TERMS USED IN PHARMACOLOGY

1. Pharmacology represents an integrated body of knowledge that deals with the actions
of chemical and biologics on cellular functions. The term pharmacology is derived from
the Greek words pharmakon, meaning drug, and logos, meaning rational discussion or
study.

Thus pharmacology is the rational discussion or study of drugs and their interactions with the
body.

2. Pharmacodynamics is the study of actions of drugs on the body—what effects a drug

has on the patient, including mechanisms of action, beneficial and adverse effects of the
drug, and the drug’s clinical applications. Pharmacodynamics refers to the relationship
between drug concentration at the site of action and the resulting effect, including the
time course and intensity of therapeutic and adverse effects
3. Pharmacokinetics is the inverse: the study of actions of the body on drugs—the
absorption, distribution, storage, and elimination of a drug. Pharmacokinetics is the
effect of the body on the drug. It is made up of four phases: absorption, distribution,
metabolism, and excretion .
4. Pharmacotherapeutics. Pharmacotherapeutics is the clinical purpose or indication for
giving a drug
5. Clinical pharmacology. is the area of pharmacology that covers the use of drugs in the
prevention (prophylaxis) and treatment of diseases.
6. Toxicology
Toxicology is the area of pharmacology concerned with the undesirable effects of chemicals
and biologicals on cellular functions.
7. Agonist:
A drug that binds to a “receptor” and produces an effect. This drug is capable of
binding and activating a receptor, leading to a pharmacological response that may
 mimic that of a naturally occurring substance. Can be classified as full, partial or
inverse.

 Full agonist - Is capable of eliciting a maximal response as it displays full

efficacy at that receptor.
 Partial agonist - Binds to and activates a receptor but is only able to elicit partial
efficacy at that receptor. A maximal effect cannot be produced, even when the
concentration is increased. When full and partial agonists are present the partial
agonist may act as a competitive antagonist.
 Inverse agonist - Produces an effect that is pharmacologically opposite to an
agonist, yet acts at the same receptor. The receptor must elicit intrinsic or basal
activity in the absence of a ligand and the addition of an inverse agonist will
decrease the activity below the basal level. A receptor that possesses basal activity
is the GABAA receptor; agonists have a sedative effect whilst inverse agonists
have an anxiogenic effect.

8. Antagonist: A molecule that prevents the action of other molecules, often by

competing for a cellular receptor; opposite of agonist.
This drug does not produce a biological response on binding to a receptor but instead blocks
or reduces the effect of an agonist. It may be competitive or non-competitive.
 Competitive antagonist - competitive antagonists bind selectively to the active
site of the receptor without causing activation, preventing the agonist from binding
and causing its effect. The antagonism may be reversible; the effect can be
overcome by increasing the concentration of the agonist, which will lead to a shift
in the equilibrium. 
 Non-competitive antagonist - non-competitive antagonists may affect the reaction
by irreversibly binding to the active site of the receptor or to an allosteric
site, therefore not competing with the agonist. The magnitude of the maximal
response is reduced, regardless of the amount of agonist present.
9. ED50 - Dose of drug that produces 50% of its maximum response or effect. Can be a
term used in vitro or in vivo (although it is more common in vivo).

10.Pharmacopoeia—it is a book published by authority of recognized body which

contains the list of drug, their properties, description, preparation and method of
prescribing.
11.Pharmacogenetics—it is that branch of pharmacology which deals with genetic
variations in the drug response.
12.Half-life Half-life of a drug is the amount of time needed to eliminate (by metabolism
and excretion) half of the drug molecules currently in the body.
13.Potency of a drug refers to how much of a drug is needed to create the desired
therapeutic effect.
14.Efficacy of a drug refers to how well the drug creates the desired therapeutic effect.
Drugs may have different potencies but the same efficacy.
15.Loading doses are larger-than-normal doses used when therapy is initiated with drugs
that have very long halflives. The purpose of the loading dose is to achieve quickly a
blood level of the drug that is in therapeutic range even though the drug has not reached
steady state.
16.Drug A drug is a chemical agent which can affect living processes. For purposes of this
course we will mainly be talking about small molecules which affect cellular
processeses.
17.Pharmacy, This is the science of preparation of drugs; much of it deals with
therapeutics, and the treatment of disease (by whatever means).
18.Therapeutics
This is a branch of medicine that deals with different methods of treatment especially the
use of drugs in the cure of diseases
19.Adverse Effect: An unintended and potentially dangerous pharmacological effect that
occurs when a medication is administered correctly.
20.Affinity: The strength of binding between drug and receptor.
21.Bioavailability:  The presence of a drug in the blood stream after it is administered.
22.First Pass Effect: The inactivation of orally or enterally administered drugs in the liver
and intestines.
23.Mechanism/mode of Action:  How a medication works at a cellular level within the
body.
24.Selectivity:  A “selective” drug binds to a primary and predictable site creating one
desired effect. A “non-selective” drug can bind to many different and unpredictable
receptor sites with potential side effects.
25.Side Effect: Effect of a drug, other than the desired effect, sometimes in an organ other
than the target organ.
26.Therapeutic Index:  A quantitative measurement of the relative safety of a drug that
compares the amount of drug that produces a therapeutic effect versus the amount of
drug that produces a toxic effect.  Medication with a large therapeutic index is safer
than a medication with a small therapeutic index.
27.Therapeutic Window: The dosing window in which the safest and most effective
treatment will occur.
28.Bioavailability: The fraction of drug administered which is actually absorbed and
reaches the systemic circulation following oral dosing. Preparations of the same drug by
different manufacturers may have a different bioavailability.
29.Pharmacovigilence The area of Pharmacovigilence focuses on the effects of drugs on
patient safety. It involves the characterization, detection, and understanding of adverse
events associated with drug administration, including adverse drug reactions, toxicities,
and side effects that arise as a consequence of the short- or long-term use of drugs.

