INTRODUCTION TO DRUGS

Remedies are methods and means to prevent, treat or cure a disease or injury. The
word comes from the latin “remedium”: “re” (again) and “mederi” (to heal). They are
classified in:
Ø Psychic remedies: hypnosis, suggestion;
Ø Physical remedies: thermotherapy, electrotherapy, radiotherapy;
Ø Chemical remedies: drugs.
A pharmaceutical drug (medication, medicine) is a chemical substance or an
association of substances with pharmacodynamic effect, used to prevent, ameliorate, cure or
diagnose a disease or symptom.
Placebo is a substance with no pharmacodynamic effect, which sometimes is effective
because of suggestion. There are two types of placebo:
Ø Pure: lactose, physiological serum;
Ø Impure: subtherapeutic doses of vitamins.

Any drug might have toxic effects, if it is administered in an inappropiate dose or condition.
“Dosis sola facit venenum” Paracelsus

CLASSIFICATION of drugs, according to:

1. The therapeutic conception:

a. Allopathic drugs, from the greek “allos” (other) and “pathos” (disease), are the
most commonly prescribed drugs in medicine. Their action is based on the
“contraria contrariis curantur” concept of Hippocrates, that everything that acts
in an opposite way will heal, and the drug will act as an antidote;
b. Homeopathic drugs, from the greek “homoios” (the same) and “pathos”
(disease) have their action based on another concept of Hippocrates “similia
similibus curantur”, according to which, everything that is acting in the same
way with the disease is efficient. Nowadays we know more than 2000
hoemeopathic drugs, of vegetal, mineral and animal origin.
From now on, the classification will include only allopathic drugs.
2. Origin:
a. Natural drugs:
i. Drugs of vegetal origin: buds, flowers, leaves, seeds, roots, bark;
ii. Drugs of mineral origin: sodium, magnesium, calcium, bismuth salts;
iii. Drugs of animal origin: organs, tissues;
b. Semisynthetic drugs, which are obtained by modifying the chemical strucutre
of the natural drug: semisynthetic penicillins;
c. Synthetic drugs, in which the whole molecule is obtained artificially, in the
laboratory: Acetylsalicylic acid, barbiturates, benzodiazepines, betablockers.
3. Toxicity:
a. Anodyne drugs, with low activity and toxicity. They are prescribed in doses
measured in grams, stored in recipients with an imprinted label including black
letters on a white background;
b. Highly active drugs are very active substances, dispensed in the pharmacy only
with prescription. They are prescribed in doses measured in centigrams, stored
in recipients with an imprinted label including red letters on a white
background. Examples of highly active drugs are: Quinidine, Diazepam,
Furosemide, Hydrocortisone hemisuccinate, Isoniazid, Nifedipine,
Paracetamol, Propranolol, Theophylline;

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 c. Toxic drugs are highly active and toxic substances, locked in the Venenum.
Their therapeutic dose, prescribed as milligrams or fractions of milligrams, is
very close to the toxic dose. They are dispensed only with a special
prescription. The label includes white letters on a black background plus a
head skull. Examples of toxic active drugs are: Atropine, Cocaine, Digoxin,
Morphine, Opium.
4. Formulation:
a. Magistral drugs are produced in small quantities, in pharmacies, according to
an individualized prescription, for a specific patient. They have a short
validity period and no preestablished formula.
b. Officinal drugs are produced in larger quantities, in pharmacies, according to
their fix formula and have a longer validity period. They have a name (e.g.
Dower powder, Bourget powder, tincture Davilla) and are dispensed
immediately in the pharmacy, with or without prescription.
c. Industrial drugs are the most common prescribed drugs (98%). They are
produced in the pharmaceutical industry, after a fix formula, in very large
quantities. Compared to magistral or officinal drugs, they have a higher
bioavailability and a longer validity period, of 1-3-5 years. The names of
industrial drugs are:
i. The chemical name is given when the drug is discovered. It describes
the atomic or molecular structure of the drug and is usually too
complex for general use. Exceptions are made in case of drugs with a
simple chemical structure, like acetylsalicylic acid or sodium
bicarbonate;
ii. The generic or official name is given after the drug is approved by the
health authority, often being a short version of the chemical name;
iii. The brand name or trademark is given by the drug company, easy to
remember, often suggesting the intended use.
5. Prescribing
a. Legend drugs – may not be dispensed by a pharmacist without a prescription
from a physician
b. Essential drugs » 200 drugs (WHO) ± prescription
c. OTC drugs (over the counter) - do not require a prescription
d. Controlled drugs - require a prescription (refills are limited)
i. Schedule I
• High abuse potential (heroin, marijuana)
• Not prescribed
ii. Schedule II
• Abuse potential and severe psychic or physical dependence
liability(opium, morphine, codeine, methadone, pentobarbital)
• No refills
iii. Schedule III
• Abuse potential < Schedules I and II (limited quantities of
narcotic analgesics)
iv. Schedule IV
• Abuse potential < Schedule III (barbital, phenobarbital,
diazepam)
v. Schedule V
• Abuse potential < Schedule IV (limited quantities of narcotics
used as antitussives or antidiarrheal drugs)

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 6. Route of administration
a. Oral
b. Parenteral
c. Local (skin, mucous membrane)

7. Consistency
a. Solid
b. Semisolid
c. Liquid
d. Gaseous

THE CLINICAL TRIALS

DEFINITION:
Clinical trials are tests in drug development that generate safety (adverse effects) and efficacy
data for drug administration.

They can be done only after the:

• preclinical studies, on animals – 3 years
• health authority (e.g. FDA – the „Food and Drug Administration“ in the United States,
EMA – the „European Medicines Agency“ in the European Union or ANMDM –
“Agenția Natională a Medicamentului și a Dispozitivelor Medicale” in Romania)
approval
• ethics committee approval

Before a drug is allowed to be sold on the market it takes aproximatively 12 years. Out of
5000 substances that are tested in the preclinical phase, only 5 will be tested on humans. Out
of this 5 only 1 will be found on the market. That makes a 1:5000 ratio.

The clinical trial design and objectives are written into a document - the clinical trial
protocol. It describes the scientific rationale, objectives, design, methodology, statistical
considerations, and organization of the trial.
No patient is allowed to participate to a clinical trial without signing the informed consent.
This includes information about the protocol, how the trial will work, the risks and
discomforts that they may experience.

Volunteers with ethical problems:

• elderly
• children
• pregnant women
• patients with cancer

Volunteers which should not be included:

• prisoners
• homeless people
• nurses
• students

THE PHASES of a clinical trial are:

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 Phase 0
• the first in human trials
• number of patients: 10-15 (healthy volunteers)
• single subtherapeutic doses of the study drug are given
• studies the pharmacodynamics and PHARMACOKINETICS of the drug

Phase 1
• number of patients: 20-80 (healthy volunteers)
• studies the SAFETY (side effects) of the drug
• duration: 1 year

Phase 2
• number of patients: 100-300 (+ disease)
• studies the EFFICACY and safety
• usually against placebo
• duration: 2 years

Phase 3
• number of patients: 1,000 – 3,000
• studies the effectiveness, side effects and compare it to other drugs

Phase 4 (postmarketing)
• studies further side effects and the optimal use of the drug

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 THE PHARMACEUTICAL DOSAGE FORMS
There are many chemicals with pharmacological properties, known as active
pharmaceutical ingredient (API), but the administration of a raw chemical is rare,
because:
• handling and accurate drug dosing can be difficult or impossible;
• administration can be impractical, unfeasible or not according to the
therapeutically aims;
• it can be degraded at the site of administration;
• it may cause local irritations or injury;
• it can have unpleasant taste or smell causing a decrease in compliance.
The pharmaceutical dosage form determines the physical form of the final
pharmaceutical preparation, made by technological processing. It must reflect
therapeutic intentions, route of administrations, dosing etc.

CLASSIFICATION ACCORDING TO PHYSICAL

PROPERTIES

1. GASEOUS DOSAGE FORMS, packaged under pressure, containing the

therapeutically active ingredients that are released upon activation of an
appropriate valve system.They are substances administered by the nasal or oral
respiratory route for local or systemic effect.
a. MEDICINAL GASES – inhalation or volatile anaesthetics (vaporised
before administration by inhalation)
b. AERODISPERSIONS of:
• solid particles;

• liquid particles.
i. The average size of the particles < 5µm.
 ii. the spacer

2. LIQUID DOSAGE FORMS:

a. SOLUTIONS - prepared by dissolving one or more solutes in a solvent;
b. EMULSIONS - a dispersion system consisting of two immiscible liquids;
- cloudy appearance;
c. SUSPENSIONS - a dispersion system where solid particles are dispersed
in liquid phase;
– may require shaking before administration;

a – drug solution, b – unstable drug suspension, c – stable drug suspension

Volume/weight for estimation of dose of liquid dosage forms

Dosing measure Approximative volume Approximative weight
(ml) (g)
1 drop 0.05 0.05
1 teaspoon 5 5
 1 tablespoon 15 15

3. SEMISOLID DOSAGE FORMS:

a. Without specific physical shape:
• GELS
• CREAMS
b. Shaped
• SUPPOSITORIES - for rectal administration;
- melting or dissolving at body temperature;
• VAGINAL SUPPOSITORIES

4. SOLID DOSAGE FORMS

• Unshaped - POWDERS for external or internal use -mixturesof dry,
finelydivideddrugs;
• Shaped
• TABLETS
• CAPSULES
• IMPLANTS - sterile disks inserted surgically into body tissues
and designed to release drugs over extended period of time;
• TRANSDERMAL PATCHES;
• LOZENGES - consists of sugar and gum to medicate the mouth
and throat.

CLASSIFICATION ACCORDING TO THE ROUTE OF

ADMINISTRATION
1. FOR SYSTEMIC ADMINISTRATION
• Oral:
1. TABLETS = compressed product = API+ excipients:
• CONVENTIONAL – can be divided (half/quarters)

• COATED (not to be divided).

Advantages:
• masks unpleasant taste or smell of API;
• avoids adhesion in oesophagus;
• ensures drug stability;
 • provides enterosolvent coating.

• EFFERVESCENT TABLETS – drug in water => CO2 produced by

chemical reaction of acid and NaHCO3.
Advantages:
• rapid absorption;
• avoids tablet adhesion to mucosa and local irritation.

