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«KARAGNDA MEDICAL UNIVERSITY»

DEPARTMENT OF CLINICAL PHARMACOLOGY AND EVIDENCE-BASED MEDICINE

GENERAL PHARMACOLOGY

LECTURER: ASSISTANT PROFESSOR DR.МANOJ KUMAR SHARMA

 The purpose of the lecture
By the end of the discipline, students should be able to analyze and understand:-
 What is Pharmacology?
 The basic concepts of Pharmacokinetics like:
 A- Absorption:- Route of Drug Administration, Bioavailability,
Plasma concentration, AUC etc
 D- Distribution:- Volume of Distribution, Redistribution, Placental
and Blood Brain Barrier.
 M- Metabolism:- Purpose, Phases, Sites of Metabolism
 E- Excretion of the drugs.
 The basic concepts of Pharmacodynamics like:
 Major mechanisms of Drug action
 Receptor-Ligand Systems
 Adverse Drug Effects
 Tolerance, Intolerance Tachyphylaxis, Therapeutic index, Synergism,
Antagonism etc.
 Science of Drugs
What is drug?
Drug also called a medication or medicine, is a chemical
substance used to treat, cure, prevent, or diagnose a
disease or to promote well being.
To produce the effect, The drug must Reach to right
place – i.e at the Site of action
In appropriate concentration and
Within appropriate time.
And once the drug reaches at the site it produces its effect,
So there are two aspects:
1.Movement of the drug and
2.Effects of the Drug
 Pharmacology
is divided into two branches
Movement of the drug Effect of the Drug

What the body does to What the drug does to the

the drug: body:
A  Absorption Action/effects of the drug
D  Distribution Mechanism of action
M  Metabolism Adverse/Toxic/Side effects
E  Excretion of the Drugs
Four pharmacokinetic properties determine
the onset, intensity, and duration of drug
 Pharmacokinetics has 4 components
Absorption: Entry of the drug into
systemic circulation.
Distribution: Movement of the drug from
systemic circulation to various tissues and
organs.
Metabolism: Biochemical transformation
of the drug into metabolites to prepare its
excretion
Excretion: Removal of the drug and its
metabolites from the body.
First and second components are related
to the entry of the drug into the body,
whereas 3rd and 4th components are
related to elimination of the drug from
the body
It is the process by which drug reaches to
the systemic circulation.
Drug in Plasma
Rate and extent of absorption of different
drugs is different and thus influences the Dose administered

Bioavailability of the drug: Drugs

which are absorbed more have higher
Bioavailability and appropriate rate of
absorption ensures therapeutically
relevant drug concentration for desired
Drug action.

Bioavailability: is defined as
the fraction of the administered
drug that reaches to the systemic
circulation in it’s unchanged form.
Rate and extent of absorption and thus Bioavailability of the Drug may be
affected by:-
•Route of Administeration
– IV route is the exception where drug instead of absorption is directly injected into the
circulation and doesn’t encounters any barriers.
•Factors dependent on Drug properties:
– Aqueous solubility of the Drug, Size of the Drug particle, Lipophilicity, Acidic or Basic
nature of the drug
•Factors dependent on the state of the recipient’s body:
– pH of the medium at site (Stomach or Intestine) from where drug is being absorbed
– Area and Vascularity of absorbing surface
– The physiological state of the body.
– First Pass metabolism.
So important point to note is that as rate and extent of absorption is different
for different drugs but it may change for the same drug if any of the above
factors changes. Accordingly you may see the variations in Bioavailabilities of
different drugs but Bioavailability of the same Drug may be different under
different conditions.
Important Points:-
To reach into systemic circulation Drugs have to cross the plasma membrane
Plasma membranes are Lipid bilayer
Lipid soluble or Lipophilic drugs can cross the membranes thus has higher
Bioavailability
Water soluble drugs cannot cross the membranes thus are poorly absorbed and have
lower Bioavailability.
Drug in ionized form is water soluble
Drug in un-ionized form is lipid soluble