30.An adverse reaction is any noxious and unintended response to a drug that occurs at
therapeutic doses used for prophylaxis, diagnosis, or therapy. Adverse reactions
associated with excessive amounts of a drug are considered drug overdoses.
 31.An idiosyncratic response is a genetically determined abnormal or excessive response
to a drug that occurs in a particular patient. The unusual responsemay indicate that the
drug has saturated or overwhelmed mechanisms that normally control absorption,
distribution, metabolism, or excretion, thus altering the expected response.

32.An allergic reaction is an adverse response that results from previous exposure to the
same drug or to one that’s chemically similar to it. The patient’s immune system reacts
to the drug as if it were a foreign invader and may produce a mild hypersensitivity
reaction, characterized by localized dermatitis, urticaria, angioedema, or
photosensitivity.

33.An anaphylactic reaction involves an immediate hypersensitivity response

characterized by urticaria, pruritus, and angioedema. Left untreated, an anaphylactic

reaction can lead to systemic involvement, resulting in shock. It’s often associated with
life-threatening hypotension and respiratory distress.

34. A drug interaction occurs when one drug alters the pharmacokinetics of another drug
—for example, when two or more drugs are given concurrently. Such concurrent
administration can increase or decrease the therapeutic or adverse effects of either drug.
Some drug interactions are beneficial.

UNDERSTANDING DRUGS

Drugs are defined as chemical substances, other than nutrients or essential dietary ingredients,
that when administered to a living organism result in a distinct biological outcome.

Drugs maybe purified chemicals, synthetic organic chemicals, substances purified from either
plant or animal products or recombinant proteins generated by genetic engineering.
In order for a drug to be effective it has to be administered by anappropriate route (i.e. oral,
intravenous or intramuscular etc) capable of achieving a sufficiently high enough concentration
within its target tissue(s) in a chemical form that allows it to interact with its biological target to
achieve its desired effect.

The factors that determine the ability of a drug to reach its target tissue and achieve its desired
therapeutic effect are determined by its inherent Pharmacokinetic and Pharmacodynamic
properties.

Drug nomenclature

A drug may have three categories of names, namely;

Chemical name

A drug’s chemical name describes its atomic and molecular structure. It describes the drug’s
chemical composition and the molecular structure.it is not normally used when prescribing
because it is cumbersome.

Generic name (non proprietary name)

Thegeneric name is the name approved by a competent drug body e.g food and drug
administration (FDA). It is much simpler than the chemical name and is commonly used in
prescribing.

Brandname (Trade or proprietary name)

The brand name is the copyrighted name that is given by the company manufacturing and
selling the drug.
Example

Chemical name (+/-)-2-(p-isobutylphenyl)propionic acid

Generic name: ibuprofen

Brand name: Brufen

SOURCES OF DRUGS

Drugs for medical use can be obtained from any of the following sources;

 Plants e.g digoxin,morphin, quinine

 Animals e.g insulin, adrenalin
 Microorganismse.g penicillins,streptomycin
 Chemical substances (made from factories)

DRUG FOMULATIONS

Solid Formulations

 Tablets – a tablet is disc-shaped and prepared by compressing a granulated powder in a

die of suitable machinery. They are mostly coated with inert substances like starch to
 help them disintegrate in the digestive tract of the patient.  A binding agent, lubricating
material, and flavors are added to the tablets to make them palatable.

 Enteric Coated Tablets – are coated with a material that does not disintegrate in the
acidic medium of the stomach but in the alkaline medium of the intestine. They can’t be
chewed but consumed only by swallowing.

 Controlled Release Tablet – is designed to release the active ingredient of the drug in a
specific amount over a specified period of time. Here, the amount of drug released is
gradual over the day and doesn’t depend upon the pH of the digestive tract of the patient.
Thus, a uniform amount of drug is released at a uniform rate.

 Sustained release preparations – release a fixed amount of drug over an extended

period of time. Thus, they improve the treatment compliance by the patient.

 Capsules – can be hard or soft. Hard capsules contain the drug in solid form, which gets
dissolved easily in water. Soft capsules have the drug in liquid or semi-solid form, which
is non-soluble in water and soluble in propylene or glycol.

Liquid and Semi-Solid Formulations

They are more readily absorbed than the solid formulations and can be administered by various
routes like:

1. Oral preparations – Oral preparations are easier to swallow and administer medicines to
children and old-age patients. Flavourings and sugar are added to some liquids to make
them palatable. They are available as solutions, suspensions, or emulsions and must be
shaken well before use.

2. Topical Preparations – The application of a drug to an area of the body for direct
treatment is called topical application. It includes:

 Eye drops

 Ear drops
  Nasal drops

 Nebulisers and inhalers

 Creams and ointments for skin application

 Gels and lotions

 Pessaries for vaginal administration of the drug

3. Sublingual and Buccal Administration – It is useful for drugs which are active in very
low concentration in the blood. Such drugs are administered as tablets under the tongue
or between the cheek and the gum and allowed to dissolve. In this manner, the drug
directly enters the bloodstream, bypassing the digestive tract and acts faster.

4. Rectal Administration

 Suppositories: are used for drugs which are administered through the rectum. The
drug is absorbed by the rectal mucosa and directly enters the bloodstream. The
method is useful when a patient is unconscious, has nausea or difficulty in
swallowing.

 Enemas: are liquid preparations for rectal administration. They can be used for
topical or systemic treatment and also for a bowel movement.

ESSENTIAL MEDICINES
Essential medicines are those that satisfy the priority health care needs of the population. They
are selected with due regard to public health relevance, evidence on efficacy and safety, and
comparative cost-effectiveness.

