P450 Pharmacology

Question 1

What is pharmacokinetics?

Answer 1

What the body does to the drug

Question 2

What is pharmacodynamics?

Answer 2

The study of the biochemical and physiological effects of drugs on the body

Question 3

What are modulators?

Answer 3

Drugs that inhibit or induce an enzyme involved in the clearance of a drug

Question 4

What are the three avenues of thought that should be used to determine a drug interaction?

Answer 4

1. Why is the drug doing too little?
2. Why is the drug doing to much?
3. The Syx are strange

Question 5

In a patient where pharmacologic effect is not seen, what could be two causes?

Answer 5

1. Noncompliance
2. Pharmacodynamic (NSAID doing the opposite of an ACEI)
3. Pharmacokinetic (Induction of enzymes)

Question 6

What is the pharmacodynamic example resulting in inadequate effect of the drug?

Answer 6

ACEI and NSAIDS. ACEI used to decrease BP, but the NSAIDS caused constriction of the afferent arterioles and increase in BP thru RAAS.

Question 7

Itraconozole is used to treat onchomycosis, but a concurrent PPI is used decreasing the absorption of the itraconozole. What type of drug interaction is this?

Answer 7

Pharmacokinetic. The itraconazole needs an acidic environment to be bioavailable. The PPI makes the stomach more basic, decreasing the bioavailability of the itraconazole

Question 8

What are the two basic pharmacokinetic scenarios that a drug is not having its desired effect?

Answer 8

Either the bioavailability is decreased, or there is enzyme induction

Question 9

What is the MOA of pharmacokinetic inducers and inhibitors?

Answer 9

• Inducers increase enzyme through transcription
• Inhibitors compete by binding to the receptor and preventing access to the substrate

Question 10

What is a pharmacokinetic example of inhibition between metoprolol and propoxyphene?

Answer 10

Propoxyphene is a potent inhibitor of Cytochrome P450. Metoprolol cannot be degraded. Therefore, regular doses of metoprolol can cause life-threatening bradycardia

Question 11

What is the cytochrome P450 group?

Answer 11

Group of oxidase enzymes

Question 12

What two general processes can the CP450s perform?

Answer 12

• Inactivation: Active Drug –> CP450 –> Inactive drug
• Activation: Inactive Prodrug –> CP450 –> Active drug

Question 13

What is significant about P450 polymorphisms?

Answer 13

Because P450 enzymes are polymorphic, amounts of an enzyme vary between a population and therefore, inactivation/activation of drugs can differ