Pharmacology

Question 1

pharmacodynamics vs pharmacokinetic vs pharmacogenomics

Answer 1

pharmacodynamics - what drug does to body
pharmacokinetic - what body does to drug
pharmacogenomics - role of genome in the drug response (study of genetic factors that underlie variations in drug response)

Question 2

explain the clinical use of clopidogrel

Answer 2

block activation of platelets AKA antiplatelets

side effect: spontaneous bleeding and secondary inhibitory effect on platelet function

Question 3

4 principles of pharmocokinetics

Answer 3

absorption, distribution, metabolism, excretion

Question 4

what does bioavailability mean

Answer 4

describes the fraction of unchanged drug that reaches the systemic circulation after administration

• intravenous will always have a 100% bioavailability
• oral administration preferred but not 100% due to incomplete absorption across gut wall and first pass elimination by liver

Question 5

describe the absorption phase

Answer 5

after oral administration, drug passes through gut, with most drugs being absorbed in the ileum
main modes of absorption: passive diffusion, facilitated passive diffusion, active transport

Question 6

factors affecting oral drug absorption

Answer 6

drug factors:
lipid solubility
molecular size
degree of ionization
pKa
stability in gastric acid 

patient factors:
area of absorptive surfaces
gut motility
presence of food or other drug

Question 7

describe the distribution phase

Answer 7

after the absorption into the bloodstream, drugs are distributed into various tissues in the body

volume of distribution (Vd) describes the amount of drug in the body, in relation to the concentration in plasma or blood

small Vd = drug mostly stays in bloodstream
large Vd = drug mostly absorbed into the tissues

Question 8

factors affecting distribution

Answer 8

drug factors:

• lipid solubility
• molecular size
• degree of ionisation
• partition coefficient
• protein binding

patient factors:

• fat and water content
• protein levels
• disease states
• concomitant drugs

Question 9

describe the metabolism phase

Answer 9

• biotransformation of drugs into more hydrophilic forms for elimination by kidneys
• most metabolism occur in liver
• 2 main enzymatic phases:
• -> phase 1: reactions of functionalisation (typically involved cytochrome P450 group of enzymes)
• -> phase 2: reactions of conjugation (add a molecule to the drug to increase hydrophilicity)
• can occur in succession or standalone
• metabolites can be active or inactive

Question 10

factors affecting metabolism

Answer 10

drug delivery factors:

• blood flow to liver
• protein binding

intrinsic factors:

• metabolizing capacity
• concomitant interacting drug
• genetic polymorphism

Question 11

describe the excretion phase

Answer 11

metabolites and parent drugs are eventually eliminated from the kidneys and excreted in the urine

Question 12

concept of half-life

Answer 12

time taken for concentration of drug in body to reduce to half. the shorter the half-life, the faster the drug clearance

dosing interval for frugs depends on T1/2, more frequent dosing required for short T1/2

Question 13

explain the dose and drug response

Answer 13

the ideal therapeutic dose of a drug for patient maximises efficacy while minimizing toxicity (side effects)

therapeutic index reflects the min effective concentration and min toxic concentration
lower dose = ineffective
higher dose = unacceptable toxicity
narrow therapeutic index drugs require close drug level monitoring

Question 14

mechanism for variations in drug responsiveness

Answer 14

1. differences in drug concentration that reaches receptor site
2. variation in concentration of endogenous receptor ligand
3. alterations in number or function of receptors
4. changes in components of response distal to the receptor