Essential medicines are those of utmost importance, basic, indispensable, and necessary for the
healthcare needs of the population.

Essential medicines are intended to be available within the context of functioning health
systems at all times in adequate amounts, in the appropriate dosage forms, with assured quality
and adequate information, and at a price the individual and the community can afford.

The implementation of the concept of essential medicines is intended to be flexible and

adaptable to many different situations. It incorporates the need to regularly update medicines
selections to reflect new therapeutic options and changing therapeutic needs; the need to ensure
drug quality; and the need for continued development of better medicines, medicines for
emerging diseases, and medicines to meet changing resistance patterns.

SELECTION CRITERIA

Selection decisions are recommended based on many different factors, such as the pattern of
prevalent diseases, treatment facilities, the training and experience of available personnel,
financial resources, and genetic, demographic and environmental factors. The following
criteria are used by the WHO Expert Committee on the Selection and Use of Essential
Medicines:

 Only medicines for which sound and adequate evidence of efficacy and safety in a variety
of settings is available should be selected.
 Relative cost-effectiveness is a major consideration for choosing medicines within the same
therapeutic category. In comparisons between medicines, the total cost of the treatment - not
only the unit cost of the medicine - must be considered, and be compared with its efficacy.

 In some cases, the choice may also be influenced by other factors such as pharmacokinetic
properties or by local considerations such as the availability of facilities for manufacture
or storage.

 Each medicine selected must be available in a form in which adequate quality, including
bioavailability, can be ensured; its stability under the anticipated conditions of storage and
use must be determined.

 Most essential medicines should be formulated as single compounds. Fixed dose

combination products are selected only when the combination has a proven advantage in
therapeutic effect, safety, adherence or in decreasing the emergence of drug resistance in
malaria, tuberculosis and HIV/AIDS.

Other criteria used for the selection of essential medicines, some of them linked to those
mentioned above, include:

 Needs – meets health care needs of the majority of the population

 Affordability for patients
 Effectiveness - proven over time in the real world
 Substantial safety and risk benefit ratio
 Quality – for example ensured regulatory bodies such as the Medical Control Councils in
South Africa
 Evidence based decision-making – sufficient proven scientific data available regarding
effectiveness and safety
 Implications for practice – viable and implementable in particular context

IMPORTANCE OF AN ESSENTIAL MEDICINES LIST (EML)

An EML promotes health delivery equity and helps to set health related priorities, by promoting
the use of a limited number of carefully selected medicines based on agreed clinical guidelines.
The use of an EML leads to:

• a better supply of medicines

• more rational prescribing
• lower costs
• improved price competition through economies scale
• more focused training of health workers
• improved medicine information for patients and health workers
• prescribers gaining more experience with fewer drugs

RATIONAL MEDICINE USE.

Definition
In simplest words rational use means “prescribing right drug, in adequate dose for the sufficient
duration & appropriate to the clinical needs of the patient at lowest cost

The rational use of drugs requires that patients receive medications appropriate to their clinical
needs, in doses that meet their own individual requirements for an adequate period of time, and
at the lowest cost to them and their community (WHO

Reasons for Irrational use of Drugs

1.Lack of information

2.Role models – Teachers or seniors

3.Lack of diagnostic facilities/Uncertainty of diagnosis – medicine for all possible causes

4.Demand from the patient

5.Patient load

6.Promotional activities of pharmaceutical industries

7.Drug promotion and exaggerated claim by companies

8.Defective drug supply system & ineffective drug regulation

INDICATORS OF IRRATIONAL USE OF DRUGS

1. Injudicious use of antimicrobials: Antibiotics in Viral fever and diarrhea

2. Unnecessary combinations

3. Use of drugs not related to diagnosis

4. Incorrect route

5. Incorrect dosing – under or overdose

6. Incorrect duration – prolong or short term use

7. Unnecessary use of expensive medicines

8. Unsafe use of corticosteroids

9. Polypharmacy

The use of drugs when no drug therapy is indicated, e.g. antibiotics for viral upper respiratory
infections.

The use of the wrong drug for a specific condition requiring drug therapy, e.g. tetracycline in
childhood diarrhea requiring ORS.

The use of drugs with doubtful or unproven efficacy, e.g. the use of antimotility agents in acute
diarrhea

 Failure to provide available, safe and effective drugs, e.g. failure to vaccinate for measles
or tetanus, or failure to prescribe ORS for acute diarrhea.

 The use of correct drugs with incorrect administration, dosage and duration, e.g. using
intravenous route where oral or suppository routes would be appropriate.

 The use of unnecessarily expensive drugs, e.g. the use of a third generation, broad-
spectrum antimicrobial when a first line, narrow spectrum agent is indicated.

Hazards of Irrational Use of drugs

Ineffective & unsafe treatment i.e over-treatment of mild illness or inadequate treatment of
serious illness

Exacerbation or prolongation of illness

Distress & harm to patient

Increased cost of treatment

Increased drug resistance - misuse of anti-infective drugs

Increased Adverse Drug Events

Increased morbidity and mortality

VARIOUS OBSTACLES IN RATIONAL DRUG USE

1. Lack of objective information & of continuing education & training in pharmacology.

2. Lack of well organized drug regulatory authority & supply of drugs.

3. Presence of large number of drugs in the market & the lucrative methods of promotion of
drugs employed by pharmaceutical industries.