Points to remember:-
Lipid soluble or Non-polar or un-ionized or Non-ionized
Drugs  can cross the cell membrane easily  Better
absorption  Higher Bioavailability
Lipid insoluble or Water soluble or ionized or polar or
charged molecules  cannot cross the cell Membrane  Poor
absorption  Low Bioavailability
Topical: Deep Tissues Arterial Supply: Enteral Paranteral
This refers to
•Intravenous (IV)
external •Intra-articular •Close intra- •Oral
application of arterial injection is •Intramuscular (IM)
the drug to used for contrast •Rectal •Subcutaneous
the surface media in •Sublingual
(skin, GI angiography.
mucosa, •Transdermal
respiratory If the drug is highly lipophilic and •Nasal
tract, urethra absorbable local route may act
etc.) for •Inhalational
localized as systemic, On the other hand if •Intradermal
action. drug is poorly absorbed enteral injection The drug is
route may be used for local injected into the skin
application for the drugs raising a bleb (e.g.
BCG Vaccine
Time until effect
intravenous 30-60 seconds
intraosseous 30-60 seconds
endotracheal 2-3 minutes
inhalation 2-3 minutes
sublingual 3-5 minutes
intramuscular 10-20 minutes
subcutaneous 15-30 minutes
rectal 5-30 minutes
ingestion 30-90 minutes
transdermal (topical) variable (minutes
to hours)
Effect of pH:-
Most of the Drugs are weak electrolytes (either weak acids or weak base)
and their degree of ionization depends on the pH of the medium, it means
that weak electrolytes in solutions exist in two forms – Ionized and Non-
ionized and the relative conc. Of these drugs depends on the pH of the
medium.
If pH of the medium is equal to pKa of the drug, then drug is 50%
ionized and 50% un-ionized.
If the pH of the medium is more than pKa (medium becomes alkaline).
• For acidic drugs, ionized form increases and non-ionized form
decreases.
• For basic drugs, un-ionized form increases and ionized form
decreases
If the pH of the medium is less than pKa, opposite happens, i.e. acidic
drugs will be in more un-ionized form and basic drugs be more ionized.
•Acidic Drugs are absorbed in acidic medium
Effect of pH:-

