and one cannot fully understand unless the human elements are
taken into consideration. A computer may be helpful in the accumulation and sorting of data, but it
can never be programmed to interpret correctly in light of human problems.

An individual becomes a patient when he or she seeks health care from a professional. The term
"patient" comes from the Latin word "pati" which means to suffer. This suffering, mental or physical,
must be remembered at all times.

Self-preservation is one of our strongest urges. Thus, in matters of health, every patient feels
emotional discomfort. There is not always pain, but there is always anxiety. In the wake of any
illness, there is a flood of fears --some based on fact, many on assumption or unwarranted beliefs.
There are fears of personal survival, financial concerns, social worries. There are fears of pain from
examination or therapy, of the doctor's competency, and of embarrassment in exposing private areas
to a stranger. Recognize these fears: they deserve understanding and recognition, never a minimizing
"put-down".

Quite often, delicate topics will have to be explored such as in sexual difficulties, menstruation
disorders, a history of venereal disease, or signs of illegal drug use. Such areas should not be covered
too early. Let a rapport be developed first, and the information will be more open and credible.
Anxiety is expressed in a wide variety of behavioral patterns --the angry patient, the hostile patient,
the dependent patient, the crying patient, the embarrassed patient, the depressed patient, the
affectionate patient, the uncooperative patient and the overly cooperative patient. A cultured
sympathetic objectivity is the best way to calm the angry and hostile, avoid dependency attachment,
sublimate the affectionate, ease the embarrassed, give hope to the depressed, and maintain necessary
cooperation in a professional atmosphere.

Take care not to act too friendly or not friendly enough. The doctor must be sincerely concerned, yet
he must maintain a degree of detachment. If objectivity is lost, judgment becomes biased, and acts
become controlled by emotions rather than by reason. By being calm, sympathetic, showing interest
and acting human, the doctor tends to reduce those anxiety forces within the patient that would not be
in the best interests of case management or honest communications.

One of the easiest methods of revealing unwarranted anxiety is one of the most overlooked; that is, to
simply ask the patient how he interprets his symptoms. If the patient's beliefs are in error, never imply
that he's ignorant. ust state your interpretation and how you will determine the facts.

Each patient has his own way of coping. Regardless of it's expression, it is the doctor's responsibility
to try to understand why the patients feels and thinks the way he or she does. This is the first
diagnosis --and the act, the first therapy. Complacency and a "matter of fact" or judgmental attitude
are negative forces in the doctor-patient relationship.
As a general rule, organic diseases present clear-cut symptoms, while emotional or mental disorders
are apt to be poorly defined and presented as seemingly unrelated complaints until the trouble for the
organ language is discovered. Today we realize that there is a close relationship between psyche and
soma. While one aspect may be far more important in a particular case, it is never alone and the other
aspect should not be neglected.

It is important to realize in both diagnosis and therapy that symptoms in chronic cases may have
become a fixed part of the personality and sublimated to have certain positive benefits. For instance, a
crutch may have been developed into an instrument to gain attention and sympathy. Periodic episodes
of pain may be used to keep a spouse nearby and restricted to the house. Thus, the doctor must
consider not only a symptom or sign and its pathophysiologic consequences but also question what a
symptom or sign means to a specific patient.

Note Taking During the Interview

Except for specific dates, numbers, and key-word reminders, note taking during the interview is poor
practice for several reasons. It distracts the doctor in giving careful concentration to the patient. It
makes it appear to the patient that the doctor is more interested in cold data than the warm person
who is undoubtedly hurting.

Although the information gathered during the interview will be a basis for the development of the
case record, interview information is far from suitable as it is presented. When entered into the case
record, this information must be greatly condensed, sifted and filtered, and put in proper sequence
and professional terminology before it is formally recorded.

Errors in Technique

The interview conversation should be designed to be subjective; that is, an account of the patient's
feelings and beliefs. A symptom can never be a diagnosis: a headache is a symptom, even if you call
it cephalgia. Anything that is an effect of something such as pain, immobilization, dystonia, myopia,
and so forth, cannot be a diagnosis. The cause of the effect is the diagnosis, and this is arrived at by
analysis and evaluation of all symptoms, signs, and findings. To seek the cause of the ailment is to
seek the diagnosis. Thus, to fail to arrive at a diagnosis or arrive at a wrong diagnosis is to fail to
determine the cause. Since chiropractic's inception, practitioners have been directed to "look to the
cause". To seek the cause is to seek the diagnosis.

Many errors in diagnosis can be traced to errors in data collection such as:

(1) failure to ask important questions,

(2) failure to obtain adequate patient response to questions,
(3) failure to adequately explore important leads, or
(4) failure to place information in proper perspective. Some patients over-emphasize symptoms while
others tend to de-emphasize them depending upon their emotional state and motivations.

Only is most rare instances can a few symptoms arrive at a clear diagnosis. Most clinical diagnoses
will be comprised of a syndrome, supported by physical signs observable to or elicited by the
examiner, and correlated with laboratory and roentgenological data interpretations. It is frequently
stated that a good clinician is a good observer, critic, communicator, decision-maker, and a good
student --now and throughout his career.

One symptom by itself usually means very little. It is its relationship to other symptoms that is
significant. For instance, vomiting accompanied by abdominal pain in the lower right quadrant may
indicate appendicitis, while vomiting with headache and failing vision would lead one to suspect
something causing intracranial pressure. The art of diagnosis is developed by learning to recognize
characteristic symptom and sign groups and their anatomical and pathophysiologic relationships.

Biorck reminds us in THE PROBLEM-ORIENTED SYSTEM that good clinical communications

require awareness that any one patient is three patients in the practical sense: there is the patient as he
is; the patient which develops within the doctor's mind; and the patient that develops in the doctor's
records. The patient within the doctor's mind may be quite different from the patient as he really is.
This is because patients will never tell you everything. They may be withholding information, they
may have forgotten something, or they might not understand what information is important to you. In
addition, doctor's are human beings, and human beings cannot help but project, identify, and
rationalize in error at times. The doctor may be able to identify with a patient's story, but his
experience can never be exactly similar. The doctor's mental image of the patient might contain
information that is not in the records. In the same token, the records might contain facts that have
been forgotten by the doctor.

Both patients and doctors are often guilty of prejudice. A patient's previous experiences with doctors
affect his perception of every doctor. A doctor's reaction to a patient of a certain age, sex, lifestyle, or
ethnic group can influence his clinical decisions. Such factors should not be a part of health care; but
they are, because patients and doctors are human.

Symptoms usually appear quite early before marked physical signs of disease are evident and before
laboratory data are useful in detecting malfunction. For this reason if for no other, a high-quality
gathered and interpreted case history is necessary to lead the doctor to correct conclusions.

The presence or lack of a symptom may be of great interest during the case history just as the
presence or lack of a sign may be of great interest during the physical examination. For this reason,
both the presence of or the lack of symptoms and signs should be recorded. To record only positive
symptoms and signs is to record only half the facts and may falsely indicate an ommission of inquiry.

A doctor may have certain routines he uses in certain situations in taking a case history and
conducting a physical examination. However, there should be no such process as a "routine"
examination, and routine or mechanical recording of data does not constitute a case history.

Regardless of how carefully an impersonal inquiry into a patient's illness has been designed (eg, a
questionnaire or routine procedure), it can never take the place of personal interest in the uniqueness
of the patient. Several studies in teaching hospitals have revealed that there is a direct correlation
between therapeutic results and the amount of effort and time spent with the patient during the initial
interview.

In recent years, there appears to be an over-emphasis in both the undergraduate and postgraduate
levels in teaching the mechanical aspects of physical diagnosis such as of the various neurological
and orthopedic signs and reflexes and methods of muscle testing. While these methods are vital to
complete assessment of the patient, there is danger that the doctor will become more concerned with
the study of disease than the study of patients. Scientific knowledge without wisdom in application is
folly.

Our technical knowledge is expanding at a rapid rate. This is well, but we must be alert that it should
not be at the expense of the ill person, else we become better technicians and poorer physicians. The
most important diagnostic skill is that which is the least taught and most difficult to learn: how to talk
with patients and obtain not just adequate but significant information.

Elements in Diagnostic Logic

Before the doctor can take rational action, such action should be preceded by careful observation and
description, interpretation and verification, and diagnosis and review.

Observation and Description

The first two steps are to observe and describe. Much of the purpose of the doctor's observation is to
understand and appreciate the patient's background, habitus, note the degree of functional difficulties
and pathological processes evident, and grade the scope and pertinence of abnormal findings found
within the interview, physical examination, and associated laboratory studies. The doctor describes
when he tabulates his obervations. This is a sifting of pertinent facts from irrelevant information that
results in condensed, logically organized, patterns of data. A typical patient will present a number of
abnoralities that will be non-related to his present illness, and a decision must be made as to what is
pertinent and what is not.

Interpretation and Verification

The next two steps are interpretation and verification. When information about the patient has been
tabulated, it must be reviewed in light of the doctor's basic science knowledge and clinical
experience. The doctor must weigh and differentiate the pattern of the patient's problem with the
pattern of known disease processes. Once an initial and possible determination(s) is made, logical
diagnostic procedures are selected, given a priority, and scheduled to verify this opinion. As the
examinations and tests are conducted, their findings must be tabulated, interpreted, and judged
against the particular patient and his situation at hand.

Diagnosis and Review

Diagnosis means more than applying a label to a disease process. While it means to identify
disease(s) accounting for a patient's illness, it means to a greater extent to determine the nature of the
patient's distress. While a label helps in identification and is necessary for various legal and
communications reasons, it may not always accurately predict therapy or prognosis even if it predicts
the course of initial therapy. If, however, patient progress does not show expected results, then the
working diagnosis and course of treatment based upon it must be modified.

The tendency to jump to conclusions based upon a few facts must be avoided. For many reasons,
interpretation of history, physical, and laboratory findings may be faulty. The patient may not be
perfectly open and honest during the interview. Symptoms being subjective are a mixture of
emotional and physiological factors. Physical findings may be misleading. Positive or negative
laboratory tests are not always accurate. All standard diagnostic procedures are helpful, none are
perfect.
Example:
Dr. Richard H. Tyler tells the story of how diagnostic procedures, in this instance a physical sign and
lab work, can indicate that something is wrong, yet not specifically identify the cause. He reports in
an article titled "Thinking Before Diagnosing" which appeared in the May 1979 issue of THE
CHIROPRACTIC FAMILY PHYSICIAN the following account. It is not unfamiliar to that
experienced by many doctors of chiropractic.

"Several years ago I had a patient come to me complaining of severe pain on the right side of the
lower thoracic--upper lumbar spine. She had been a patient of mine for quite some time but I had
never seen her in such distress as she was this day. The adjustments that I usually made in that region
couldn't be performed due to the acute pain. I examined the abdominal area and found McBurney's
point exceptionally sensitive. Something was radically wrong. Appendicitis was the first condition I
thought of. 'It's probably just gas', said my patient. 'Why don't I just go home', she continued, 'and call
you in the morning'. I hesitated. I had a full schedule of patients so such a plan would be easier on
me. I looked at her for a long time. No, I decided to send her to the lab in the building for a CBC. I
put a stat on the order and within the hour the report came back with an extremely high WBC count. I
referred her immediately to the surgeon in the building. Soon he was on the phone asking me for the
CBC differential. 'I believe it's a hot appendix', he said. 'I'd like to put her in the hospital right away.'
That evening my patient underwent surgery for appendicitis. The following morning the surgeon
called me and told me that we both had made a misdiagnosis. 'We found that she had a ruptured
ovarian cyst and was bleeding to death internally. Had she gone home to call you in the morning, as
she wanted, she undoubtedly would have died in her sleep.'"

Patient Profile

The patient profile is the opening statement in the patient's record. It usually consists of a brief
narrative about the patient's way of life:

(l) life history, including usual day's activities, and education,

(2) marital status,
(3) occupation,
(4) finances,
(5) personality,
(6) habits,
(7) hobbies and special interests,
(8) religion, and last but not least,
(9) posture.
The purpose of the patient profile is for the doctor to form a picture of the patient's present lifestyle:
home, work, and recreational activities to see:

(1) if anything therein may be the cause of or contributing to the patient's health status, and
(2) gain insight into the impact of the patient's problems on his daily activities.

Any of these factors may be a contributor of stress leading to lowered resistance and disease. Life
history may indicate certain socioeconomic burdens or recent relocation frustrations. Marital status
may present a mate incompatibility or a divorce maladjustment. The occupation may contain peer or
superior friction, postural strains, or chemical or physical work hazards. A financial strain may be
causing abnormal tension in a personality that is habitually "high strung" without the added pressures
of money worries. Habits in diet, sleeping, or exercise may be a factor. Habits and addictions to
tobacco, alcohol, diet fads, laxatives, and drugs may be causative or contributing factors. Religion
may have an influence on diet, on fears behind anxiety, or on guilt behind depression.

Activities

By inquiring into a patient's usual day's activities, you deepen rapport with the patient and gain
additional insight into specific problem areas. Such knowledge gives an understanding of how the
patient is coping with his or her environment: physically, mentally, emotionally. Inquiries should be
directed to the patient's quantity and quality of sleep; how he feels upon arising; evacuation problems;
ability to dress one's self, prepare meals, drive a car, do housework or yardwork; difficulty of work
activities and amount of overtime worked; amount of recreation and exercise; and other such factors
of lifestyle.

Occupation

Occupation is often associated with physical and mental stress. Inquire as to how the patient
perceives his job, future career, and rapport with associates. Explore specific tasks and
responsibilities. Try to determine if there is any link between the patient's symptoms and occupational
hazards. Chemicals, dust, gases, postural strain, physical abuse, inadequate lighting or temperature
control should be discussed. Excessive noise, arc lights, job boredom, stymied promotion, salary
level, poor job benefits, and deadline pressures may also be pertinent.

Postural strains peculiar to the patient's line of work are always vital to a complete case history. Probe
to see if musculoskeletal symptoms are related in any way to other somatic or visceral problems. Are
any occupational stresses being superimposed on other complaints?

Automobile seats have a tendency to place the pelvis lower than the knees and to flatten the lumbar
curve. The smaller and lower cars create awkward stooping and bending motions upon entering and
leaving. These factors must be considered in people who drive a lot such as traveling salesmen.

Farmers who drive tractors and other large farm equipment, as well as workers who operate large
construction equipment, frequently steer with one hand and twist their torso to view behind. This
contributes to both lumbosacral and cervicodorsal strain, almost as much as shoveling and tossing
dirt, gravel, or snow.

Dentists are taught to work in the sitting position, but many still stand and work in a bent position
causing lumbosacral strain and with their upper thorax rotated to one side causing middorsal strain.
Forward bending and rotaion is also a common problem with barbers and beauticians.

Each occupation has its postural features. Rare is the energetic housewife who does not complain of a
nagging backache. Making beds, ironing, carrying groceries, vacuuming the rugs, picking up the
children's toys, amount to about every bending, twisting motion imaginable. Assembly line workers
maintain a stressful forward bending of head, neck, and upper dorsal spine. Typists and writers often
assume the same posture while sitting. Packing and loading workers must constantly pick up a load
from one side of their body, rotate their spine, and place the load on the other side.

Musicians commonly have postural defects peculiar to their instrument. The cello player rotates his
trunk slightly to the left. The violinist must hold his instrument by force of his rotated flexed neck.
The pianist sits for hours on end in practice with his trunk and shoulders flexed. The bass viol player
bends his thorax to the right and rotates left with the right shoulder anterior.
Loosening of pelvic supports and the adominal weight of pregnancy is a well-recognized cause of
backache. Less recognized is the awkward position during ottle feeding resulting in mid-dorsal strain.
Bending from the waist and lifting the growing child frequently causes sacroiliac involvement if not
lumbosacral strain. Carrying a toddler on one hip results in abnormal side bending and lower spine
rotation with compensatory curves above.

Some practitioners such as Nelson feel strongly that posture and position is not the cause of most
musculoskeletal problems: "Experience indicates the muscle sensitized by reflex irritation and
prolonged or repetitive effort merely raises the irritability to exceed the threshold. Functional visceral
irritations are a frequent cause of a low-level unconscious hypertonicity waiting to be further
irritated."

Education

Inquiries into a patient's educational background may indicate a low intelligence level which would
make it difficult to follow normal instructions or to comprehend their significance. If normal
explanations appear too complex for the patient, drawing pictures and using stories are helpful to get
your points across. There also appears to be a relationship between educational level and
effectiveness of treatment. The more a person comprehends his disorder, the more he is motivated to
modify behavior.

Finances

Money worries can contribute significant stress, especially if a sudden loss or burden is recent.
Questions regarding income must be asked with great tact and assured confidence. Once income level
has been determined, inquiries as to size of household and debt responsibilities will help to profile the
situation.

Nelson feels that "Worry of considerable magnitude but of short duration does not seem to be as
hard on the nervous system as long, continued, but lower-level anxiety. Our primitive nervous system
is well-suited for 'natural' or catastrophic stresses, but has difficulty with long drawn-out stress found
in modern civilization."

Diet

While poor nutrition is usually regarded as the outcome of poor habits and conditioned tastes, other
factors must be considered. Diet habits may be associated with income, poor storage or cooking
facilities, ethnic food preferences, lack of planning or preparation knowledge, or anorexia associated
with disease.

While obtaining a dietary history appears burdensome, it is necessary in obtaining a complete patient
profile. If a 24-hour recall appears inadequate, have the patient develop a food diary for a week so
that you may assess caloric, vitamin, mineral, and protein intake. Inquire into snacks and "junk" food
habits. Frequent use of peanuts, popcorn, and chips may be associated with sodium imbalance
contributing to hypertension, for example. Food allergies, sensitivities, and food fads should be
discussed.

Nutrition commonly denotes food ingestion. While intake is important, facors of digestion,
assimilation, transport, the regulation of metabolic end products, and elimination of metabolic and
bulk wastes are also significant. The nutritional picture is complicated because almost all systems
have some influence on nutrition. A comprehensive systems review helps to clarify the problems as
long as it is recognized that the digestive, musculoskeletal, nervous, urinary, endocrine, circulatory,
respiratory systems and psyche are interrelated.

Hobbies and Special Interests

Hobbies and recreational interests often give clues to emotional interests, intellectual level, and motor
skills. Athletic participation assesses heart, lung, muscle, joint function, and coordination. Particularly
significant is a recreational activity recently stopped such as an avid golfer who has recently given up
the game. Inquire if any regular activity has recently been abandoned and why. Many hobbies require
certain degrees of stamina, dexterity, visual acuity, and other functions that help to profile the patient.
A lack of interests may indicate a physical impairment or be a barometer of emotional health (eg,
depression). Such knowledge is often helpful in establishing therapeutic goals.

Posture

Inquiries should be made about the patient's typical posture while lying, sitting, or standing.
Occupational postures have been previously discussed, but may be probed into further if it is felt
necessary. Discuss the amount of time spent in these positions and whether or not symptoms are
eased or aggravated by certain positions and motions.