4. The prevalent belief that “every ill has a pill.”

STEPS OF RATIONAL DRUG USE OF DRUGS

Step I: Identify the patient’s problem based on symptoms & recognize the need for action
Step:- II Diagnosis of the disease – define the diagnosis

Step:- III List possible intervention or treatment (drug or no drug) – Identify the drug

Step:- IV Start the treatment by writing an accurate & complete prescription e.g. name of drugs
with dosage forms, dosage schedule & total duration of the treatment

Step:-V Give proper information, instruction & warning regarding the treatment given e.g. side
effects (ADR), dosage schedule & dangers/risk of stopping the therapy suddenly

Step:-VI Monitor the treatment to check, if the particular treatment has solved the patient’s
problem. Passive monitoring – done by the patient himself. Explain him what to do if the
treatment is not effective or if too many side effect occurs Active monitoring - done by
physician and makes an appointment to check the response of the treatment

STRATEGIES TO IMPROVE RATIONAL USE OF DRUGS

1. Educational strategies

 Training for Providers

 Undergraduate education
 Continuing in-service medical education (seminars, workshops)
 Face-to-face persuasive outreach e.g. academic detailing
 Clinical supervision or consultation
 Printed Materials
 Clinical literature and newsletters
 Formularies or therapeutics manuals
 Persuasive print materials
 Media-Based Approaches e. g Posters, Audio tapes, plays, Radio, television
2. Managerial strategies

 Changes in selection, procurement, distribution to ensure availability of essential drugs

 Essential Drug Lists, morbidity-based quantification, kit systems
 targeted face-to-face supervision with audit, peer group monitoring, structured order
forms, evidence-based standard treatment guidelines
 course of treatment packaging, labelling, generic substitution

3. Economic strategies

Avoid perverse financial incentives e.g

• prescribers’ salaries from drug sales

• insurance policies that reimburse non-essential drugs or incorrect doses

• flat prescription fees that encourage polypharmacy by charging the same amount
irrespective of number of drug items or quantity of each item

4. Regulatory strategies
 Drug registration
 Banning unsafe drugs - but beware unexpected results
 substitution of a second inappropriate drug after banning a first inappropriate or
unsafe drug
 Regulating the use of different drugs to different levels of the health sector e.g.
 licensing prescribers and drug outlets
 scheduling drugs into prescription-only & over-the-counter
 Regulating pharmaceutical promotional activities
 PHARMACOKINETICS

The effect of the body on the drug. To produce its characteristic effects, a drug must be
present in appropriate concentrations at its sites of action. Thus, it is important to know
the interrelationship of the administration, absorption, distribution, metabolism, and
excretion/elimination of a drug and its concentration at its locus of action.

ROUTES OF ADMINISTRATION OF DRUGS

Definition

- A route of administration in pharmacology and toxicology is the path by

which a drug, fluid, poison, or other substance is taken into the body.
- Most of the drugs can be administered by different routes. Drug- and patient-
related factors determine the selection of routes for drug administration. The
factors are:
1. Characteristics of the drug.
2. Emergency/routine use.
3. Site of action of the drug—local or systemic.
4. Condition of the patient (unconscious, vomiting, diarrhoea).
5. Age of the patient.
6. Effect of gastric pH, digestive enzymes and first-pass metabolism.
7. Patient’s/doctor’s choice (sometimes).
1. LOCAL ROUTES

- It is the simplest mode of administration of a drug at the site where the

desired action is required. Systemic side effects are minimal.

i. Topical: Drug is applied to the skin or mucous membrane at various sites for local
action.

a) Oral cavity: As a suspension, e.g. nystatin; as a troche, e.g.

clotrimazole (for oral candidiasis); as a cream, e.g. acyclovir (for
herpes labialis); as ointment and jelly, e.g. 5% lignocaine
hydrochloride (for topical anaesthesia); as a spray, e.g. 10%
lignocaine hydrochloride (for topical anaesthesia).
b) GI tract: As tablet that is not absorbed, e.g. neomycin (for
sterilization of gut before surgery).
c) c) Rectum, Vaginal and anal canal:

 As an enema (administration of drug into the rectum in liquid form):

- Evacuant enema (for evacuation of bowel): For example, soap water enema
—soap acts as a lubricant and water stimulates the rectum.
 - Retention enema: For example, methylprednisolone in ulcerative colitis.

 As a suppository (administration of the drug in a solid form into the rectum), e.g.
bisacodyl— for evacuation of bowels.

 Advantages

- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any
surgical or radiological procedure.

 Disadvantages

- Inconvenient.
- Drug absorption is slow and erratic.
- Irritation or inflammation of rectal mucosa can occur.

d) Eye, ear and nose: As drops, ointments and sprays (for infection, allergic
conditions, etc.), e.g. gentamicin eye/ear drops.
e) Bronchi: As inhalation, e.g. salbutamol (for bronchial asthma and chronic
obstructive pulmonary disease). Gases, volatile liquids and solids (in the form of
finely divided powders) are inhaled for systemic and local effects. Inhalation of
solids is called insufflation.  Advantages
- Rapid absorption of the drug due to large surface area.
- First pass effect is avoided.
- Rapid local effects.
  Disadvantages

- Only few drugs can be administered.

- May produce irritation of pulmonary mucosa.
- Inconvenient procedure.
- Chances of cardiotoxicity.

f) Skin: As ointment, cream, lotion or powder, e.g. clotrimazole (antifungal) for

cutaneous candidiasis.
g) Transdermal: Transdermal patches can provide prolonged or controlled
(iontophoresis) drug delivery. Systemic absorption (Transdermal) is better with low
dose, low MWt, lipid soluble drugs

ii. Intra-arterial route: This route is rarely employed. It is mainly used during
diagnostic studies such as coronary angiography and for the administration of some
anticancer drugs, e.g. for treatment of malignancy involving limbs.
iii. Administration of the drug into some deep tissues by injection, e.g. administration
of triamcinolone directly into the joint space in rheumatoid arthritis.