2. CAPSULES(not to be divided) = API + excipients - enclosed in the hard

or soft water soluble container made of gelatin. Filling = solid, liquid;
3. POWDERS
Advantages:
o because of their greater surface area, powders disperse and
dissolve more readily than compacted dosage forms;
o suitable for children and those adults who experience
difficulty in swallowing tablets or capules.
4. SOLUTIONS
• SYRUPS – aqueous solution with sugar (sugar substitute) with or
without flavouring and colouring agents.
Advantages:
o rapid absorption;
o easier for administration (children);
o good compliance.
Disadvantages:
o accurate dosing;
o stability.
 THE PHARMACEUTICAL DOSAGE FORMS (cont.)
• Sublingual:
• Solid dosage forms:
o TABLETS
• Liquid dosage forms:
o SOLUTIONS
o Advantages: rapid absorption => rapid onset of action => used in
emergencies
• Rectal:
• Semisolid dosage forms:
o SUPPOSITORIES
o size – children 1-2 g; adults 2-3 g;
o form - „torpedo“-like;
o storage – cool place;
o API: anti-inflammatory drugs, antiemetics, antipyretics;
o Advantages: an alternative to p.o., useful when patient can not swallow the
drug (children, coma, vomiting) or when we need to avoid local adverse
reactions (anti-inflammatory drugs).
o Disadvantages: poor compliance; can cause local irritation; instability of
the dosage form.

• Liquid dosage forms:

o ENEMA
o Liquids introduced into the rectum and colon via the anus
o Types:
§ Evacuant enema: < 2 l (warmed at body temperature), in
constipation, drug intoxications
§ Retention enema: < 100 ml (no warming needed)
o For:
§ Local effect: barium enema
§ Systemic effect
• Parenteral:
1. INJECTABLES
• liquids or powders for preparation of the solution;
• must be: sterile, apyrogenic, isotonic.
• IV injections:
o must be particle-free;
 o slow administration.
• IM and SC injections:
o oil-based vehicles may be used

2. INFUSIONS (available in plastic bags)

Advantages:
o approach of choice in the case of problems with oral absorption,
gastrointestinal instability, uncompliant patients;
o in emergencies;
Disadvantages:
o non-compliance (children);
o pain at the site of injection;
o need for trained personnel using aseptic procedures;
o higher risk of severe adverse effects.

• Inhalation.

2. FOR LOCAL ADMINISTRATION (TOPICAL) ON:

• SKIN or HAIR:
1. AERODISPERSION – sprays;
2. Liquid dosage forms – LOTIONS, MEDICATED SHAMPOO, FOAM;
3. Semisolid dosage forms: GELS, CREAMS, OINTMENTS, used for skin hydration,
to form a protective barrier or as a vehicle for incorporation of API;
4. Solid dosage forms – POWDER;
5. TRANSDERMAL PATCHES applied on healthy and clean skin assure controlled
drug delivery into the systemic circulation.
Advantages:
o pain and stress-free;
o no need for trained specialist;
o long-term drug delivery with minimal fluctuations of drug concentrations;
o good compliance;
o the treatment can be immediately discontinued.
§ MUCOSA of:
1. EYE:
§ liquid dosage forms:
o DROPS, LOTIONS;
o must be sterile;
o isotonic with tears to avoid local irritation;
§ semisolid dosage forms:
o GELS, CREAMS, OINTMENTS;
o must be sterile and clear;
o direct application on the conjunctival mucosa to avoid contamination
§ solid dosage forms:
o INSERTS.
2. NOSE, EAR:
§ liquid dosage forms:
o DROPS;
o isotonic;
o must be nonirritating;
o require special dropping device;
o should be warmed in hands before administration
§ semisolid dosage forms:
o GELS, CREAMS, OINTMENTS.
3. ORAL CAVITY
• Solid dosage forms:
o TABLETS
• Liquid dosage forms:
o GARGLES
o aqueous solution used in the prevention and treatment of throat infection
o Prepared in a concentrated solution
o To dilute in warm water before administration
o MOUTHWASHES – similar to gargles, but for oral hygiene or to treat
infections
4. VAGINA:
§ tablets;
o different appearance compared to oral tablets;
o application device is needed.

§ vaginal suppositories;
 § vaginal ring:
o doughnut-shaped polymeric drug delivery device;
o provides controlled release of drugs over long periods of time.

• the intrauterine device (IUD):

o a birth control device;
o has to be placed inside or removed from the uterus by a doctor;
o approved for 5-10 years;
o types:
§ copper device;
§ hormonally based device, releasing progesterone.

2. RECTUM:suppositories;gels, creams;enemas
 THE MEDICAL PRESCRIPTION

The medical prescription is an oral, written or electronic transmission directive

by a medical doctor to a pharmacist to dispense a medication, device or therapy
to a specific patient for a specified period of time.

The word "prescription" derives from "pre-", meaning "before" and "script",
meaning "writing“ or „written". It refers to the fact that the prescription is an order
that must be written down before a compound drug can be prepared or dispensed
in the pharmacy.

THE PARTS OF A PRESCRIPTION

1. THE SUPERSCRIPTION is the header of the prescription and consists of:

¨ Information related to the prescribing provider: name, address,
phonenumber, email and any other legal requirement;
¨ Information related to the patient: name, age, gender, address, medical file
number, social security number, the identifying number of the patient's
private health insurance company (if applicable), diagnosis;
¨ The date of issue, name and signature of the prescriber.

2. THE PRAESCRIPTION (INSCRIPTION) is the prescription itself, the

directions to the dispensing pharmacist to supply medication, made up of the
following:
¨ INVOCATIO, consisting of „Rx“ or „Rp/“, the symbol meaning
"prescription", the abbreviation of the Latin verb „recipe“, meaning „to
take“ or „take thus“. It was established centuries ago and has been carried
down to the present time. The invocatio should be written on the top left
corner of the blank space and in front of each drug name in the prescription;
¨ ORDINATIO, consisting of the:
o brand name (or generic name). The names of the drugs should be
written in capital letter (e.g. Aspirin). Abbreviations or chemical
structures are not allowed;
o type of dosage forms (e.g. tab., caps, supp.). Abbreviations are
allowed;
o strength of a particular drug.
In the magistral medical prescription it contains:
o Remedium cardinale, a basis or chief ingredient, intended to cure:
o with pharmacodynamic effect;
o always present in the prescription.
o Remedium adjuvans, one or more substances to assist its action and
make it cure quickly:
 o with pharmacodynamic effect;
o sometimes present in the prescription.
o Remedium corrigens or corrective, to prevent or lessen any
undesirable effects:
o without pharmacodynamic effect;
o sometimes present in the prescription;
o e.g. sugar, flavours.
o Remedium constituens, an excipient, to make it suitable for
administration and pleasant to the patient:
o without pharmacodynamic effect;
o always present in the prescription;
o e.g. fillers, binders, lubricants, coatings, preservatives; for
solutions: water, for creams and ointments: lanolin, vaseline,
for suppositories: cocoa butter.

3. THE SUBSCRIPTION which consists of the directions to the pharmacist,

regarding the number of dosage forms or original packages that have to be
dispensed. In the magistral prescription it contains information according to
which the medicament is to be prepared.

4. THE SIGNA which incudes the directions to the patient on how to take the
medication correctly, written always in the official language, avoiding Latin
abbreviations or symbols. It consists of:
o „D.S.“ the abbreviation from the latin „dentur signetur“, meaning
„give and label“;
o the route of administration;
o frequency: e.g. „3 x 1 tablet/day“;
o moment: e.g. „before meal“;
o period: e.g. „for 10 days“;
o any other details regarding the treatment.

CHARACTERISTICS OF A PRESCRIPTION

Ø The prescription is a legal document which might be used in the court of

law;
Ø It is handwritten in permanent ink on preprinted prescription forms, or
printed on the computer;
Ø Corrections are not allowed in the prescription, or else the pharmacist will
reject it;
Ø The prescription is extemporaneous, meaning: written on the spot for a
specific patient;
Ø Prescribed drugs are separated in the prescription by the „#“ sign;
Ø If the doctor wishes to write on the second page, on the bottom right corner
he should specify „verte“, meaning „turn“ and the pharmacist will
understand that the prescription continues on the other side;
Ø If the doctor wishes to prescribe a higher dose than the maximum dose, he
should specify: „sic volo“, meaning „this is what I want“;
Ø The electronic form often has a "label" box.
o when checked, the pharmacist is instructed to label the
medication;
o when not checked, the patient only receives instructions for
taking the medication and no information about the
prescription itself.
Ø Some prescriptions will specify whether and how many "repeats" or
"refills" are allowed; that is whether the patient may obtain more of the
same medication without getting a new prescription from the medical
practitioner. Regulations may restrict some types of drugs from being
refilled;
Ø Narcotics are prescribed on special prescriptiom forms, with the doses
written in numbers and letters.