Ask about the patient's mattress and the degree of rest noticed in the morning. Is the patient sleeping
in a twisted position that would cause a pelvic torsion? Are the arms placed over the head, thus
contributing to a brachial plexus condition? Are large pillows used in the supine position which tend
to aggravate a dorsal kyphosis or strain the cervico-dorsal junction? Are the pillows too soft or too
small to support the neck and head in the side position? If so, lateral cervical strain may be present.

Does sitting ease or aggravate any discomfort? Discuss the type of chair used at home and at work. Is
there firm back support? Discuss chair height to desk height. Desk height should be level with the
undersurface of the forearm flexed 90 degrees. Chair height should allow 90-degree knee flexion with
thighs parallel to the floor. It's best that knees be slightly higher than hip than below hip. Does poor
lighting affect sitting posture?

While standing, is weight shifting excessive? Is weight borne more on one side than the other? Which
side? Does the heel of one shoe wear more or differently than the other? Do slacks or skirts have to be
tailored so that they hang equal? Does one hip appear larger or one shoulder higher during tailoring?
Women are often aware that one brassiere strap or slip strap seems to slide off a low shoulder
frequently.

Patient History
The patient history consists of the:

(1) presenting symptom,

(2) present illness,
(3) personal history, including past sicknesses, hospitalizations, medications,
(4) family history,
(5) accident history, and
(6) a systems review. The goal of the patient history is for the doctor to have an accurate record of,
understanding of, and appreciation for these factors.

The presenting symptom is the chief complaint; that is, the major problem for which the patient has
sought relief. A detailed description of the patient's current problems developed chronologically is
called the "present illness". Every symptom and sign has a beginning and a course of development
that may be progressive or fluctuating. Symptoms and signs are products of the body that produced
them. Each body creates symptoms and signs in an unique way, and each personality adapts to them
in an unique way.

The chief complaint consists of a brief statement, preferably in the patient's own words, concerning
his reason for seeing the doctor. It also portrays the patient's sense of priorities about his problems.
Actually, the term "present illness" is a relic of the past in which a patient saw a physician for a single
illness. Years ago patients rarely sought relief for chronic, multiple, interacting problems as they do
today. Thus, "active problems" would be a better descriptor, but "present illness" is commonly used
today with a more modern interpretation. Ascertaining the presenting symptom and present illness
has been previously discussed.

Personal History

To assess the patient's personal health history, inquiries should be directed toward childhood diseases,
major illnesses, operations, pregnancies (deliveries and abortions), allergies (air-borne, contact,
medications, food), serious accidents, immunizations and reactions to such.
Previous hospitalizations may give clues to active conditions. Surgery for a ruptured appendix several
years ago may result in adhesion troubles today, for example. Record dates of surgery,
hospitalizations, length of confinement, and complications. Chronic diseases may be superimposed
upon an acute condition. For example, infections hamper diabetes control, a sudden rise in blood
pressure may bring out a cardiac weakness, an acute abdominal strain may interfere with a
compensated lordosis, or sneezing may aggravate a chronic cervical disorder.

Medications direct attention to problems presently being treated or controlled. It is also well to
remember that medications interact with other drugs. Some patients do not know what medications
they are taking or why they are taking them. If this is the case, note the prescriptions and look up the
drugs, their actions and side effects. Determine if the patient is following the instructions on the
bottles. Inquire into use of non-prescription drugs. Overuse of aspirin, for example, is a common
cause of gastritis, especially compounded with alcohol intake. Many drugs interfere with gastric pH,
enzyme quality, normal renal excretion, intestinal bacteria, and normal blood chemistries. Drugs may
also confuse the significance of certain signs and symptoms. For instance, a black tarry stool may be
the result of bismuth powders or an iron tonic.

Family History

Genetic factors are sometimes involved in diabetes, renal disease, hypertension, mental illness, heart
disease, cancer, and allergies. Inquiries should be directed toward the health status of grandparents,
parents, and siblings. Ages and causes of death are important information. Determine if one or more
members of the family is or has experienced symptoms similar to those presented by the patient.
Genetic counseling may be advisable later with presymptomatic members of the family, and
reproduction risks should be discussed if appropriate.

Accident History

A detailed accident history is vital to a complete patient history. Discuss in detail the where, when,
and how each accident or severe strain occurred. Ascertain the care administered, the scope and
degree of trauma, the diagnostic tests taken and the care administered. For example, many allopathic
whiplash cases are dismissed upon the relief of pain. Joint stiffness and fixation often result because
of compensatory connective tissue effects of the over mobilization, similiar to traumatic arthritis
effects. Proper manipulation would prevent this: if not completely, then to a large extent.

In an automobile accident, for instance, it is important to know from which side the force came, the
position of the patient at the time of impact and after. Was a seat belt or shoulder harness fastened?
Did the patient's head strike anything? Was there unconsciousness? What were the immediate
symptoms? What were the later manifestations? These and many more similar questions must be
deeply probed.

UNIT-II:CLINICAL LABORATORY TESTS USED IN EVALUATION OF DISEASE

STATES AND INTERPRETATION OF TEST RESULTS

A.HEAMATOLOGICAL,LIVER FUNCTION,RENAL FUNCTION,THYROID TESTS:

HEAMATOLOGICAL TESTS:

Say you had a blood test done. You call the laboratory to see if results are in, but the receiver says,
''This is chemistry; you need micro'' or ''Let me transfer you to hematology.'' Did you know there
were labs within the lab? There are. Each department within a laboratory specializes in certain tests.
Let's see just what's going on in the hematology department of the lab.

Hematology ('hema-' is from the Greek word for 'blood') is the study of blood in regards to a person's
health or disease. It includes blood, blood-forming organs, and the proteins involved in bleeding and
clotting.

Hematological tests can evaluate numerous conditions involving blood and its components. They can
also be used to diagnose inflammation, anemia, infection, hemophilia, blood-clotting disorders,
leukemia, and response to chemotherapy, among many other things. Let's take a look at some of these
tests.
 Hematology often looks at red and white blood cell levels

Complete Blood Count Test and Components

A complete blood count (CBC) measures several components and features of your blood. A CBC
and its individual components are tested on whole blood. It can include measurements of the
following:

White Blood Cells

White blood cells (WBC) make up the body's primary defense system and knowing their number is
an important tool in diagnosing and monitoring infection and leukemic disorders. A normal WBC
level is 4,500 - 11,000 per mm³ of blood.

Increased WBC levels are most notably found in those with any type of infection, but are also found
in anemia, collagen disorders, and those with physiologic stress, such as pregnancy. Low WBC levels
are seen in malnutrition, rheumatic disorders (lupus, arthritis), some viral infections, and those
undergoing chemotherapy or other forms of bone marrow suppression.

Red Blood Cells

Red blood cells (RBC) are responsible for the transport and exchange of oxygen. Measurement of
RBCs is important in monitoring the effects of blood loss and the progression of chronic disease.
Normal counts of RBCs are 3,900,000 - 5,800,000 per mm³ of blood.
RBC values are increased in those with anxiety or stress, bone marrow failure, and dehydration. A
decreased RBC value will be found in those with chronic inflammatory diseases, chemotherapy
patients, anemia, blood loss, and many cancers.

In addition to a count of WBCs and RBCs, a complete blood count can include further tests to
evaluate the size, weight, and shape, of those cells. These more detailed tests are helpful in
diagnosing and monitoring therapy for cancer and anemic patients.

A hematologist prepares a slide to check for RBC abnormalities

Hemoglobin

Hemoglobin (HgB) is the oxygen-carrying protein in red blood cells. Hemoglobin levels are a direct
reflection of the amount of oxygen in the blood. A normal hemoglobin concentration is 11-15 grams
per deciliter (g/dL) of blood.

Increased HgB is seen in those with dehydration, chronic obstructive pulmonary disease (COPD) and
congestive heart failure (CHF), and those at high altitude. A decreased HgB value is seen in anemia,
blood loss, liver disease, as well as leukemia and lymphomas.
Hematocrit and Platelets

Hematocrit (HCT) is the proportion of red blood cells to plasma, the fluid component of your blood.
HCT helps to evaluate anemia and hydration. A normal percentage of hematocrit is 33 to 49%. The
increase and decrease levels of HCT mirror those of hemoglobin.

RBC, HgB and HCT tests parallel each other and are frequently used together to evaluate anemia.

Platelets (PLT) have an essential function in blood clotting. A normal value is 150,000 - 450,000
platelets per mm³ of blood.

An increased platelet value is seen in conditions that involve inflammation such as acute infection,
trauma, and some malignant cancers. A decreased platelet count is found in alcohol toxicity, anemia,
blood loss, infection, many congenial conditions, and coagulation disorders.

Routine hemogram (CBC):

This is performed in all mammalian species. Testing is performed with our hematology analyzer, the
ADVIA 2120. The CBC provides white blood cell results (white blood cell count, differential cell
count and leukocyte morphology), red cell results (red cell count, hemoglobin concentration,
hematocrit, red cell indices and red cell morphology), platelet results (platelet count, mean platelet
volume and smear estimate), total protein (by refractometer) and plasma appearance.

A reticulocyte count is automatically added to a CBC in anemic dogs and cats only. We also provide
an absolute reticulocyte count, which gives a more accurate assessment of the bone marrow response
to anemia than the reticulocyte percentage in these species.

Non-mammalian CBC:
These tests are run manually using bench methods. EDTA is the preferred sample for non-
mammalian hemograms.

Also note that we do not have reference intervals for non-mammalian species.

Non-mammalian species represent a challenge to the clinician and clinical pathologist. Only small
amounts of blood can be collected from most patients, necessitating the use of microtainer tubes.
Similar to mammals, EDTA is the preferred anticoagulant for non-mammalian hematology. However,
there are certain species of birds, e.g. cranes, and reptiles, e.g. turtles, whose blood hemolyzes on
contact with EDTA. This hemolysis invalidates the PCV and affects assessment of red blood cell
morphology during blood smear examination. For these species collection of blood into citrate or
heparin may be needed. Please note that heparin will cause leukocyte and thrombocyte clumping
which can invalidate WBC counts and differential cell counts.

Automated hemograms:
Our Advia hematology analyzer also provides an automated hemogram or an automated WBC panel.
This is available for certain species only, including dogs, cats, horses, cattle, sheep, goats, pigs, mice,
rats and certain species of monkeys. The only acceptable sample for a mammalian hemogram is
EDTA (lavender top tube).

The automated hemogram (and WBC panel) is recommended for research samples and for pre-
surgical screening in relatively healthy animals. These panels are not recommended for use in sick
animals, because they do not include morphologic features, such as assessment of red and white cells,
which can provide valuable information on underlying disease states.

Blood smear evaluation:

Included as part of the routine CBC and non-mammalian CBC. Can be requested separately if
automated leukogram is abnormal or no EDTA sample is available (slides only).

Individual Tests

Many of our hematology tests can be ordered individually, rather than as group tests. This is useful
for research samples. In this case, samples other than EDTA may be acceptable, however before
samples are submitted to the laboratory for hematology testing in any other anticoagulant than EDTA,
please contact the laboratory. Other individual tests performed in the laboratory are fibrinogen by
heat precipitation and fecal occult blood. See below for more information.

Reticulocyte count:
Reticulocytes are automatically included as part of the routine (not automated) hemogram in anemic
dogs and cats. A reticulocyte count will have to be specifically requested (and will be added at extra
charge). We also provide absolute reticulocyte counts when a reticulocyte count is requested or added
automatically to a hemogram. Please note, however, that an absolute reticulocyte count cannot be
provided if a red cell count is not available for that sample (the absolute reticulocyte count is
calculated from the product of the reticulocyte percentage and the red cell count).

Fibrinogen by Heat Precipitation:

This test is performed on EDTA samples only and is used for determination of fibrinogen
concentration as an indicator of inflammation in large animals. Fibrinogen is an acute phase
reactant protein and elevated values are seen in inflammation and renal disease (for the latter, in
the cat and cow especially). This method of fibrinogen determination is not sensitive enough to
detect decreased fibrinogen concentration in coagulation abnormalities.

Fecal occult blood:

The indication for this test is to help confirm suspected gastrointestinal blood loss. This test is
performed on feces and is based on the pseudo-peroxidase activity of the heme component of
hemoglobin using a guaiac paper test. In the test, heme (iron in the middle of a poryphyrin ring)
oxidizes phenolic compounds in guaiac acid to quinones, producing a color change. The animal
should be on a meat-free and peroxidase vegetable-free diet for up to 3 days prior to the test. This is
because meat contains large amounts of hemoglobin and myoglobin, both of which contain heme, and
plant peroxidases (e.g. from turnip, cauliflower, cantaloupe, parsnip, broccoli, horseradish, radish)
will catalyze the reaction in the absence of heme, causing false positive reactions. To eliminate false
positive reactions from plant peroxidases, any positive fecal occult test is confirmed by retesting 48
hours later. Plant peroxidase activity will decrease during this time, thus eliminating false positives.
Note that with intermittent blood loss, a single fecal occult blood test may be negative. Testing on
several different fecal samples is advised if gastrointestinal blood loss is strongly suspected.

LIVER FUNCTION TESTS:

Liver function tests (LFTs or LFs) are groups of blood tests that give information about the state of

a patient's liver. These tests include prothrombin time (PT/INR), aPTT, albumin, bilirubin (direct and

indirect), and others. The liver transaminases aspartate transaminase (AST or SGOT) and alanine

transaminase (ALT or SGPT) are useful biomarkers of liver injury in a patient with some degree of
intact liver function. Most liver diseases cause only mild symptoms initially, but these diseases must

be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This

testing is performed on a patient's blood sample. Some tests are associated with functionality (e.g.,

albumin), some with cellular integrity (e.g., transaminase), and some with conditions linked to the

biliary tract (gamma-glutamyl transferase and alkaline phosphatase). Several biochemical tests are

useful in the evaluation and management of patients with hepatic dysfunction. These tests can be used

to detect the presence of liver disease, distinguish among different types of liver disorders, gauge the

extent of known liver damage, and follow the response to treatment. Some or all of these

measurements are also carried out (usually about twice a year for routine cases) on those individuals

taking certain medications, such as anticonvulsants, to ensure the medications are not damaging the

person's liver.

Standard liver panel[edit]

Although example reference ranges are given, these will vary depending on age, gender and his/her
health, ethnicity, method of analysis, and units of measurement. Individual results should always be
interpreted using the reference range provided by the laboratory that performed the test.

Total bilirubin[edit]
Main article: Bilirubin

Reference range in adults

Parameters/units Total bilirubin Unconjugated bilirubin Conjugated bilirubin

mg/dL 0.1–1.0 0.2-0.7 0.1–0.4

 μmol/l 2.0 to 21 < 12 <8

Measurement of total bilirubin includes both unconjugated (indirect) and conjugated (direct)

bilirubin. Unconjugated bilirubin is a breakdown product of heme (a part of hemoglobin in red blood

cells). The liver is responsible for clearing the blood of unconjugated bilirubin, by 'conjugating' it

(modified to make it water-soluble) through an enzyme named UDP-glucuronyl-transferase. When

the total bilirubin level exceeds 17 μmol/l, it indicates liver disease. When total bilirubin level

exceeds 40 μmol/l, bilirubin deposition at the sclera, skin, and mucous membranes will give these

areas yellow colour, thus it is called jaundice.

The increase in predominantly unconjugated bilirubin is due to overproducion, reduced hepatic

uptake of the unconjugated bilirubin and reduced conjugation of bilirubin. Overproduction can be due
to reabsorption of haematoma and ineffective erythropoiesis that increased red blood cell
destruction. Gilbert's syndrome and Crigler–Najjar syndromehave defects in UDP glucuronyl
transferase defect, affecting bilirubin conjugation.

The degree of rise in conjugated bilirubin is directly proportional to the degree of hepatocyte injury.
Viral hepatitis can also cause the rise in conjugated bilirubin. In parenchymal liver disease and
incomplete extrahepatic obstruction, the rise in conjugated bilirubin is less than the
complete common bile duct obstruction due to malignant causes. In Dubin–Johnson syndrome, a
mutation in multiple drug-resistance protein 2 (MRP2) causes a rise in conjugated bilirubin.

In acute appendicitis, total bilirubin can rise from 20.52 μmol/l to 143 μmol/l. In pregnant women, the
total bilirubin level is low in all three trimesters.

The measurement of bilirubin levels in the newborns is done through the use of bilimeter or
transcutanoeus bilirubinometer instead of performing LFTs. When the total serum bilirubin increases
over 95th percentile for age during the first week of life for high risk babies, it is known as
hyperbilirubinemia of the newborn (neonatal jaundice) and requires light therapyto reduce the amount
of bilirubin in the blood. Pathological jaundice in newborns should be suspected when the serum
bilirubin level rises by more than 5 mg/dL per day, serum bilirubin more than the physiological
range, clinical jaundice more than 2 weeks, and conjugated bilirubin (dark urine staining
clothes). Haemolytic jaundice is the commonest cause of pathological jaundice. Those babies with Rh
hemolytic disease, ABO incompatibility with the mother, Glucose-6-phosphate dehydrogenase (G-6-
PD) deficiency and minor blood group incompatibility are at increased risk of getting haemolytic
jaundice.[7]

Alanine transaminase (ALT)

Main articles: Alanine transaminase and Elevated transaminases

Apart from being found in high concentrations in liver, ALT is found in kidneys, Reference range

heart, and muscles. It catalyses the transamination reaction, and only exists in
7-56 IU/L
cytoplasmic form. Any kind of liver injury can cause the rise in ALT. A rise up to
300 IU/L is not specific to liver, but can be due to the damage of other organs such
as kidneys or muscles. When ALT rises to more than 500 IU/L, causes are usually from the liver. It
can be due to hepatitis, ischemic liver injury, and toxins that causes liver damage. The ALT levels
in Hepatitis C rises more than in Hepatitis A and B. Persistent ALT elevation more than 6 months is
known as chronic hepatitis. Alcoholic liver disease, Non-alcoholic fatty liver disease (NAFLD), fat
accumulation in liver during childhood obesity, steatohepatitis (inflammation of fatty liver disease)
are associated with rise in ALT. Rise in ALT is also associated with reduced insulin response,
reduced glucose tolerance, and increased free fatty acids and triglycerides. Bright liver syndrome
(bright liver on ultrasound suggestive of fatty liver) with raised ALT is suggestive of metabolic
syndrome

In pregnancy, ALT levels would rise during second trimester. In one of the studies, measured ALT
levels in pregnancy-related conditions such as hyperemesis gravidarum was 103.5 IU/L, pre-
eclampsia was 115, HELLP syndrome was 149. ALT levels would reduce by greater than 50% in
three days after child delivery. Another study also shows that caffeineconsumption can reduce the
risk of ALT elevation in those who consume alcohol, overweight people, impaired glucose
metabolism, and viral hepatitis.

