Pharmacokinetics

Question 1

What are the four stages?

Answer 1

Absorption, distribution, metabolism, excretion.

Question 2

Which drug, hydrophobic (low pKa) or ionic (high pKa), will have the larger volume of distribution?

Answer 2

Hydrophobic (low pKa), because it can diffuse wrought phospholipid bilayers.

Question 3

What is volume of distribution?

Answer 3

The volume of fluid required to contain the total amount, Q, of the drug in the body at the same concentration as that present in the plasma.
Vd = Q/Cp

Question 4

What happens in Phase 1 of drug metabolism in the liver?

Answer 4

Cytochrome P450 enzymes strip away groups from the drug by oxidation, reduction, hydrolysis, hydration, to expose the functional groups of the drugs and make them more reactive.

Question 5

What happens in Phase 2 of drug metabolism in the liver?

Answer 5

Glucuronidation, amino acid conjugation, sulfoconjugation - the drug is conjugated to glucuronide to make it hydrophilic so it can be excreted by the kidney.

Question 6

Would a drug that took longer to be absorbed have a longer or shorter half life (T1/2)?

Answer 6

Longer.

E.g an IV drug will remain in the therapeutic window for less time.

Question 7

Why is it safer to have lower doses more frequently?

Answer 7

Less likelihood of exceeding therapeutic window, but takes longer to reach therapeutic window.

Question 8

In the two compartment model, what is the fast phase and what is the slow phase?

Answer 8

Fast phase = transfer of drug from central compartment (plasma) to peripheral compartment (tissues).
Slow phase = elimination of drug from peripheral compartment out of body (gives T1/2).