Weak Acids Weak Bases

Barbiturates e.g. phenobarbitone Morphine, Atropine
NSAIDs e.g. aspirin, diclofenac • Amphetamines, Quinine
Methotrexate, Sulfonamides Penicillins • Hyoscine
Effect of pH:-
Most of the Drugs are weak electrolytes (either weak acids or weak base)
and their degree of ionization depends on the pH of the medium, it means
that weak electrolytes in solutions exist in two forms – Ionized and Non-
ionized and the relative conc. Of these drugs depends on the pH of the
medium.
If pH of the medium is equal to pKa, then drug is 50% ionized and
50% un-ionized.
If the pH of the medium is more than pKa (medium becomes alkaline).
• For acidic drugs, ionized form increases and non-ionized form
decreases.
• For basic drugs, un-ionized form increases and ionized form
decreases
If the pH of the medium is less than pKa, opposite happens, i.e. acidic
drugs will be in more un-ionized form and basic drugs be more ionized.
•Acidic Drugs are absorbed in acidic medium
•Basic Drugs are absorbed in Basic medium
 First pass effect
The first pass effect (also known as first-
pass metabolism or presystemic
metabolism) is the fraction of drug lost during
the process of absorption which is generally
related to the liver and gut wall.
First pass metabolism may occur
•in the liver (for propranolol,
lidocaine, clomethiazole, and GTN) or
•in the gut (for benzylpenicillin and insulin).
Drugs with High First pass Metabolism
Nitrates - Nitrates
Have - Hydrocortisone
Large - Lignocaine
Pre - Propranolol
Systemic - Salbutamol
Metabolism - Morphine
A.Blood flow
• The rate of blood flow to the tissues and organs varies widely and so is
the degree of Distribution
• Rate of blood flow is more to richly vascularized organs like Brain, Liver
and Kidneys than to Skeletal Muscles and even lower to Adipose tissues,
Skin and Viscra
• Highly lipid-soluble drugs given by intravenous or inhalation methods are
initially distributed to organs with high blood flow. Later, less vascular
but more bulky tissues (such as muscle and fat) take up the drug—
plasma concentration falls and the drug is withdrawn from these sites.
This phenomenon is called Redistribution
• For example, the anaesthetic action of thiopentone is terminated in a
few minutes due to redistribution.
B.Capillary permeability:
 The permeability of capillary endothelium varies in
different organs due to structural variations in the
endothelium of blood capillaries.
 Endothelium of blood capillaries to the brain have tight
junctions and there are no slit junctions. (Blood
Brain Barrier BBB) so only highly lipid soluble
drugs can penetrate into the CNS.
 Similarly many drugs cannot cross the Placental
Barrier. But Placental Barrier is not as strong barrier
as that of BBB.
C. Drug Binding:-
1. Plasma Protein Binding: Some drugs have the capacity to bind with
certain types of proteins that are carried in blood plasma.
 Common blood proteins that drugs bind to are human serum albumin,
lipoprotein, glycoprotein, and α, β‚ and γ globulins.
 Only free or unbound drug undergoes distribution and metabolism and is
pharmacologically active. To Albumin TO α1-acid
 Drugs that are bound to plasma proteins glycoprotein
therefore act as a reservoir of the drug. Barbiturates β-blockers
 Drugs that are bound to plasma proteins Benzodiazepines Bupivacaine
therefore act as a reservoir of the drug. NSAIDs Lidocaine
 Valproic acid Disopyramide
Drugs with high degree of PPB:
Phenytoin Imipramine
Results in longer duration of action. Penicillins Methadone
Are difficult to be removed by dialysis. Sulfonamides Prazosin
Have low volume of distribution and tends to Tetracyclines Quinidine
stay in the systemic circulation Tolbutamide Verapamil
Achieves high plasma concentration Warfarin
 Skeletal muscle, heart — digoxin, emetine
C. Drug Binding:- (bound to muscle proteins).
2. Binding to tissue proteins:- Liver — chloroquine, tetracyclines,
emetine, digoxin.
• Many drugs accumulate in tissues, Kidney — digoxin, chloroquine, emetine.
leading to higher concentrations in Thyroid — iodine.
tissues than in interstitial fluid and blood. Brain — chlorpromazine, acetazolamide,
• Drugs may accumulate in tissues because isoniazid.
of Retina — chloroquine (bound to
nucleoproteins).
 binding to lipids, proteins, or Iris — ephedrine, atropine (bound to
nucleic acids. melanin).
 Active transport into tissues. Bone and teeth — tetracyclines, heavy
metals (bound to mucopolysaccharides of
• Tissue reservoirs may serve as a major connective tissue), bisphosphonates
source of the drug and prolong its actions (bound to hydroxyapatite).
or cause local drug toxicity. (For Adipose tissue — thiopentone, ether,
example, acrolein, the metabolite of minocycline, phenoxybenzamine, DDT
cyclophosphamide, can cause dissolve in neutral fat due to high lipid-
hemorrhagic cystitis because it solubility; remain stored due to poor blood
accumulates in the bladder.) supply of fat.
D. Lipophilicity
•The chemical nature of a drug strongly influences its ability to cross cell
membranes. Lipophilic drugs readily move across most biologic membranes
So Lipophillic Drugs are distributed throughout the entire body fluids and
have high volume of Distribution

The extent of Distribution is determined by

a hypothetical parameter:-

Volume of distribution (Vd)

• Volume of distribution (Vd) is the volume that would be
required to contain the administered dose if that dose was evenly
distributed at the concentration measured in plasma.