Aspartate transaminase (AST)

Main articles: Aspartate transaminase and Elevated transaminases
AST exists in two isoenzymes namely mitochondrial form and cytoplasmic form. It Reference range
is found in highest concentration in the heart, followed by liver, muscle, and
kidney. The increase of mitochondrial AST in bloods is highly suggestive of 0-35 IU/L
tissue necrosis in myocardial infarction and chronic liver disease. More than 80% of
the liver AST activity are contributed by mitochondrial form of the isoenzymes,
while the circulating AST in blood are contributed by cytoplasmic form of AST. AST is especially
markedly raised in those with liver cirrhosis.

In certain pregnancy conditions such as hyperemesis gravidarum, AST can reach as high as 73 IU/L,
66 IU/L in pre-eclampsia, and 81 IU/L in HELLP syndrome.

AST/ALT ratio
Main article: AST/ALT ratio

The AST/ALT ratio increases in liver functional impairment. In alcoholic liver disease, the mean ratio
is 1.45, and mean ratio is 1.33 in post necrotic liver cirrhosis. Ratio is greater than 1.17 in viral
cirrhosis, greater than 2.0 in alcoholic hepatitis, and 0.9 in non-alcoholic hepatitis. Ratio is greater 4.5
in Wilson disease or hyperthyroidism.[6]

Alkaline phosphatase (ALP)

Main article: Elevated alkaline phosphatase Reference range

Alkaline phosphatase (ALP) is an enzyme in the cells lining the biliary ducts of the 41 to 133 IU/L
liver. It can also be found on the mucosal epithelium of the small
intestine, proximal convoluted tubule of the kidneys, bone, liver, and placenta. It
plays an important role in lipid transposition in small intestines and calcification of bones. 50% of all
the serum ALP activities in blood are contributed by bone. Acute viral hepatitis usually has normal or
increased ALP. For example, hepatitis A has increased ALP due to cholestasis (impaired bile
formation or bile flow obstruction) and would have the feature of prolonged itching. Other causes
include: infiltrative liver diseases, granulomatous liver disease, abscess, amyloidosis of the liver
and peripheral arterial disease. Mild elevation of ALP can be seen in liver cirrhosis, hepatitis,
and congestive cardiac failure. Transient hyperphosphataemia is a benign condition in infants, and
can reach normal level in 4 months. In contrast, low levels of ALP is found
in hypothyroidism, pernicious anemia, zinc deficiency, and hypophosphatasia.[6]
ALP activity is significantly increased in the third trimester due to increased synthesis from the
placenta. In pregnancy conditions such as hyperemesis gravdirum, ALP levels can reach 215 IU/L,
meanwhile, in pre-eclampsia, ALP can reach 14 IU/L, and HELLP syndromme, ALP levels can reach
15 IU/L.[6]

Gamma glutamyl transpeptidase (GGT)

Main article: Gamma-glutamyltransferase Reference range

GGT is a microsomal enzyme found in hepatocytes, biliary epithelial cells, renal 9 to 85 IU/L
tubules, pancreas, and intestines. It helps in glutathione metabolism by transporting
peptides across the cell membrane. In acute viral hepatitis, the GGT levels can peak
at 2nd and 3rd week of illness, and remained elevated at 6 weeks of illness. GGT is also elevated in
30% of the hepatitis C patients. GGT can increase by 10 times in alcoholism. GGT can increase by 2
to 3 times in 50% of the patients with non-alcoholic liver disease. When GGT levels is elevated,
the triglyceride level is elevated also. With insulin treatment, the GGT level can reduce. Other causes
of elevated GGT are: diabetes mellitus, acute pancreatitis, myocardial infarction, anorexia
nervosa, Guillain–Barré syndrome, hyperthyroidism, obesity and myotonic dystrophy.[6]

In pregnancy conditions GGT activity is reduced in 2nd and 3rd trimesters. In hyperemesis
gravidarum, GGT level value can reach 45 IU/L, 17 IU/L in pre-eclampsia, and 35 IU/L in HELPP
syndrome.

Albumin[edit]
Reference range
Albumin is a protein made specifically by the liver, and can be measured cheaply
and easily. It is the main constituent of total protein (the remaining constituents are 3.5 to 5.3 g/dL
primarily globulins). Albumin levels are decreased in chronic liver disease, such
as cirrhosis. It is also decreased in nephrotic syndrome, where it is lost through the
urine. The consequence of low albumin can be edema since the intravascular oncotic
pressure becomes lower than the extravascular space. An alternative to albumin measurement is
prealbumin, which is better at detecting acute changes (half-life of albumin and prealbumin is about 2
weeks and about 2 days, respectively).

Other tests
Other tests are requested alongside LFT to rule out specific causes.

5' Nucleotidase
Reference range
5' Nucleotidase (5'NTD) is a glycoprotein found throughout the body, in the
cytoplasmic membrane, catalyzing the conversion to inorganic phosphates from 0 to 15 IU/L[6]
nucleoside-5-phosphate. Its level is raised in conditions such as obstructive
jaundice, parenchymal liver disease, liver metastases, and bone disease. [6]

GGT levels are higher during 2nd and 3rd trimesters in pregnancy.[6]

Ceruloplasmin
Main article: Ceruloplasmin Reference range

Ceruloplasmin is an acute phase protein synthesized in the liver. It is the carrier of 200–600 mg/l[6]
the copper ion. Its levels is increased in infections, rheumatoid arthritis, pregnancy,
non Wilson liver disease and obstructive jaundice. In Wilson disease, the
ceruloplasmin level is depressed which lead to copper accumulation in body tissues. [6]

Alpha-fetoprotein (AFP)
Main article: Alpha-fetoprotein Reference range

AFP is significantly expressed in foetal liver. However, the mechanism that led to 0-15 μg/L[6]
the suppression of AFP synthesis in adults is not fully known. Exposure of the liver
to cancer-causing agents and arrest of liver maturation in childhood can lead to the
rise in AFP. AFP can reach until 400–500 μg/L in hepatocellular carcinoma. AFP concentration of
more than 400 μg/L is associated with greater tumour size, involvement of both lobes of liver, portal
vein invasion and a lower median survival rate. [6]

Coagulation test

The liver is responsible for the production of the vast majority of coagulation factors. In patients with
liver disease, INR can be used as a marker of liver synthetic function as it includes factor VII, which
has the shortest half life (2–6 hours) of all coagulation factors measured in INR. An elevated INR in
patients with liver disease, however, does not necessarily mean the patient has a tendency to bleed, as
it only measures procoagulants and not anticoagulants. In liver disease the synthesis of both are
decreased and some patients are even found to be hypercoagulable (increased tendency to clot)
despite an elevated INR. In liver patients, coagulation is better determined by more modern tests such
as thromboelastogram (TEG) or thomboelastrometry (ROTEM).

Prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international
normalized ratio (INR) are measures of the extrinsic pathway of coagulation. This test is also called
"ProTime INR" and "INR PT". They are used to determine the clotting tendency of blood, in the
measure of warfarin dosage, liver damage, and vitamin K status.

Serum glucose

The serum glucose test, abbreviated as "BG" or "Glu", measures the liver's ability to produce glucose
(gluconeogenesis); it is usually the last function to be lost in the setting of fulminant liver failure.

Lactate dehydrogenase

Lactate dehydrogenase (LDH) is found in many body tissues, including the liver. Elevated levels of
LDH may indicate liver damage.[citation needed] LDH isotype-1 (or cardiac) is used for estimating
damage to cardiac tissue, although troponin and creatine kinase tests are preferred.

RENAL FUNCTION TESTS:

Renal function, in nephrology, is an indication of the kidney's condition and its role in renal
physiology. Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the
kidney. Creatinine clearance rate (CCr or CrCl) is the volume of blood plasma that is cleared
of creatinine per unit time and is a useful measure for approximating the GFR. Creatinine clearance
exceeds GFR due to creatinine secretion,[citation needed] which can be blocked by cimetidine. In
alternative fashion, overestimation by older serum creatinine methods resulted in an underestimation
of creatinine clearance, which provided a less biased estimate of GFR. Both GFR and CCr may be
accurately calculated by comparative measurements of substances in the blood and urine, or estimated
by formulas using just a blood test result (eGFR and eCCr).

The results of these tests are used to assess the excretory function of the kidneys. Staging of chronic
kidney disease is based on categories of GFR as well as albuminuria and cause of kidney disease.[2]

Dosage of drugs that are excreted primarily via urine may need to be modified based on either GFR
or creatinine clearance.
Indirect markers

Most doctors use the plasma concentrations of the waste substances of creatinine and urea (U), as
well as electrolytes (E), to determine renal function. These measures are adequate to determine
whether a patient is suffering from kidney disease.

However, blood urea nitrogen (BUN) and creatinine will not be raised above the normal range until
60% of total kidney function is lost. Hence, the more accurate Glomerular filtration rate or its
approximation of the creatinine clearance is measured whenever renal disease is suspected or
careful dosing of nephrotoxic drugs is required.

Elevated protein levels in urine mark some kidney disease. The most sensitive marker
of proteinuria is elevated urine albumin. Persistent presence of more than 30 mg albumin per gram
creatinine in the urine is diagnostic of chronic kidney disease (microalbuminuria is a level of 30 mg/L
to 299 mg/L urine or 30–299 mg/24 h; a concentration of albumin in the urine that is not detected by
usual urine dipstick methods).

Glomerular filtration rate

Glomerular filtration rate (GFR) is the volume of fluid filtered from

the renal (kidney) glomerular capillaries into the Bowman's capsule per unit time.[3] Central to the
physiologic maintenance of GFR is the differential basal tone of the afferent and efferent arterioles
(see diagram). In other words, the filtration rate is dependent on the difference between the higher
blood pressure created by vasoconstriction of the input or afferent arteriole versus the lower blood
pressure created by lesser vasoconstriction of the output or efferent arteriole.

GFR is equal to the Clearance Rate when any solute is freely filtered and is neither reabsorbed nor
secreted by the kidneys. The rate therefore measured is the quantity of the substance in the urine that
originated from a calculable volume of blood. Relating this principle to the below equation – for the
substance used, the product of urine concentration and urine flow equals the mass of substance
excreted during the time that urine has been collected. This mass equals the mass filtered at the
glomerulus as nothing is added or removed in the nephron. Dividing this mass by the plasma
concentration gives the volume of plasma which the mass must have originally come from, and thus
the volume of plasma fluid that has entered Bowman's capsule within the aforementioned period of
time. The GFR is typically recorded in units of volume per time, e.g., milliliters per minute (mL/min).
Compare to filtration fraction.

There are several different techniques used to calculate or estimate the glomerular filtration rate
(GFR or eGFR). The above formula only applies for GFR calculation when it is equal to the
Clearance Rate.

Measurement using inulin

The GFR can be determined by injecting inulin or the inulin-analog sinistrin into the plasma.
Since both inulin and sinistrin are neither reabsorbed nor secreted by the kidney after glomerular
filtration, their rate of excretion is directly proportional to the rate of filtration of water and
solutes across the glomerular filter. Compared to the MDRD formula[clarification needed], the inulin
clearance slightly overestimates the glomerular function. In early stage renal disease, the inulin
clearance may remain normal due to hyperfiltration in the remaining nephrons.[4] Incomplete
urine collection is an important source of error in inulin clearance measurement. [5]

Measurement with radioactive tracers

GFR can be accurately measured using radioactive substances, in particular Chromium-

51 and Technetium-99m. These come close to the ideal properties of Inulin (undergoing only
glomerular filtration) but can be measured more practically with only a few urine or blood
samples.[6] Measurement of renal or plasma clearance of 51Cr-EDTA is widely used in Europe but
not available in the United States, where 99mTc-DTPA may be used instead.[7] Renal and plasma
clearance 51Cr-EDTA has been shown to be accurate in comparison with the gold standard,
Inulin.[8][9][10] Use of 51Cr-EDTA is considered a reference standard measure in UK guidance. [11]

Pressure definition

More precisely, GFR is the fluid flow rate between the glomerular capillaries and the Bowman's
capsule:

Where:

 is the GFR.
 is called the filtration constant and is defined as the product of the hydraulic
conductivity and the surface area of the glomerular capillaries.

 is the hydrostatic pressure within the glomerular capillaries.

 is the hydrostatic pressure within the Bowman's capsule.

 is the colloid osmotic pressure within the glomerular capillaries.

 and is the colloid osmotic pressure within the Bowman's capsule.

Kf

Because this constant is a measurement of hydraulic conductivity multiplied by the capillary

surface area, it is almost impossible to measure physically. However, it can be determined
experimentally. Methods of determining the GFR are listed in the above and below sections and it

is clear from our equation that can be found by dividing the experimental GFR by the net
filtration pressure:[12]

PG

The hydrostatic pressure within the glomerular capillaries is determined by the pressure
difference between the fluid entering immediately from the afferent arteriole and leaving through
the efferent arteriole. The pressure difference is approximated by the product of the total
resistance of the respective arteriole and the flux of blood through it: [13]

Where:

 is the afferent arteriole pressure.

 is the hydrostatic pressure within the glomerular capillaries.

 is the efferent arteriole pressure.

 is the afferent arteriole resistance.

 is the efferent arteriole resistance.

 is the afferent arteriole flux.

 And, is the efferent arteriole flux.

PB

The pressure in the Bowman's capsule and proximal tubule can be determined by the difference
between the pressure in the Bowman's capsule and the descending tubule: [13]

Where:

 is the pressure in the descending tubule.

 And, is the resistance of the descending tubule.

∏G

Blood plasma has a good many proteins in it and they exert an inward directed force called
the colloid osmotic pressure on the water in hypotonic solutions across a membrane, i.e., in the
Bowman's capsule. Because plasma proteins are virtually incapable of escaping the glomerular
capillaries, this oncotic pressure is defined, simply, by the ideal gas law: [12][13]

Where:

 R is the universal gas constant

 T is the temperature.
 And, c is concentration in mol/L of plasma proteins (remember the solutes can freely diffuse
through the glomerular capsule).

∏B

This value is almost always taken to be equal to zero because, in a healthy nephron, there should
be no proteins in the Bowman's Capsule.

Creatinine-based approximations of GFR

In clinical practice, however, creatinine clearance or estimates of creatinine clearance based on

the serum creatinine level are used to measure GFR. Creatinine is produced naturally by the body
(creatinine is a breakdown product of creatine phosphate, which is found in muscle). It is freely
filtered by the glomerulus, but also actively secreted by the peritubular capillaries in very small
amounts such that creatinine clearance overestimates actual GFR by 10% to 20%. This margin of
error is acceptable, considering the ease with which creatinine clearance is measured. Unlike
precise GFR measurements involving constant infusions of inulin, creatinine is already at a
steady-state concentration in the blood, and so measuring creatinine clearance is much less
cumbersome. However, creatinine estimates of GFR have their limitations. All of the estimating
equations depend on a prediction of the 24-hour creatinine excretion rate, which is a function of
muscle mass which is quite variable. One of the equations, the Cockcroft and Gault equation (see
below) does not correct for race. With a higher muscle mass, serum creatinine will be higher for
any given rate of clearance.

A common mistake made when just looking at serum creatinine is the failure to account for
muscle mass. Hence, an older woman with a serum creatinine of 1.4 mg/dL may actually have a
moderately severe degree of renal insufficiency, whereas a young muscular male can have a
normal level of renal function at this serum creatinine level. Creatinine-based equations should be
used with caution in cachectic patients and patients with cirrhosis. They often have very low
muscle mass and a much lower creatinine excretion rate than predicted by the equations below,
such that a cirrhotic patient with a serum creatinine of 0.9 mg/dL may have a moderately severe
degree of renal insufficiency.
Creatinine clearance CCr

One method of determining GFR from creatinine is to collect urine (usually for 24 h) to
determine the amount of creatinine that was removed from the blood over a given time interval. If
one removes 1440 mg in 24 h, this is equivalent to removing 1 mg/min. If the blood concentration
is 0.01 mg/mL (1 mg/dL), then one can say that 100 mL/min of blood is being "cleared" of
creatinine, since, to get 1 mg of creatinine, 100 mL of blood containing 0.01 mg/mL would need
to have been cleared.

Creatinine clearance (CCr) is calculated from the creatinine concentration in the collected urine
sample (UCr), urine flow rate (Vdt), and the plasma concentration (PCr). Since the product of urine
concentration and urine flow rate yields creatinine excretion rate, which is the rate of removal
from the blood, creatinine clearance is calculated as removal rate per min (U Cr×Vdt) divided by
the plasma creatinine concentration. This is commonly represented mathematically as

Example: A person has a plasma creatinine concentration of 0.01 mg/ml and in 1 hour
produces 60ml of urine with a creatinine concentration of 1.25 mg/mL.

The common procedure involves undertaking a 24-hour urine collection, from empty-
bladder one morning to the contents of the bladder the following morning, with a
comparative blood test then taken. The urinary flow rate is still calculated per minute,
hence:

To allow comparison of results between people of different sizes, the C Cr is often

corrected for the body surface area (BSA) and expressed compared to the average
sized man as mL/min/1.73 m2. While most adults have a BSA that approaches 1.7
m2 (1.6 m2 to 1.9 m2), extremely obese or slim patients should have their
CCr corrected for their actual BSA.
BSA can be calculated on the basis of weight and height.

Twenty-four-hour urine collection to assess creatinine clearance is no longer

widely performed, due to difficulty in assuring complete specimen collection.
To assess the adequacy of a complete collection, one always calculates the
amount of creatinine excreted over a 24-hour period. This amount varies with
muscle mass, and is higher in young people vs. old, in blacks vs. whites, and
in men vs. women. An unexpectedly low or high 24-hour creatinine excretion
rate voids the test. Nevertheless, in cases where estimates of creatinine
clearance from serum creatinine are unreliable, creatinine clearance remains a
useful test. These cases include "estimation of GFR in individuals with
variation in dietary intake (vegetarian diet, creatine supplements) or muscle
mass (amputation, malnutrition, muscle wasting), since these factors are not
specifically taken into account in prediction equations."[14]

Estimated values[edit]

A number of formulae have been devised to estimate GFR or Ccr values on

the basis of serum creatinine levels. Where not otherwise stated serum
creatinine is assumed to be stated in mg/dL, not µmol/L—divide by 88.4 to
convert from µmol/Lto mg/dL.

Estimated creatinine clearance rate (eCCr) using Cockcroft-Gault

formula[edit]

A commonly used surrogate marker for estimate of creatinine clearance is the

Cockcroft-Gault (CG) formula, which in turn estimates GFR in ml/min: [15] It
is named after the scientists, the asthmologist Donald William
Cockcroft (de) (b. 1946) and the nephrologist Matthew Henry Gault (1925–
2003), who first published the formula in 1976, and it employs
serum creatinine measurements and a patient's weight to predict the creatinine
clearance.[16][17] The formula, as originally published, is:
 This formula expects weight to be measured in kilograms and creatinine to be measured in
mg/dL, as is standard in the USA. The resulting value is multiplied by a constant of 0.85 if the
patient is female. This formula is useful because the calculations are simple and can often be
performed without the aid of a calculator.

