Isonizid Adverse reactions o Immunologic reactions o Direct toxicity o Isoniazid-induced hepatitis Peripheral neuropathy pyrido×ine(吡哆醇, /itminB6)
Adverse Reactions Immunologic reactions Direct toxicity ⚫ Isoniazid-induced hepatitis ⚫ Peripheral neuropathy: pyridoxine(吡哆醇, VitminB6 ) Isonizid
Rifampin rifampin(利福平) o Antimicrobial activity: in vitro against gram-positive and gram negative cocci, some enteric bacteria mycobacteria, and chlamydia o Mechanism of action bactericidal HO inhibits DNA-dependent RNA polymerase OHOH o Adverse effects: O o hepatotoxicity o Resistance rapidly o no crossresistance to other classes of OH antimicrobial drugs cross-resistance to other rifamycin derivatives eg, rifabutin and rifapentine
rifampin(利福平 ) Antimicrobial activity: ⚫ in vitro against gram-positive and gramnegative cocci, some enteric bacteria, mycobacteria, and chlamydia. Mechanism of action: bactericidal ⚫ inhibits DNA-dependent RNA polymerase Adverse effects: ⚫ hepatotoxicity. Resistance : rapidly. ⚫ no crossresistance to other classes of antimicrobial drugs ⚫ cross-resistance to other rifamycin derivatives, eg, rifabutin and rifapentine. Rifampin
Rifampin Pharmacokinetics o Absorbtion: well absorbed after oral administration o excretion mainly through the liver into bile enterohepatic recirculation(肝肠循环) bulk excreted as a deacylated metabolite in feces a small amount in the urine o Distribution widely in body fluids and tissues relatively highly protein-bound adequate cerebrospinal fluid concentrations are achieved only in the presence of meningeal inflammation
Pharmacokinetics Absorbtion: ⚫ well absorbed after oral administration excretion: ⚫ mainly through the liver into bile ⚫ enterohepatic recirculation(肝肠循环) ⚫ bulk excreted as a deacylated metabolite in feces ⚫ a small amount in the urine. Distribution: ⚫ widely in body fluids and tissues. ⚫ relatively highly protein-bound ⚫ adequate cerebrospinal fluid concentrations are achieved only in the presence of meningeal inflammation. Rifampin
Rifampin Clinical Uses O MyCOBACTERIAL INFECTIONS Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug- resistant mycobacteria Rifampin 600 mg daily, or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophy laxis for patients with latent tuberculosis only who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazidresistant, rifampin susceptible strain O OTHER INDICATIONS prophylaxis meningococcal carriage-600 mg twice daily for 2 days rophylaxis in Haemophilus influenzae type b(流感嗜血杆菌) disease O mg/kg/d for 4 days eradicate staphylococcal carriage: combination other agents o serious staphylococcal infections such as osteomyelitis(骨髓炎) prosthetic valve endocarditis(人工瓣膜性心内膜炎)
Clinical Uses MYCOBACTERIAL INFECTIONS ⚫ Rifampin, usually 600 mg/d (10 mg/kg/d) orally, must be administered with isoniazid or other antituberculous drugs to patients with active tuberculosis to prevent emergence of drug-resistant mycobacteria. ⚫ Rifampin 600 mg daily or twice weekly for 6 months also is effective in combination with other agents in some atypical mycobacterial infections and in leprosy. ⚫ Rifampin, 600 mg daily for 4 months as a single drug, is an alternative to isoniazid prophylaxis for patients with latent tuberculosis only, who are unable to take isoniazid or who have had exposure to a case of active tuberculosis caused by an isoniazidresistant, rifampinsusceptible strain. OTHER INDICATIONS ⚫ prophylaxis meningococcal carriage— 600 mg twice daily for 2 days ⚫ prophylaxis in Haemophilus influenzae type b (流感嗜血杆菌)disease: 20 mg/kg/d for 4 days, ⚫ eradicate staphylococcal carriage: combination other agents serious staphylococcal infections such as osteomyelitis (骨髓炎) prosthetic valve endocarditis(人工瓣膜性心内膜炎) Rifampin
Rifampin Adverse reactions o harmless orange color: urine, sweat, tear, and contact lenses(soft lenses may bepermanently stained) o Occasional adverse effects: rashes, thrombocytopenia(血小板减少症), and nephritis(肾炎) cholestatic jaundice(胆汁淤积性黄疸) and occasionally hepatitis. oflu- like syndrome: fever,chi(寒战), myalgias(肌痛), anemia(贫血),and thrombocytopenia and sometimes is associated with acute tubular necrosIs(急性肾小管坏死 o Cytochrome P450 isoforms(CyPs 1A2, 2C9, 2C19, 2D6, and 3A4 inducer: o increases the elimination of numerous other drugs including methadone(美沙酮 anticoagulanTs 抗凝剂 cyc| osporine(环 孢素) some anticonvulsants, protease inhibitors some nonnucleoside reverse transcriptase inl libitors(非核苷逆转录酶抑制剂) contraceptives, and a host of others lower serum levels of these drugs
Adverse Reactions harmless orange color : urine, sweat, tear, and contact lenses (soft lenses may bepermanently stained). Occasional adverse effects : ⚫ rashes, thrombocytopenia(血小板减少症), and nephritis(肾炎). ⚫ cholestatic jaundice(胆汁淤积性黄疸) and occasionally hepatitis. flu-like syndrome : fever, chills(寒战), myalgias(肌痛), anemia(贫血), and thrombocytopenia and sometimes is associated with acute tubular necrosis(急性肾小管坏死). Cytochrome P450 isoforms (CYPs 1A2, 2C9, 2C19, 2D6, and 3A4) inducer : ⚫ increases the elimination of numerous other drugs including methadone(美沙酮) , anticoagulants(抗凝剂), cyclosporine(环孢素), some anticonvulsants, protease inhibitors, some nonnucleoside reverse transcriptase inhibitors(非核苷逆转录酶抑制剂), contraceptives, and a host of others. ⚫ lower serum levels of these drugs. Rifampin