2. a) Systemic Routes (Enteral)

 Drugs administered by this route enter blood and produce systemic effects. Enteral
Routes It includes (i) Oral route, (ii) Buccal or Sublingual route and (iii) Rectal route.

i. ORAL ROUTE

 It is the most common and acceptable route for drug administration. Dosage forms are
tablet, capsule, syrup, mixture, etc., e.g., paracetamol tablet for fever, omeprazole capsule
for peptic ulcer are given orally.
 Advantages:
 - Convenient - portable, safe, no pain, can be self-administered.
- Cheap - no need to sterilize (but must be hygienic of course)
- Variety of dosage forms available - fast release tablets, capsules, enteric coated,
layered tablets, slow release, suspensions, mixtures
- Convenient for repeated and prolonged use.
 Disadvantages:
- Sometimes inefficient :- high dose or low solubility drugs may suffer poor
availability, only part of the dose may be absorbed. Griseofulvin was reformulated to
include the drug as a micronized powder. The recommended dose at that time was
decreased by a factor of two because of the improved bioavailability.
- First-pass effect :- drugs absorbed orally are transported to the general circulation
via the liver. Thus drugs which are extensively metabolized will be metabolized in the
liver during absorption. e.g. the propranolol oral dose is somewhat higher than the IV, the
same is true for morphine. Both these drugs and many others are extensively metabolized
in the liver.

Food :- Food and G-I motility can effect drug absorption. Often patient instructions
include a direction to take with food or take on an empty stomach. Absorption is slower
with food for tetracyclines and penicillins, etc. However, for propranolol
bioavailability is higher after food, and for griseofulvin absorption is higher after a fatty
meal.

- Local effect :- Antibiotics may kill normal gut flora and allow overgrowth of
fungal varieties. Thus, antifungal agent may be included with an antibiotic.
- Unconscious patient :- Patient must be able to swallow solid dosage forms. Liquids
may be given by tube.

ii. BUCCAL and SUBLINGUAL ROUTE (SL)

 Some drugs are taken as smaller tablets which are held in the mouth or under the tongue.
 These are buccal or sublingual dosage forms.
 Buccal tablets are often harder tablets [4 hour disintegration time], designed to dissolve
slowly. Nitroglycerin, as a softer sublingual tablet [2 min disintegration time], may be used
for the rapid relief of angina.
 This Route of administration is also used for some steroids such as testosterone and
oxytocin. Nicotine containing chewing gum may be used for cigarette smoking
replacement.

 Advantages:

- Quick onset of action.

- Action can be terminated by spitting out the tablet.
- Bypasses first-pass metabolism.
- Self-administration is possible.
 Disadvantages

- It is not suitable for bitter tasting and unpalatable drug.

- It is not suitable for Irritant and lipid-insoluble drugs.
- cannot give to unconscious patient.
- Large quantities cannot be given.
- Cannot be given in severe vomiting.

iii. RECTAL ROUTE  Drugs can be given in the form of solid or liquid.

- Suppository: It can be used for local (topical) effect as well as systemic effect, e.g.
indomethacin for rheumatoid arthritis.
 - Enema: Retention enema can be used for local effect as well as systemic effect.
The drug is absorbed through rectal mucous membrane and produces systemic effect, e.g.
diazepam for status epilepticus in children.
 Advantages

- Used in children.
- Little first pass effect.
- Can be given in vomiting.
- Can be given in unconscious patient.
- Higher therapeutic concentrations of drug are achieved rapidly in rectum.
- For rapid evacuation of bowel, usually during gut sterilization before any surgical
or radiological procedure.
 Disadvantages

- Inconvenient, not well accepted. May be some discomfort - Drug absorption is

slow and erratic.
- Irritation or inflammation of rectal mucosa can occur

2. b) Systemic Routes (Parenteral)

• Routes of administration other than enteral route are called parenteral routes.
• Advantages of parenteral routes
- Onset of action of drugs is faster; hence it is suitable for emergency.
- Useful in:
- Unconscious patient.
- Uncooperative and unreliable patients.
- Patients with vomiting and diarrhoea.
- It is suitable for:
- Irritant drugs.
- Drugs with high first-pass metabolism.
 - Drugs not absorbed orally.
- Drugs destroyed by digestive juices.
• Disadvantages of parenteral routes - Require aseptic conditions.
- Preparations should be sterile and is expensive.
- Requires invasive techniques that are painful.
- Cannot be usually self-administered.

- Can cause local tissue injury to nerves, vessels, etc.

i. INTRAVENOUS (IV)
 Drugs may be given into a peripheral vein over 1 to 2 minutes or longer by infusion, or
Drugs are injected directly into the blood stream through a vein.

• Drugs are administered as:

a) Bolus: Single, relatively large dose of a drug injected rapidly or slowly as a single
unit into a vein. For example, i.v. ranitidine in bleeding peptic ulcer.
b) Slow intravenous injection: For example, i.v. morphine in myocardial infarction.
c) Intravenous infusion: For example, dopamine infusion in cardiogenic shock;
mannitol infusion in cerebral oedema; fluids infused intravenously in dehydration. 
Advantages

- Bioavailability is 100%.
- Quick onset of action; therefore, it is the route of choice in emergency, e.g. intravenous
diazepam to control convulsions in status epilepticus.
- Large volume of fluid can be administered, e.g. intravenous fl uids in patients with severe
dehydration.
- Highly irritant drugs, e.g. anticancer drugs can be given because they get diluted in blood.
- Hypertonic solution can be infused by intravenous route, e.g. 20% mannitol in cerebral
oedema.
- By i.v. infusion, a constant plasma level of the drug can be maintained, e.g. dopamine
infusion in cardiogenic shock.
• Disadvantages
- Once the drug is injected, its action cannot be halted.
- Local irritation may cause phlebitis.
- Self-medication is not possible.
- Strict aseptic conditions are needed.
- Extravasation of some drugs can cause injury, necrosis and sloughing of tissues.
- Depot preparations cannot be given by i.v. route.
• Precautions
 - Drug should usually be injected slowly.
- Before injecting, make sure that the tip of the needle is in the vein.

ii. SUBCUTANEOUS (s.c.) ROUTE

The drug is injected into the subcutaneous tissues of the thigh, abdomen and arm, e.g.
adrenaline, insulin, etc.

