Pharmacokinetics

Question 1

where do benzodiazepines bind? and what are there effects?

Answer 1

• Bind GABA-A receptor in neuronal membranes in the CNS.
• GABA-A receptor functions as a chloride ion channel and is activated by the inhibitory NT GABA
• Benzos binding enhances the ability of GABA to open the chloride channel, thereby hyperpolarizing the neuron.

Question 2

Factors that influence bioavailability

Answer 2

Drug formulation
Chemical instability 
Food and drug interactions
First pass hepatic metabolism
Drug solubility
P-Glycoprotein

Question 3

factors that influence drug absorption

Answer 3

pH on drug absorption
surface area available for absorption
blood flow to absorption site
contact time at absorption surface
P-glycoprotein

Question 4

What drug can initially commence from a phase II through acetylation from N-acetyltransferase?

Answer 4

Isoniazid

- I then undergoes a phase I reaction: hydrolysis to isonicotinic acid

Question 5

WHat drugs increase the synthesis of P450?

Answer 5

phenobarbital, rifampin, and carbamazepine

Question 6

Drugs that inhibit cytochrome P450:

Answer 6

Amiodarone
Cimetidine
Ketoconazole (antifungal)
Erythromycin (antibacterial)
chloramphenicol (antibacterial)
Grapefruit juice (inhibits both CYP 3A4 & P-glycoprotein)

Question 7

P-glycoprotein spits what drugs back into the intestinal lumen?
and what drugs inhibit P-glycoprotein?

Answer 7

1) Digoxin, HIV-1 protease inhibitor

2) Macrolide antibiotics (Clarithromycin)

Question 8

drugs that transcriptionally induce PXR also induce what cellular components?

Answer 8

P-glycoprotein

Question 9

TXT of acetaminophen

Answer 9

N-acetylcysteine

Question 10

Three types of interindividual genetic variation that influence pharmacotherapy:

Answer 10

• Variation in proteins involved in drug metabolism or transport (Pharmacokinetic variation)- most common
• Variation in drug targets or pathways associated with those targets (Pharmacodynamic variation)
• Genetic variation associated with idiosyncratic drug effects.