Although Vd has no physiologic or physical basis, Value of Vd gives an idea

Drug will stay in which water compartment of the body:
 Drugs with high molecular weight or having high PPB can not leave vascular
compartment and will be dissolved only in Plasma fluids i.e in 4L
So these drugs will have low Vd of approx. 4L ( 0.057 L/Kg for average body)
 Drugs with low mol. Weight and hydrophilic can pass through slit junctions of
vascular endothelium but being hydrophilic can not cross cell membranes. So these
drugs will be distributed in Plasma volume 4L + Interstitial Fluid 10L = 14L
So Vd of these drugs approximate 14L (0.2 L/Kg)
 Highly Lipophillic Drugs can cross slit junctions of Vascular Endothelium, being
lipophilic can penetrate the cell membrane also. So these drugs will be distributed in
Plasma Fluid 4L + Interstitial Fluid 10L + Intracellular Fluid 28 L = 42L (Total Body
Fluid of average person
So Vd of these drugs approximates 42L (0.6 L/Kg)
 If Drug is highly lipophilic and has high binding capability to tissue components
then These type of Drugs tends to accumulate in the tissues or organs and has very
high Vd.
So Vd of these drugs is more than 42L and for some drugs it is even in thousands
litres. For eg. Chloroquine has Vd of 15000 Litres (200 L/Kg to 250 L/Kg)
 Irreversible modification of drugs into metabolites is called
Metabolism
Metabolism
A B
Purpose of Metabolism:-
Metabolisms prepares the drug for excretion by making it
more polar that is water soluble so that it could not be
reabsorbed from renal tubules and is excreted out in the urine
In actual sense metabolism eliminates the drug because after
metabolism the drug is transformed into metabolite which is
no more drug and is another molecule
Metabolism of the drug may lead to anyone of the following 3
consequences:
1.Inactivation: Most of the active Drugs become inactive or less active after
metabolism
2.Active drug is metabolised into active metabolite
3.Inactive Drug is converted into active metabolite
Metabolism
A ----------------------------> B
Active drug is metabolised Inactive drug is metabolised
into active metabolite into active metabolite
Active Drug  Active Metabolite Prodrugs Active Metabolites