• Advantages:
- Actions of the drugs are sustained and uniform.
- Drugs can be given in presence of vomiting and diarrhea.
- Drugs can be given to unconscious patients.
- First pass effect is avoided.
- Drugs that are not absorbed from G.I.T can be given.
- Self-administration is possible (e.g. insulin).
- Depot preparations can be inserted into the subcutaneous tissue, e.g. norplant for
contraception.
• Disadvantages
- Only non-irritant drugs can be given otherwise severe irritation, pain and necrosis
of subcutaneous tissues can occur.
- Absorption of the drugs is slow than I/M injection.
- Expensive.
- Danger of infection, if proper sterilization techniques are not used.
- Large volumes of drug cannot be given.

iii. INTRAMUSCULAR (i.m) ROUTE

 The drug is injected deep in the belly of a large skeletal muscle. The muscles that are
usually used are detoid, triceps, Gluteus,. Maximus, rectus, femurs depending on the
specie of animal.

• The muscle is less richly supplied with sensory nerves, hence injecting a drug 1m is less
painful.
• Absorption of drug from gluteal region is slow especially in females due to high fat
deposition.
• Deep intramuscular injections are given at upper outer quadrant of buttock to prevent the
injury to major nerves.
• Deep I/M injections are less painful than I/M injections on arm due to high fat content.
• Intramuscular injections are given at an angle of 90 degrees.
• Advantages
- Rate of absorption is uniform.
- Rapid onset of action.
- Irritant substances can be given.
- Drugs can be given to unconscious patients.
- Accuracy of dosage is ensured.
- Useful in emergency situations.
- First pass effect is avoided.
- Drugs producing gastric irritation can be given.
- Drugs that are not absorbed from G.I.T can be given.
• Disadvantages
- Small quantities up to 10 ml of the drug can be given at a time.
- Local pain and abscess formation.
- Technical person is needed, self-administration is difficult.
- Expensive.
- Danger of infection, if proper sterilization techniques are not used. - Chances of
nerve damage.
 iv. INTRATHECAL ROUTE

• Drug is injected into the subarachnoid space (spinal anaesthetics, e.g. lignocaine;
antibiotics, e.g. amphotericin B, etc.).

v. INTRA-ARTICULAR ROUTE

• Drug is injected directly into the joint space, e.g. hydrocortisone injection for rheumatoid
arthritis. Strict aseptic precautions should be taken. Repeated administration may cause
damage to the articular cartilage.

v. TRANSDERMAL ROUTE

The drug is administered in the form of a patch or ointment that delivers the drug into the
circulation for systemic effect.

• For example, scopolamine patch for sialorrhoea and motion sickness, nitroglycerin
patch/ointment for angina,
 oestrogen patch for hormone replac ement therapy (HRT).

• INTRAPERITONEAL ROUTE
• Peritoneal space has much surface area; may not be reached by IV chemo
• Catheters used: implanted port
• Chemotherapy agents used: Cisplatin, Taxol

 Advantages: less systemic side effects

 Disadvantages: infection, pain.

• vii. INTRAPLEURAL
• Seeding of pleura
• Used as sclerosing agent to stop pleural effusions
• Injected by physician into chest tube and clamped. Patient changes position 15 min for 1
hour
• Chemotherapy agents used: Bleomycin, Adriamycin, Talc slurry  Side effects: severe
pain
ABSORPTION

Before a drug can begin working, it must be transformed from its pharmaceutical dosage
form to a biologically available (bioavailable) substance that can pass through various
biological cell membranes to reach its site of action. This process is known as absorption.
A drug’s absorption rate depends on its route of administration, its circulation through the
tissue into which it’s administered, and its solubility—that is, whether it’s more water-
soluble (hydrophilic) or fatsoluble (lipophilic).
Factors affecting drug absorption and bioavailability:

a) Physico-chemical properties of drug

b) Nature of the dosage form

c) Physiological factors

d) Pharmacogenetic factors

e) Disease states.

a) Physico-chemical properties of drug:

i) Physical state: Liquids are absorbed better than solids and crystalloids absorbed better
than colloids.

ii) Lipid or water solubility: Drugs in aqueous solution mix more readily than those in
oily solution. However at the cell surface, the lipid soluble drugs penetrate into the cell
more rapidly than the water soluble drugs.

iii) Ionization: Most of the drugs are organic compounds. Unlike inorganic compounds,
the organic drugs are not completely ionized in the fluid. Unionized component is
predominantly lipid soluble and is absorbed rapidly and an ionized is often water soluble
component which is absorbed poorly. Most of the drugs are weak acids or weak bases.

It may be assumed for all practical purposes, that the mucosal lining of the G.I.T is

impermeable to the ionized form of a weak organic acid or a weak organic base. These
drugs exist in two forms.
Acidic drugs: rapidly absorbed from the stomach e.g. salicylates and barbiturates.

Basic drugs: Not absorbed until they reach to the alkaline environment i.e. small

intestine when administered orally e.g. pethidine and ephedrine.

b) Dosage forms:

i) Particle size: Small particle size is important for drug absorption.

Drugs given in a dispersed or emulsified state are absorbed better e.g. vitamin D and

vitamin A.

ii) Disintegration time and dissolution rate.

Disintegration time: The rate of break up of the tablet or capsule into the drug granules.