CONVENTIONS FOR AVOIDING AMBIGUITY

¨ careful use of decimal points:

o avoiding unnecessary decimal points: a prescription will be written
as 5 mL instead of 5.0 mL to avoid possible misinterpretation of 5.0
as 50;
o always using zero prefix decimals: e.g. 0.5 instead of .5 to avoid
misinterpretation of .5 as 5;
o avoiding trailing zeros on decimals: e.g. 0.5 instead of .50 to avoid
misinterpretation of .50 as 50.
¨ "mL" is used instead of "cc" or "cm³" to avoid misinterpretation of :
o „c“ as „0“;
o the common medical abbreviation for "with" (the Latin "cum"),
which is written as a „c“ with a bar above the letter;
o "c.c.", which is an uncommonly used abbreviation for "take with
meals" (the Latin "cum cibo").
¨ where possible, usage directions should specify times (7 am, 3 pm, 11 pm)
rather than simply frequency (three times a day) and especially relationship
to meals for orally consumed medication;
¨ avoid units such as "teaspoons" or "tablespoons";
¨ don’t use of the degree symbol (°), since it can be confused with a „0“.
 LIST OF ABBREVIATIONS USED IN MEDICAL PRESCRIPTIONS

Abbreviation Latin Meaning

aa ana partes aequales of each
ad ad up to
a.c. ante cibum before meals
use as much as one
ad lib. ad libitum
desires
a.m. ante meridiem morning, before noon
bis bis twice
b.d./b.i.d. bis in die twice daily
bol. bolus as a large single dose
cap., caps. capsula capsule
cc cum cibo with food
dieb. alt. diebus alternis every other day
d.t.d. dentur tales doses give of such doses
ID intradermal
IJ, inj injectio injection
IM intramuscular
IN intranasal
IU international unit
IV intravenous
non rep. non repetatur no repeats
o.p.d. once per day
per per by or through
p.c. post cibum after meals
p.m. post meridiem evening or afternoon
p.o. per os by mouth or orally
p.r. per rectum by rectum
PRN, prn pro re nata as needed
pulv. pulvis powder
q.a.d. quoque alternis die every other day
quaque die ante
q.a.m. every day before noon
meridiem
q.d.s. quater die sumendus four times a day
quaque die post
q.p.m. every day after noon
meridiem
q.h. quaque hora every hour
q.h.s. quaque hora somni every night at bedtime
q.s. quantum sufficiat a sufficient quantity
rep., rept. repetatur repeats
s.a. secundum artum use your judgement
SC, subc, subcut, subq,
subcutaneous
SQ
sol solutio solution
supp suppositorium suppository
susp suspension
syr syrupus syrup
tab tabella tablet
tbsp tablespoon
t.i.d. ter in die three times a day
t.i.w. three times a week
tsp teaspoon

EXAMPLES OF PREPRINTED PRESCRIPTION FORMS

1. The general prescription form

2. The electronic prescription form

3. The form for prescribing narcotics

 IMPORTANCE OF PHARMACOKINETIC PARAMETERS IN
ESTABLISHING A RATIONALE THERAPEUTIC SCHEDULE

I. THEORETICAL PART

1. Pharmacokinetic parameters

Pharmacokinetics is the part of pharmacology that studies the drug circulation into the
body, from administration to elimination. In order to establish the optimal dose of a drug, direct
measurements or calculations of the pharmacokinetic parameters are necessary. The main
parameters are:
a. Primary pharmacokinetic parameters, which are established by direct measurement:
- The plasma concentration (Cp)
b. Secondary pharmacokinetic parameters, which are established through calculation:
- The volume of distribution (Vd)
- Bioavailability (Bd)
- The halflife (T1/2)
- The clearance (Cl)
There are certain categories of drugs in which pharmacokinetic monitoring is necessary:
- Antiepileptics: Fenitoin, Carbamazepin, Valproic acid, Lamotrigin, Etosuximid,
Fenobarbital, Primidone
- Cardioactive : Digoxin, Lidocaine
- Bronhodilating agents : Theophyline
- Antibiotics : Gentamycin, Tobramycin, Amykacin, Vancomycin
- Antivirals : Efavirenz, Tenofovir, Ritonavir
- Citostatics : Metotrexat, 5-Fluorouracil
- Imunosupressants : Ciclosporin, Tacrolimus, Sirolimus, Micofenolat

The plasma concentration

3
medium plasma concentration (mg/ml)

2,5 IV ADMINISTRATION

2 MAX. PLASM. c%

1,5 ADMINISTRATION THROUGH A ROUTE

THAT REQUIRES ABSORPTION

1 Cp 1/2

0,5
AUC
0
0 1 2 3 4 5 6 7
Tmax T1/2 time (hours)
 AD = Vd x Cp
AD = attack dose, Vd = volume of distribution, Cp = plasma concentration

The volume of distribution

D
Vd = ----------
Cp max
D = dose of drug administered IV, Cp max = maximum plasma concentration

Bioavailability (after IV administration, the Bd = 100%)

Cp oral (other route with abs)

Bd% = ----------------------------------------- x 100
Cp after IV
or

AUC oral (other route with abs)

Bd% = ------------------------------------------ x 100
AUC after IV
Cp – plasma concentration, AUC – area under the curve

In the medical practice, by calculating the Bd, we can compare 2 doses after different routes of
administration. An example: if a drug has a Bd of 25 % after oral administration, than the oral dose
will be four times higher compared to IV.

The half-life can be determined from the concentration/time graphic or through calculation,
beeing directly proportional with the volume of distribution and inversely proportional with the
clearance of the specific drug. In general, the half life is not related to the dose.

ln 2 x Vd 0,693 x Vd
T1/2 = ---------------- = ------------------
Cl Cl
Vd = volume of distribution, Cl = clearance of the drug

The plasmatic clearance

0,693
Cl = Ke x Vd = ---------- x Vd
T1/2
or
D
Cl = --------
AUC
Ke = elimination constant, Vd = volume of distribution, T1/2 = half-life, D = dose of administered
drug, AUC – area under the curve

The value of clearance is important for the calculation of the maintainning dose.

MD = Cp const. x Cl x t
MD – maintaining dose, Cp – plasma concentration which has to be maintained at a steady level,
Cl = clearance of the drug, t = time between administrations, in minutes

The main organs of drug elimination are the kidney and the liver. The clearance of an organ
depends on the capacity of elimination, called intrinsic clearance and on the blood perfusion of
this specific organ. Liver, renal or heart diseases can influence the clearance of an organ.

Qs x Cl int.
Cl organ = ------------------
Qs + Cl int.
Qs = blood flow through an organ, Cl int. = intrinsic clearance

The total systemic clearance :

Cltotal = Clrenal + Clhepatic + Clother organs

Pharmacokinetic parameters of some drugs for a 70 kg patient

Drug Oral bioavailability Total clearance Vol. of distribution

(%) (ml/min) (l)
Acetaminophen 63 350 67
Valproic acid 100 8,4 9,1
Amikacin - 77 15
Amoxicillin 93 370 29
Ampicillin 25-70 270 20
Aspirin 68 650 11
Carbamazepin > 70 89 98
Cephalexin 90 300 18
Cephalotin - 470 18
Chloramphenicol 75-90 250 64
Chlordiazepoxide 100 26 21
Cimetidin 62 840 150
Clonidine 74 210 150
Diazepam 100 27 77
Digitoxin > 90 3,2 36
Digoxin 60-70 130 640
Disoyramide 83 90 55
Erythromycin 18-45 420 50
Ethambutol 77 600 110
Furosemid 40-60 140 7,7
Gentamycin - 90 18
Hydralazine 20-60 420 110
Imipramine 47 1400 1050
Indometacin 98 110 65
Lidocaine 35 640 77
Meperidine 52 1200 290
Methotrexate 65 105 28
Morphine 20-30 1100 220
Nortriptyline 51 500 1300
Phenobarbital > 80 6,5 62
Prazosin 57 210 42
 Procainamide 83 350-840 130
Propranolol 36 840 270
Quinidine 70 330 190
Sulphamethoxazol 100 22 15
Tetracycline 77 130 91
Theophylline 96 48 35
Tobramycin - 77 18
Tolbutamide 93 21 11
Trimethoprim 100 150 130
Tubocurarine - 160 21
Verapamil 19 830 280

The therapeutic index is a parameter of risk or safety of a drug.

DL50
TI = ----------
DE50
DL50 = medium lethal dose, DE50 = medium efficient dose

TI < 10 => the drug is very active and needs special supervision
TI > 10 => the drug needs no special precautions

II. PRACTICAL PART

1. Calculate the half-life of ……………………., in hours (days), for a patient with 70 kg.

2. A patient, having the bodyweight of 70 kg, is hospitalized with the following diagnosis :
pneumonia with Klebsiella pneumonie, senzitive to Tobramycin. Because of the severity
he will receive immediately Tobramycin IV, in order to obtain a therapeutic plasma
concentration of 4 mg/l. Calculate :
a. The necessary attack dose
b. The dose which has to be administered every 6 hours to maintain this concentration

3. A drug with sedativ-hypnotic effect is in the process of evaluation, in order to introduce a

new drug on the market. According to the graphic below :
a. Calculate the therapeutic index of the drug
b. State if the drug requires special attention or not
 110

100
NUMBER OF PATIENTS WHICH RESPONDED TO THE

90

80

70
TREATMENT (%)

60

50

40

30

20

10

0
0 100 200 300 400 500 600
DOSE OF THE DRUG (mg)

blue line – sleeping, red line - coma

 PHARMACOKINETIC PARAMETERS, WHICH ARE USEFUL IN MEDICAL
PRACTICE

I. THEORETICAL PART

1. Pharmacokinetic parameters

Pharmacokinetics is the part of pharmacology that studies the drug circulation into the
body, from administration to elimination. In order to establish the optimal dose of a drug, direct
measurements or calculations of the pharmacokinetic parameters are necessary. The main
parameters are:
a. Primary pharmacokinetic parameters, which are established by direct measurement:
- The plasma concentration (Cp)
b. Secondary pharmacokinetic parameters, which are established through calculation:
- The volume of distribution (Vd)
- Bioavailability (Bd)
- The halflife (T1/2)
- The clearance (Cl)
There are certain categories of drugs in which pharmacokinetic monitoring is necessary:
- Antiepileptics: Fenitoin, Carbamazepin, Valproic acid, Lamotrigin, Etosuximid,
Fenobarbital, Primidone
- Cardioactive : Digoxin, Lidocaine
- Bronhodilating agents : Theophyline
- Antibiotics : Gentamycin, Tobramycin, Amykacin, Vancomycin
- Antivirals : Efavirenz, Tenofovir, Ritonavir
- Citostatics : Metotrexat, 5-Fluorouracil
- Imunosupressants : Ciclosporin, Tacrolimus, Sirolimus, Micofenolat

The plasma concentration

3
medium plasma concentration (mg/ml)

2,5 IV ADMINISTRATION

2 MAX. PLASM. c%

1,5 ADMINISTRATION THROUGH A ROUTE

THAT REQUIRES ABSORPTION

1 Cp 1/2

0,5
AUC
0
0 1 2 3 4 5 6 7
Tmax T1/2 time (hours)
 AD = Vd x Cp
AD = attack dose, Vd = volume of distribution, Cp = plasma concentration

The volume of distribution

D
Vd = ----------
Cp max
D = dose of drug administered IV, Cp max = maximum plasma concentration

Bioavailability (after IV administration, the Bd = 100%)

Cp oral (other route with abs)

Bd% = ----------------------------------------- x 100
Cp after IV
or

AUC oral (other route with abs)

Bd% = ------------------------------------------ x 100
AUC after IV
Cp – plasma concentration, AUC – area under the curve

In the medical practice, by calculating the Bd, we can compare 2 doses after different routes of
administration. An example: if a drug has a Bd of 25 % after oral administration, than the oral dose
will be four times higher compared to IV.