Morphine  Morphine-6 glucuronide All ACE inhibitors (except
Cefotaxime  Desacetyl Captopril and Lisinopril
. cefotaxime Prefer Prednisone, Proguanil
Allopurinol  Alloxanthine Proton Pump Inhibitors
Procainamide  N-acetyl
Doing Dipivefrine
. procainamide
Diazepam  Desmethyl-diazepam M Mercaptopurine,
. Oxazepam Methyldopa, Minoxidil
Digitoxin  Digoxin D Levodopa
lmipramine  Desipramine In Irinotecan
Amitriptyline  Nortriptyline
Clinical Cyclophoshamide,
Codeine  Morphine Clopidogril, Carbimazole
Subjects Sulfasalazine
Biotransformation reactions can be classified into:
(a) Nonsynthetic/Phase I/Functionalization reactions:
a functional group is generated or exposed—metabolite may be
active or inactive.
Oxidation: It is the most important Drug Metabolising Reaction.
More than 100 cytochrome P-450 isoenzymes differing in their affinity for
various substrates (drugs), have been identified.
Reduction: Chloramphenicol and Warfarin
Hydrolysis: procaine, lidocaine, procainamide, aspirin,
indomethacin
Cyclization: proguanil
Decyclization: barbiturates, phenytoin
Biotransformation reactions can be classified into:
(b) Synthetic/Conjugation/ Phase II reactions:
An endogenous radical is conjugated to the drug—metabolite is mostly inactive;
Exceptions: e.g. glucuronide conjugate of morphine and sulfate conjugate of
minoxidil are active.
•Glucuronide conjugation: chloramphenicol, aspirin, paracetamol, diazepam,
lorazepam, morphine, metronidazole
•Acetylation: sulfonamides, isoniazid, PAS, dapsone, hydralazine, clonazepam,
procainamide
•Methylation: drenaline, histamine, nicotinic acid, methyldopa, captopril,
mercaptopurine.
Sulfate conjugation: chloramphenicol, methyldopa
Glycine conjugation:
Glutathione conjugation: paracetamol
Microsomal: These are located on smooth endoplasmic reticulum
(a system of microtubules inside the cell), primarily in liver, also in
kidney, intestinal mucosa and lungs.
Involves mostly Phase-I reactions plus glucuronide conjugation of
Phase-II
Can be induced or inhibited by drugs, diet or
other agents.
Non-Microsomal enzymes: These are present in the cytoplasm and
mitochondria of hepatic cells as well as in other tissues including
plasma.
All Phase-II reactions except glucuronidation plus some of the Phase-I
reactions like many hydrolytic and some oxidations / reductions
Not inducible
Microsomal: These are located on smooth endoplasmic reticulum
(a system of microtubules inside the cell), primarily in liver, also in
kidney, intestinal mucosa and lungs.
Involves mostly Phase-I reactions plus glucuronide conjugation of
Phase-II
Can be induced or inhibited by drugs, diet or
other agents.
Non-Microsomal enzymes: These are present in the cytoplasm and
mitochondria of hepatic cells as well as in other tissues including
plasma.
All Phase-II reactions except glucuronidation plus some of the Phase-I
reactions like many hydrolytic and some oxidations / reductions
Not inducible
CYT-P450 Drugs metabolized Inhibitors Inducers
Isozyme
CYP3A4 Terfenadine, Astemizole Cisapride, Losartan Macrolides, Tri-azole Rifampin, Barbiturates,
CYP3A5 Carbamazepine, Hydrocortisone Paracetamol, antifungals Phenytoin, Carbamazepine,
Diazepam Buspirone, Mifepristone Ritonavir, CCBs, TCA Glucocorticoids, Nevirapine
saquinavir, Simvastatin, Quinidine, Verapamil, Grape Fruit Juice
Lidocaine, Dapsone, Nevirapine
CYP2D6 Metoprolol, Debrisoquine, Nebivolol, Qunidine, Fluoxetine Barbiturates, Rifampin
Amitryptyline, Clomipramine, Fluoxetine, Paroxetine
Paroxetine, Venlafaxine, Haloperidol, Clozapine,
Risperidone, Codeine, Propafenone, Flecainide
CYP2C8 Phenytoin, Carbamazepine, Warfarin, Fluvoxamine, Barbiturates,
CYP2C9 Tolbutamide, Repaglinide, Pioglitazone, Fluconazole, Gemfibrozil, Carbamazepine, Rifampin
Diclofenac, Ibuprofem, Losartan Trimethoprim
CYP2C19 Omeprazole, Lansoprazole, Amitriptyline, Omeprazole, Fluconazole Carbamazepine, Rifampin
Citalopram, Phenytoin, Diazepam, Propranolol,
Clopidogrel
CYP1A1 Theophylline, Caffeine, Paracetamol, Warfarin, Fluvoxamine, Fluoxetine Polycyclic hydrocarbons,
CYP1A2 Carbamazepine Cigarette smoke Rifampin,
Carbamazepine
CYP2E1 Alcohol, Halothane, Paracetamol* Disulfiram, Fomepizole Chronic alcoholism,
Isoniazid
CYP2B6 Efavirenz, Nevirapine, Cyclophosphamide, Paroxetine, Sertraline, Phenobarbitone,
Methadone, Sertraline, Clopidogrel Clopidogrel Cyclophosphamide
This refers to inactivation of the drug in
the body fluids by spontaneous
molecular rearrangement without the
agency of any enzyme,
e.g. Atracurium.
 Excretion
Excretion is the removal of systemically absorbed drugs and
their metabolites
Drugs and their Metabolites are excreted in:-
Urine: Most of the drugs are excreted by Renal Excretion
 Renal Excretion = Glomerular Filteration + Tubular Secretion
+Tubular Re-absorption
Feaces:- Unabsorbed Drug + Active transport of the drug by liver into
bile
Exhaled air:- Gases and volatile liquids (general anaesthetics,
alcohol) are eliminated by lungs
Saliva and Sweat:- Lithium, KI, Rifampicin, Nitro-imidazoles are
secreted in Saliva
Breast Milk: This excretion is not important for the mother but may
affect the Breast fed infant. It is advisable to administer drug to the
Lactating woman only when essntial
Drug Elimination is the result of combined
activity of Metabolism accompanied by the
excretion
The knowledge of Kinetics of Elimination is very
important to design:-
The Dosage regime of the Drug
Frequency of the Drug administration
Making required changes in Dose and frequency of the
Drug
To understand Kinetics of Elimination we must have clear concept of
 Bioavailability  Plasma Half Life of Drug
 Plasma Concentration  First order Elimination
 Volume of Distribution Kinetics
 Rate of Elimination  Second order Elimination
 Clearance Kinetics