Dissolution rate: The rate at which the drug goes into solution.

iii) Formulation: Usually substances like lactose, sucrose, starch and calcium phosphate
are used as inert diluents in formulating powders or tablets. Fillers may not be totally
inert but may affect the absorption as well as stability of the medicament. Thus a faulty
formulation can render a useful drug totally useless therapeutically.

c) Physiological factors:

i) Gastrointestinal transit time: Rapid absorption occurs when the drug is given on
empty stomach. However certain irritant drugs like salicylates and iron preparations are
deliberately administred after food to minimize the gastrointestinal irritation. But some
times the presence of food in the G.I tract aids the absorption of certain drugs e.g.
griseofulvin, propranolol and riboflavin.
ii) Presence of other agents: Vitamin C enhances the absorption of iron from the G.I.T.

Calcium present in milk and in antacids forms insoluble complexes with the tetracycline
antibiotics and reduces their absorption.

iii) Area of the absorbing surface and local circulation:

Drugs can be absorbed better from the small intestine than from the stomach because of
the larger surface area of the former. Increased vascular supply can increase the
absorption.

iv) Enterohepatic cycling: Some drugs move in between intestines and liver before they
reach the site of action. This increases the bioavailability e.g. phenolphthalein.

v) Metabolism of drug/first pass effect: Rapid degradation of a drug by the liver during
the first pass (propranolol) or by the gut wall (isoprenaline) also affects the
bioavailability.

Thus a drug though absorbed well when given orally may not be effective because of its
extensive first pass metabolism.

d) Pharmacogenetic factors:

Individual variations occur due to the genetically mediated reason in drug absorption and
response.

e) Disease states:

Absorption and first pass metabolism may be affected in conditions like malabsorption,
thyrotoxicosis, achlorhydria and liver cirrhosis.
 DISTRIBUTION OF DRUGS

Definition:
Penetration of a drug to the sites of action through the walls of blood vessels from the
administered site after absorption is called drug distribution. Drugs distribute through
various body fluid compartments such as (a) plasma (b) interstitial fluid compartment
(c)trans-cellular compartment.

Factors determining the rate of distribution of drugs:

1. Protein binding of drug:

A variable and other significant portion of absorbed drug may become reversibly bound
to plasma proteins. The active concentration of the drug is that part which is not bound,
because it is only this fraction which is free to leave the plasma and site of action.

(a) Free drug leave plasma to site of action

(b) binding of drugs to plasma proteins assists absorption

(c) protein binding acts as a temporary store of a drug and tends to prevent large
fluctuations in concentration of unbound drug in the body fluids

(d) protein binding reduces diffusion of drug into the cell and there by delays its
metabolic degradation e.g. high protein bound drug like phenylbutazone is long acting.

Low protein bound drug like thiopental sodium is short acting.

2. Plasma concentration of drug (PC): It represents the drug that is bound to the plasma
proteins (albumins and globulins) and the drug in free form. It is the free form of drug
that is distributed to the tissues and fluids and takes part in producing pharmacological
effects.

The concentration of free drug in plasma does not always remain in the same level e.g.

i) After I.V. administration plasma concentration falls sharply

ii) After oral administration plasma concentration rises and falls gradually.

iii) After sublingual administration plasma concentration rise sharply and falls gradually.

3. Clearance: Volume of plasma cleared off the drug by metabolism and excretion per
unit time.

Protein binding reduces the amount of drug available for filtration at the glomeruli and
hence delays the excretion, thus the protein binding reduces the clearance.

4. Physiological barriers to distribution: There are some specialized barriers in the

body due to which the drug will not be distributed uniformly in all the tissues. These
barriers are:
a) Blood brain barrier (BBB) through which thiopental sodium is easily crossed but not

dopamine.

b) Placental barrier: which allows non-ionized drugs with high lipid/water partition

coefficient by a process of simple diffusion to the foetus e.g. alcohol, morphine.

5. Affinity of drugs to certain organs: The concentration of a drug in certain tissues

after a single dose may persist even when its plasma concentration is reduced to low.
Thus the hepatic concentration of mepacrine is more than 200 times that of plasma level.
Their concentration may reach a very high level on chronic administration. Iodine is
similarly concentrated in the thyroid tissue.

METABOLISM OF DRUGS

Drugs are chemical substances, which interact with living organisms and produce some
pharmacological effects and then, they should be eliminated from the body unchanged or
by changing to some easily excretable molecules. The process by which the body brings
about changes in drug molecule is referred as drug metabolism or biotransformation.

EXCRETION OF DRUGS

Excretion of drugs means the transportation of unaltered or altered form of drug out of
the body. The major processes of excretion include renal excretion, hepatobiliary
excretion and pulmonary excretion. The minor routes of excretion are saliva, sweat, tears,
breast milk, vaginal fluid, nails and hair.
The rate of excretion influences the duration of action of drug. The drug that is excreted
slowly, the concentration of drug in the body is maintained and the effects of the drug
will continue for longer period.

DIFFERENT ROUTES OF DRUG EXCRETION

a) Renal excretion: A major part of excretion of chemicals is metabolically unchanged

or changed. The excretion of drug by the kidney involves.

i) Glomerular filtration

ii) Active tubular secretion

iii) Passive tubular reabsorption.

The function of glomerular filtration and active tubular secretion is to remove drug out of
the body, while tubular reabsorption tends to retain the drug.

b) Hepatobiliary excretion: the conjugated drugs are excreted by hepatocytes in the bile.

