Drug Metabolism Flashcards
Four important prodrugs
Carbamazepine, Irinotecan, Codeine, Prednisone
3A4 Inducers (7)
Rifampin Carbamazepine Phenobarbital Phenytoin Glucocorticoids Pioglitazone St. John’s wort
Grapefruit Juice (S) (+where + how)
3A4 Inhibitor (in the GI tract, but not the liver)
**Note: grapefruit juice affects bioavailability of drug, NOT half life
Conflict: Cyclosporin v. Rifampin
Drugs- Cyclosporin (immunosuppressant drug) is a 3A4 substrate, and rifampin induces everything (antituberculosis drug)
Interaction- reduced levels of cyclosporin
Consequence - increased the risk of organ rejection
Conflict: Clopidrogel v. Rifampin
Drugs- Clopidrogel (antiplatelet drug) is a 2C19 substrate and PRODRUG, and rifampin (antituberculosis) is an inducer.
Interaction- increased levels of active clopidrogel
Consequence - increased risk of bleeding
Conflict: Cyclosporin v. Itranaconazole
Drugs- Cyclopsorin (immunosuppressant) is a 3A4 substrate, and itranaconazole (antifungal) is a potent 3A4 inhibitor
Interaction- increased levels of cyclosporin
- immunosuppressant drug - antifungal agent
- concentration-dependent nephrotoxicity
Consequence - increased risk of nephrotoxicity
Conflict: Lopinavir v. Ritonavir
Drugs: Lopinavir is a 3A4 substrate (HIV inhibitor) that experiences a significant first pass reduction (decreased bioavailability), and Ritonavir (HIV inhibitor) is a potent 3A4 inhibitor that has significant adverse GI affects at therapeutic concentrations.
Interaction- increased levels of active lopinavir via increased bioavailability
Consequences- improved anti-HIV effect
Dosing concerns with treating the eldery
Decreased activity of Phase I metabolism in the elderly requires a 30-40% dose reduction
Concerns with treating newborn babies with chloramphenicol
A conjugating enzyme (Phase II) deficiency in infants leads to gray baby syndrome. They cannot fully metabolize chloramphenicol (antibacterial), so a phase I metabolite accumulates, resulting in circulatory collapse and cyanosis
Which enzymes does pregnancy induce?
2C9, 2D6 & 3A4
Which enzymes does pregnancy inhibit?
1A2 & 2C19
chemicals in cigarette smoke, charbroiled food and cruciferous vegetable
chemicals in cigarette smoke, charbroiled food and cruciferous vegetables all induce CYP 1A2
smokers sometimes need higher doses of certain drugs metabolized by CYP1A2 e.g. theophylline (Asthma/COPD), and some antidepressants
Chronic alcohol abuse
Induces CYP2E1
Inhibitors (7): Meat (2) and Cheese (3) with Ritz crackers and grapefruit juice
- mycin (Erytrhromycin, clarithromycin)
- conazole (Fluconazole, ketoconazole, itraconazole)
- Ritonavir
- Grapefruit juice
Inducers:
Chronic alcoholics STeal PHen-PHen but Probably Refuse Greasy Carbs
Chronic alcohol abuse St John's Wort Phenobarbital Phenytoin Pioglitazone Rifampin Glucocorticoids Carbamazepine