We already have discussed Bioavailability, Plasma

Concentration and Volume of Distribution
Rate of Elimination:- It is the amount of drug eliminated per unit time
and is measured as mg/second or minute or hour.

Clearance (CL):- is the theoretical volume of the plasma from which the
given drug has been completely removed per unit time.
Mathematically
Clearance = Rate of Elimination/Plasma concentration

Plasma Half Life of Drug (t1/2):- is the time by which the plasma
concentration of the drug is reduced to half of it’s original Plasma
concentration.
It is calculated as:
t1/2 = 0.693 x Vd / CL
Some important points to note regarding Drug
elimination by First Order Kinetics:-
Approx. 93.75 % of the drug is eliminated after the completion
of 4 half lives of any drug, what so ever high may be the initial
concentration of the drug
 So we can say that if a single dose of drug is administered, it would
achieve a certain peak plasma concentration it would almost
completely be eliminated in 4 to 5 half lives.
Some important points to note regarding Drug
elimination by First Order Kinetics:-
If constant Dose of a drug is administered before the expiry of 4
half lives,
 it would achieve higher peak plasma concentration as some amount
of drug will still be present in the body.
 And on repeated administration of the same dose at same interval
of time a new peak concentration would be achieved and every time
this new peak is greater than that achieved by it’s previous dose.
Some important points to note regarding Drug
elimination by First Order Kinetics:-
 So with every repeated dose peak plasma concentration keeps on
increasing, but you should not forget that this is first order
elimination kinetics in which RoE increases with increase in Cp.
 So after few repeated doses a time will come when RoE balances
the amount of dose administered and the steady state is achieved
Some important points to note regarding Drug
elimination by First Order Kinetics:-
Important to note,
 if dose is increased higher Cpss is achieved
 If total amount of drug per day is same but only frequency of dose is
increased magnitude of fluctuations will be less.
 Peak of fluctuation is closer to the Toxic dose and trough of
fluctuation is closer to the sub-therapeutic conc.\
 Therefore Dose interval of the drug is so adjusted that it should be
convenient and at the same time peak of fluctuation should not
exceed toxic level and trough should not be below therapeutic level.
 Two Dose Strategy
Loading Dose and Maintenance Dose
• As we know that Target level Therapeutic Concentration is
achieved in 4 to 5 half lives
• There may be two types of conditions of disease:
• First condition is that we can wait for the drug to achieve the
target level Plasma concentration after 4 to 5 t1/2
• may be as the disease condition is not so severe
• or t1/2 is short due to which Therapeutic concentration is achieved in
short duration
• 2nd condition may be opposite of the first where delay in achieving the
target level Cpss can worsen the disease condition. So under this situation
and for the drugs which have longer t1/2 and high value of Vd, Drug
dosage regime needs Two Dose Strategy:-->
 Two Dose Strategy
Loading Dose and Maintenance Dose
• First a large dose (loading dose) is
administered to attain the steady state quickly
and
• later on, to maintain the plasma concentration
smaller dose is given (maintenance dose).
• Loading Dose = Vd x Target Plasma concentration
• Maintenance Dose = CL x Target Plasma concentration
 Therapeutic Drug Monitoring (TDM)