When serum creatinine is measured in µmol/L:

Where Constant is 1.23 for men and 1.04 for women.

Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD) formula

The most recently advocated formula for calculating the GFR is the one that was developed by
the Modification of Diet in Renal Disease Study Group. Most laboratories in Australia,] and The
United Kingdom now calculate and report the MDRD estimated GFR along with creatinine
measurements and this forms the basis of chronic kidney disease.[20]The adoption of the automatic
reporting of MDRD-eGFR has been widely criticised.[21][22][23]

The most commonly used formula is the "4-variable MDRD," which estimates GFR using four
variables: serum creatinine, age, ethnicity, and gender. [24] The original MDRD used six variables with
the additional variables being the blood urea nitrogen and albumin levels.[18] The equations have been
validated in patients with chronic kidney disease; however, both versions underestimate the GFR in
healthy patients with GFRs over 60 mL/min. [25][26] The equations have not been validated in acute
renal failure.

For creatinine in µmol/L:

For creatinine in mg/dL:

Creatinine levels in µmol/L can be converted to mg/dL by dividing them by 88.4. The 32788
number above is equal to 186×88.41.154.

A more elaborate version of the MDRD equation also includes serum albumin and blood
urea nitrogen (BUN) levels:
 where the creatinine and blood urea nitrogen concentrations are both in mg/dL. The albumin
concentration is in g/dL.

These MDRD equations are to be used only if the laboratory has NOT calibrated
its serum creatinine measurements to isotope dilution mass spectrometry (IDMS).
When IDMS-calibrated serum creatinine is used (which is about 6% lower), the
above equations should be multiplied by 175/186 or by 0.94086. [27]

Since these formulae do not adjust for body mass, they (relative to the Cockcroft-
Gault formula) underestimate eGFR for heavy people and overestimate it for
underweight people. (see Cockcroft-Gault formula above).

Importance of calibration of the serum creatinine level and the IDMS standardization effort

One problem with any creatinine-based equation for GFR is that the methods used to assay creatinine
in the blood differ widely in their susceptibility to non-specific chromogens, which cause the
creatinine value to be overestimated. In particular, the MDRD equation was derived using serum
creatinine measurements that had this problem. The NKDEP program in the United States has
attempted to solve this problem by trying to get all laboratories to calibrate their measures of
creatinine to a "gold standard", which in this case is isotope dilution mass spectrometry (IDMS). In
late 2009 not all labs in the U.S. had changed over to the new system. There are two forms of the
MDRD equation that are available, depending on whether or not creatinine was measured by an
IDMS-calibrated assay. The CKD-EPI equation is designed to be used with IDMS-calibrated serum
creatinine values only.

Cystatin C

Problems with creatinine (varying muscle mass, recent meat ingestion (much less dependent on the
diet than urea), etc.) have led to evaluation of alternative agents for estimation of GFR. One of these
is cystatin C, a ubiquitous protein secreted by most cells in the body (it is an inhibitor of cysteine
protease).

Cystatin C is freely filtered at the glomerulus. After filtration, Cystatin C is reabsorbed and
catabolized by the tubular epithelial cells, with only small amounts excreted in the urine. Cystatin C
levels are therefore measured not in the urine, but in the bloodstream.
Equations have been developed linking estimated GFR to serum cystatin C levels. Most recently,
some proposed equations have combined (sex, age and race) adjusted cystatin C and creatinine. The
most accurate is (sex, age and race) adjusted cystatin C, followed by (sex, age and race) adjusted
creatinine and then cystatine C alone in slightly different with adjusted creatinine. [38]

Normal ranges

The normal range of GFR, adjusted for body surface area, is 100–130 average 125 mL/min/1.73m2 in
men and 90–120 ml/min/1.73m2 in women younger than the age of 40. In children, GFR measured by
inulin clearance is 110 mL/min/1.73 m2 until 2 years of age in both sexes, and then it progressively
decreases. After age 40, GFR decreases progressively with age, by 0.4–1.2 mL/min per year.

Decreased renal function

A decreased renal function can be caused by many types of kidney disease. Upon presentation of
decreased renal function, it is recommended to perform a history and physical examination, as well as
performing a renal ultrasound and a urinalysis.[39] The most relevant items in the history
are medications, edema, nocturia, gross hematuria, family history of kidney
disease, diabetes and polyuria. The most important items in a physical examination are signs
of vasculitis, lupus erythematosus, diabetes, endocarditis and hypertension.

A urinalysis is helpful even when not showing any pathology, as this finding suggests an extrarenal
etiology. Proteinuria and/or urinary sediment usually indicates the presence of glomerular
disease. Hematuria may be caused by glomerular disease or by a disease along the urinary tract.[39]

The most relevant assessments in a renal ultrasound are renal sizes, echogenicity and any signs
of hydronephrosis. Renal enlargement usually indicates diabetic nephropathy, focal segmental
glomerular sclerosis or myeloma. Renal atrophy suggests longstanding chronic renal disease.[39]

Chronic kidney disease stages

Main article: Chronic kidney disease

Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic
group and smoking. For most patients, a GFR over 60 mL/min/1.73m2 is adequate. But significant
decline of the GFR from a previous test result can be an early indicator of kidney disease requiring
medical intervention. The sooner kidney dysfunction is diagnosed and treated the greater odds of
preserving remaining nephrons, and preventing the need for dialysis.

CKD stage GFR level (mL/min/1.73 m2)

Stage 1 ≥ 90

Stage 2 60–89

Stage 3 30–59

Stage 4 15–29

Stage 5 < 15

The severity of chronic kidney disease (CKD) is described by six stages; the most severe three are
defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of
kidney disease (e.g., proteinuria):

0) Normal kidney function – GFR above 90 mL/min/1.73 m2 and no proteinuria

1) CKD1 – GFR above 90 mL/min/1.73 m2 with evidence of kidney damage
2) CKD2 (mild) – GFR of 60 to 89 mL/min/1.73 m2 with evidence of kidney damage
3) CKD3 (moderate) – GFR of 30 to 59 mL/min/1.73 m2
4) CKD4 (severe) – GFR of 15 to 29 mL/min/1.73 m2
5) CKD5 kidney failure – GFR less than 15 mL/min/1.73 m2 Some people add CKD5D for
those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis.

Note: others add a "T" to patients who have had a transplant regardless of
stage.
 Not all clinicians agree with the above classification, suggesting that it may
mislabel patients with mildly reduced kidney function, especially the elderly,
as having a disease. A conference was held in 2009 regarding these
controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on
CKD: Definition, Classification and Prognosis, gathering data on CKD
prognosis to refine the definition and staging of CKD.

THYROID FUNCTION TESTS:

Thyroid function tests (TFTs) is a collective term for blood tests used to check the function of
the thyroid.

TFTs may be requested if a patient is thought to suffer from hyperthyroidism (overactive thyroid)
or hypothyroidism (underactive thyroid), or to monitor the effectiveness of either thyroid-suppression
or hormone replacement therapy. It is also requested routinely in conditions linked to thyroid disease,
such as atrial fibrillation and anxiety disorder.

A TFT panel typically includes thyroid hormones such as thyroid-stimulating hormone (TSH,
thyrotropin) and thyroxine (T4), and triiodothyronine (T3) depending on local laboratory policy.

Thyroid function tests

MeSH D013960

MedlinePlus 003444

Thyroid-stimulating hormone

Thyroid-stimulating hormone (TSH, thyrotropin) is generally increased in hypothyroidism and

decreased in hyperthyroidism, making it the most important test for early detection of both of these
conditions. The result of this assay is suggestive of the presence and cause of thyroid disease, since a
measurement of elevated TSH generally indicates hypothyroidism, while a measurement of low TSH
generally indicates hyperthyroidism.[2] However, when TSH is measured by itself, it can yield
misleading results, so additional thyroid function tests must be compared with the result of this test
for accurate diagnosis.

TSH is produced in the pituitary gland. The production of TSH is controlled by thyrotropin-releasing
hormone (TRH), which is produced in the hypothalamus. TSH levels may be suppressed by excess
free T3 (fT3) or free T4 (fT4) in the blood.

History

First-generation TSH assays were done by radioimmunoassay and were introduced in 1965. There
were variations and improvements upon TSH radioimmunoassay, but their use declined as a new
immunometric assay technique became available in the middle of the 1980s The new techniques
were more accurate, leading to the second, third, and even fourth generations of TSH assay, with each
generation possessing ten times greater functional sensitivity than the last. Third generation
immunometric assay methods are typically automatedFourth generation TSH immunometric assay
has been developed for use in research.

Current status

Third generation TSH assay is the current requirement for modern standards of care. At present, TSH
testing in the United States is typically carried out with automated platforms using advanced forms of
immunometric assay. Nonetheless, there is currently no international standard for measurement of
thyroid-stimulating hormone.

Interpretation

Accurate interpretation takes a variety of factors into account, such as the thyroid hormones
i.e. thyroxine (T4) and triiodothyronine (T3), current medical status (such as pregnancy[3]),[4] certain
medications like propylthiouracil, temporal effects including circadian rhythm[7] and hysteresis,[8] and
other past medical history.

Thyroid hormones

Total thyroxine

Total thyroxine is rarely measured, having been largely superseded by free thyroxine tests.
Total thyroxine (Total T4) is generally elevated in hyperthyroidism and decreased
in hypothyroidism. It is usually slightly elevated in pregnancy secondary to increased levels
of thyroid binding globulin (TBG).[2]

Total T4 is measured to see the bound and unbound levels of T4. The total T4 is less useful in cases
where there could be protein abnormalities. The total T4 is less accurate due to the large amount of
T4 that is bound. The total T3 is measured in clinical practice since the T3 has decreased amount that
is bound as compared to T4.

Reference ranges depend on the method of analysis. Results should always be interpreted using the
range from the laboratory that performed the test. Example values are:

Lower limit Upper limit Unit

4, 5.5 11, 12.3 μg/dL

60 140, 160 nmol/L

Free thyroxine

Free thyroxine (fT4) is generally elevated in hyperthyroidism and decreased in hypothyroidism.[2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the
range from the laboratory that performed the test. Example values are:

Patient type Lower limit Upper limit Unit

0.7,[13] 0.8[11] 1.4,[13] 1.5,[11] 1.8[14] ng/dL

Normal adult

9,[15][16] 10,[10] 12 [12] 18,[15][16] 23[12] pmol/L

Infant 0–3 d 2.0[13] 5.0[13] ng/dL

 26[16] 65[16] pmol/L

0.9[13] 2.2[13] ng/dL

Infant 3–30 d

12[16] 30[16] pmol/L

0.8[13] 2.0[13] ng/dL

Child/Adolescent
31 d – 18 y
10[16] 26[16] pmol/L

0.5[13] 1.0[13] ng/dL

Pregnant

6.5[16] 13[16] pmol/L

Total triiodothyronine

Total triiodothyronine (Total T3) is rarely measured, having been largely superseded by free T3 tests.
Total T3 is generally elevated in hyperthyroidism and decreased in hypothyroidism. [2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the
range from the laboratory that performed the test. Example values are:

Test Lower limit Upper limit Unit

60,[11] 75[10] 175,[10] 181[11] ng/dL

Total triiodothyronine

0.9,[15] 1.1[10] 2.5,[15] 2.7[10] nmol/L

Free triiodothyronine

Free triiodothyronine (fT3) is generally elevated in hyperthyroidism and decreased in

hypothyroidism.[2]

Reference ranges depend on the method of analysis. Results should always be interpreted using the
range from the laboratory that performed the test. Example values are:

Patient type Lower limit Upper limit Unit

3.0[10] 7.0[10] pg/mL

Normal adult

3.1[17] 7.7[17] pmol/L

3.0[18] 7.0[18] pg/mL

Children 2–16 y

1.5[17] 15.2[17] pmol/L

Carrier proteins

Thyroxine-binding globulin

An increased thyroxine-binding globulin results in an increased total thyroxine and total

triiodothyronine without an actual increase in hormonal activity of thyroid hormones.

Reference ranges:

Lower limit Upper limit Unit

12[11] 30[11] mg/L

Thyroglobulin
Reference ranges:

Lower limit Upper limit Unit

1.5 30 pmol/L

1 20 μg/L

Other binding hormones

 Transthyretin (prealbumin)
 Albumin

Protein binding function

Thyroid hormone uptake

Thyroid hormone uptake (Tuptake or T3 uptake) is a measure of the unbound thyroxine binding
globulins in the blood, that is, the TBG that is unsaturated with thyroid hormone. [2]Unsaturated TBG
increases with decreased levels of thyroid hormones. It is not directly related to triiodothyronine,
despite the name T3 uptake

Reference ranges:

Patient type Lower limit Upper limit Unit

Females 25[2] 35[2] %

In pregnancy 15[2] 25[2] %

Males 25[2] 35[2] %

Other protein binding tests

 Thyroid Hormone Binding Ratio(THBR)

 Thyroxine-binding index (TBI)

Mixed parameters[edit]

Free thyroxine index

The Free Thyroxine Index (FTI or T7) is obtained by multiplying the total T 4 with T3 uptake.[2] FTI is
considered to be a more reliable indicator of thyroid status in the presence of abnormalities in plasma
protein binding.[2] This test is rarely used now that reliable free thyroxine and free triiodothyronine
assays are routinely available.

FTI is elevated in hyperthyroidism and decreased in hypothyroidism.[2]

Patient type Lower limit Upper limit Unit

Females 1.8[2] 5.0[2]

Males 1.3[2] 4.2[2]

Structure parameters[edit]

Derived structure parameters that describe constant properties of the overall feedback control
system may add useful information for special purposes, e.g. in diagnosis of nonthyroidal illness
syndrome or central hypothyroidism. [19][20][21][22]

Secretory capacity (GT)[edit]

Thyroid's secretory capacity (GT, also referred to as SPINA-GT) is the maximum stimulated amount
of thyroxine the thyroid can produce in one second. [23] GT is elevated in hyperthyroidism and reduced
in hypothyroidism.[24]

GT is calculated with
or

: Dilution factor for T4 (reciprocal of apparent volume of distribution, 0.1 l−1)

: Clearance exponent for T4 (1.1e-6 sec−1)

K41: Dissociation constant T4-TBG (2e10 l/mol)
K42: Dissociation constant T4-TBPA (2e8 l/mol)
DT: EC50 for TSH (2.75 mU/l)[23]

Lower limit Upper limit Unit

1.41[23] 8.67[23] pmol/s

Sum activity of peripheral deiodinases (GD)[edit]

The sum activity of peripheral deiodinases (GD, also referred to as SPINA-GD) is reduced in
nonthyroidal illness with hypodeiodination.

Effects of drugs[edit]

Drugs can profoundly affect thyroid function tests. Listed below is a selection of important effects.

Effects of some drugs on Tests of Thyroid function [29][22][30]

Effect on Effect on
Cause Drug hormone structur
concentrati e
 ons paramet
ers

↔SPINA
Inhibited TSH ↓T4; ↓T3;
Dopamine, L-DOPA, glucocorticoids, somatostatin -GT;
secretion ↓TSH
↓JTI

Inhibited
synthesis or ↓SPINA-
↓T4; ↓T3;
release of Iodine, lithium GT;
↑TSH
thyroid ↔JTI
hormone

Inhibited
conversion of ↓T3; ↑rT3; ↓,
T4 to T3 (Step- Amiodarone, glucocorticoids, propranolol, propylthiouraci ↔, ↑T4 and ↓SPINA-
up l, radiographic contrast agents fT4; ↔, GD
hypodeiodinat ↑TSH
ion)

Inhibited ↓T4; ↓T3;

binding of Salicylates, phenytoin, carbamazepine, furosemide, nonste ↓fT4E, ↔, ↓T4/fT4
T4/T3 to serum roidal anti-inflammatory agents, heparin (in vitro effect) ↑fT4; ratio
proteins ↔TSH

Stimulated ↓T4; ↓fT4;

metabolism of Phenobarbital, phenytoin, carbamazepine, rifampicin ↔TSH
iodothyronine
s

Inhibited Aluminium hydroxide, ferrous

↓T4; ↓fT4;
absorption of sulfate, cholestyramine, colestipol,
↑TSH
ingested T4 iron sucralfate, soybean preparations, kayexalate

↔SPINA
-GT;
Increase in
↑T4; ↑T3; ↔SPINA
concentration Estrogen, clofibrate, opiates (heroin, methadone), 5-
↔fT4; -GD;
of T4-binding fluorouracil, perphenazine
↔TSH ↔JTI;
proteins
↑T4/fT4
ratio

↔SPINA
-GT;
Decrease in
↓T4; ↓T3; ↔SPINA
concentration
Androgens, glucocorticoids ↔fT4; -GD;
of T4-binding
↔TSH ↔JTI;
proteins
↓T4/fT4
ratio

↓: reduced serum concentration or structure parameter; ↑: increased serum concentration or structure

parameter; ↔: non change; TSH: Thyroid-stimulating hormone; T3: Total triiodothyronine; T4: Total
thyroxine; fT4: Free thyroxine; fT3: Free triiodothyronine; rT3: Reverse triiodothyronine

B.TESTS ASSOCIATES WITH CARDIAC DISORDERS:

New tests are constantly being developed to further the understanding of disease, injury, and
congenital (present at birth) or acquired abnormalities of the heart. These are just a few of the tests
that have been used to diagnose heart and blood vessel disease (cardiovascular). For more
information, talk to your cardiologist or other healthcare provider:

 Electrocardiogram (ECG). This test records the electrical activity of the heart, shows abnormal
rhythms (arrhythmias), and can sometimes detect heart muscle damage.
 Stress test (also called treadmill or exercise ECG). This test is done to monitor the heart while
you walk on a treadmill or pedal a stationary bike. Your doctor also monitors your breathing and
blood pressure. A stress test may be used to detect coronary artery disease, or to determine safe
levels of exercise after a heart attack or heart surgery. This test can also be done using special
medicines that stress the heart in a similar manner as exercise does.
 Echocardiogram (also known as echo). An echo is a noninvasive test that uses sound waves to
evaluate your heart's chambers and valves, as well as its pumping function. The echo sound waves
create an image on the monitor as an ultrasound probe is passed across the skin over your heart.
 Transesophageal echocardiogram (TEE). In this test, you will swallow a small probe, about the
size of a little finger. The probe passes down the esophagus nearer to the heart. It allows a closer
look at the heart's structure and function. It also shows any abnormal tissue around your heart
valves, if blood is leaking backward through a valve, and if blood clots are present in your heart
chambers.
 Positron emission tomography (PET) scan. This is a nuclear scan that gives information about
the flow of blood through the coronary arteries to the heart muscle:
 PET F-18 FDG (fluorodeoxyglucose) scan. This specialized PET scan uses a form of
glucose to help determine if any specific areas of heart tissue have permanent damage. Your
doctor may use it after a heart attack to determine which procedure, such as angioplasty,
stenting, or bypass surgery, may be beneficial. Your doctor will inject a glucose solution
through an IV into your blood. Then a special camera takes pictures of where the solution
collects in your heart.
 Thallium scans or myocardial perfusion scans. Similar to the PET scan, these tests involve an
IV injection and a special camera:
 Resting SPECT thallium scan or myocardial perfusion scan. A nuclear scan done while
you rest. It is done to view areas of the heart muscle that are not getting enough blood.
  Exercise thallium scan or myocardial perfusion scan. A nuclear scan is done while you are
exercising. It is done to view areas of the heart muscle that are not getting enough blood
during activity.
 Adenosine or persantine thallium scan or myocardial perfusion scan. A nuclear scan done
on if you are unable to exercise. It is done to view areas of the heart muscle that are not
getting enough blood. It uses special medicines that stress the heart in the same way exercise
does.
 MUGA scans/radionuclide angiography (RNA) scans. Similar to the PET scan, these tests
involve an IV injection and a special camera:
 Resting gated blood pool scan (RGBPS), resting MUGA, or resting radionuclide
angiography. A nuclear scan to evaluate how well the heart wall moves and how much
blood is pumped with each heartbeat, while you rest.
 Exercise gated blood pool scan, exercise MUGA, or exercise radionuclide
angiography. A nuclear scan to evaluate how well the heart wall moves and how much
blood is pumped with each heartbeat, just after you have walked on a treadmill or ridden
on a stationary bike.
 Holter monitor. For this test, you wear a small, portable, battery-powered ECG machine to
record heartbeats over a period of 24 to 48 hours during normal activities. At the end of the time
period, you will return the monitor to the doctor's office so it can be read and evaluated.
 Event recorder. For this test, you wear a small, portable, battery-powered machine used to
record ECG over several weeks. Each time you have symptoms, you press a button on the
recorder to record the ECG sample. As soon as possible, you will transmit this sample to the
doctor's office for evaluation.
 Loop recorder. Your doctor uses surgery to implant this device about the size of a zip drive
under the skin to monitor and record the heartbeats for up to 2 years.
 Tilt table test. Your doctor will connect you to an ECG and blood pressure monitor. Your will be
strapped to a table that tilts you from a lying to standing position. This test is used to determine if
you are prone to sudden drops in blood pressure (orthostatic hypotension), or slow pulse rates
with position changes.
 Electrophysiology study. For this test, insulated electric catheters are placed through the large
vein in the upper leg and thread into the heart. It is used to test the heart's electrical system to find
irregular heart rhythms.
 Cardiac catheterization (also called coronary angiogram). For this test, your doctor guides a
small catheter (hollow tube) through the large artery in your upper leg, or sometimes your wrist or
arm, into your heart. Dye is given through the catheter, and moving X-ray pictures are made as
the dye travels through your heart. This comprehensive test shows: narrowing in the arteries, heart
chamber size, how well your heart pumps, and how well the valves open and close, as well as a
measurement of the pressures within the heart chambers and arteries.
 Magnetic resonance imaging (MRI) of the heart. This procedure uses a combination of large
magnets, radiofrequencies, and a computer to make detailed images of organs and structures in
your body. Your doctor may use MRI of the heart to evaluate the heart valves and major vessels,
detect coronary artery disease, and the extent of damage it has caused, evaluate congenital
defects, and detect the presence of tumors or other abnormalities. Your doctor may do this test
before other procedures such as angioplasty or stenting of the coronary arteries and heart or
vascular surgery:
 Magnetic resonance angiography (MRA) of the heart. This is a specialized type of MRI
procedure used to evaluate blood vessels in your heart.
 Cardiac CT scan. This imaging procedure uses an X-ray machine and a computer to create a 3-
dimensional pictures of the heart. Sometimes a dye is injected into a vein so that your heart
arteries can be seen as well.

C.FLUID AND ELECTRLYTE BALANCE:

The kidneys are essential for regulating the volume and composition of bodily fluids. This page
outlines key regulatory systems involving the kidneys for controlling volume, sodium and potassium
concentrations, and the pH of bodily fluids.

A most critical concept for you to understand is how water and sodium regulation are integrated to
defend the body against all possible disturbances in the volume and osmolarity of bodily fluids.
Simple examples of such disturbances include dehydration, blood loss, salt ingestion, and plain water
ingestion.
Water balance

Water balance is achieved in the body by ensuring that the amount of water consumed in food and
drink (and generated by metabolism) equals the amount of water excreted. The consumption side is
regulated by behavioral mechanisms, including thirst and salt cravings. While almost a liter of water
per day is lost through the skin, lungs, and feces, the kidneys are the major site of regulated excretion
of water.

One way the the kidneys can directly control the volume of bodily fluids is by the amount of water
excreted in the urine. Either the kidneys can conserve water by producing urine that is concentrated
relative to plasma, or they can rid the body of excess water by producing urine that is dilute relative
to plasma.

Direct control of water excretion in the kidneys is exercised by vasopressin, or anti-diuretic hormone
(ADH), a peptide hormone secreted by the hypothalamus. ADH causes the insertion of water
channels into the membranes of cells lining the collecting ducts, allowing water reabsorption to
occur. Without ADH, little water is reabsorbed in the collecting ducts and dilute urine is excreted.

ADH secretion is influenced by several factors (note that anything that stimulates ADH secretion also
stimulates thirst):

1. By special receptors in the hypothalamus that are sensitive to increasing plasma osmolarity (when
the plasma gets too concentrated). These stimulate ADH secretion.

2. By stretch receptors in the atria of the heart, which are activated by a larger than normal volume of
blood returning to the heart from the veins. These inhibit ADH secretion, because the body wants to
rid itself of the excess fluid volume.

3. By stretch receptors in the aorta and carotid arteries, which are stimulated when blood pressure
falls. These stimulate ADH secretion, because the body wants to maintain enough volume to
generate the blood pressure necessary to deliver blood to the tissues.

Sodium balance
In addition to regulating total volume, the osmolarity (the amount of solute per unit volume) of
bodily fluids is also tightly regulated. Extreme variation in osmolarity causes cells to shrink or swell,
damaging or destroying cellular structure and disrupting normal cellular function.

Regulation of osmolarity is achieved by balancing the intake and excretion of sodium with that of
water. (Sodium is by far the major solute in extracellular fluids, so it effectively determines the
osmolarity of extracellular fluids.)

An important concept is that regulation of osmolarity must be integrated with regulation of volume,
because changes in water volume alone have diluting or concentrating effects on the bodily fluids.
For example, when you become dehydrated you lose proportionately more water than solute
(sodium), so the osmolarity of your bodily fluids increases. In this situation the body must conserve
water but not sodium, thus stemming the rise in osmolarity. If you lose a large amount of blood from
trauma or surgery, however, your loses of sodium and water are proportionate to the composition of
bodily fluids. In this situation the body should conserve both water and sodium.

As noted above, ADH plays a role in lowering osmolarity (reducing sodium concentration) by
increasing water reabsorption in the kidneys, thus helping to dilute bodily fluids. To prevent
osmolarity from decreasing below normal, the kidneys also have a regulated mechanism for
reabsorbing sodium in the distal nephron. This mechanism is controlled by aldosterone, a steroid
hormone produced by the adrenal cortex. Aldosterone secretion is controlled two ways:

1.The adrenal cortex directly senses plasma osmolarity. When the osmolarity increases above
normal, aldosterone secretion is inhibited. The lack of aldosterone causes less sodium to be
reabsorbed in the distal tubule. Remember that in this setting ADH secretion will increase to conserve
water, thus complementing the effect of low aldosterone levels to decrease the osmolarity of bodily
fluids. The net effect on urine excretion is a decrease in the amount of urine excreted, with an
increase in the osmolarity of the urine.

2. The kidneys sense low blood pressure (which results in lower filtration rates and lower flow
through the tubule). This triggers a complex response to raise blood pressure and conserve volume.
Specialized cells (juxtaglomerular cells) in the afferent and efferent arterioles produce renin, a
 peptide hormone that initiates a hormonal cascade that ultimately produces angiotensin II.
Angiotensin II stimulates the adrenal cortex to produce aldosterone.

*Note that in this setting, where the body is attempting to conserve volume, ADH secretion is also
stimulated and water reabsorption increases. Because aldosterone is also acting to increase sodium
reabsorption, the net effect is retention of fluid that is roughly the same osmolarity as bodily fluids.
The net effect on urine excretion is a decrease in the amount of urine excreted, with lower osmolarity
than in the previous example.

D.MICROBIOLOGICAL CULTURE SENSITIVITY TESTS:

According to the new ISO 20776-1 standard, which is valid all over the world, these terms are
defined as follows:
 Susceptible (s):
 A bacterial strain is said to be susceptible to a given antibiotic when it is inhibited in vitro by a
concentration of this drug that is associated with a high likelihood of therapeutic success.
 Intermediate (i):
 The sensitivity of a bacterial strain to a given antibiotic is said to be intermediate when it is
inhibited in vitro by a concentration of this drug that is associated with an uncertain
therapeutic effect.
 Resistant (r):
 A bacterial strain is said to be resistant to a given antibiotic when it is inhibited in vitro by a
concentration of this drug that is associated with a high likelihood of therapeutic failure.
 The results for a particular tested strain of E. coli.
 The MIC values for this strain and the sensitivity ratings that will be assigned to them
henceforward by EUCAST (The European Committee on Antimicrobial Susceptibility
Testing) , are:
 ampicillin = 4 mg/L (i);
 ampicillin/sulbactam = 1 mg/L฀ (i);
 piperacilin/tazobactam = 2 mg/L (s);
 cefuroxime = 4 mg/L (i);
 cefotaxime = 0.125 mg/L (s);
  imipenem = 0.5 mg/L (s);
 gentamicin = 0.25 mg/L (s);
 doxycycline = 8 mg/L (Ø);
 cotrimoxazole >128 mg/L (r); ciprofloxacin
 Antimicrobial susceptibility testing (AST) is indicated for pathogens contributing to an
infectious process that warrants antimicrobial therapy if susceptibility to antimicrobials cannot
be predicted reliably based on knowledge of their identity. Some organisms have predictable
susceptibility to antimicrobial agents (ie, Streptococcus pyogenes to penicillin), and empirical
therapy for these organisms is typically used. Therefore, AST for such pathogens is seldom
required or performed. In addition, AST is valuable in evaluating the activity of new and
experimental compounds and investigating the epidemiology of antimicrobial resistant
pathogens.
 Once we have identified the bacterium which is causing the infection we need to find out the
antibiotics that would be effective against it. This is done by antibiotic sensitivity testing.
 Antibiotic sensitivity or microbiological culture sensitivity are the in-vitro procedures to
determine the susceptibility of bacteria to antibiotics.
 Because susceptibility can vary even within a species (with some strains being more resistant
than others), antibiotic susceptibility testing (AST) is usually carried out to determine which
antibiotic will be most successful in treating The same can be used to study the emergence of
antibiotic resistance and spread of resistant organism in a population.
 Antibiotic sensitivity testing will control the use of Antibiotics in clinical use. Testing will
assist the clinicians in the choice of drugs for the treatment of infections.
 It helps us to measure only the antimicrobial activity against a bacteria under laboratory
conditions and not in the patients.
 The patients clinical condition, type and site of infection, drug hypersensitivity, ADME,
characters of the patients are not taken in to consideration in sensitivity testing techniques.
Culturing and Sensitivity Testing:
Specimen Collection:
Samples must be collected and handled properly to obtain reliable results. Poor collection techniques
may result in lack of bacterial growth or abundant growth of bacterial contaminats. Sample shoud be
collected before the antibiotic therapy to assure the best growth of the pathogen. If antibiotic therapy
is already initiated, then the sample must be collected before the next dose.
Identifying Bacteria
 When a sample is submitted to laboratory for bacterial culture and antibiotic sensitivity, the
clinician should include the information like the site of sample collection and type of lesion.
 This help the microbiologist to choose which nutrient media and growth conditions to be used.
 Samples of bacterial culture are applied to plates of various growth media with a sterile loop,
effectively spreading the bacterial organism over the surface of each plate in a single layer.
 Once inoculated the plates are incubated in an environment with controlled temperature,
humidity, oxygen and carbon dioxide levels are optimum for bacterial replication.
 Each bacterial organism grows into a cluster called a colony, and individual colonies are
inoculated onto new separate media, creating pure samples.
 Identification of the cultured bacteria is based on the characteristics of colony growth and
appearance as well as biochemical testing of the individual colonies.
Antibiotic Sensitivity Testing:
Once identified the bacteria undergoes testing to identify the antibiotic most likely to inhibit their
growth. For this purpose generally two methods฀ are used,
1) Disk Diffusion techniques.
2) Broth Dilution techniques.
E.PULMONARY FUNCTION TESTS:
Pulmonary function tests (PFTs) are noninvasive tests that show how well the lungs are working. The
tests measure lung volume, capacity, rates of flow, and gas exchange. This information can help your
healthcare provider diagnose and decide the treatment of certain lung disorders.

There are 2 types of disorders that cause problems with air moving in and out of the lungs:

 Obstructive. This is when air has trouble flowing out of the lungs due to airway resistance. This
causes a decreased flow of air.
 Restrictive. This is when the lung tissue and/or chest muscles can’t expand enough. This creates
problems with air flow, mostly due to lower lung volumes.
PFT can be done with 2 methods. These 2 methods may be used together and perform different tests,
depending on the information that your healthcare provider is looking for:

 Spirometry. A spirometer is a device with a mouthpiece hooked up to a small electronic

machine.
 Plethysmography. You sit or stand inside an air-tight box that looks like a short, square
telephone booth to do the tests.
PFT measures:

 Tidal volume (VT). This is the amount of air inhaled or exhaled during normal breathing.
 Minute volume (MV). This is the total amount of air exhaled per minute.
 Vital capacity (VC). This is the total volume of air that can be exhaled after inhaling as much as
you can.
 Functional residual capacity (FRC). This is the amount of air left in lungs after exhaling
normally.
 Residual volume. This is the amount of air left in the lungs after exhaling as much as you can.
 Total lung capacity. This is the total volume of the lungs when filled with as much air as
possible.
 Forced vital capacity (FVC). This is the amount of air exhaled forcefully and quickly after
inhaling as much as you can.
 Forced expiratory volume (FEV). This is the amount of air expired during the first, second, and
third seconds of the FVC test.
 Forced expiratory flow (FEF). This is the average rate of flow during the middle half of the
FVC test.
 Peak expiratory flow rate (PEFR). This is the fastest rate that you can force air out of your
lungs.
Normal values for PFTs vary from person to person. The amount of air inhaled and exhaled in your
test results are compared to the average for someone of the same age, height, sex, and race. Results
are also compared to any of your previous test results. If you have abnormal PFT measurements or if
your results have changed, you may need other tests.
Why might I need pulmonary function tests?

There are many different reasons why pulmonary function tests (PFTs) may be done. They are
sometimes done in healthy people as part of a routine physical. They are also routinely done in
certain types of work environments to ensure employee health (such as graphite factories and coal
mines). Or you may have PFTs if your healthcare provider needs help to diagnose you with a health
problem such as:

 Allergies

 Respiratory infections

 Trouble breathing from injury to the chest or a recent surgery

 Chronic lung conditions, such as asthma, bronchiectasis, emphysema, or chronic bronchitis

 Asbestosis, a lung disease caused by inhaling asbestos fibers

 Restrictive airway problems from scoliosis, tumors, or inflammation or scarring of the lungs

 Sarcoidosis, a disease that causes lumps of inflammatory cells around organs, such as the liver,
lungs, and spleen

 Scleroderma, a disease that causes thickening and hardening of connective tissue

PFTs may be used to check lung function before surgery or other procedures in patients who have
lung or heart problems, who are smokers, or who have other health conditions. Another use of PFTs
is to assess treatment for asthma, emphysema, and other chronic lung problems. Your healthcare
provider may also have other reasons to advise PFTs.

What are the risks of pulmonary function tests?

Because pulmonary function testing is not an invasive procedure, it is safe and quick for most people.
But the person must be able to follow clear, simple directions.
All procedures have some risks. The risks of this procedure may include:

 Dizziness during the tests

 Feeling short of breath

 Coughing

 Asthma attack brought on by deep inhalation

In some cases, a person shouldn’t have PFTs. Reasons for this can include:

 Recent eye surgery, because of increased pressure inside the eyes during the procedure

 Recent belly or chest surgery

 Chest pain, recent heart attack, or an unstable heart condition

 A bulging blood vessel (aneurysm) in the chest, belly, or brain

 Active tuberculosis (TB) or respiratory infection, such as a cold or the flu

Your risks may vary depending on your general health and other factors. Ask your healthcare
provider which risks apply most to you. Talk with him or her about any concerns you have.

Certain things can make PFTs less accurate. These include:

 The degree of patient cooperation and effort

 Use of medicines that open the airways (bronchodilators)

 Use of pain medicines

 Pregnancy
 Stomach bloating that affects the ability to take deep breaths

 Extreme tiredness or other conditions that affect a person’s ability to do the tests (such as a head
cold)

How do I get ready for pulmonary function tests?

Your healthcare provider will explain the procedure to you. Ask him or her any questions you have.
You may be asked to sign a consent form that gives permission to do the procedure. Read the form
carefully. Ask questions if anything is not clear.

Tell your healthcare provider if you take any medicines. This includes prescriptions, over-the-counter
medicines, vitamins, and herbal supplements.

Make sure to:

 Stop taking certain medicines before the procedure, if instructed by your healthcare provider

 Stop smoking before the test, if instructed by your healthcare provider. Ask your provider how
many hours before the test you should stop smoking.

 Not eat a heavy meal before the test, if instructed by your healthcare provider

 Follow any other instructions your healthcare provider gives you

Your height and weight will be recorded before the test. This is done so that your results can be
accurately calculated.

What happens during pulmonary function tests?

You may have your procedure as an outpatient. This means you go home the same day. Or it may be
done as part of a longer stay in the hospital. The way the procedure is done may vary. It depends on
your condition and your healthcare provider's methods. In most cases, the procedure will follow this
process:
 You’ll be asked to loosen tight clothing, jewelry, or other things that may cause a problem with
the procedure.

 If you wear dentures, you will need to wear them during the procedure.

 You’ll need to empty your bladder before the procedure.

 You’ll sit in a chair. A soft clip will be put on your nose. This is so all of your breathing is done
through your mouth, not your nose.

 You’ll be given a sterile mouthpiece that is attached to a spirometer.

 You’ll form a tight seal over the mouthpiece with your mouth. You’ll be instructed to inhale and
exhale in different ways.

 You will be watched carefully during the procedure for dizziness, trouble breathing, or other
problems.

 You may be given a bronchodilator after certain tests. The tests will then be repeated several
minutes later, after the bronchodilator has taken effect.

What happens after pulmonary function tests?

