B2E1 Pharm Enzymes

UGT1A1 + Irinotecan`

Phase II

Irinotecan —> Inactive

Poor Metabolizers: Increase severe/life-threatening toxicities

• Neutropenia + Diarrhea

G6PD + Rasburicase

Misc. Enzyme

• Decreased glutathione to neutralize H2O2

Increased Severe/Fatal AdRXNs related to oxidative cell death

• Hemolytic anemia, methemoglobinemia

OATP1B1 + Simvastatin

Transporter, Blood-Facing Side, Uptake of Weakly Acidic

In liver to block cholesterol production

• 2 bad alleles = decreased function + no uptake

Treatment failure + increased lipid levels

Increased serum + skeletal muscle toxicity

BCRP + Rosuvastatin

Efflux on Kidney/Liver/Intestinal Epithelial Cells

• Increased excretion to bile + urine

Decreased Function: Increased serum + skeletal muscle toxicity

HLA Genetic Mutations

Liver Injury, Epidermal Necrosis, Stevens-Johnson Syndrome

• Sulfonamides, NSAIDs, ABX, Steroids, Anti-epileptics, and Methotrexate

VKORC1 + Warfarin

Decreased warfarin binding = increased warfarin resistance

Reduced VKORC1 = increased warfarin sensitivity

CYP2CP + Warfarin

Warfarin —> Inactive

Poor Metabolizers: Increased Serum + AdRXNs

TMPT + Azathioprine

Phase II, Azathioprine + 6-Mercaptopurine —> Inactive

Poor Metabolizer: Increased Cytotoxic Metabolite

• Immunosuppression, Leukopenia, Infections, Hepatotoxicity, and Pancreatitis

DPD + Fluropyrimidine Chemotherapy

Phase I, Severe/Fatal AdRXNs

Increased Levels of Cytotoxic Metabolites

CYP2B6 + Efavirenz

Phase I, Efavirenz → Inactive

Poor Metabolize = Increased AdRXNs + D/C Rx, decreased LD

CYP3A4/5 Inhibitors

Grapefruits

PPIs

Azoles (Anti-Fungals)

Cyclosporine

Macrolides (Erythro)

Amiodarone
Non-Dihydropyridine CCBs

CYP2C19 + Clopidorgrel

Phase I, Prodrug → Active Metabolite

• Essential for efficacy

Poor/Intermediate Metabolizer: Increased Risk of Treatment Failure

CYP2CP + NSAIDs

Prevents NSAID → Inactive, Phase I

Poor Metabolizers: Increased Serum + AdRXNs

CYP2D6 + Codeine

Phase I, Prodrug (Codeine) → Active Metabolite (Morphine)

Poor/Intermediate Metabolizers: Increased Treatment Failure

Ultra-Rapid Metabolizer: Increased Resp. Depression

CYP1A2 Inhibitors

Fluoroquinolones (Ciprofloxacin)

CYP1A2 Inducers

Broccoli, Brussel Sprouts, Chargrilled Meats, and Tobacco

CYP1A2 Substrates

Caffeine, Fluvoxamine, Theophylline, and Warfarin

CYP2C9 Substrates

Clopidogrel

Phenytoin

S-Warfarin

CYP2C9 Inducers

Carbamazepine

CYP2C9 Inhibitors

Amiodarone

Fluconazole

Voriconazole

Sulfamethoxazole

CYP2C19 Substrates

Clopidogrel (Prodrug)

R-Warfarin

CYP2C19

Esomeprazole

Omeprazole

CYP2D6 Substrates

Tamoxifen

Codeine

Dextromethorphan

CYP2D6 Inhibitors

Fluoxetine

Paroxetine

CYP2E1 Substrates

APAP (Acetominophen)

CYP2E1 Inducers

Ethanol

Isoniazid

CYP3A4/5 Substrates

Statins

Carbamazepine

Estradiol

CYP3A4/5 Inducers

Barbiturates

Carbamazepine

Griseofulvin

Rifampin

Phenytoin