1It is required for those drugs which has wide variations in pharmacokinetic
parameters with low therapeutic index
 Literature

1. Essentials of Medical Pharmacology – 8th Edition, by KD Tripathi

2. Review of Pharmacology – 14th Edition, by Gobind Rai Garg and Sparsh
Gupta
3. Goodman & Gillman’s – The Pharmacological Basis of Therapeutics
4. Lippincott Illustrated Reviews – Pharmacology – Seventh Edition
 Feedback Questions

1. What are two branches of Pharmacology?

2. Name the 4 components of Pharmacokinetics
3. What is Bioavailability and what are the factors that affect Bioavailability
4. Explain Drug Binding to Plasma Proteins and to tissues components and the
consequences of PPB and Tissue Binding
5. Give the advantages and disadvantages of various routes of Drug administration.
6. What is the clinical significance of Volume of Distribution?
7. What are the two phases of Drug metabolism?
8. What is the clinical relevance of Microsomal enzymes and Non-microsomal
enzymes explain with suitable examples.
9. How microsomal enzyme inducers and inhibitors are responsible for Drug-drug
interactions. Give 5 examples of Microsomal Enzyme Inducers and Inhibitors
10. How change in plasma concentration affect Clearance, Rate of Elimination and
Plasma half life of the Drug in First order Elimination Kinetics and Zero order
Elimination Lkinetics
11. What is Two dose strategy and under what conditions and for which types of drugs
Loading dose is required? Explain with suitable example
12. What is Therapeutic Drug Monitoring and for which type of drugs TDM is
clinically relevant? Explain with suitable examples.
 Feedback Questions
One of the major indicator of drug elimination from the human body is:
a). Bioavailability
b). Volume of distribution
c). Bioequivalence
d) Plasma half life
e). Highest concentration in blood

Drug addicts upon termination of action a drug have heavy psychical,

neurological and somatic violations. What is the name of this symptom
complex?
A Abstinence syndrome
B Tachyphylaxis
C Sensitization
D Cumulation
E Tolerance
 Feedback Questions
For rapid relief of symptoms of anginal pain a patient takes nitroglycerine in
capsules. What is the most rational rout administration for this preparation?
A Sublingual
B Oral
C Rectal
D E Hypodermic
Answer to the doctor question, what is the name of the phenomenon, when at
the prolonged using of preparation its efficiency goes down?
A Adaptation (tolerance)
C Cumulation
D Addiction
E Tachyphylaxis
Apparent volume of distribution (Vd) of a drug exceeds total body fluid
volume, if a drug is:
(a) Sequestrated in body tissues
(b) Slowly eliminated from body
(c) Poorly soluble in plasma
 Feedback Questions
 All of the following statements regarding bioavailability of a drug are true
except:
A. It is a fraction of administered drug that reaches the systemic
circulation in unchanged form
B. Bioavailability of an orally administered drug can be calculated by
comparing the Area Under Curve after oral and intravenous
administration
C. Low oral bioavailability always and necessarily means poor absorption
D. Bioavailability can be determined from plasma concentration or
urinary excretion data.

