U01.05.042 Cytochrome P-450 interactions

Cytochrome P450 enzymes play a pivotal role in drug metabolism, influencing the pharmacokinetics and effectiveness of many drugs. Understanding inducers, substrates, and inhibitors of these enzymes is crucial for predicting drug interactions, which is an essential topic for the USMLE Step 1.

Key Components of Cytochrome P450 Interactions

Inducers (+): Increase the activity of P450 enzymes, leading to faster drug metabolism and reduced drug efficacy.
Substrates: Drugs metabolized by P450 enzymes, potentially affected by inducers or inhibitors.
Inhibitors (–): Decrease P450 enzyme activity, slowing drug metabolism, and potentially increasing drug toxicity.

1. Cytochrome P450 Inducers (+)

Mnemonic: “Most chronic alcoholics Steal Phen-Phen and Never Refuse Greasy Carbs”

Inducers
Modafinil
Chronic alcohol use
St. John’s wort
Phenytoin
Phenobarbital
Nevirapine
Rifampin
Griseofulvin
Carbamazepine

2. Cytochrome P450 Substrates

Mnemonic: “War Against The OCPs”

Substrates
Warfarin
Anti-epileptics
Theophylline
Oral contraceptive pills (OCPs)

3. Cytochrome P450 Inhibitors (–)

Mnemonic: “SICKFACES.COM (when I Am Really drinking Grapefruit juice)”

Inhibitors
Sodium valproate
Isoniazid
Cimetidine
Ketoconazole
Fluconazole
Acute alcohol abuse
Chloramphenicol
Erythromycin/clarithromycin
Sulfonamides
Ciprofloxacin
Omeprazole
Metronidazole
Amiodarone
Ritonavir
Grapefruit juice

Points to Remember

Inducers speed up drug metabolism, potentially decreasing therapeutic drug levels.
Inhibitors slow drug metabolism, increasing the risk of drug toxicity.
Understanding these interactions is crucial for preventing adverse drug reactions and ensuring therapeutic efficacy.
Mnemonic mastery simplifies memorization and recall during exams.

Bibliography

Katzung BG, Trevor AJ. Basic & Clinical Pharmacology. McGraw-Hill Education.
Brunton LL, Knollmann BC, Hilal-Dandan R. Goodman & Gilman’s: The Pharmacological Basis of Therapeutics. McGraw-Hill Education.

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