If you have a history of lung or breathing problems, you may be tired after the tests. You will be
given a chance to rest afterwards. Your healthcare provider will talk with you about your test results.
 UNIT-III: DRUG AND POISON INFORMATION
A.INTRODUCTION TO DRUG INFORMATION RESOURCES AVAILABLE:

 Tertiary sources provide information that has been filtered and summarized by an author or
editor to provide a quick easy summary of a topic.
 Community pharmacy settings are a unique environment to practice One Medicine, a blending
of veterinary medicine and human medicine for the benefit of public health, and to better
serve human and animal patients alike.
 Comprehensive searches for information will require the use of multiple databases and
resources.
 Primary literature may be a variety of types of articles, not just clinical trials.
 At times even well-designed searches of standard medical literature will not yield sufficient
information to make clinical decisions or recommendations, and alternative resources may be
needed.
 Understanding where to access information is only the first step in the provision of quality
drug information.

The quantity of medical information and medical literature available is growing at an astounding rate.
The technology by which this information can be accessed is also improving exponentially. The
introduction of PDAs/smartphones and Internet resources has radically changed the methods and
technology by which information is accessed, but not the process of providing drug information.

On a daily basis, pharmacists are being asked to provide responses to numerous drug information
requests for a variety of people. It is tempting just to select the easiest, most familiar resources to find
information; however, by doing that, there is the possibility of missing new resources or limiting the
comprehensiveness of the information found. It is for these reasons that the systematic approach
discussed is helpful in order to streamline the search process.

Generally the best method to find information includes a stepwise approach moving first through
tertiary (e.g., textbooks, full-text databases, review articles), then secondary (e.g., indexing or
abstracting service), and finally primary (e.g., clinical studies) literature. The tertiary sources will
provide the practitioner with general information needed to familiarize the reader with the topic. This
is also an opportunity for the practitioner to gain general information about the disease or drug in
question, which will ultimately result in a more structured and productive search.

If the information obtained in the tertiary resources is not recent or comprehensive enough, a
secondary database may be employed...

B.systematic approach in answering DI queries:

Whether you’re on a drug information, community, or hospital rotation, these 7 steps will help you
provide the best possible answer to any medication question.

1. Secure requestor demographics.

It’s important to know your audience, as your response technique may differ depending on whether
the question comes from a health care professional or a patient. For example, you’d use the word
“renal” with a pharmacist and “kidney” with a patient. It’s always best to inquire how the requestor
would like the information delivered (eg, phone or fax), as this will help ensure adequate follow-up.

2. Obtain background information.

This is historically the most difficult step because you must act as a detective. Determine whether it’s
a general or patient-specific question, and then identify resources the requestor has already consulted
to help facilitate the process. For patient-specific questions, it’s important to inquire about pregnancy,
weight, and renal function.

3. Determine and categorize the question.

If a pharmacist requests information about whether a patient who’s breastfeeding can take
amoxicillin, this would be classified as a lactation question. Various categories may include
pregnancy, drug interaction, pharmacy law, or pill identification.

4. Develop a strategy and conduct a search.

First, begin with tertiary literature, which is a compilation of primary literature. This may include text
books like Drugs in Pregnancy and Lactation or drug information databases like Clinical
Pharmacology or Lexicomp. Next, consult your secondary literature resources, which is the path to
 primary literature. Secondary resources include PubMed and EMBASE, which will enable you to
locate primary literature or original research. It’s important to use reputable resources when
researching. When using websites, be sure to consult ones ending in .gov or .org.

4. Perform evaluation, analysis, and synthesis.

Objectively critique all of the information you retrieve from your comprehensive literature search.
Also, consider the background information of your question. Consult with pharmacists and other
health care professionals with expertise in your specific drug information question.

6. Formulate and provide a response.

Inform the requestor when one course of action is more desirable. Present competing viewpoints and
considerations. Also, describe your evaluation of the research. Written responses should always be
concise and fully referenced.

7. Conduct follow-up and documentation.

Following up is important for ensuring the information was received. Always document your drug
information questions so you can refer back to them. You’ll likely see the same question in the future,
and this well help serve as a reference point.

When I managed a drug information center, I’d always review these 7 steps with students on my
rotation. These tips will enable you to become confident in answering drug information questions and
prepare you for your pharmacy career.

C.CRITICAL EVALUATION OF DRUG INFORMATION AND LITERATURE:

According to “About the Authors” section of this book, Marie A. Abate and Matthew L. Blommel,
bring a combined tenure of 28 years to West Virginia University's Center for Drug and Health
Information. Abate is nationally known in the arena of drug information and serves as director of the
center, while Blommel serves as assistant director at the center. Blommel instructs in pharmacy-
related information resources as well as precepts more than 150 pharmacy students in the advanced
practice pharmacy experience drug information rotation program. Both authors are indexed in
PubMed, reflecting their articles and studies conducted from the 1990s to present time.
Collaborating as primary investigator and coinvestigator, Abate and Blommel authored two articles
that were published in the February and August 2007 issues of the American Journal of
Pharmaceutical Education. The first article deals with a drug information self-assessment tool used
by pharmacy students; the second article deals with a rubric that pharmacy students use to assess
critical literature evaluative skills. Both articles reveal the importance behind data collection based
upon self-assessment and feedback that goes toward fine-tuning a curriculum program and
assessment tool. This attests to their knowledge and professionalism in the area of pharmaceutics.

Drug Information and Literature Evaluation is one of several titles in the Remington Education
Series. It should be noted that these beginning titles are aimed especially at those students who are
pursuing an undergraduate pharmacy degree. Other series titles include Introduction to
Pharmacotherapy, Physical Pharmacy, Law & Ethics in Pharmacy Practice, and Pharmaceutics.

This book is similar in content and scope as Basic Skills in Interpreting Laboratory Data by Mary
Lee, Fundamental Skills for Patient Care in Pharmacy Practice by Colleen Doherty Lauster and
Sneha Baxi Srivastava, and Clinical Pharmacokinetics by John E. Murphy. Amazon.com states that
these titles are often purchased or bundled together. Drug Information and Literature Evaluation is
described as being written by pharmacists for pharmacists to assist in making their transition from the
classroom realm of undergraduate pharmacy students to the pharmaceutical world as bona-fide
pharmacists.

Early on in the book's “Introduction,” the reader is provided with a listing of the twelve chapters and
a brief synopsis for each chapter. Topics range from a suitable approach to an information request; to
tertiary, secondary, and Internet information resources; and finally, to six specific steps one takes
when evaluating clinical studies.

The text of each chapter includes: learning objectives, tips and tricks, key points, illustrations,
assessment questions, and further reading. This type of arrangement style reinforces the chapter's
content and offers a quick glance at each chapter's contents. The answers are provided within the
working examples, and answers to the self-assessments are located at the end of the book, along with
a bibliography and subject index.

In addition to being a guide for pharmacy students in evaluating medical literature such as clinical
studies, this book would benefit novice librarians who are looking to augment their collections. In
particular, the chapters on tertiary, secondary, and Internet resources offer a foundational starting
point for available resources. These will be applicable in addressing a plethora of medication-related
and health-related questions. The tertiary resources are divided into general drug information
resources and information-specific resources. The secondary resources include abstracting or
indexing services found at databases such as CINAHL, Cochrane Library, EMBASE, or International
Pharmaceutical Abstracts (IPA). The chapter on Internet services reminds savvy public health
consumers, when seeking their own information from the Internet, to take time to apply provided
criteria and questions referenced in Table 4.1 (pp. 43–44). These questions should cover issues
concerning the site's reliability, its accuracy, and its completeness.

D.PREPARATION OF WRITTEN AND VERBAL REPORTS;

Preparation of written response: Goal is to prepare a document that is clear, concise, complete
and correct.

General rules:

• Organize the information before starting to write (what and how to write)
• Use proper spelling and grammar
• Preferably avoid passive voice throughout
• Avoid writing in the first person and second person wherever possible
• Prepare a document in a presentable manner (neat)
• Keep things as simple and direct as possible
• Consider whether tables or graph or figures would make the document simpler
• Avoid using abbreviations or acronyms (or quote at first instance in parenthesis)
• If the document is long, use sub headings
• Present it in correct order as required
• Write in your own words

At first make sure that all of the information is down on paper. Once that occurs, go back, revise
and perhaps reorganize the document

Specific document sections:

It should contain

• Introduction
• Body
• Conclusion

Specific document sections:

• Should inform what the remainder of the document is to cover.

• Should contain all the details of the document

• Do not include unnecessary information (even if it is interesting)
• Do not stray from the subject.
• Sub divide the document further in a logical order and as appropriate when necessary
• Always focus end point
• Should be placed at the end of the document
• Avoid extrapolating beyond the information available
• Readers need something to bring their thoughts together at end.
• Verbal communications are most frequently used in practice settings
• Need to use good verbal communications skills

Preparation of verbal response:

• Deliver the information at an ideal place

• Deliver the content confidently
• Make analogous to the delivery of a presentation or lecture
• Use appropriate language with good grammar
• Use correct pronunciation of all terms of the document
• Listen carefully when clarification is sought
• Don’t interrupt while clarification is sought
• Clarify all doubts confidently
• Must be prepared for additional questions
• Show evidence where necessary/ appropriate
E.ESTABLISHING A DRUG INFORMATION CENTRE:

World Health Organization (WHO) defines drug information centre as an independent centre
that is accessible to any healthcare professional to ask all questions about drug therapy.

There are three physical criteria, which define an information centre:

1. Specific room set aside as location for drug information centre

2. At least one dedicated and trained pharmacist must be available to answer queries

3. Sufficient information resources should be available to answer a broad scope of queries.

A strategic plan should be developed when establishing a drug information centre

The plan should include:

 mission statement
 goals and objectives
 action plan with performance indicators
 details of budget
 methods for evaluating the services provided
 Establishment of a drug information centre needs the consideration of:

 Justification of the need for a centre
 Services to be offered by the centre
 Resources, facilities and ongoing maintenance for the centre.

Establishment and minimum requirements:

To be successful, DI centre requires a

 -- stable location and environment

-- idealistic commitment to provide needed drug information

-- physical space to house the service

-- basic information references

-- staff

-- equipment to support information access and dissemination, and

communication equipment

-- Philosophical commitment

-- Location of the centre

-- Space allocation

-- Facilities and equipments

-- Financial issues

-- Staff

-- Organization

-- Resources

-- Operational Procedures

-- Documentation

-- Quality assurance

Philosophical commitment:
Drug information centers should work both in reactive and proactive ways

o The reactive or passive responsibilities of the centers include providing the

information to the individuals who approach the centre

o Proactive responsibilities include reaching out with drug information for the
people who need it, in a format that is convenient and effective
o The centers should work according to the needs and expectations of its users and
should create demand and expectations .

Location of the centre: Should be centrally located & the location selected should have good
access to requestors and not too much of distraction

Few ideal locations

-- In or adjacent to a hospital

-- Medical teaching institution

-- Within the hospital

-- University/academic institution

-- Within/adjacent to a medical / pharmacy association

-- Relevant governmental agency (such as ministry of health,

drug control authority, drug approval unit, or quality control lab)

Space allocation:

An independent area must be set aside for the drug information services
 It may depend upon the size of the centre and the number of queries received by the
centre

A secure space of 25 square meters in one or two rooms allows for office workspace,
storage of references, placement of communication equipment, research and educational
activities, and space for visitors to use the drug information resources

Facilities and equipments:

DIC should have sufficient lighting, ventilation and aeration

It should also have essential access to a medical library

The basic equipments needed for effective functioning of a drug information centre
include, basic office equipment, photocopier (preferably), microfiche reader/printer, computer
equipment and Internet, printer, telephones, calculator (or computer programs), visual aids
and fax machine.

The minimum equipments required for effective operation of a major teaching hospital based
drug information centre:
Financial issues:

The source of finance depends on the objectives and operational modalities

Ideally funding may be sought from governmental authorities [as DI is public service]

Other sources

--donors supporting essential drugs projects

-- professional associations,

-- universities/pharmacy and medical institutions

-- non-governmental organizations
 Collation of several of these groups can also fund the drug information centers

No matter how the drug information centre is financed, the integrity of the unit is paramount

No special interests should be able to influence what information is or is not given out

Drug information centre should devote suitable amount for both human resources and
non human resources

Sample budget for establishing & maintaining a DI centre:

Staff:

The DI centre should have a multidisciplinary team

Ideally the number of personnel should be related to call volume

In case of hospital based drug information centre, the number depends on beds strength

Basic requirements for drug information pharmacists:

-- Master of Pharmacy degree

(Preferably Clinical Pharmacy / Pharmacy Practice)

-- Registered pharmacist

-- Training in computer based information systems

-- Two years of experience in DI services

-- Knowledge about literature identification, selection, utilization and critical evaluation

--Training in verbal, written and telephone communication skills

-- Involvement with in-service educational activities

Organization:

The drug information services should have an organization that should involve in the
preparation of

 guidelines & policies

 procedures
 manuals
  establishment of staff
 allocation of staff
 deciding the hours of the operation

Resources:

 The drug information centre must well equipped with current information resources
based on services provided
 The source of information may include primary, secondary and tertiary resources
 The collection of resources must represent variety of pharmaceutical and therapeutic
literature available and must be adequate to ensure timely response to the enquiries
 Access to the medical journals (local and international), which may be through a library
attached to the hospital
 Adequate number of appropriate reference texts
 In house information system (with relevant articles)
 Access to on-line data retrieval systems and drug information databases for obtaining
the published articles
Tertiary sources:

Documentation:

 Documentation is one of the essential elements in the practice of drug information

service in terms of both legal and future reference purpose
 Should maintain the documentation of drug information queries received and the
responses provided
 All the documented enquiries should be stored for a minimum of 5 years and may be for
the longer period (25 years) for the queries related to pregnancy and lactation
 Date and time of receipt of the enquiry.
 Requester’s name, address, professional status/occupation/discipline, method of contact
(e.g., telephonically, direct access)
 Previous references consulted by the enquirer
 Information about the pharmacist receiving the enquiry
 Category of the enquiry
  Question asked
 Patient data [specific information related to the enquiry]
 Answer provided
 Date and time of answering

Quality assurance:

The aims of the drug information centre need to be met and this can be assessed by the
application of quality assurance program

The drug information centre should measure how well the services were provided, and if the
services were not found to be acceptable or optimal, centre should undertake some correctional
measures to ensure that future services will be acceptable

General assessment techniques that can be used for the quality assurance of DI services

Workload statistics

Auditing

Peer review

Enquirer’s assessment/Users’ survey

F.POISONS INFORMATION-ORGANISATION AND INFORMATION RESOURCES:

• The poison information centre is a specialized unit providing information on poisoning

to the whole community

Functions:

• Provision of toxicological information and advise

• Management of poisoning cases
• Provision of laboratory analytical services
• Toxicovigilance activities
• Research education and training in the prevention &treatment of poisoning
Benefits:
Establishing a PIC:
 ORGANIZATION & OPERATION:

UNIT-IV: PHARMACOVIGILANCE

SCOPE,DEFINITION AND AIMS OF PHARMACOVIGILANCE:

WHO defines pharmacovigilance as the science and activities relating to the detection, assessment,
understanding and prevention of adverse effects or any other medicine-related problem.

The aims of pharmacovigilance

Events such as the thalidomide tragedy highlight the extreme importance of effective drug monitoring systems
for all medicines. The principal aims of pharmacovigilance programmes are:

• to improve patient care and safety in relation to the use of medicines, and all medical and paramedical
interventions;

• to improve public health and safety in relation to the use of medicines;

• to contribute to the assessment of benefit, harm, effectiveness and risk of medicines, encouraging their safe,
rational and more effective (including cost-effective) use;

• to promote understanding, education and clinical training in pharmacovigilance and its effective
communication to health professionals and the public.

Over the last decade, it has been increasingly recognized that the scope of pharmacovigilance needs to be
extended beyond the strict confines of detecting new signals of safety concerns. Globalization, consumerism, the
resulting explosion in free trade and communication across borders, and increasing use of the Internet have all
contributed to a change in the way people access medicinal products and information about them. These
changing patterns in drug use require a shift in the approach to pharmacovigilance, more specifically, towards
one that is more closely linked, and thus better able to respond, to the prevailing patterns of drug use within
society.

Pharmacovigilance Programme of India (PvPI)

The Central Drugs Standard Control Organization (CDSCO), Directorate General of Health Services under the
aegis of Ministry of Health & Family Welfare, Government of India in collaboration with Indian Pharmacopeia
commission, Ghaziabad is initiating a nation-wide Pharmacovigilance programme for protecting the health of the
patients by assuring drug safety. The programme shall be coordinated by the Indian Pharmacopeia commission,
Ghaziabad as a National Coordinating Centre (NCC). The centre will operate under the supervision of a Steering
Committee.

3. Steering Committee

Pharmacovigilance Programme of India

 Chairman

Drugs Controller General (India), New Delhi, ex- officio

Members
1. Scientific Director, Indian Pharmacopoeia Commission, Ghaziabad, ex-officio

2. Head of Department, Pharmacology, AIIMS, ex - officio

3. Nominee of Director General, ICMR, ex-officio

4. Assistant Director General ( Extended Programme of Immunization [ ADG(EPI)] as representative

Directorate General Health Services

5. Under Secretary (Drugs Control) as representative of The Ministry of Health & family Welfare

6. Nominee of Vice Chancellor of Medical/Pharmacy University, ex-officio

7. Nominee of the Medical Council of India, ex-officio

8. Nominee of Pharmacy Council of India, ex-officio

ember Secretary
fficer-in-Charge (New Drugs), CDSCO, New Delhi, ex-officio

Goal and Objectives

Goals

To ensure that the benefits of use of medicine outweighs the risks and thus safeguard the health of the Indian
population.

Objectives

 To monitor Adverse Drug Reactions (ADRs) in Indian population

 To create awareness amongst health care professionals about the importance of ADR reporting in India

 To monitor benefit-risk profile of medicines

 Generate independent, evidence based recommendations on the safety of medicines
 Support the CDSCO for formulating safety related regulatory decisions for medicines
 Communicate findings with all key stakeholders
 Create a national centre of excellence at par with global drug safety monitoring standards

4.3 Programme governance and reporting structures

The Pharmacovigilance Programme of India will be administered and monitored by the following two
committees.
I. Steering Committee
II. Strategic Advisory Committee

Technical support will be provided by the following committees:

I. Signal Review Panel

II. Core Training Panel
III. Quality Review Panel
ADR MONITORING CENTRES
 MCI Approved Medical Colleges & Hospitals

 Private Hospitals

 Public Health Programmes

 Autonomous Institutes (ICMR etc.)

Collaboration with World Health Organization-Uppsala Monitoring Centre (UMC)

WHO and UMC work with and/or provide technical support to more than 94 countries worldwide. The long
term objective of the PvPI is to establish a ‘Centre of Excellence’ for Pharmacovigilance in India. To achieve
this objective, the PvPI National Coordinating Centre will collaborate with the WHO Collaborating Centre -
Uppsala Monitoring Centre (UMC) based in Sweden.

