Introduction

Question 1

Define pharmacology

Answer 1

Study of interactions of exogenously administered drugs with living system

Question 2

Define drug

Answer 2

Any substance that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient

Question 3

Pharmacotherapuetics

Answer 3

Application of pharmacological info with knowledge of disease for prevention mitigation and cure

Question 4

Clinical pharmacology

Answer 4

Scientific study of drugged in man

Question 5

Chemotherapy

Answer 5

Treatment of systemic infection/ malignancy with specific drugs that have selective toxicity

Question 6

Drugs divided into

Answer 6

Pharmacodynamic agents
Chemotherapeutic agents

Question 7

Pharmacology divided into

Answer 7

Pharmacodynamics - what drug does to the body
Pharmacokinetics - what body does to the drug

Question 8

Four major routes of drug administration

Answer 8

enteral
parentral
pulmonary
topical

Question 9

Commonly used routes:

Answer 9

Commonly used routes: oral(po), intravenous(iv), intramuscular(im), and subcutaneous(sc)

Question 10

Weak acids exist more in non-ionized form in

Answer 10

Weak acids exist more in non-ionized form in the stomach, more in ionized form in the intestine

Question 11

ion trapping

Answer 11

Non-ionized form of acidic drug which crosses the gastric mucosal membrane, reverts into ionized form(pH 7.0) and then slowly passes into ECF

Question 12

Bioavailability (F)

Answer 12

Bioavailability (F)is the term used to indicate the fraction of the administered dose reaching systemic circulation

Question 13

Rate of absorption must be at least …. times greater than rate of elimination to achieve meaningful plasma concentration

Answer 13

10

Question 14

Distribution of drugs-

Answer 14

Distribution of drugs-is the process of dissemination of drug molecules from the blood stream to body tissues and fluids

Question 15

Four basic patterns of drug distribution:

Answer 15

1) Drugs with relatively high molecular weight e.g. dextran are confined to plasma water
2) Drugs that can pass capillary wall but can not pass across cell membranes e.g mannitol
3) Drugs that can pass freely across cell membranes but do not have a special affinity for a specific tissue e.g. alcohol
4) Drugs that concentrate specifically in one or more tissues of the body e.g. chloroquine in the liver

Question 16

Apparent volume of distribution(Vd ) can be calculated by

Answer 16

Apparent volume of distribution(Vd ) can be calculated by dividing the administered dose with plasma concentration

Question 17

Vd implications

Answer 17

Drugs extensively bound to plasma proteins are largely restricted to vascular compartment and have low Vd values,e.g. warfarin(99% bound) has a Vd 0.15L/kg

Drugs sequestered in other tissues have values much greater than the total body water or body mass,e.g. chloroquine Vd approx. 13000L

Question 18

PPs that bind acidic drugs

PPs that bind basic drugs:

Answer 18

PPs that bind acidic drugs: albumins (mol. wt 66000);
PPs that bind basic drugs: alpha1 –acid glycoproteins

Question 19

Drug metabolism (biotransformation):

Answer 19

Drug metabolism (biotransformation): irreversible chemical alteration of the drug in the body to another compound(metabolite

Question 20

Biotransformation reactions are classified into two:

Answer 20

Biotransformation reactions are classified into two: phase I and phase II reactions

Question 21

phase 1

Answer 21

Phase I introduce or unmask functional groups(-OH, -NH2, -SH)

Reactions involve oxidation, reduction and hydrolysis

Question 22

phase 2

Answer 22

endogenous substrates such as glucuronic acid, sulphate, acetic acid or an amino acid combine with newly incorporated functional groups to form a highly polar conjugate

Question 23

microsomal enzymes

Answer 23

These are located on
smooth endoplasmic reticulum

monooxygenases, cytochrome P450, UGTs,
epoxide hydrolases

They catalyse most of the oxidations, reductions, hydrolysis and glucuronide conjugation.

Question 24

non microsomal enzymes

Answer 24

Present in the cytoplasm and mitochondria of hepatic cells as well as plasma. The
esterases, amidases, some flavoprotein oxidases and most conjugases are nonmicrosomal.

Reactions catalysed are:
Some oxidations and reductions, many hydrolytic reactions and all conjugations except glucuronidation.

Question 25

Microsomal drug oxidations require

Answer 25

cytochrome P450, P450 reductase, NADPH and molecular oxygen
Drug+O2 +NADPH+H+ =Drug-OH +H2O+NADP+

Question 26

Enzyme induction

Answer 26

process by which the expression and activity of an enzyme is increased in response to a specific stimulus, typically a molecule or compound that the enzyme is capable of metabolizing.

Question 27

consequences of inducers

Answer 27

results in accelerated metabolism of the inducer(autoinduction) and other co-administered drugs

decreased efficacy of drugs(e.g. failure of contraception with oral contraceptives);
tolerance development

Prodrug’s effect is increased with inducers

Question 28

Possible uses of enzyme induction:

Answer 28

Possible uses of enzyme induction:
Congenital nonhemolytic jaundice(due to deficient glucuronidation of bilirubin) ; phenobarbitone hastens clearance of bilirubin

Cushings syndrome; phenytoin reduces manifestations by enhancing degradation of adrenal steroids

Chronic poisoning; by faster metabolism of accumulated poisonous substance

Liver disease

Question 29

Enzyme inducers include

Answer 29

Enzyme inducers include barbiturates, carbamazepine, rifampin, phenytoin, etc.

Question 30

Enzyme inhibition: and inhibitor-

Answer 30

Enzyme inhibition: Some drug substrates inhibit CYP enzymes
Inhibitors: cimetidine, erythromycin, ketoconazole, etc.

Question 31

Clinical consequences of enzyme inhibition:

Answer 31

increased concentration of the inhibitors or co-administered drugs which increases the effect, with likelihood of toxicity

Prodrugs effect can be decreased

Question 32

Excretion of drugs and metabolites by kidney involves three processes:

Answer 32

Excretion of drugs and metabolites by kidney involves three processes:
Glomerular filtration
Active tubular secretion and
Passive tubular reabsorption(urinary pH plays a key role)

Question 33

Drug elimination is the sum total of

Answer 33

Drug elimination is the sum total of metabolic inactivation and excretion

Question 34

Kinetics of elimination:

Answer 34

Kinetics of elimination:
First order (exponential)kinetics
Zero order(linear) kinetics

Question 35

first order

Question 36

zero order

Question 37

half life

Answer 37

t1/2= 0.7xVd /CL

Question 38

maintainance dose

Answer 38

F

Question 39

loading dose

Answer 39

F

Question 40

cpss max

Answer 40

Cp,ss max =F x Dose / Vd / fraction lost in a dosing interval

Question 41

cpss min

Answer 41

cpss max x fraction remaining

Question 42

Revised dose rate

Answer 42

Revised dose rate = Previous dose rate x Target Cpss/ Measured Cpss