The half-life can be determined from the concentration/time graphic or through calculation,
beeing directly proportional with the volume of distribution and inversely proportional with the
clearance of the specific drug. In general, the half life is not related to the dose.

ln 2 x Vd 0,693 x Vd
T1/2 = ---------------- = ------------------
Cl Cl
Vd = volume of distribution, Cl = clearance of the drug

The plasmatic clearance

0,693
Cl = Ke x Vd = ---------- x Vd
T1/2
or
D
Cl = --------
AUC
Ke = elimination constant, Vd = volume of distribution, T1/2 = half-life, D = dose of administered
drug, AUC – area under the curve

The value of clearance is important for the calculation of the maintainning dose.

MD = Cp const. x Cl x t
MD – maintaining dose, Cp – plasma concentration which has to be maintained at a steady level,
Cl = clearance of the drug, t = time between administrations, in minutes

The main organs of drug elimination are the kidney and the liver. The clearance of an organ
depends on the capacity of elimination, called intrinsic clearance and on the blood perfusion of
this specific organ. Liver, renal or heart diseases can influence the clearance of an organ.

Qs x Cl int.
Cl organ = ------------------
Qs + Cl int.
Qs = blood flow through an organ, Cl int. = intrinsic clearance

The total systemic clearance :

Cltotal = Clrenal + Clhepatic + Clother organs

Pharmacokinetic parameters of some drugs for a 70 kg patient

Drug Oral bioavailability Total clearance Vol. of distribution

(%) (ml/min) (l)
Acetaminophen 63 350 67
Valproic acid 100 8,4 9,1
Amikacin - 77 15
Amoxicillin 93 370 29
Ampicillin 25-70 270 20
Aspirin 68 650 11
Carbamazepin > 70 89 98
Cephalexin 90 300 18
Cephalotin - 470 18
Chloramphenicol 75-90 250 64
Chlordiazepoxide 100 26 21
Cimetidin 62 840 150
Clonidine 74 210 150
Diazepam 100 27 77
Digitoxin > 90 3,2 36
Digoxin 60-70 130 640
Disoyramide 83 90 55
Erythromycin 18-45 420 50
Ethambutol 77 600 110
Furosemid 40-60 140 7,7
Gentamycin - 90 18
Hydralazine 20-60 420 110
Imipramine 47 1400 1050
Indometacin 98 110 65
Lidocaine 35 640 77
Meperidine 52 1200 290
Methotrexate 65 105 28
Morphine 20-30 1100 220
Nortriptyline 51 500 1300
Phenobarbital > 80 6,5 62
Prazosin 57 210 42
 Procainamide 83 350-840 130
Propranolol 36 840 270
Quinidine 70 330 190
Sulphamethoxazol 100 22 15
Tetracycline 77 130 91
Theophylline 96 48 35
Tobramycin - 77 18
Tolbutamide 93 21 11
Trimethoprim 100 150 130
Tubocurarine - 160 21
Verapamil 19 830 280

The therapeutic index is a parameter of risk or safety of a drug.

DL50
TI = ----------
DE50
DL50 = medium lethal dose, DE50 = medium efficient dose

TI < 10 => the drug is very active and needs special supervision
TI > 10 => the drug needs no special precautions

II. PRACTICAL PART

1. Calculate the half-life of ……………………., in hours (days), for a patient with 70 kg.

2. A patient, having the bodyweight of 70 kg, is hospitalized with the following diagnosis :
pneumonia with Klebsiella pneumonie, senzitive to Tobramycin. Because of the severity
he will receive immediately Tobramycin IV, in order to obtain a therapeutic plasma
concentration of 4 mg/l. Calculate :
a. The necessary attack dose
b. The dose which has to be administered every 6 hours to maintain this concentration

3. A drug with sedativ-hypnotic effect is in the process of evaluation, in order to introduce a

new drug on the market. According to the graphic below :
a. Calculate the therapeutic index of the drug
b. State if the drug requires special attention or not
 110

100
NUMBER OF PATIENTS WHICH RESPONDED TO THE

90

80

70
TREATMENT (%)

60

50

40

30

20

10

0
0 100 200 300 400 500 600
DOSE OF THE DRUG (mg)

blue line – sleeping, red line - coma

 PRACTICAL APPLICATIONS OF THE AUTONOMIC DRUGS

ADRENERGIC DRUGS

I. THEORETICAL PART

CLASSIFICATION

Sympathomimetic drugs
§ Direct acting
o Non-selective:
§ a1 a2 β1 β2: ADRENALINE (Epinephrine)
§ a1 a2 β1: NORADRENALINE (Norepinephrine)
§ β1 β2 : ISOPRENALINE
o Selective:
§ a1 : PHENYLEPHRINE, METHOXAMINE, XYLOMETAZOLINE
§ a2 : CLONIDINE, GUANABENZ, GUANFACINE, METHYLDOPA
§ β1 : DOPAMINE, DOBUTAMINE
§ β2 : SALBUTAMOL, SALMETEROL, TERBUTALINE,
FORMOTEROL, FENOTEROL, METAPROTERENOL,
CLENBUTEROL
§ Mixed acting
o a1 a2 β1 β2, releasing agent: EPHEDRINE
§ Indirect acting
o releasing agents: AMPHETAMINE, TYRAMINE
o uptake inhibitor: COCAINE
o MAO/COMT inhibitors: PARGYLINE, ENTACAPONE
Sympatholytic drugs
§ Alpha-blockers
o Synthetic:
§ Non-selective agents (a1 and a2): PHENTOLAMINE,
PHENOXYBENZAMINE, TOLAZOLINE
§ Selective agents (a1): DOXAZOSIN, PRAZOSIN, TERAZOSIN
o Natural: ergot alkaloids: ERGOTAMINE, DIHYDROERGOTAMINE,
ERGOTOXINE, DIHYDROERGOTOXINE, ERGOMETRINE,
METHYLERGOMETRINE
§ Alpha- and beta-blockers: LABETOLOL
§ Beta-blockers

GENERAL PRINCIPLES OF ADMINISTRATION

1. Adrenaline is a drug which can be administered SC (0.1-0.5 ml), IM (onset of action 3-

10 min, peak 20 min, duration 20-30 min), IV(0.1-0.25 ml; onset of action immediate,
peak 2-5 min, duration 5-10 min), intracardial or local;
2. Adrenaline is useful in the emergency systemic treatment of anaphylactic shock,
bronchial asthma crisis, cardiac arrest, or local in epistaxis, conjunctivitis, rhinitis or in
association with Lidocaine;
3. Special precautions have to be considered due to possible side effects after Adrenaline
administration: nausea, vomiting, tremor, agitation, insomnia, dizziness, pallor, HBP,
stroke, arrhythmias (ventricular fibrillation), dyspnea and pulmonary edema;
 4. Noradrenaline is administered: IV (4 mg in 250-500 ml Dextrose 5% in water or normal
saline solution infused initially 8-12 µg/min, then 4 µg/min) in serious acute
hypotensive states to vascular collapse, with systolic blood pressure less than 50 mmHg.
The blood pressure should be closely monitored every 2-5 min during infusion;
5. Adverse effects after Noradrenaline administration could be: anorexia, palpitations,
headache and HBP;
6. Isoprenaline is administered: SL (10-20 mg t.i.d.), IV (0.01-0.02 mg or infusion 2-20
µg/min), inhalatory (1-2 puffs every 4-6 h) in congestive heart failure or bronchial
asthma crisis. Tachycardia is a side effect;
7. Phenylephrine can be administered: nasal instillation (2-3 sprays or drops of 0.25-0.5%)
in patients with nasal congestion in patients with common cold, sinusitis, allergic
rhinitis, or IM, IV in hypotension. Other drugs used as local vasoconstrictors are:
Xylometazoline and Ephedrine;
8. Clonidine can be administered: orally (0.2-0.4 mg daily), local (transdermal patches –
0.1-0.2 mg daily), IM, IV, in anxiety, panic disorder, insomnia, Tourette syndrome,
withdrawal symptoms after narcotics, alcohol, nicotine or migraine. Blood pressure
fluctuations, dizziness, nausea, dry mouth could appear as adverse effects.
9. Dopamine is administered in heart failure or shock (except hypovolemic shock). At
doses of 2-10 μg/kg/min, the predominant action is inotrope positive, but at 10-20
μg/kg/min, more vasopressant. Possible side effects are: HBP, tachycardia, skin
necrosis;
10. Dobutamine is administered only IV (5-20 μg/kg/min), in patients with acute congestive
heart failure or after heart surgery;
11. Phentolamine, Phenoxybenzamine and Tolazoline have limited indication to
feocromocytoma;
12. Doxazosin, Prazosin and Terazosin are administered in HBP, but may produce low
blood pressure, especially after the first administrations;
13. Ergot alkaloids are useful as vasodilators (Ergotoxine, Dihydroergotoxine),
vasoconstrictors (Ergotamine, Dihydroergotamine) or oxytocics (Ergometrine,
Methylergometrine);
14. Beta-blockers are used in the treatment of HBP, arrhythmias, cardiac ischemia, heart
failure or glaucoma (local administration).

TREATMENT OF ANAPHYLACTIC SHOCK

Anaphylaxis is a medical emergency that requires immediate recognition and intervention.
Untreated it may lead to the death of your patient. Basic equipment and medication should be
readily available in the physician’s office.
Causes:
Ø Drugs: penicillin
Ø Insect sting, snake bite
Ø Radiocontrast media
Ø Food: peanuts, shellfish, milk, eggs
Ø Latex
Ø Rare: physical effort
Risk factors:
Ø a previous anaphylactic reaction
Ø allergies or asthma
Ø a family history of anaphylaxis
Treatment:
Ø Remove the source of the antigen, if possible: stop drug administration, remove stinger
 after honeybee sting
Ø High-flow oxygen
Ø Place the patient in a supine position (or position of comfort if dyspneic or vomiting)
with the legs elevated.
Ø Check the airway
Ø Cardiac monitoring, pulse oximetry
Ø IV access; administer physiological serum. A keep-vein-open (KVO) rate is appropriate
for patients with stable vital signs and only cutaneous manifestations. If hypotension or
tachycardia is present, administer a fluid bolus 1 L. Further fluid therapy depends on
patient response.
Ø Epinephrine:
o is the drug of first choice in anaphylactic shock, whith lifesaving potential
(anaphylactic deaths correlate with delayed administration of epinephrine)
o immediately 0,3-0,5 mg IM, in the thigh, repeated as necessary, depending on
the response
o maintains blood pressure
o antagonizes the effects of the released mediators and inhibits further release of
mediators
o via a nebulizer can be used to reduce laryngeal swelling, but it does not replace
IM administration of epinephrine
o if bronchospasm has not responded to IM epinephrine, administer inhaled beta2
-adrenergic agonists (albuterol)
Ø Corticosteroids:
o Hydrocortisone 100-200 mg IV, increase dose if necessary
o Prednisone 20-80 mg/day orally for 2-5 days
Ø H1 blocker and an H2 blocker:
o the combination is superior to an H1 blocker alone, in relieving the histamine-
mediated symptoms
o Diphenhydramine: 25 mg orally (IV) every 6 hours for 2-5 days
o Ranitidine: 150 mg orally or 50 mg IV
o bronchial asthma crisis.