B.ADVERSE DRUG REACTIONS:

An adverse drug reaction (ADR) is an injury caused by taking a medication.[1] ADRs may occur
following a single dose or prolonged administration of a drug or result from the combination of two
or more drugs. The meaning of this expression differs from the meaning of "side effect", as this last
expression might also imply that the effects can be beneficial. [2] The study of ADRs is the concern of
the field known as pharmacovigilance. An adverse drug event (ADE) refers to any injury occurring
at the time a drug is used, whether or not it is identified as a cause of the injury.[1] An ADR is a
special type of ADE in which a causative relationship can be shown.
CLASSIFICATION:

ADRs may be classified by e.g. cause and severity.

Cause

 Type A: Augmented pharmacologic effects - dose dependent and predictable

Type A reactions, which constitute approximately 80% of adverse drug reactions, are usually
a consequence of the drug’s primary pharmacological effect (e.g. bleeding when using the
anticoagulant warfarin) or a low therapeutic index of the drug (e.g. nausea from digoxin), and
they are therefore predictable. They are dose-related and usually mild, although they may be
serious or even fatal (e.g. intracranial bleeding from warfarin). Such reactions are usually due
to inappropriate dosage, especially when drug elimination is impaired. The term ‘side effects’
is often applied to minor type A reactions. [3]

 Type B: Idiosyncratic

Types A and B were proposed in the 1970s, [4] and the other types were proposed subsequently
when the first two proved insufficient to classify ADRs. [5]

Severity

The U.S Food and Drug Administration defines a serious adverse event as one when the patient
outcome is one of the following:[6]

 Death
 Life-threatening
 Hospitalization (initial or prolonged)
 Disability - significant, persistent, or permanent change, impairment, damage or disruption in
the patient's body function/structure, physical activities or quality of life.
 Congenital anomaly
 Requires intervention to prevent permanent impairment or damage

Severity is a point on an arbitrary scale of intensity of the adverse event in question. The terms
"severe" and "serious" when applied to adverse events are technically very different. They are
easily confused but can not be used interchangeably, requiring care in usage.
 A headache is severe, if it causes intense pain. There are scales like "visual analog scale" that help
clinicians assess the severity. On the other hand, a headache is not usually serious (but may be in
case of subarachnoid haemorrhage, subdural bleed, even a migraine may temporally fit criteria),
unless it also satisfies the criteria for seriousness listed above.

Mechanisms

As research better explains the biochemistry of drug use, fewer ADRs are Type B and more are Type
A. Common mechanisms are:

 Abnormal pharmacokinetics due to

 genetic factors
 comorbid disease states
 Synergistic effects between either
 a drug and a disease
 two drugs

Abnormal pharmacokinetics

Comorbid disease states

Various diseases, especially those that cause renal or hepatic insufficiency, may alter drug
metabolism. Resources are available that report changes in a drug's metabolism due to disease
states.[8]

Genetic factors

Abnormal drug metabolism may be due to inherited factors of either Phase I oxidation or Phase II
conjugation. Pharmacogenomics is the study of the inherited basis for abnormal drug reactions.

Phase I reactions

Inheriting abnormal alleles of cytochrome P450 can alter drug metabolism. Tables are available to
check for drug interactions due to P450 interactions. [11][12]

Inheriting abnormal butyrylcholinesterase (pseudocholinesterase) may affect metabolism of drugs

such as succinylcholine[13]
Phase II reactions

Inheriting abnormal N-acetyltransferase which conjugated some drugs to facilitate excretion may
affect the metabolism of drugs such as isoniazid, hydralazine, and procainamide.[12][13]

Inheriting abnormal thiopurine S-methyltransferase may affect the metabolism of

the thiopurine drugs mercaptopurine and azathioprine.[12]

Interactions with other drugs

The risk of drug interactions is increased with polypharmacy.

Protein binding

These interactions are usually transient and mild until a new steady state is achieved. [14][15] These are
mainly for drugs without much first-pass liver metabolism. The principal plasma proteins for drug
binding are:[16]

1. albumin
2. α1-acid glycoprotein
3. lipoproteins

Some drug interactions with warfarin are due to changes in protein binding.[16]

Cytochrome P450

Patients have abnormal metabolism by cytochrome P450 due to either inheriting abnormal alleles or
due to drug interactions. Tables are available to check for drug interactions due to P450
interactions.[11]

Synergistic effects

An example of synergism is two drugs that both prolong the QT interval.

Assessing causality

Causality assessment is used to determine the likelihood that a drug caused a suspected ADR. There
are a number of different methods used to judge causation, including the Naranjo algorithm, the
Venulet algorithm and the WHO causality term assessment criteria. Each have pros and cons
associated with their use and most require some level of expert judgement to apply.[17] An ADR
should not be labeled as 'certain' unless the ADR abates with a challenge-dechallenge-
rechallenge protocol (stopping and starting the agent in question). The chronology of the onset of the
suspected ADR is important, as another substance or factor may be implicated as a cause; co-
prescribed medications and underlying psychiatric conditions may be factors in the ADR. [2]

Assigning causality to a specific agent often proves difficult, unless the event is found during a
clinical study or large databases are used. Both methods have difficulties and can be fraught with
error. Even in clinical studies some ADRs may be missed as large numbers of test individuals are
required to find that adverse drug reaction. Psychiatric ADRs are often missed as they are grouped
together in the questionnaires used to assess the population.

C.REPORTING, EVALUATION, MONITERING, PREVENTING AND MANAGEMENT OF

ADR’S:

A comprehensive ADR‐monitoring and reporting program should be an integral part of an

organization’s overall drug use system.

An ADR‐ monitoring and reporting program should include the following features:

1.The program should establish

( a.) An ongoing and concurrent (during drug therapy) surveillance system based on the reporting
of suspected ADRs by pharmacists, physicians, nurses, or patients.

(b.) A prospective (before drug therapy) surveillance system for high‐risk drugs or patients with
a high risk for ADRs.

• (c.) A concurrent surveillance system for monitoring alerting orders. Alerting orders include the
use of “tracer” drugs that are used to treat common ADRs (e.g., orders for immediate doses of
antihistamines, epinephrine, and corticosteroids), abrupt discontinuation or decreases in dosage of a
drug, or stat orders for laboratory assessment of therapeutic drug levels.

• 2. Prescribers, caregivers, and patients should be notified regarding suspected ADRs.

• 3. Information regarding suspected

• including the patient’s name, the patient’s medical and medication history, a description of the
suspected ADR, the temporal sequence of the event, any remedial treatment required, and sequelae.

• 4. High‐risk patients should be identified and monitored. High‐risk patients include but are not
limited to pediatric patients, geriatric patients, patients with organ failure (e.g., hepatic or renal
failure), and patients receiving multiple drugs.

• 5. Drugs likely to cause ADRs (“high ‐risk” drugs) should be identified, and their use should be
monitored. Examples of drugs that may be considered as high risk include aminoglycosides,
amphotericin, antineoplastics, corticosteroids, digoxin, heparin, lidocaine, phenytoin, theophylline,
thrombolytic agents, and warfarin.

• 6. The cause(s) of each suspected ADR should be evaluated on the basis of the patient’s medical and
medication history, the circumstances of the adverse event, the results of dechallenge and rechallenge
(if any), alternative etiologies, and a literature review.

• 5. Drugs likely to cause ADRs (“high ‐risk” drugs) should be identified, and their use should be
monitored. Examples of drugs that may be considered as high risk include aminoglycosides,
amphotericin, antineoplastics, corticosteroids, digoxin, heparin, lidocaine, phenytoin, theophylline,
thrombolytic agents, and warfarin.

• 6. The cause(s) of each suspected ADR should be evaluated on the basis of the patient’s medical and
medication history, the circumstances of the adverse event, the results of dechallenge and rechallenge
(if any), alternative etiologies, and a literature review.

• a. Was there a temporal relationship between the onset of drug therapy and the adverse reaction

• b. Was there a dechallenge; i.e., did the signs and symptoms of the adverse reaction subside when
the drug was withdrawn

• c. Can signs and symptoms of the adverse reaction be explained by the patient’s disease state

• d. Were there any laboratory tests that provide evidence for the reaction being an ADR
• e. What was the patient’s previous general experience with the drug

• f. Did symptoms return when the agent was readministered

• 8. A method for ranking ADRs by severity should be established.

• 9. A description of each suspected ADR and the outcomes from the event should be documented in
the patient’s medical record.

• 10. Serious or unexpected ADRs should be reported to the Food and Drug Administration (FDA) or
the drug’s manufacturer (or both).

• 11. All ADR reports should be reviewed and evaluated by a designated multidisciplinary committee
(e.g., a pharmacy and therapeutics committee).

• 12. ADR ‐report information should be disseminated to health care professional staff members for
educational purposes. Good topics for medical staff education include preventing ADRs and
appropriate and effective care for patients who experience ADRs. Educational programs can be
conducted as morning “report” discussions, newsletters, “grand rounds” presentations, algorithms for
treatment, and multidisciplinary reviews of drug ‐use evaluations. Patient confidentiality should be
preserved.

• 13. In settings where it is possible, a pharmacy ‐coorddinated ADR team or committee, consisting
of a physician, nurse, quality improvement leader, an administrator, anda pharmacist is
recommended.The team should be charged with adopting a definition for the organization, promoting
awareness of the consequences of ADRs,establishing mechanisms for identifying and reporting
ADRs, reviewing ADR patterns or trends, and developing preventive and corrective interventions.

• 14. Continuous monitoring of patient outcomes and patterns of ADRs is imperative. Findings from
an ADRmonitoring and reporting program should be incorporated into the organization’s ongoing
quality improvement activities. The process should include the following:

• a. Feedback to all appropriate health care staff,

• b. Continuous monitoring for trends, clusters, or significant individual ADRs,

• c. Educational efforts for prevention of ADRs, and

• d. Evaluation of prescribing patterns, patient monitoring practices, patient outcomes, and the ADR
program’s effect on overall and individual patient outcomes

.An overall goal of the ADR process should be the achievement of positive patient outcomes.

• Benefits

• An ongoing ADR ‐monitoring and reporting program can provide benefits to the organization,
pharmacists, other health care professionals, and patients.

These benefits include (but are not limited to) the following:

• 1. Providing an indirect measure of the quality of pharmaceutical care through identification of

preventable ADRs and anticipatory surveillance for high ‐risk rugs or patients.

• 2. Complementing organizational risk ‐management activities and efforts to minimize liability.

• 3. Assessing the safety of drug therapies, especially recently approved drugs.

• 4. Measuring ADR incidence.

• 5. Educating health care professionals and patients about drug effects and increasing their level of
awareness regarding ADRs.

• 6. Providing quality ‐assurance screening findings for use in drug ‐use evaluation programs.

• 7. Measuring the economic impact of ADR prevention as manifested through reduced

hospitalization, optimal and economical drug use, and minimized organizational liability

• Management
• Rapid action is sometimes important because of the serious nature of a suspected adverse drug
reaction, forexample anaphylactic shock. Emergency treatment and

• withdrawal of all medicines is occasionally essential, in which case cautious reintroduction of

essential medicines should be considered. Otherwise, using clinical benefit ‐risk judgment, together
with help from investigations, one

• decides which medicine or medicines should be with drawn as a trial. A problem immediately arises
if one or more of the medicines is essential to the patient. If the culprit is fairly clear, a benefit ‐risk
decision needs to be taken about the need for the drug (are there equally effective substitutes that are
unlikely to produce the same adversedrug reaction?), the severity of the reaction, and its potential for
treatment. If several medicines could be causative, the non ‐essential medicines should be withdrawn
first, preferably one at a time, depending on the severity of the reaction. If the reaction is likely to be
dose related, dose reduction should be considered. Many prescribers unnecessarily withhold a drug
when interactions are suspected, rather than adjusting the dose.

• The patient should be observed during withdrawal. The waiting period will vary, depending on the
rate of elimination of the drug from the body and the type of pathology.

• For example, urticaria usually disappears quickly when the drug is eliminated, whereas fixed
psoriatic skin reactions can take weeks to resolve. If the patient is clearly getting better, in keeping
with the prediction, alternative medicines for the basic disease can be introduced if necessary. If the
patient is not doing well after withdrawal of the first drug, the next most likely culprit should be
considered, and the process repeated. On the other hand, the patient may be suffering through being
deprived of the medicine withheld. In that case, either another suitable drug should be substituted
(remembering the possibility of cross ‐sensitivity), or the same drug should be tried at a lower dosage
(for a dose ‐related reaction).

• The latter approach should be tried if more than one drug was withheld, for instance if an interaction
was suspected or if the seriousness of the reaction made it wise to withhold several possible drugs.
Reintroduce apparently essential medicines one at a time, starting with the one least likely to be the
culprit. • If the patient cannot manage without a medicine that has caused an adverse reaction, provide
symptomatic relief while continuing the essential treatment.
• For example:

• severe nausea and vomiting are routinely treated symptomatically in patients receiving anti ‐cancer
drugs.

• However, when treating an adverse drug reaction, it is important not to introduce more medicines
than are essential. Always have a clear therapeutic objective in mind, do not treat for longer than is
necessary, and review the patient regularly and look for ways to simplify management.

• The investigation and identification of an adverse drug reaction still depands Largely on
circumstantial evidence and the clinical skills of the attending physician. A knowledge of the clinical
criteria and the varied manifeststions Ascribed to drug allergy,and syndromes commonly associated
with certain drugs,is of great value in evaluating suspected adverse drug reactions.unfortunately, none
of the clinical manifestations is unique or specific for drug reaction.

• REPORTING TO THE FDA:

• Three of the five major centers at the FDA are involved with evaluating the safety and efficacy of
drug and efficacy of drugs.

• The largest center is the center for drug evaluation and research (CDER) which overseas both
prescription and non prescription over the counter (OTC) drugs.

• In 2002, CDER established the adverse events reporting system (AERS), a computerized data base
designed to support FDA’S post marketing safety program for drugs and therapeutics biological
products.

• The center for biological evaluation and research (CBER), ensures the safety and efficacy of blood
products, Vaccines, biological therapeutics, Gene therapy, medical devices and tests,
xenotransplantation products, banked human tissue and cellular products.

• The center for food safety and applied nutrition(CFSAN) established the CFSAN adverse events
reporting system (CAERS) in 2002
• The CAERS provides a monitoring system to identify potentially serious problem secondary to
non ‐FDA‐approved herbs, minerals, vitamins, dietary supplements, and other substances. •

• The National vaccine adverse event reporting system (VAERS) is co administered by the FDA and
the centers for disease control and prevention (CDC).Although vaccines protect many people from
dangerous diseases they do have the potential to cause adverse effects

• 1.The national childhood vaccine injury act(NCVIA) requires health professionals to report

• a. adverse events after the administration of vaccines specified in the act, as described in the
“Reporting events tables”with in the specified time period.

• b.any event listed in the manufacter package insert as an contraindication to subsequent doses of the
vaccine •

• 2. in 1990 VAERS was set up to receive all reports of suspected adverse events caused by any
U.S.licensed vaccine

• 3. the VAERS depends on voluntary reporting by health professionals to :

• a.identify rare adverse reaction not detected in pre‐ licensing studies

• b.monitor for Increased in already known reactions

• c.identify risk factors or pre existing conditions that promote reactions

• d. identify particular vaccines lots with unusually high rates or unusual type of events. •

• B.MEDWATCH ,the FDA’S medical products reporting program established in 1993,is a voluntary
system for healthcare products.The goals of the program are to increase awareness of reporting of
medical product induced diseases and the importance,to clarify what should be reported, to make
reporting as easy as possible,and to provide feedback to health professionals

• A.preventing of ADR’S is an important startegy in health care.It has been further noted that
preventable ADR’S tend to be treat and cause the greatest degree of patient morbidity.
• B.recognition of previously undiscovered ADR’S attributable to a drug is particulary true in the
case of newly marketed products

• C.prompt recall in cases of product problems are accomplished when the Medwatch programm is
used to report product problems or device defects

• Role of the Pharmacist

• Pharmacists should exert leadership in the development, maintenance, and ongoing evaluation of
ADR programs. They should obtain formal endorsement or approval of such programs through
appropriate committees (e.g., a pharmacy and therapeutics committee and the executive committee of
the medical staff) and the organization’s administration. In settings where applicable, input into the
design of the pro‐gram should be obtained from the medical staff, nursing staff,quality improvement
staff, medical records department, and risk managers.

• The pharmacist should facilitate

• 1. Analysis of each reported ADR,

• 2. Identification of drugs and patients at high risk for being involved in ADRs,

• 3. The development of policies and procedures for the ADR‐monitoring and reporting program,

• 4. A description of the responsibilities and interactions of pharmacists, physicians, nurses, risk

managers, and other health professionals in the ADR program,

• 5. Use of the ADR program for educational purposes,

• 6. Development, maintenance, and evaluation of ADR records within the organization,

• 7. The organizational dissemination and use of information obtained through the ADR program,

• 8. Reporting of serious ADRs to the FDA or the manufacturer (or both), and

• 9. Publication and presentation of important ADRs to the medical community.

• Direct patient care roles for pharmacists should include patient counseling on ADRs, identification
and documentation in the patient’s medical record of high‐risk patients, monitoring to ensure that
serum drug concentrations remain within acceptable therapeutic ranges, and adjusting doses in
appropriate patients (e.g., patients with impaired renal or hepatic function).

D.ROLE OF PHARMACIST IN MANAGEMENT OF ADR:

• To describe and identify the role of the clinical pharmacist in all aspects of the management of
adverse drug reactions (ADRs).

These include

– Prevention (& patient counseling)

– Detection

– Treatment

– Reporting

– Alerting health care providers and patients

Outline of this session:

• Intro – Definitions

– ADR statistics

– ADRs within the healthcare system

• Small groups to evaluate patient profiles and focus on ADR related aspects

(1) • Qs about ADR reporting

(2) • Small groups to evaluate patient profiles and focus on ADR related aspects
(2) • Pharmacovigilance
(3) • Conclusion
“Any noxious, unintended, and undesired effect of a drug that occurs at doses used in man for
prevention, diagnosis, or treatment of disease, or modification of physiological function”

Pharmacists should exert leadership in the development, maintenance, and ongoing evaluation of
ADR programs. They should obtain formal endorsement or approval of such programs through
appropriate committees (e.g., a pharmacy and therapeutics committee and the executive committee of
the medical staff) and the organization’s administration. In settings where applicable, input into the
design of the pro-gram should be obtained from the medical staff, nursing staff, quality improvement
staff, medical records department, and risk managers.

The pharmacist should facilitate

1. Analysis of each reported ADR,
2. Identification of drugs and patients at high risk for being involved in ADRs,
3. The development of policies and procedures for the ADR-monitoring and reporting program,
4. A description of the responsibilities and interactions of pharmacists, physicians, nurses, risk
managers, and other health professionals in the ADR program,
5. Use of the ADR program for educational purposes,
6. Development, maintenance, and evaluation of ADR records within the organization,
7. The organizational dissemination and use of information obtained through the ADR program,
8. Reporting of serious ADRs to the FDA or the manufacturer (or both), and
9. Publication and presentation of important ADRs to the medical community.

