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Nitroimidazoles : Metronidazole and Tinidazole

Nitroimidazoles : Metronidazole and Tinidazole. Mark S. Johnson, Pharm.D ., BCPS Associate Professor and Director of Postgraduate Education. Metronidazole (Flagyl ®) . Nitroimidazole class Antiparasitic and antibacterial activity MOA

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Nitroimidazoles : Metronidazole and Tinidazole

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  1. Nitroimidazoles:Metronidazole and Tinidazole Mark S. Johnson, Pharm.D., BCPS Associate Professor and Director of Postgraduate Education

  2. Metronidazole (Flagyl®) • Nitroimidazole class • Antiparasitic and antibacterial activity • MOA • Diffuses into organism by passive diffusion then interacts with DNA to cause loss of helical DNA structure and strand breakage, which results in inhibition of protein synthesis and cell death • Needs to be reduced for it’s action • Bactericidal

  3. Metronidazole dailymed.nlm.nih.gov

  4. Metronidazole (Flagyl®)Spectrum of Activity • Good • Anaerobes: gram positive and gram negative • Bacteroides, Fusobacterium, Clostridium, Prevotella • Protozoa: • Trichomonas, Entamoeba, Giardia • Moderate • Helicobacter pylori • Poor • Peptostreptococcus, Actinomyces, Propionibacterium

  5. Metronidazole (Flagyl®)PKS • Absorption • BA 100% • Distribution • Saliva, bile, seminal fluid, bone, liver, liver abcesses, lung, vagina, crosses BBB • Protein binding 20% • Metabolism • Hepatic (30-60%) • t1/2 of 6-8h (prolonged in hepatic and ESRD) • Excretion • Urine (60-80% as unchanged drug) • Feces (6-15%)

  6. Metronidazole (Flagyl®)ADR’s • GI: • Common: nausea, vomiting, diarrhea, metallic taste • Rarely hepatitis, pancreatitis • Neurologic • Dose-related peripheral neuropathy • Can also be optic or autonomic neuropathy • Headache • Rarely confusion, seizures • Skin—urticaria • Dark Urine • Pregnancy (category B, avoid in 1st trimester)

  7. Metronidazole (Flagyl®)Drug Interactions • Inhibits 2C9 (weak), 3A4 (moderate) • Disulfiram-like reaction when given with alcohol (inhibition of aldehydedehydrogenase) • Warfarin—increased INR • Phenytoin, phenobarbital can decrease metronidazole levels

  8. Metronidazole (Flagyl®)Clinical Uses • Anaerobic infections in general, including intra-abdominal infections • Trichomoniaisis • Bacterial vaginosis, vaginitis • GI infections caused by protozoa (amebiasis, giardiasis, others) • Pseudomembranous colitis (Clostridium difficile) • Helicobacter pylori infections

  9. Metronidazole (Flagyl®)Dosage Forms • IV: • 500mg (7.5mg/kg) Q6h-8h • possibly 15mg/kg Q12h • Not to exceed 4gm/d • Oral • Regular Release: 250mg-500mg PO Q8-12h (depending on indication) • Extended Release: 750mg QD • Topical (acne rosacea): 0.75% or 1%

  10. Tinidazole (Tindamax™) • Structurally similar to metronidazole – 2nd-generation nitroimidazole • Antiprotozoal • Mechanism: similar to metronidazole • Indications • Intestinal amebiasis and amebic liver absess– Entamoebahistolytica • Giardiasis– Giardialamblia • Trichomoniasis– Trichomonasvaginalis • Bacterial vaginosiscaused by Bacteroidesspp, Gardnerellavaginalis, Prevotella

  11. Tinidazole (Tindamax™) • t1/2: 13h (once daily dosing) • Similar ADR’s to metronidazole • Substrate for 3A4 • Availability: • 250mg and 500mg tabs • 2gm once daily with food • More expensive

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