Sources of variability

Question 1

Sources of pharmacodynamic variability

Answer 1

Gender related differences, circadian rhythms, drug tolerance

Question 2

What are circadian rhythms

Answer 2

Biological processes in the body running in cycles of 24 hours, often related to daylight and night-time

Question 3

Elements of asthma related to circadian rhythms

Answer 3

Cortisol (anti-inflammatory) lowest at night, histamine (mediates bronchoconstriction) highest at night

Question 4

What is drug tolerance

Answer 4

Ability of body to adapt in presence of drug, effect declines over time, need larger doses to produce the same effect

Question 5

Why does drug tolerance occur

Answer 5

Changes in receptor sensitivity, can be due to receptor downregulation or cellular adaptation

Question 6

Factors in pharmacokinetic variability

Answer 6

Absorption, distribution, metabolism, excretion

Question 7

What are p-glycoprotein transporters

Answer 7

Membrane transporters expressed in many organs that export drug out of cells

Question 8

What does inhibiting p-glycoprotein do

Answer 8

Increase drug absorption from the gut

Question 9

What does p-gp induction do

Answer 9

Decrease intestinal absorption, reduce CNS transport, increase secretion into renal tubules

Question 10

Common inhibitors of p-gp

Answer 10

Cimetidine, grapefruit juice

Question 11

What issues does p-gp cause in chemotherapy

Answer 11

Overexpression of p-gp transporters can cause multi-drug resistance, efflux drug out of cells, don’t get desired concentration

Question 12

Genetic polymorphism effects on metabolism

Answer 12

Different ethnicities can be slow or fast acetylators

Question 13

P-gp differences in men and women

Answer 13

Women have less than men

Question 14

How does body size and composition affect metabolism

Answer 14

Differences in distribution due to smaller body weight, smaller organ size and blood flow, variation in Vd

Question 15

What is GFR proportional to

Answer 15

Body weight, less in women

Question 16

Affects of pregnancy on pharmacokinetics

Answer 16

Changes in clearance, decreased elimination half life, changes in enzyme activity, GFR increases throughout pregnancy and decreases in last 3 weeks

Question 17

What is the effect of smoking on pharmacokinetics/dynamics

Answer 17

PAHs induce CYP450 which decreases pharmacological effect of drugs that are substrates, need higher doses

Question 18

How does obesity affect pharmacokinetics

Answer 18

Excess adipose tissue, affect Vd, if drug has high affinity for adipose tissue it will accumulate (hydrophobic drugs), GFR may be increased