P450 Drug Interactions

Question 1

Which interactions are predictable from knowledge of MOA, manipulate receptors and pathways involved in a therapeutic effect, and have broad clinical relevance?

Answer 1

pharmacodynamic

Question 2

Which interactions are involved with changing the activity of an enzyme involved in clearance of a substrate, are not predictable based on MOA, and are not necessarily clinically significant?

Answer 2

pharmacokinetic

Question 3

A man is in your office with a history of good BP control using enalapril. Today, his BP is 160/98. What common OTC drug should you ask about?

Answer 3

• ask about NSAIDs!
• NSAIDs cause Na retention and volume expansion, so use of these causes ACEIs and diuretics to have less of an effect on BP
• this is an example of pharmacodynamic interaction

Question 4

What are some general examples of pharmacokinetic drug interactions?

Answer 4

• decreased substrate bioavailability
• induction of enzyme that enhances substrate clearance
• inhibition of an enzyme to slow clearance
• P450 interactions

Question 5

What are the characteristics of P450 subfamilies involved in drug metabolism?

Answer 5

• all are oxidases (phase I metabolism)
• polymorphisms are common (fast or slow acetylators)
• all have specific substrates and modulators

Question 6

What drugs are examples of inducers of P450 (i.e. more activity and lower plasma levels)?

Answer 6

• Barbituates
• Phenytoin
• Carbamazepine (ex: Decreases effectiveness of warfarin)
• Rifampin (ex: Decreases effectiveness of amlodipine to treat BP)
• Glucocorticoids
• Chronic Alcohol

Question 7

What drugs are examples of inhibitors of P450 (i.e. less activity and higher plasma levels)?

Answer 7

• Paroxetine (ex. Increased activity of metoprolol causing bradycardia, stops conversion of codeine to morphine, making it ineffective in pain tx)
• Cimetidine
• Omeprazole
• Ketoconazole
• Macrolids (except for azithryomycin)
• Acute Alcohol
• Propoxyphene (ex: Increased activity of metoprolol causing AV block)