Preparations

Generic drug Brand name Route of Pharmaceutical

administration dosage form
Adrenaline Adrenaline s.c, IM, IV vial 1 ‰, 1ml
EpiPen IM prefilled pen
0,15 mg; 0,3 mg
Noradrenaline Noradrenaline Tartrate PEV conc. sol. inf.
Aguettant 0,2%, vial 4ml,
8ml
Dopamine Dopamine Admeda PEV conc. sol. inf.
20mg/ml, vial
10ml
Dopamine clorhidrat PEV conc. sol. inf.
5mg/ml, vial 10ml
Xylometazoline Bixtonim Xylo intranasal Nasal drops
0,5mg/ml,
Olynth 1mg/ml; nasal
spray 1mg/ml
Phenylephrine Coldrex Lemon p.o. Powder for oral
(paracetamol+ susp.
phenylephrine +
ascorbic acid)
Ibuprofen/Clorhidrat p.o. tab 200 mg/5 mg
of Phenylephrine
Zentiva
Clonidine Clonidine p.o. tab 0,15 mg
Isoprenaline Bronhodilatin SL, SC, IM, tab subling. 10
IV, PEV mg, vial
0,2mg/1ml
Novodrin inhalator aerosoles 0,5%
Dobutamine Dobutamida Admeda PEV vial 50mg/250ml
Ephedrine Efedrina IV vial 50mg/1ml
Ser efedrinat intranasal Nasal drops 0,5%;
1%
Phenoxybenzamine Fenoxibenzamina p.o. tab 10 mg
Tolazoline Tolazolin p.o., IM, IV, tab 25mg, vial
i.a. 10mg/1m
Phentolamine Regitine p.o., IV tab 50mg, vial
10mg/ml
Prazosin Minipress p.o. tab 1 mg, 5 mg
Terazosin Terazosin p.o. tab 1mg, 2mg,
5mg
Doxazosin Cardura p.o. tab 1,2 mg
Aniprosin p.o. tab 2 mg, 4 mg
Ergotoxine Ergoceps p.o. int. sol. 1mg/ml
Dihidroergotoxine Redergin p.o. int. sol. 1mg/ml
Ergotamine Cofedol p.o. dj.1mg
ergotamine + 100
mg coffein
Dihidroergotamine Cornhidral p.o. int. sol. 2mg/ml
Migranal intranasal spray nasal 0,5
SC, IM, IV mg/puff, vial
1mg/1ml
Ergometrine Maleat de ergometrină IM, IV vial 0,2 mg/ml
Metilergometrine Metilergometrina p.o. dj. 0,125 mg,
maleat IM, IV vial 0,2mg/1ml
II. PRACTICAL PART
1. Write a medical prescription to a patient with cerebral aterosclerosis and symtoms of
imbalance.
2. Write a medical prescription to a patient with HBP.
3. Write a medical prescription to a patient with migraine.
4. A patient of 80 kg with cardiogenic shock receives Dopamine IV infusion 5 μg/kg/min.
Calculate the rythm of administration in ml/hours.
Available: Dopamine vial 50 mg/10 ml. Syringe pump of 100 ml (1 vial of Dopamine
in Physological serum).
 PRACTICAL APPLICATIONS OF THE AUTONOMIC DRUGS

CHOLINERGIC DRUGS

I. THEORETICAL PART

CLASSIFICATION

Parasympathomimetic drugs
§ Direct acting (stimulating the nicotinic or muscarinic receptors)
o Choline esters: ACETYLCHOLINE, CARBACHOL, METHACOLINE,
BETHANECHOL
o Natural alkaloids: PILOCARPINE, ARECOLINE, MUSCARINE, NICOTINE
§ Indirect acting
o Reversible cholinesterase inhibitors: NEOSTIGMINE, PHYSOSTIGMINE,
PYRIDOSTIGMINE, EDROPHONIUM, DONEPEZIL
o Irreversible cholinesterase inhibitors (organophosphate compounds):
ECHOTHIOPHATE, ISOFLUROPHATE, MALATHION

Cholinergic antagonists
§ Natural: ATROPINE, SCOPOLAMINE
§ Synthetic: PIRENZEPINE, HOMATROPINE, PROPANTELINE,
TRIHEXYPHENIDYL, TROPICAMIDE, BUTILSCOPOLAMINE

GENERAL PRINCIPLES OF ADMINISTRATION

1. Acetylcholine is used in eye surgery as ophtalmic solution instillation in the anterior

chamber to obtain miosis and prevent the anterior movement of the crystalline implant.
2. Bethanechol stimulates the atonic urinary bladder or intestine after surgical procedures,
but with cholinergic adverse effects: sweating, hypersalivation, skin congestion, low
blood pressure, nausea, abdominal pain, diarrhea and bronchoconstriction. To treat
bradycardia or bronchoconstriction we can administer Atropine sulphate.
3. Carbachol is indicated only in glaucoma. Miosis appears after 10-20 minutes and the
intraocular pressure decreases after 4-8 hours.
4. Pilocarpine is used in the emergency treatment of gaucoma. The latency is of a few
minutes. Pilocarpine intoxication is characterised by intense sweating and
hypersalivation, which is treated with parenteral Atropine.
5. Neostigmine and Physostigmine are administered in atonic urinary bladder or intestine.
6. Atropine is indicated in preanestesia, bradycardia or atrioventricular block, as an
antispastic drug or antidote in intoxication with parasympathomimetics. Applied
locally, it produces cycloplegia and prolonged mydriasis (7 days). Side effects of
Atropine include: dry mouth, constipation, photophobia and urinary retention. The
intoxication include the following symtoms: mydriasis, photophobia, tachycardia,
dysphagia, constipation, urinary retention, hyperthermia, hallucinations and coma. The
best treatment is the administration of Physostigmine IV and benzodiazepines.
7. Atropine should not be administered in patients with glaucoma, prostate adenoma or
pyloric stenosis.
8. Scopolamine is one of the most efficient treatments in motion sickness, useful in
preanestesia, Parkinson’s disease, billiary or renal colic.
 9. Homatropine, Ciclopentolat and Tropicamide are indicated to obtain mydriasis, with a
shorter duration of action compared to Atropine.

Generic drug Brand name Route of Pharmaceutical

administration dosage form
Acetylcholine Miochol intraconjunctival opht. sol. 1%
Carbachol Isopto carbachol intraconjunctival opht. sol. 3%
Bethanechol Urecholine p.o. tab.5mg,10mg,
25mg, 50mg;
SC vial 50mg/10ml;
Pilocarpine Dropil intraconjunctival opht. sol. 2%, 1-
2 drops, 3-4x/day
Isopto Carpine intraconjunctival opht. sol. 1%,
2%
Pilogel intraconjunctival opht. gel 4%
Ocusert pilo-20 intraconjunctival opht. insert
20μg/h; 40μg/h
Ocusert pilo-40 intraconjunctival
Neostigmine Miostin p.o.; tab. 15 mg,
SC, IV slow vial 0,5‰
Physostigmine Ezerina intraconjunctival eye drops 0,5%,
1% (4 - 6 x 1
drops/day)
Atropine sulphate Atropina SC, IM, IV vial 0,25‰; 1‰;
slow; eye drops 1%
intraconjunctival
Scopolamine Scopoderm TTS retroauricular 0,5mg/72h;
1mg/72h
Butylscopolamine Scobutil p.o. tab.10mg;
IM vial 10mg/1ml
Propanteline Propantelina p.o. dg. 15mg
Pirenzepine Gastrozepin p.o. tab. 25 mg
Homatropine Homatropina intraconjunctival eye drops 1%
Ciclopentolat Ciclopentolat intraconjunctival eye drops 1%
Tropicamide Mydrum intraconjunctival opht. sol. 0,5%

II. PRACTICAL PART

1. Write a medical prescription to a patient with chronic glaucoma.
2. Write a medical prescription to a patient with myasthenia gravis.
3. Write a medical prescription to a patient with renal colic.
4. Prescription: Atropine sulphate 0,5mg IV bolus.
Avialable: Atropine sulphate 1‰, vial 1ml.
Calculate how many ml to administer.
 PRACTICAL APPLICATIONS OF THE DRUGS USED IN RESPIRATORY
DISEASES

I. THEORETICAL PART

CLASSIFICATION

ANTICOUGHING AGENTS

Antitussives
• Opioids: OPIUM, MORPHINE, CODEINE (METHILMORPHINE), NOSCAPINE
• Non-opioids: GLAUCINE, CLOFEDANOL, OXELADINE

Expectorants
• Secretolytic expectorants (mucolytics): BROMHEXIN, AMBROXOL,
ACETYLCYSTEINE, CARBOCISTEINE
• Secretostimulant expectorants: GUAIAFENESIN

ANTIASTHMATICS

Bronchodilators
• Beta 2 adrenergic agonists:
With short action: TERBUTALINE, CLENBUTEROLE, SALBUTAMOLE, REPROTEROL,
FENOTEROLE, METAPROTERENOL
With long action: SALMETEROL, FORMOTEROL
• Cholinergic antagonists: IPRATROPIUM BROMIDE
• Musculotropes: THEOPHYLLINE, AMINOPHYLLINE

