Keshvara Exam 4 PDF

Drug Mechanism ADME issues Toxicity issues Other issues Isoniazid Activated by bacterial enzymes Take on empty stomach Heptatoxicity (Box...

Drug Mechanism ADME issues Toxicity issues Other issues Isoniazid Activated by bacterial enzymes Take on empty stomach Heptatoxicity (Boxed warning) Depletes Vit B6 Reactive metabolite inhibits mycolic acid synthesis Metabolized by acetylation Peripheral neuropathy Take B6 supplements Optic neurotis Drug-induced lupus; hemolytic anemia Rifampin Inhibits RNA polymerase Take on empty stomach Body fluid discoloration Con: HIV protease inhibitors Inactivated by deacetylation ↑LFT, hepatotoxicity Potent inducer of CYPs Hemolytic anemia (if + Coomb's test) Pyrazinamide Converted to pyrazinoic acid (PA) Take on empty stomach Hepatotoxicity (at high dose) PA inhibits mycolic acid synthesis Hepatic/renal elimination ↑LFTs Inhibits uric acid excretion; acute gout Ethambutol Inhibits arabinosyl transferase Metabolized by alcohol Dhase Optic neuritis/retrobulbar neuritis Monitor vision Inhibits synthesis of arabinoglycan cell wall Loss of visual acuity (color) CNS--confusion, hallucinations Ethionamide Inhibits mycolic acid synthesis Hepatic metabolism Severe gastric distress--pain Strange taste, nausea, salivation Mouth sores P-amino salicylic acid Inhibits folate synthesis Acid resistant granules Severe GI irritation Con: renal failure Better to take with acidic drink Hypersensitivity Acetylation; renal excretion Hemolytic anemia Inhibits B12 & rifampin absorption Capreomycin Inhibits protein synthesis Injectable nephrotoxicity; ototoxicity Clofazimine Lipophilic dye; multiple mechanisms Skin accumulation Skin discoloration/disfigurement GI obstruction Cycloserine Analog of D-Ala; inhibits cell wall synthesis CNS (headache, seizure, psychosis) Allergic rxns Sleepiness Bedaquiline Inhibits ATP synthesis CYP3A4 metabolism Increased mortality (Boxed warning) QT prolongation (Boxed warning) Avoid CYP3A4 inducers Pretomanid Activated by bacterial enzymes CYP3A4 metabolism Optic & peripheral neuropathy BPaL Inhibits arabinogalactan synthesis Hepatotoxicity Bedaquiline+Pretomanid+Linezolid Myelosuppression Lactic acidosis