Molecular weight more than 300 daltons and polar drugs are excreted in the bile.
Excretion of drugs through bile provides a back up pathway when renal function is
impaired. After excretion of drug through bile into intestine, certain amount of drug is
reabsorbed into portal vein leading to an enterohepatic cycling which can prolong the
action of drug e.g. chloramphenicol, oral estrogen are secreted into bile and largely
reabsorbed and have long duration of action. Tetracylines which are excreted by biliary
tract can be used for treatment of biliary tract infection.
c) Gastrointestinal excretion:

When a drug is administered orally, a part of the drug is not absorbed and excreted in the
faeces. The drugs which do not undergo enterohepatic cycle

after excretion into the bile are subsequently passed with stool e.g. aluminium hydroxide

changes the stool into white colour, ferrous sulfate changes the stool into black and
rifampicin into orange red.

d) Pulmonary excretion: Drugs that are readily vaporized, such as many inhalation

anaesthetics and alcohols are excreted through lungs. The rate of drug excretion through

lung depends on the volume of air exchange, depth of respiration, rate of pulmonary
blood flow and the drug concentration gradient.

e) Sweat: A number of drugs are excreted into the sweat either by simple diffusion or
active secretion e.g. rifampicin, metalloids like arsenic and other heavy metals.

f) Mammary excretion: Many drugs mostly weak basic drugs are accumulated into the
milk.

Therefore lactating mothers should be cautious about the intake of these drugs because
they may enter into baby through breast milk and produce harmful effects in the baby e.g.

ampicillin, aspirin, chlordiazepoxide, coffee, diazepam, furosemide, morphine,

streptomycin
Pharmacodynamics

Pharmacodynamics is the study of a drug's molecular, biochemical, and physiologic

effects or actions.

It comes from the Greek words "pharmakon" meaning "drug" and "dynamikos" meaning

"power." 

Pharmacodynamics is the study of how drugs have effects on the body.

All drugs produce their effects by interacting with biological structures or targets at the
molecular level to induce a change in how the target molecule functions in regards to
subsequent intermolecular interactions.

The most common mechanism is by the interaction of the drug with tissue receptors
located either in cell membranes or in the intracellular fluid. The extent of receptor
activation, and the subsequent biological response, is related to the concentration of the
activating drug (the 'agonist').

Some drugs acting at the same receptor (or tissue) differ in the magnitude of the
biological responses that they can achieve (i.e. their 'efficacy') and the amount of the drug
required to achieve a response (i.e. their 'potency').

Drug receptors are the cellular components affected at the site of action.Many drugs
form chemical bonds with drug receptors, but a drug can bond with a receptor only if it
 has a similar shape—much the same way that a key fits into a lock.

Classification of Drugs

Classification of drugs can be done on the basis of certain criteria. Some of them are
given below.

Classification of Drugs on the basis of the Pharmacological Effect:

 How a drug or medicine affects or influences the cells of an organism is referred to as the
pharmacological effect. Different types of drugs have various pharmacological effects on
an organism.
 For example, an analgesic reduces pain while an anti-inflammatory drug reduces the
inflammation of the body. Thus, drugs can be classified based on the pharmacological
effect.

Classification of Drugs on the basis of Drug Action:

 Different drugs act differently i.e., each drug has its own way of generating a response
called drug action.
 Drug action is more specified according to how it generates a response. For example,
there are lots of medicines to treat hypertension but each type of drug has different drug
actions.
 All the hypertension medicines reduce the blood pressure but in a different pathway.

Classification of Drugs on the basis of Chemical Structure:

 This is a common classification of drugs. Generally, drugs that have the same drug action
and pharmacological effect have a basic skeletal structure and a minute variation in the
branching.
 This is why some drugs have more potential than the other. For example, all
sulphonamides have the same skeletal structure.

Classification of Drugs on the basis of Molecular Targets:

 Drugs target the macromolecules inside the body to generate a biological response.
 Such macromolecules are called target molecules or drug targets. Drugs that have the
same mechanism of action will have the same target.
 This basis for the classification of drugs is more helpful during clinical trials.

CONTROLLED SUBSTANCES

The Harrison Narcotics Act of 1914 first regulated drugs of abuse.

The Controlled Substance Act of 1970 (Public Law 91-513) replaced the original Act and
classifies drugs covered by the law in five (5) Schedules according to their potential for
abuse and risk of bodily harm.

Controlled substances are considered to have a high potential for abuse and are regulated
by the Drug Enforcement Administration (DEA). There are special laws at the state and
federal level dealing with controlled drugs. Maine has specific regulations that cover their
use in assisted housing programs, nursing facilities/homes, and hospitals.

Controlled (scheduled) drugs, substances, and certain chemicals are ones whose use and
distribution are tightly controlled because of their abuse potential or risk. Controlled
drugs are rated in the order of their abuse risk and placed in Schedules by the Federal
Drug Enforcement Administration (DEA).

The drugs with the highest abuse, and potential for psychological and/or physical
dependence, are placed in Schedule I, and those with the lowest abuse potential are in
Schedule V. These schedules are commonly shown as C-I, C-II, C-III, C-IV, and C-V.
Some examples of drugs in these Schedules are as follows:

Schedule I — drugs with a high abuse risk. These drugs have NO safe, accepted medical
use .. Some examples are heroin, marijuana, and crack cocaine.

Schedule II — drugs with a high abuse risk, but also have safe and accepted medical
uses. These drugs can cause severe psychological or physical dependence. Schedule II
drugs include certain narcotics, stimulants, and depressant drugs.

Some examples are morphine, cocaine, oxycodone (OxyContin®), , methylphenidate

(Ritalin®), and dextroamphetamine (Dexedrine®).

Schedule III, IV, or V — drugs with an abuse risk less than Schedule II. These drugs
also have safe and accepted medical uses. Schedule III, IV, or V drugs include those
containing smaller amounts of certain narcotic and non-narcotic drugs, anti-anxiety
drugs, tranquilizers, sedatives, stimulants, and non-narcotic analgesics. Some examples
are acetaminophen with codeine (Tylenol® No.3), paregoric, diazepam (Valium®),
alprazolam (Xanax®) and pentazocine (Talwin®).