Anti-inflammators
• Corticotherapy
• Inhalatory: BECLOMETASONE, FLUTICASONE, FLUNISOLIDE,
BUDESONIDE
• Systemic corticotherapy
• Oral administration – PREDNISONE
• IV administration - HEMISUCCINATE HYDROCORTISONE
• Inhibitors of mastocitar degranulation: DISODIC CROMOGLICATE,
NEDOCROMILE, KETOTIFENE
• Antileukotrienes: MONTELUKAST SODICUM
• Lipooxygenase inhibitors: ZILEUTON

TREATMENT IN BRONCHIAL ASTHMA ATTACK

• Oxygen
• Beta2 agonist (short acting) aerosol
• Aminophylline IV slowly 1 vial 240 mg/10 ml
If the crisis persists:
• Aminophylline IV repeat the initial dose or IV drip 1 mg/kg/hour
• Hemisuccinate hydrocortisone 100-200 mg IV
• Antibiotics if necessary
GENERAL PRINCIPLES OF ADMINISTRATION

1. Antitussives are symptomatic drugs, used in dry cough, exhausting for the patient
(especially with cardiovascular problems) or to avoid local complication (irritation,
bronchiectasis, emphysema).
2. Opium and Morphine have limited use, in case the anticoughing plus analgesic and
sedative effect are desired: bronchopulmonary cancer, costal fractures, pneumothorax,
aortic aneurism, pulmonary infarction.
3. Expectorants are administered in acute and chronic bronchitis, mucoviscidosis, COPD,
rhinitis, sinusitis. They decrease the viscosity of the secretions.
4. Beta 2 adrenergic agonists are usually for inhalatory administration (rarely orally or IV).
5. Usually 2 puffs are enough in an asthma attack of medium severity.
6. Long acting beta 2 adrenergic agonists are not to be administered in crisis, because their
effect appears after 20 minutes.
7. Hemisuccinate hydrocortisone is an incompatible solution with other drugs. It should
not be mixed with other substances in the same syringe.

Generic drug Brand name Route of Pharmaceutical dosage form

administration
Codeine Codeina fosfat p.o. Tab. 15 mg
phosphate (1-2 tab. 3-4 x/day)
Oxeladine Paxeladine p.o. Caps. 40 mg, syrup 0,2%
(1 caps./5 ml 2-3 x/day)
Bromhexin Bronhosolv p.o. Tab. 8 mg (1-2 tab. 3-4 x/day)
Ambroxol Mucosolvan p.o. Tab. 30 mg, 75 mg
Acetylcysteine ACC p.o. Eff. tab. 200 mg (2-3 tab.
x/day) 600 mg (1 tab./day)
Salbutamol Ventolin Inhal. Aerosole 100 mcg/dose
Terbutaline Bricanyl Inhal. Inhal. powder 250 mcg/dose
Turbuhaler
Salmeterol Serevent Inhal. Aerosole 25 mcg/dose
(2 puffs/day)
Formoterol Pneumera Inhal. Powder 12 mcg/dose
Ipratropium Ipraxa Inhal. Sol. 250 mcg/ml
bromide
Tiotropium Spiriva Inhal. Caps. 18 mcg
Theophylline Teotard p.o. Caps. 200 mg, 350 mg
(10-13 mg/kg/day)
Aminophylline Miofilin p.o. Caps. 100 mg,
IV Vial 24 mg/ml
(0.4-0.6 mg/kg/h)
Beclometasone Becotide Inhal. Aerosole 50 mcg/dose
Prednisone Prednison p.o. Tab. 5 mg
Hemisuccinate Hemisuccinate IV Vial 25 mg/5 ml
hydrocortisone hydrocortisone
 Disodic Intal Inhal. Caps. 20 mg
cromoglicate
Nedocromile Tilade Inhal. Aerosole 2 mg/dose
Ketotifene Ketof p.o. Caps. 1 mg
Montelukast Singulair p.o. Tab. 4 mg, 5 mg, 10 mg
sodicum (1 tab. before bedtime)
Zileuton Zyflo p.o. Tab. 600 mg

II. PRACTICAL PART

1. Write a medical prescription to a patient with chronic bronchitis
2. Write a medical prescription to a patient with acute brochitis
3. Write a medical prescription to a patient with bronchial asthma stage I
4. Write a medical prescription to a patient with bronchial asthma stage IV
 PRACTICAL APPLICATIONS OF THE ANTIHYPERTENSIVE DRUGS

I. THEORETICAL PART

CLASSIFICATION

Diuretics

§ Thiazides and related agents: HYDROCHLOROTHIAZIDE, INDAPAMIDE,

CHLORTHALIDONE
§ Loop diuretics: FUROSEMIDE, ETHACRYNIC ACID, BUMETANIDE
§ Potassium sparing diuretics: AMILORIDE, SPIRONOLACTONE, TRIAMTERENE

Sympatholytics

§ Beta-blockers:
o Non-selective agents (β1 and β2): ALPRENOLOL, PINDOLOL, CARTEOLOL,
PROPRANOLOL, NADOLOL, SOTALOL, OXPRENOLOL, TIMOLOL
o Selective agents (β1): ACEBUTOLOL, ESMOLOL, ATENOLOL,
METOPROLOL, BETAXOLOL, NEBIVOLOL, BISOPROLOL
§ Alfa-blockers: DOXAZOSIN, PRAZOSIN, TERAZOSIN
§ Alfa and beta blockers: LABETOLOL, CARVEDILOL
§ Sympathetic inhibitors with central action: METHYLDOPA, CLONIDINE,
GUANABENZ, GUANFACINE
§ Sympathetic inhibitors with peripheral action: GUANADREL, RESERPINE

Calcium channel blockers:

§ Dihydropyridines: AMLODIPINE, NIFEDIPINE, FELODIPINE, NIMODIPINE,

LACIDIPINE, NITRENDIPINE, NICARDIPINE
§ Phenylalkylamine: VERAPAMIL, GALLOPAMIL
§ Benzothiazepine: DILTIAZEM

Renine-angiotensine-aldosterone system inhibitors

§ Angiotensin converting enzyme (ACE) inhibitors: CAPTOPRIL, ENALAPRIL,

FOSINOPRIL, LISINOPRIL, PERINDOPRIL, QUINAPRIL, RAMIPRIL,
TRANDOLAPRIL, BENAZEPRIL
§ Angiotensin II receptor antagonists: CANDESARTAN, EPROSARTAN,
IRBESARTAN, LOSARTAN, TELMISARTAN, VALSARTAN

Vasodilators: HYDRALAZINE, MINOXIDIL, DIAZOXID, SODIUM NITROPRUSSIDE

GENERAL PRINCIPLES OF ADMINISTRATION

1. Antihypertensive drugs are administered in low doses, which can be increased every 2-
3 weeks if nececssary, according to the blood pressure values.
 2. The patient should not drink alcohol (decreases BP) or smoke (decreases the effect of
ACE inhibitors).
3. Diuretics are administered as first intention treatment in case of elderly patients with
mild to moderate hypertension. For the long term treatment a low dose of thiazide
diuretic is to be administered.
4. Loop diuretics are administered usually in emergencies. Furosemide, IV rapidly, could
determine deafness. To avoid this side effect, the rhythm of administration should be
lower than 4 mg/min.
5. During the treatment with diuretics, monitoring of plasmatic potassium, magnesium,
calcium, chloride, glycemia and uric acid concentration is necessary.
6. The most frequent side effect of thiazide diuretics is hypopotasemia. For this reason,
the association with potassium sparing diuretics is useful.
7. ACE inhibitors are the golden standard in case of heart failure and can be administered
in high risk patients with HBP (elderly, with diabetes). If dry cough appears, we can
choose an angiotensin II receptor antagonist. Direct renin inhibitors are not considered
to be first line drugs, because there are insufficient long term studies.
8. Betablockers are administered in young hypertensive patients with hyperkinetic
syndrome, ischemia or patients under treatment with direct vasodilators.
9. Betablockers have a high risk of rebound and we have to reduce the dose slowly.
10. Nonselective betablockers should not be administered in patients with bronchial asthma,
chronic bronchitis or COPD. In case of selective betablockers, selectivity will be lost
after high doses.
11. Betablockers should be avoided in diabetic patients because they mask the symptoms
of hypoglycemia.
12. Acute intoxication with betablockers are treated with Atropine IV (for bradycardia),
temporary pace-maker, Isoprenaline or alfa agonists (increase the blood pressure) and
antiseizure agents.
13. Verapamil and Diltiazem have an inotrop negative effect and should not be administered
in association with betablockers. Nifedipine produces vasodilation and should not be
associated with nitrates (hypotension and reflex tachycardia).
14. The antihypertensive drug should be choosen according to the associated pathology:

Associated disease Antihypertensive drug

Left ventricular hypertrophy ACE inhibitors, calcium channel blockers, sartans
Atherosclerosis Calcium channel io, ACE inhibitors
Renal disease ACE inhibitors, sartans
Acute myocardial infarction in Betablockers, ACE inhibitors, sartans
the past
Pectoral angina Betablockers, calcium channel blockers
Heart failure Diuretics, betablockers, ACE inhibitors, sartans
Aortic aneurism Betablockers
Atrial fibrillation Betablockers, non-dihydropyridines
Peripheral arteriopathy ACE inhibitors, calcium channel blockers
Diabetes ACE inhibitors, sartans
Pregnancy Methyl-dopa, betablockers, calcium channel blockers