Direct patient care roles for pharmacists should includes

patient counseling on ADRs,

identification and documentation in the patient’s medical record of high-risk patients,

monitoring to ensure that serum drug concentrations remain within acceptable therapeutic ranges,

and adjusting doses in appropriate patients (e.g., patients with impaired renal or hepatic function).
UNIT-V: COMMUNICATION SKILLS, INCLUDING PATIENT
COUNSELLING TECHNIQUES, MEDICATION HISTORY INTERVIEW,
PRESENTATION OF CASES.

A medication history is a detailed, accurate and complete account of all prescribed and non-
prescribed medications that a patient had taken or is currently taking prior to a newly initiated
institutionalized or ambulatory care.

It provides valuable insights into patients’ allergic tendencies, adherence to pharmacological and
nonpharmacological treatments, social drug use and probable self-medication with complementary
and alternative medicines.

Interviewing a patient in collecting the data medical history is called medication history interview.

Goals:

The goal of medication history interview is to obtain information on aspects of drug use that may
assist in over all care of patient. The information gathered can be utilized to:

‰Compare medication profiles with the medication administration record and investigate the
discrepancies.

‰Verify medication history taken by other staffs and provide additional information where
appropriate.

 ‰Document allergies and adverse reactions.

 ‰Screen for drug interactions.
 ‰Assess patient medication compliance.
 ‰assess the rationale for drug prescribed.
 ‰Assess the evidence of drug abuse.
  ‰Appraise the drug administration techniques.
 ‰Examine the needs for medication aids.
 ‰Document patient initiated medication administration.

Importance of accurate drug history:

• Medication histories are important in preventing prescription errors and consequent risks to patients.

• Apart from preventing prescription errors, accurate medication histories are also useful in detecting
drug-related pathology or changes in clinical signs that may be the result of drug therapy.

• A good medication history should encompass all currently and recently prescribed drugs, previous
adverse drug reactions including hypersensitivity reactions, any over-the counter medications,
including herbal or alternative medicines, and adherence to therapy for the better health care plan.

• A full medication history

• Identifies patients’ needs

• Explores the patient’s perspective of illness and its treatment (needs and concerns)

To review current medical treatment and identify suitable additional treatments, medical professionals
will require complete and reliable medication history.

Research has established that in routine practice, pharmacist provide the most accurate history when
compared to other health professionals. It is an important role that pharmacists are well prepared to
fulfill. A well prepared, structured approach helps to obtain relevant complete information and avoid
omissions.

The fallowing information is commonly recorded:

 Currently or recently prescribed medicines.

 OTC medication.
 Vaccinations.
 Alternative or traditional remedies.
  Description of reaction and allergies to medicines.
 Medicines found to be ineffective.
 Adherence to past treatment courses and the use of adherence aids.

Interviewing the client:

• Introduce yourself

• Inform client of reason for you being there

• Inform client of importance of maintaining a current medication list in chart.

Information sources:

• Patient

• Family or Caregiver

• Medication Vials / Bubblepacks

• Medication List

• Community Pharmacy

• Medication Profile from other facility

• DPIN (Drug Programs Information Network)

QUESTIONS to ASK:

• Which community pharmacy do you use?

• Any allergies to medications and what was the reaction?

Which medications are you currently taking:

• The name of the medication

• The dosage form

• The amount (specifically the dose)

• How are they taking it (by which route)

• How many times a day

• Any specific times

• For what reason (if not known or obvious)

• What prescription medications are you taking on a regular or as needed basis?

• What over-the-counter (non-prescription) medications are you taking on a regular or as needed

basis?

• What herbal or natural medicines are you taking on a regular or as needed basis?

• What vitamins or other supplements are you taking?

Medication History Taking TIPS:

• Balance open-ended questions (what, how, why, when) with yes/no questions

• Ask non-biased questions

• Avoid leading questions

• Explore vague responses (non-compliance)

• Avoid medical jargon – Keep it simple

• Avoid judgmental comments

• Various approaches can be used:

• 24 hours survey (morning, lunch, supper, bedtime)

• Review of Systems (head to toe review)

• Link to prescribers (family physician, specialists)

PHARMACEUTICAL CARE CONCEPTS:

FUNCTIONS
 COLLECTION OF PATIENT DATA
 IDENTIFICATION OF PROBLEMS
 ESTABLISHING OUTCOME GOALS THROUGH A
GOOD THERAPEUTIC PLAN
 EVALUATING TREATMENT ALTERNATIVES , BY
MONITORING AND MODIFYING THERAPEUTIC
PLAN
 INDIVIDUALISING DRUG REGIMENS
 MONITORING OUTCOMES

www.revolutionpharmd.com
COLLECTION OF PATIENT DATA:
 Demographics
 Current problems
 Past medical history
 Current medication
 Social habits
 Relevant laboratory data
 Subsequent modifications of therapy plan
IDENTIFICATION OF PROBLEMS:
 The data collected can be used to identify actual or potential drug related problems.
 ACTUAL: A condition that requires the initiation of a new or additional drug.
 POTENTIAL: The patient may be at risk to develop a new medical problem.
 These problems may be related to the patient’s current drug therapy, drug administration, drug
compliance, drug toxicity, ADR’s and a failure to achieve desired outcomes by the treatment.
ESTABLISHING OUTCOME GOALS:
 Drug therapy can produce positive outcome:
 Cure of the disease
 Elimination or reduction of patient’s symptomology
 Arresting or slowing of a disease process
 Preventing a disease or symptoms
 It may also produce negative result, i.e. resulting in disease morbidity and sometimes
mortality.
EVALUATING TREATMENT ALTERNATIVES BY MONITORING AND MODIFYING
THERAPEUTIC PLAN:
 Efficacy, safety, availability and cost of treatment and suitability of the treatment to the
patient should be considered while evaluating.
 The risk-benefit ratio factors should also be considered: seriousness of the disease,
complications if untreated, efficacy of drug, ADR’s.
INDIVIDUALISING DRUG REGIMENS:
  When more than one therapeutic alternatives exist, the following factors to be considered:
 Patient factors:- diagnosis, treatment goals, past medical and medication history,
contraindication, allergies, compliance
 Drug factors:- efficacy, adverse effects, dosage form, cost, drug-drug interactions
MONITORING OUTCOMES:
 The goals are: Cure of the disease, elimination or reduction of patient’s
symptomology, arresting or slowing of a disease process, preventing a disease or
symptoms.
 But often leads to suboptimal outcomes due to:- inappropriate or unnecessary
prescribing or drug regimen, dispensing error, non-compliance, inappropriate
monitoring.
 To ensure good monitoring outcomes;
 Regularly should review whether satisfactory progression is made or not according to
the therapeutic plan.
 To determine whether original plan should continue or any treatment modifications to
be made or not.
 Reviews ongoing progress and provides report to patient’s other healthcare providers.
Should regularly update patient’s medical/pharmacy records with information concerning patient’s
progress.
PHARMACEUTICAL CARE IN HOSPITALS:
 Prescription monitoring
 Prescribing advice to medical and nursing staff
 Medication errors and adverse reaction monitoring
 Medication history interview
 Patient education and counselling
 Pharmacokinetics and therapeutic drug monitoring
Hospital formulary
PHARMACEUTICAL CARE FOR THE COMMUNITY:
 Participate in health screening
 Participate in health promotion and education
  Serve as a source of drug and poison information
 Collaborate with other health care professionals to develop treatment guidelines
 Design and monitor procurement and drug distribution system including storage and disposal.
BARRIERS TO PHARMACEUTICAL CARE:
 Pharmacist barrier
 Practice setting constraints
 System impediments
 Intra professional barrier
Critical Evaluation of Biomedical Literature:
There are more than 20,000 biomedical journals available worldwide
Approximately 9000 articles are being published everyday
Updating scientific knowledge is an Herculean task for the healthcare professionals
Majority of biomedical literature conforms to the Vancouver guidelines
Over 500 journals recommend Vancouver guidelines
The Vancouver guidelines format include

 Format of abstract
 Text
 Tables/graphs
 Reference
 Permissible abbreviations and symbols
 Authorship recommendation
 Acknowledgements
 Although majority of biomedical literature confirms to the Vancouver guidelines, the
content and quality of scientific publication vary enormously

 Thus drug information pharmacist requires the skills to be able to critically evaluate
and interpret the literature prior to formulating answers and making recommendations
Reputed journal usually demonstrate

o The editorial policy specifying types and format of articles

o Publishes results of well-conducted research
o Articles undergo peer review
o Texts exceeds pages of advertising /promotional material
Researchers and facilities:
 Are researchers have appropriate qualification and or experience in the field of
research?

 Has a statistician been included?

 Authors have any connection with pharmaceutical company?

 Are the authors from the same research facility or is the study multicentre study?

The manuscript:
Includes:
title
abstract/summary
introduction
objectives
methods
results and data analysis
discussion/ conclusion
references
Title:
Is the title indicative of content?
Look for any positive or negative title
Should be succinct description of research and / or results of study
Should not relay on title alone to determine if the paper is worth reviewing or discarding
Abstract:
It should outline purpose of study
-- Brief methodology
-- Important/ major results
-- Authors’ conclusion [based on study findings]
-- Should not be used alone to evaluate the study as it does not provide full
description

Study design and methods:

Is the study design appropriate for the question being assessed?
Look for Power of the study – Based on sample size [power of the study is its ability to detect
the worthwhile difference between two treatment groups]
Patients selection demographic data, inclusion & exclusion criteria, settings of patient selection
[ in-patient / outpatient, research institution or general practice settings]
Study methods and measurements:
Are the methods employed in the study appropriate?
When evaluating a study one should consider drug therapy, measurement of therapeutic
outcome or adverse effects.
Study results and analysis:
i) Data presentation
- Table/graph/chart format
- Data should be presented clearly
- All the data collected should be presented
ii) Patient drop out and data collection
Reasons for patient dropout quoted?
- In case of ADR event and incidence should be quoted
- Errors in patients should be mentioned
- Ineligible patient, decrease sample size and protocol deviation
Adverse events:
Discussion and conclusion:
Interpretation of results should be presented should address the results with previous studies
should demonstrate how the results answer the study hypothesis Conclusion should be based on
study results
MEDICATION ERRORS:

Like many terms of this form (e.g. ‘definition’, ‘prescription’), ‘medication’ can mean either a
process or an object that undergoes the process. A medication (the object) can be considered to be the
same as a medicinal product, which has been defined in terms of what a medicinal product is and
what it does. Thus, a medication is ‘[a product that] contains a compound with proven biological
effects, plus excipients, or excipients only; it may also contain contaminants; the active compound is
usually a drug or prodrug, but may be a cellular element’

There is a codicil to this definition, which is not strictly part of the definition, but describes certain
attributes of a medicinal product. The codicil stipulates that a medicinal product is one that is
intended to be taken by or administered to a person or animal for one or more of the following
reasons: as a placebo; to prevent a disease; to make a diagnosis; to test for the possibility of an
adverse effect; to modify a physiological, biochemical, or anatomical function or abnormality; to
replace a missing factor; to ameliorate a symptom; to treat a disease; to induce anaesthesia.
Medication (the process) is the act of giving a medication (the object) to a patient for any of these
purposes.

This definition reminds us of the distinction between the drug itself (the active component) and the
whole product. It includes chemical compounds, either drugs or prodrugs (which themselves may
have no pharmacological activity), or, in racemic mixtures, stereoisomers that may have only adverse
effects, or compounds that are used for diagnostic purposes (such as contrast media); it also includes
cellular elements, such as inactivated or attenuated viruses for immunization, blood products (such as
erythrocytes), viruses for gene therapy, and embryonic stem cells; ‘contaminants’ includes chemical
and biological contaminants and adulterants, the former being accidentally present, the latter
deliberately added.
Thus, the definition covers a wide range of compounds. However, it does not include medications
when they are used to probe systems for nondiagnostic purposes, such as the use of phenylephrine to
study baroreceptor reflexes in a physiological or pharmacological experiment.

An error

An error is ‘something incorrectly done through ignorance or inadvertence; a mistake, e.g. in

calculation, judgement, speech, writing, action, etc.’ or ‘a failure to complete a planned action as
intended, or the use of an incorrect plan of action to achieve a given aim’.Other definitions have been
published.

A medication error

With these definitions in mind, a medication error can be defined as ‘a failure in the treatment process
that leads to, or has the potential to lead to, harm to the patient’ The use of the term ‘failure’ signifies
that the process has fallen below some attainable standard. The ‘treatment process’ includes treatment
for symptoms or their causes or investigation or prevention of disease or physiological changes. It
includes not only therapeutic drugs but also the compounds referred to above. It also includes the
manufacturing or compounding, prescribing, transcribing (when relevant), dispensing, and
administration of a drug, and the subsequent monitoring of its effects. ‘Harm’ in the definition also
implies ‘lack of benefit’, a form of treatment failure. Note that the definition does not specify who
makes the error – it could be a doctor, a nurse, a pharmacist, a carer, or another; nor does it specify
who is responsible for preventing errors.

Different definitions of medication errors have been tested, as all technical definitions should be. In
this case it was done by devising scenarios and determining which would constitute an error under
each of the definitions. The above definition, slightly amended, was the only definition that
categorized all error scenarios, and only error scenarios.

Figure 1 shows how medication errors, defined in this way, fit into the overall pattern of adverse drug
reactions.
Figure 1

A Venn diagram showing the relation between adverse events, adverse drug reactions, and
medication errors; the sizes of the boxes do not reflect the relative frequencies of the events illustrated
(reproduced from references 14 and 15, with permission from Wolters Kluwer Health/Adis©; Adis
Data Information BV (2005, 2006); all rights reserved)
Prescribing faults, prescription errors, and balanced prescribing

The two terms ‘prescribing’ and ‘prescription’ must be distinguished. ‘Prescribing’ is (i) the process
of deciding what to prescribe and naming it (e.g. ‘I prescribe rest and relaxation’); and (ii) the act of
writing the prescription. ‘Prescription’ is (i) the act of writing a prescription; and (ii) the prescription
itself. Because of this ambiguity, it is best to use ‘prescribing’ to mean the decision-making process
and ‘prescription’ the act of writing the prescription.

Various types of faults can occur in the decision-making process: irrational prescribing, inappropriate
prescribing, underprescribing, overprescribing, and ineffective prescribing. These form a class of
errors, but are different in type from the class of errors that can be made in the act of writing a
prescription. This leads to the distinct concepts of ‘prescribing faults’ and ‘prescription errors’, a
distinction that has not previously been made. The term ‘prescribing errors’ ambiguously
encompasses both of these.

Adapting the definition of a medication error, a prescribing fault can be defined as ‘a failure in the
prescribing process that leads to, or has the potential to lead to, harm to the patient’. A previous
definition, which resulted from a Delphi process (a form of committee) stated that ‘a clinically
meaningful prescribing error occurs when, as a result of a prescribing decision or prescription writing
process, there is an unintentional significant (i) reduction in the probability of treatment being timely
and effective; or (ii) increase in the risk of harm when compared with generally accepted practice’.
However, this rules out prescribing faults that do not result in harm, and ignores the fact that it is
desirable to detect and examine all errors, whether ‘clinically meaningful’ or significant, since an
error indicates a weakness in the system, which might on a future occasion lead to an error of clinical
relevance.

A prescription is ‘a written order, which includes detailed instructions of what medicine should be
given to whom, in what formulation and dose, by what route, when, how frequently, and for how
long’ Thus, a prescription error can be defined as ‘a failure in the prescription writing process that
results in a wrong instruction about one or more of the normal features of a prescription’. The
‘normal features’ include the identity of the recipient, the identity of the drug, the formulation and
dose, and the route, timing, frequency and duration of administration (although this list is by no
means exhaustive).
It is possible to define individually the various types of prescribing faults, listed above, but there is
considerable overlap amongst them and it is preferable to unify them into a single definition of their
opposite, which I call ‘balanced prescribing’, defined as ‘the use of a medicine that is appropriate to
the patient's condition and, within the limits created by the uncertainty that attends therapeutic
decisions, in a dosage regimen that optimizes the balance of benefit to harm’ This definition excludes
all forms of prescribing faults.

Classification of medication errors

The best way to understand how medication errors happen and how to prevent them is to consider
their classification, which can be contextual, modal, or psychological. Contextual classification deals
with the specific time, place, medicines, and people involved. Modal classification examines the ways
in which errors occur (e.g. by omission, repetition, or substitution). However, classification based on
psychological theory is to be preferred, as it explains events rather than merely describing them. Its
disadvantage is that it concentrates on human rather than systems sources of errors. These
classifications have been discussed in detail elsewhere.

Psychologists consider an error to be a disorder of an intentional act, and they distinguish between
errors in planning an act and errors in its execution. If a prior intention to reach a specified goal leads
to action, and the action leads to the goal, all is well. If the plan of action contains some flaw, that is a
‘mistake’. If a plan is a good one but is badly executed, that is a failure of skill.

This approach yields four broad types of medication error (numbered 1–4 in Figure 2).

Mistakes can be divided into (i) knowledge-based errors and (ii) rule-based errors. Failures of skill
can be divided into (iii) action-based errors ('slips', including technical errors) and (iv) memory-based
errors (‘lapses’).
Figure 2

The classification of medication errors based on a psychological approach (reproduced from reference
15, with permission from Wolters Kluwer Health/Adis©; Adis Data Information BV (2006); all rights
reserved)

Knowledge-based errors can be related to any type of knowledge, general, specific, or expert. It is
general knowledge that penicillins can cause allergic reactions; knowing that your patient is allergic
to penicillin is specific knowledge; knowing that co-fluampicil contains penicillins is expert
knowledge. Ignorance of any of these facts could lead to a knowledge-based error.

Rule-based errors can further be categorized as (a) the misapplication of a good rule or the failure to
apply a good rule; and (b) the application of a bad rule.

An action-based error is defined as ‘the performance of an action that was not what was intended’ A
slip of the pen, when a doctor intends to write diltiazem but writes diazepam, is an example.
Technical errors form a subset of action-based errors. They have been defined as occurring when ‘an
outcome fails to occur or the wrong outcome is produced because the execution of an action was
imperfect’. An example is the addition to an infusion bottle of the wrong amount of drug

Memory-based errors occur when something is forgotten; for example, giving penicillin, knowing the
patient to be allergic, but forgetting.

Preventing errors through classification

This classification can help understand how errors can be prevented, as discussed in detail elsewhere

Knowledge-based errors can obviously be prevented by improving knowledge, e.g. by ensuring that
students are taught the basic principles of therapeutics and tested on their practical application and
that prescribers are kept up to date. Computerized decision-support systems can also train prescribers
to make fewer errors

Mistakes that result from applying bad rules, or misapplying or failing to apply good rules (rule-based
errors), can be prevented by improving rules.

Training can help in preventing technical (action-based) errors.

Memory-based errors are the most difficult to prevent. They are best tackled by putting in place
systems that detect such errors and allow remedial actions. Check lists and computerized systems can
help.