Pharmacokinetics

Question 1

Define pharmacokinetics

Answer 1

What the body does to the drug

Question 2

Define pharmacodynamics

Answer 2

What the drug does to the body

Question 3

Describe clearance

Answer 3

Volume of plasma cleared of a drug per unit time

Question 4

What is half-life?

Answer 4

Time taken for drug concentration to decline to half its original value.
Depends on volume of distribution and clearance

Question 5

What is the volume of distribution?

Answer 5

 Volume into which a drug appears to distribute.
 High for lipid-soluble drugs
 Low for water soluble drugs

Question 6

Define bioavailability

Answer 6

 Percentage of the dose of a drug which reaches the systemic circulation.
 100% for IV administration

Question 7

When are loading doses needed?

Give 4 examples

Answer 7

 If a drug given at intervals the concentration will reach a steady state in ~ 5 half-lives.
 Loading dose: ↓ time needed to reach a steady state.  Useful if long or short t1⁄2
 Phenytoin, digoxin, amiodarone, theophylline

Question 8

When are drugs monitored?

Answer 8

 Ix lack of drug efficacy or possibility of poor compliance
 Suspected toxicity
 Prevention of toxicity

Question 9

What drugs need their plasma drug levels to be monitored?

Answer 9

 Aminoglycosides (essential)
 Vancomycin (essential)
 Li (essential)
 Phenytoin
 Carbamazepine
 Digoxin
 Ciclosporin
 Theophylline

Question 10

Describe first pass metabolism

Answer 10

 Metabolism and inactivation of a drug before it reaches the systemic circulation.
 i.e. pre-systemic elimination
 Occurs in gut wall and liver
 E.g. propranolol, verapamil, morphine, nitrates

Question 11

Describe phase 1 metabolism

Answer 11

Creation of reactive, polar functional groups
 Oxidation: usually by CyP450 system
 Reduction and hydrolysis

Question 12

Describe phase 2 metabolism

Answer 12

 Production of polar compounds for renal elimination  Either the drug or its phase 1 metabolite
 Conjugation reactions
 Glucuronidation, sulfonation, acetylation, methyl

Question 13

Name the 2 most important CyP450 systems

Answer 13

CyP3A4
 Most important subtype
 ≥ 30% of drugs: CCBs, β-B, statins, benzos
CyP2D6
 Second most important
 ≥20% of drugs: antidepressants, some β-B,
opiates

Question 14

What is the pro-drug of dopamine?

Answer 14

L-dopa

Question 15

What is enalapril the pro-drug of?

Answer 15

Enalaprilat

Question 16

What is methyldopa the prodrug of?

Answer 16

alpha-methylnorepinephrine

Question 17

Which drugs do you need to be aware of G6PD deficiency?

Answer 17

Quinolones
Primaquine
Nitrofurantoin

Question 18

Which drugs are affected if someone is a genetically slow/fast acetylators

Answer 18

Isoniazid