Generic drug Brand name Route of Pharmaceutical dosage

administration form
Hydrochlorothiazide Nefrix p.o. Tab. 25 mg, 50 mg
Indapamide Tertensif p.o. Tab. 1,5 mg
Chlorthalidone Hygroton p.o. Tab. 25 mg, 50 mg
Furosemide Lasix p.o. Tab. 40 mg
IM, IV Vials 20 mg/2 ml, 40
mg/ 4 ml, 250 mg/ 2 ml
Ethacrynic acid Edecrin p.o. Tab. 25 mg
Spironolactone Aldactona p.o. Dj. 25 mg, 50 mg
Caps. 100 mg
Amiloride Moduretic p.o. Tab. 5 mg/50 mg
(+Hydrochlorothiazide)
Triamteren Maxzide p.o. Tab. 75 mg/50 mg
(+Hydrochlorothiazide)
Captopril Captopril p.o. Tab. 25 mg, 50 mg
(2-3 times/day)
Enalapril Enap p.o. Tab. 2,5 mg, 5 mg, 10
mg, 20 mg (1- 2
times/day)
IV Vials 1,25 mg
Lisinopril Ranolip p.o. Tab. 5 mg, 10 mg, 20
mg (1 tab./day)
Ramipril Tritace p.o.. Tab. 2,5 mg, 5 mg, 10
mg
Fosinopril Monopril p.o. Tab. 10 mg, 20 mg
Perindopril Prestarium p.o. Tab. 5 mg, 10 mg
Trandolapril Gopten p.o. Caps. 4 mg (1 caps./day)
Quinapril Accupro p.o. Tab. 5 mg, 10 mg, 20
mg
Losartan Cozaar p.o. Tab. 12,5 mg, 50 mg
Valsartan Diovan p.o. Tab. 80 mg, 160 mg
Irbesartan Aprovel p.o. Tab. 150 mg, 300 mg
Telmisartan Micardis, Pritor p.o. Tab. 40 mg, 80 mg
Candesartan Atacand p.o. Tab. 4 mg, 8 mg, 16 mg
Propranolol Propranolol fabiol p.o. Tab. 10 mg, 40 mg
Sotalol Darob, Sotalex p.o. Tab. 80 mg, 160 mg
Atenolol Tenormin p.o. Tab. 50 mg, 100 mg
Metoprolol Betaloc, Betaloc-zok, p.o. Tab. 50 mg, 100 mg,
Egiloc 200 mg
Betaloc IV vials 1mg/1 ml
Bisoprolol Concor p.o. Tab. 5 mg, 10 mg
Nebivolol Nebilet p.o. Tab. 5 mg
Betaxolol Lokren p.o. Tab. 20 mg
Carvedilol Dilatrend p.o. Tab. 12,5 mg, 25 mg
Nifedipine Nifedipin p.o. Tab. 20 mg (2-3
times/day)
Amlodipine Norvasc p.o. Caps. 5 mg, 10 mg
Felodipine Plendil p.o. Tab. 2,5 mg, 5 mg, 10
mg
Lercanidipine Leridip p.o. Tab. 20 mg
Nitrendipine Lusopress p.o. Tab. 20 mg
Diltiazem Dilzem p.o. Tab. 60 mg, 90 mg
 Verapamil Isoptin p.o. Tab. 40 mg, 240 mg
i.v. Vials 5 mg/2 ml

II. PRACTICAL PART

1. Write a medical prescription to a patient with HBP stage II.
2. Write a medical prescription to a patient with HBP stage I and COPD.
3. Write a medical prescription to a patient with HBP stage I and diabetes mellitus type
II.
 PRACTICAL APPLICATIONS OF THE ANTIANGINAL DRUGS

I. THEORETICAL PART
Antianginal drugs reestablish the balance between the oxygen demand and supply in
the ischemic myocardium, with decreasing the frequency of angina crisis. They act through:
• Decreasing the cardiac activity (lower intotropism, chronotropism)
• Decreasing the peripheral resistance (vasodilation)
• The association of both
Antianginal substances increase the oxygen supply and decrease the myocardial oxygen
consumption, modifying the factors that have an influence upon this consumption:
• The stress in the myocardial wall (dependent to the intraventricular pressure, ventricular
radius, wall thickness)
• Heart rate
• Contractility

CLASSIFICATION
Organic nitrates
• GLYCERYL TRINITRATE (GTN) – NITROGLYCERINE
• ISOSORBIDE DINITRATE (ISDN)
• ISOSORBIDE 5 MONONITRATE (ISMN)
• PENTAERYTHRITYL TETRANITRATE
Other antianginal drugs
• MOLSIDOMIN
• BETA BLOCKERS
• CALCIUM CHANNEL BLOCKERS
• IVABRADIN (inhibitor of the SN)
• RANOLAZINE (inhibitor of the sodium influx)

GENERAL PRINCIPLES OF ADMINISTRATION

1. Nitrates are indicated in coronary diseases (ischemic cardiopathy, AMI) and in heart
failure (only in association with other drugs).
2. In angina pectoris crisis, short acting, sublingual nitrates are administered:
Nitroglycerine 1 tablet or 1 puff. The dose may be repeated after a few minutes. If there
is no relief after the third administration, the patient should see a doctor, suspecting an
AMI.
3. The patient should always have Nitroglycerin available, which can be used also in
prophylaxis, if the patient knows the determing circumstances of an angina crisis
(physical effort, stress).
4. Nitroglycerine for sublingual use expires quickly, after 6 months (do not prescribe
several packages).
5. Nitrates with a long duration of action (oral or transdermic) are prescribed for the
prophylaxis of angina crisis together with beta blockers or calcium channel blockers, in
the daily treatment of ischemic cardiopathy.
6. The transdermic patch with Nitroglycerine should be applied on healthy, dry, hairless
and clean skin. For a better adhesion to the skin, it should be kept pressed with the palm
for several seconds. A patch that has been used, should be never reapplied. Nitroderm
TTS 5 (5 mg/24 hours) releases a dose of 0.2 mg/hour for a contact surface of 10 cm2.
7. Nitrates can be responsible of hypotension (especially after the first dose or in case of
increasing the dose) and reflex tachycardia, with dizziness and fatigue. Another adverse
effect of nitrates is the tolerance, which appears after a prolonged treatment. For the
 prevention, nitrates should be discontinued during the therapy and replaced by another
antianginal drug.
8. Molsidomin is a vasodilator with an antiplatelet effect. It is used as an alternative in
patients with severe headache after nitrates, 2 tab./day.
9. In patients with ischemic cardiopathy, the antianginal treatment should be associated
with an antiplatelet agent (Aspirin 75-100 mg/day, Ticlopidin 2 tab/day) and sometimes
with an antilipemic drug.
10. The administration of Ivabradine or Ranolazine require EKG monitoring.

THE TREATMENT IN AMI

1. Oxygen 4-8 l/min

2. Antianginal treatment
• GTN
• 1 tab/puff sublingual every 5 min, max. 3x
• IV infusion 1-3 mg/h (in left heart failure up to 6 mg/h)
• Beta blockers, in case of GTN failure or tachycardia, but without left heart
failure
• Calcium channel blockers (not dihydropyridines), in case of GTN and beta
blockers failure
3. Antiplatelet agents
• Aspirin
• 150-300 mg p.o. (250 mg IV), continue with 75-100 mg/day, plus
• ADP antagonist (asap, plus 12 months)
• 60 mg Prasugrel or 180 mg Ticagrelor
• 600 mg Clopidogrel in absence of Prasugrel or Ticagrelor
4. Anticoagulants
• In NSTEMI: Fondaparinux or Enoxaparin or UFH
• In STEMI:
• First choice: PCI, plus Enoxaparin or UFH
• Second choice: Streptokynase 1.5 mil. IU in 30-60 min or Alteplase
(expensive) 15 mg bolus IV => 0.75 mg/kg in 30 min => 0.5 mg/kg in
60 min.
5. Analgesics
• 3-5 mg IV Morphin, possibly repeat in min.

Preparations

Generic drug Brand name Route of Pharmaceutical

administration dosage form
Glyceryl trinitrate Nitroglicerina sublingual Tab. 0,5 mg

Nitromint sublingual Spray 0,4 mg/puff

Nitroderm(R) transdermic Patch 5mg/24h
TTS 5
Trinitrosan IV Conc. for infusion
5mg/ml
Nitroglicerina apply on skin Ointment 2%,
precordial
 Isosorbide dinitrate Isodinit p.o. Tab. 10 mg
Isosorbide mononitrate Olicard p.o. Tab. 40 mg, 60 mg

Pentaerythrityl Pentalong p.o. Tab. 20 mg, 50 mg

tetranitrate
Molsidomin Corvasal p.o. Tab. 2 mg
IV Vials 2 mg/l ml
Ivabradin Bixebra p.o. Tab. 5 mg, 7,5 mg

Ranolazine Ranexa p.o. Tab. 375 mg, 500 mg,

750 mg

PRACTICAL APPLICATIONS OF THE ANTIARRHYTHMIC DRUGS

Antiarrhythmics are drugs which depress the myocardial automatism, conductance and
excitability, administered in the prophylaxis and treatment of cardiac arrhythmias.

CLASSIFICATION
I. Sodium channel blockers
• I.A prolong repolarization: QUINIDINE, PROCAINAMIDE, DISOPYRAMIDE
• I.B shorten repolarization: LIDOCAINE, TOCAINIDE, MEXILETINE, PHENYTOIN
• I.C little effect on repolarization: FLECAINIDE, PROPAFENONE, MORICIZINE
II. Beta blockers: PROPRANOLOL, ESMOLOL, METOPROLOL, ATENOLOL
III. Potassium channel blockers : AMIODARONE, SOTALOL, BRETYLIUM
IV. Calcium channel blockers: VERAPAMIL, DILTIAZEM
V. Antiarrhythmics that work by other or unknown mechanism: ADENOSINE, DIGOXIN

GENERAL PRINCIPLES OF ADMINISTRATION

1. The antiarrhtythmic should be prescribed only after the arrhythmia was proven on the
EKG/Holter and the risk is superior compared to the side effects of the drug. All
antiarrhythmics have the paradoxal proarrhythmic effect.
2. Before starting the treatment, the patient’s heart function should be evaluated, the
favouring factors for arrhythmias treated (hypokalemia, hypomagnesemia) and
arrhythmogenic drugs administration should be stopped (sympathomimetics, Miofilin,
tricyclic antidepressants).
3. The dose should be individualised, according to the EKG and the response to the
treatment.
4. Most of the antiarrhythmics have a negative inotropic effect and should not be given in
heart failure. Exceptions: Amiodarone, Lidocaine, beta blockers.
5. The pharmacological conversion to sinus rhythm in recurrent atrial fibrillation can be
made outside the hospital by administering a single dose of Propafenone or Flecainide
(„pill-in-the-pocket”).
6. In atrial fibrillation, besides the antiarrhythmic, an anticoagulant treatment should be
administered to prevent a stroke or AMI.