 Answer to the doctor question, what is the name of the phenomenon,

when at the prolonged using of preparation its efficiency goes down?
A. Adaptation (tolerance)
B. Allergy
C. Cumulation
D. Addiction
E. Tachyphylaxis
 Feedback Questions
 In metabolism of xenobiotics, all of the following reactions occur in phase
one except?
A. (a) Oxidation
B. (b) Reduction
C. (c) Conjugation
D. (d) Hydrolysis

 Alkalinization of urine is required for decreasing the poisoning due to:

A. (a) Barbiturates
B. (b) Amphetamine
C. (c) Alcohol
D. (d) Morphine

 A highly ionized drug:

A. (a) Is excreted mainly by the kidney
B. (b) Can cross the placental barrier easily
C. (c) Is well absorbed from the intestine
D. (d) Accumulates in the cellular lipids
 Feedback Questions
Most variable absorption is seen with which route?
(a) Oral
(b) Intramscular
(c) Intravenous
(d) Per rectal

A drug X was administered by continuous IV infusion at the rate of 1.6 mg/min.

Clearance of drug X is 640 mL/min. If the half-life of the drug is 1.8 h, what would be the
concentration of drug after achieving steady state?
(a) 0.0025 mg/mL
(b) 0.004 mg/mL
(c) 3.25 mg/mL
(d) 1.22 mg/mL

Digoxin has a half-life of 40 hours. It helps to determine:

(a) Regimen for smooth discontinuation
(b) Need for loading dose in order to get immediate effect
(c) Regimen for maintenance dose
(d) Single dose will work for 40 hours
 Feedback Questions
 Which type of drug has the capability to penetrate through the blood brain
barrier?
A. lipids solubility
B. water solubility
C. strong protein bond
D. ionization state
E. long term of half- rearing
 Cytochrome P450 enzyme most commonly involved in drug metabolism is:
A. CYP 3A4
B. CYP 1AI
C. CYP 2E1
D. CYP 2D6

Which of the following is an enzyme inhibitor?

(a) Ketoconazole
(b) Rifampicin
(c) Tolbutamide
(d) Phenobarbitone
 Feedback Questions
 All of the following antiepileptics are microsomal enzyme inducers except
A. Valproate
B. Phenobarbitone
C. Phenytoin
D. Rifampicin

Which of the following is not an example of Phase II drug metabolic reaction:

(a) Glucuronidation
(b) Decyclization
(c) Methylation
(d) Acetylation

Which of the following statement is true about first order kinetics:

(a) Alcohol is eliminated from body by 1st order kinetic
(b) Constant concentration of drug eliminated in unit time
(c) Constant fraction of drug eliminated in unit time
(d) Half-life is dependent on plasma concentration
 Feedback Questions

A 30-year-old mother of 2 children weighing 60 kg was taking

combined oral contraceptive pill containing levonorgestrel 0.15
mg + ethinylestradiol 30 μg per day cyclically (3 weeks treatment
—1 week gap). She developed fever with cough and was
diagnosed as a case of pulmonary tuberculosis after sputum
smear examination. She was put on isoniazid (300 mg) + rifampin
(600 mg) + pyrazinamide (1.5 g) + ethambutol (1.0 g) daily for 2
months, followed by isoniazid (600 mg) + rifampin (600 mg) thrice
weekly. In the 3rd month she failed to have the usual withdrawal
bleeding during the gap period of contraceptive cycle. After 10
days her urinary pregnancy test was found to be positive.
(a) What could be the reason for failure of the oral
contraceptive?
(b) What precaution could have prevented the unwanted
pregnancy?
 Feedback Questions

A 20-year-old patient weighing 60 kg has to be prescribed an

antiepileptic drug (available as 200 and 400 mg tablets) for
generalized tonic-clonic seizures. The pharmacokinetic
parameters and therapeutic plasma concentration of the selected
drug are:
Target steady-state plasma concentration (Cpss) – 6 mg/L
Oral bioavailability (F) – 70%
Volume of distribution (V) – 1.4 L/kg
Clearance (CL) – 80 ml/hr/kg
Plasma half life (t½) – 15 hours
What should be the loading dose and the daily maintenance
dose of the drug for this patient?
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