PK And PD

Question 1

Volume of distribution

Answer 1

Theoretical volume occupied by total amount of drug in body rel to amount in plasma

If high, means drug has distributed into tissue (eg fat), so less in blood

Question 2

Clearance

Answer 2

Volume of plasma cleared of drug/time

= rate of elimination of drug/plasma drug concentration

= Vd*Ke (elimination constant)

Question 3

Half life

Answer 3

t1/2 = 0.693*Vd/Cl

Drug infused at constant rate takes 4-5 half lives to reach SS

Question 4

Loading and maintenance dose formulas

Answer 4

Loading dose = [target plasma conc] * Vd /F (bioavailability)

Maint dose = [target conc]Cltime between doses / F

Question 5

Drugs eliminated by zero order kinetics

Answer 5

Phenytoin
Ethanol
Aspirin

(PEA)

constant amount of drug eliminated/time

Question 6

Weak acids that end up in urine

Answer 6

Phenobarbital, methotrexate, aspirin, TCAs

Treat overdose with bicarb to alkalinize urine and trap the drugs in urine in charged form

Question 7

Weak bases that can be trapped in urine

Answer 7

Amphetamines (treat overdose with ammonium chloride –> ammonia)

Question 8

Drug metabolism phases

Answer 8

Phase I - reduction, oxidation, hydrolysis with cytochrome P450 to yield slightly polar, water-soluble metabolites (decreases with age)

Phase II - conjugation (glucoronidation, acetylation, sulfation) –> VERY POLAR for renal excretion

Question 9

Therapeutic index

Answer 9

= TD50 (median toxic dose) / ED50 (median effective dose)

higher = safer

Question 10

Efficacy vs potency

Answer 10

Eff = maximal effect a drug can produce (measured by Vmax - increased Vmax = increased eff)

Potency = amt of drug needed for given effect (increased potency/EC50 = decreased drug needed)

Question 11

Drugs with low therapeutic indices (less safe)

Answer 11

digoxin, theophylline, warfarin, lithium