THE EMERGENCY TREATMENT IN ATRIAL FIBRILLATION

• WITH HEART FAILURE

• Amiodarone IV 150-300 mg. If no response:
 • Digoxin IV 0.25 mg every 2 hours until reaching the dose of 1.5 mg
• WITHOUT HEART FAILURE
• Beta blocker IV: Esmolol 0.5 mg/kg in one min. => 0.05-0.2 mg/kg/min or
Metoprolol 2.5-5 mg in 2 min. or Propranolol 0.15 mg/kg or
• Verapamil IV 0.075-0.15 mg/kg in 2 min or Diltiazem IV 0.25 mg/kg in 2 min
=> 5-15 mg/h

THE EMERGENCY TREATMENT IN VENTRICULAR TACHYCARDIA

• IN HEMODYNAMICALLY STABLE PATIENT

• First line: Amiodarone
• Second line: Lidocaine IV 1-2 mg/kg or infusion 2-4 mg/min
• Potassium and magnesium
• IN HEMODYNAMICALLY UNSTABLE PATIENT
• Short IV anesthesia and cardioversion
• In cardiorespiratory arrest: cardiopulmonary resuscitation

II. PRACTICAL PART

1. Write a medical prescription to a patient with ischemic cardiopathy. Effort induced
angina pectoris.
 PRACTICAL APPLICATIONS OF THE BLOOD MEDICATION

I. THEORETICAL PART

ANTIANEMIA AGENTS

GENERAL PRINCIPLES OF ADMINISTRATION

1. Oral iron preparations are the treatment of choice for iron deficiency anemia,
administered for at least 6 months.
2. The average dose for the treatment of iron-deficiency anemia is 2-3 mg iron/kg/day,
divided into three equal portions. Vitamin C administered at the same time increases the
iron absorption.
3. The effectiveness of iron therapy is evaluated by tracking the reticulocyte count
(increases after 4-7 days) and the rise of hemoglobin (2 g/dl) or hematocrit.
4. The creation of iron stores requires many months of oral therapy.
5. If the response to oral iron therapy is inadequate, the diagnosis must be reconsidered.
6. If oral iron therapy fails (because of malabsorption or severe intolerance), parenteral
iron administration (IV or IM) may be an alternative.
7. Parenteral iron therapy can cause hypersensitivity, including anaphylactic shock
reactions, which may be fatal despite treatment. Always use a test dose of 25 mg of iron
before parenteral iron administration. If hypersensitivity symptoms occurs, parenteral
iron therapy must be abandoned.
8. The required dose of iron for parenteral administration is calculated through the
Ganzoni formula:

Iron req. (mg) = Body weight (kg) x (target Hb – current Hb) x 2.4 + Iron stores (mg)

Iron stores
Children < 35 kg = 15 mg/kg
Women = 500 mg
Men = 700 – 900 mg
Normal Hb
Women = 11 - 15 g/100 ml
Men = 13 – 16 g/100 ml

9. Vitamin B12 is indicated in megaloblastic anemia, intramuscular or subcutaneous.

10. The administration of Vitamin B12:

2 vials of 50 mcg/day for 2 weeks, continued with

2 vials of 50 mcg/week for 1 month, continued with
2 vials of 50 mcg/month for the whole life

11. Folic acid can be associated in megaloblastic anemia, 3 dj./day.

Generic drug Brand name Route of Pharmaceutical dosage form

administration
Ferrous sulphate Ferrogradumet p.o. Tab with 105 mg Fe2+
Ferrous Ferronat p.o. Suspension 3% with 45 mg Fe2+/5mL
fumarate
 Ferrous Ascofer p.o. Tab 40 mg Fe2+ + 100 mg Vitamin C
gluconate
Iron sucrose Venofer IV Vials 100 mg/5 ml
Cyanocobalamin Vitamin B12 IM, SC Vial 50 μg/mL, 1000 μg/mL
Folic acid Acifol p.o. Dj 5 mg
Erythropoetin Eprex IV, SC Vial 2 000, 4 000 or 10 000 UI/mL

ANTITHROMBOTICS

GENERAL PRINCIPLES OF ADMINISTRATION

1. The parenteral (IV, SC) dose of unfractionated heparin should be calculated according
to the aPTT, which should be maintained at levels of 1.5-2.5 times higher than normal.
2. The treatment with heparin should never be stopped suddenly, because of the
hypercoagulation risk.
3. Low molecular weight heparins are administered always SC, once or twice daily. There
is no need for aPTT monitoring.
4. Antivitamin K anticoagulants are administred orally, ½-1 tablet/day, according to the
INR value (should be maintained between 2-3). The duration of treatment can be for 4-
6 weeks in patients with low risk (young adults), for 6 months in those with medium
risk (AMI, heart failure, venous thrombosis) and for life in case of high risk patients
(elderly, chronic atrial fibrillation, cancer).
5. During the treatment with antivitamin K drugs, surgical procedures are forbidden.
6. The treatment with fibrinolytics should be initiated as soon as possible after the ischemic
event, for a short period of time (maximum 2-3 days, according to the type of drug) and
only if thrombin time checking is possible.
7. 250 mg of Hydrocortisone hemisuccinate should be administered before starting the
Streptokinase treatment, to prevent an allergic reaction.

Generic drug Brand name Route of Pharmaceutical dosage form

administration
Unfractionated Heparine IV Vial 5 ml, 5000 IU/ml; Initial 50
heparin sodique IU/Kg bolus, then 20 IU/Kg/h
panpharma according to APTT
Heparina IV Vial 1 ml, 5000 IU/ml; Initial 10,000
IU then 5000-10,000 IU every 4-6 h
Lioton gel local Tube 100 g, 1000 IU/g, apply 3x1 /day
AntiflebiticMK local Tube 25 g, 45 g, 50,000 IU heparin +
Gel, Alle gel 1g diclofenac /100 g; apply 3x1 day
Hepatrombin local Tube 40 g with 50,000IU/100 g or
30,000 IU/100 g; apply 3x1/day
Calciparine SC Vial 1 ml, 0.5 ml with 25,000 IU/ml ;
prefilled syringe of 5000 IU (0.2 ml).
SC 250 IU/kg every 12 h
Enoxaparin Clexane SC Prefilled syringe with 20 mg (2000 IU
anti-Xa)/0.2 ml, 40 mg (4000 IU anti-
Xa)/0.4 ml, 60 mg (6000 IU anti-
Xa)/0.6 ml; 2000 IU anti-Xa every 12
h or 4000 IUanti-Xa every 24 h.
Dalteparin Fragmin SC Prefilled syringe with 10,000 IU anti-
Xa/0,4 ml; 10,000 IU anti-Xa/ml;
 12,500 IU anti-Xa/0,5 ml; 18,000 IU
anti-Xa/0,72 ml; 2,500 IU anti-Xa/0.2
ml; 25,000 IU anti-Xa/ml; 5000 IU
anti-Xa/0.2 ml; 7500 IU anti-Xa/0.3
ml; 15,000 IU anti-Xa/0.6 ml
200 IU anti-Xa/kg every 12 h or 24 h.
Nadroparin Fraxiparine SC Prefilled syringe with 2850 IU anti-
Xa/0.3 ml; 3800 IU anti-Xa/0.4
ml; 5700 IU anti-Xa/0.6 ml; 7600 IU
anti-Xa/0.8 ml; 9500 IUanti-Xa/1 ml
38 IU anti-Xa/kg every 12 h.
Reviparin Clivarine SC Prefilled syringe with 1432 IU anti –
Xa/0.25 ml; 3436 IU anti – Xa/0.60 ml
One syringe of 0.25 ml or 0.6 ml every
24 h.
Tinzaparin Innohep SC Prefilled syringe with 3500 IU anti-
Xa/0.35 ml; 4500 IU anti-Xa/0.45 ml
175 IU anti-Xa/kg every 24 h.
Fondaparinux Arixtra SC Prefilled syringe with 2.5 mg/1 ml
2.5 mg/day
Lepirudin Refludan IV Vial 20 mg; initial 0.4 mg/kg in bolus
then 0.15 mg/kg IV cont. 2-10 days
Bivalirudin Angiox IV Vial 250 mg; initial 0.75 mg/kg in
bolus then 1.75 mg/kg and h IV cont.,
maximum 4 h
Acenocumarol Sintrom p.o. Tab 4 mg; 1-8 mg/day
Trombostop p.o. Tab 2 mg; 1-8 mg/day
Warfarin Coumadin p.o. Tab 2.5 mg, 3 mg, 5 mg; 2-10 mg/day

Streptokinase Streptase IV drip Vials 250,000 IU, 750,000 IU,

1,500,000 IU; initial 250,000 IU in IV
DRIP for 30 min, then 100,000 IU/h
Alteplase Actilyse IV, IV drip Vials 50 mg; 15 mg IV in bolus then
50 mg in IV drip 30 min, then 35 mg
in IV drip 60 min until max. 100 mg
Reteplase Rapilysin IV, IV drip Vials 10 IU; 10 IU IV bolus, wait 30
min then 10 IU in the second bolus
Tenecteplase Metalyse IV Vials 8000 IU; one bolus of 100 IU/kg

Aspirin Aspenter, p.o. Tab. 75 mg, 150 mg; 75-150 mg/day,

Santepirin, after lunch
Ticlopidin Ticlodin p.o. Tab. 250 mg; 2x1 tab./day, after meal
Clopidogrel Clopidogrel p.o. Tab. 75 mg; 1 tab./day
Dipiridamol Dipiridamol p.o., IV Tab. 25 mg, 75 mg, vials 10 mg/2 ml;
75-100 mg/day 4 times/day between
meals; IV for CV stress test
Abciximab ReoPro IV, IV drip Vials 5 ml with 2 mg/ml; 0.25 mg/kg
IV bolus, then IV drip 0.125
mg/kg/min for 12 h
Tirofiban Aggrastat IV IV drip Vials 50 ml with 0.25 mg/ml; bolus IV
0.4 mg/kg/min for 30 min then IV drip
0.1 mg/kg/min
Eptifibatide Integrilin IV, IV drip Vials 2 mg/ml, 0.75 mg/ml; initial
bolus of 0.18 mg/kg then 0.002
mg/kg/min for 72 h

II. PRACTICAL PART

1. Write a medical prescription to a 45 year old male patient with iron defficiency anemia,
body weight of 80 kg and Hgb = 10 g/dl.
2. Calculate the necessary iron dose and specify the iron preparation and route of
administration for a 50 year old female patient with iron defficiency anemia, body
weight of 90 kg, Hgb = 8 g/dl and intolerance to oral iron therapy.
3. Write a medical prescription to a 60 year old patient with megaloblastic anemia and
gastric cancer, after total gastrectomy, in the first 2 weeks of treatment.
4. Write a medical prescription to a patient with chronic atrial fibrillation.