Nitroimidazoles: Pharmacology and Therapeutics PDF

NITROIMIDAZOLES By Dr. T.S. SUBASHINI M.Sc., Ph.D., D.Acu., Lecturer, Dept. of Pharmacology, SRM DENTAL COLLEGE, RAMAPURAM  NITROIMIDAZOLES METRONIDAZOLE TINIDAZOLE ORNIDAZOLE SECNIDAZOLE SATRANIDAZOLE  NITROIMIDAZOLES ROUTES OF ADMIN...

NITROIMIDAZOLES By Dr. T.S. SUBASHINI M.Sc., Ph.D., D.Acu., Lecturer, Dept. of Pharmacology, SRM DENTAL COLLEGE, RAMAPURAM  NITROIMIDAZOLES METRONIDAZOLE TINIDAZOLE ORNIDAZOLE SECNIDAZOLE SATRANIDAZOLE  NITROIMIDAZOLES ROUTES OF ADMINISTRATION METRONIDAZOLE ORAL, IV INFUSION, DENTAL GEL, RECTAL SUPPOSITORY, VAGINAL GEL TINIDAZOLE ORAL, IV INFUSION, VAGINAL GEL ORNIDAZOLE ORAL, IV INFUSION SECNIDAZOLE - ORAL SATRANIDAZOLE - ORAL  NITROIMIDAZOLES ANTIMICROBIAL SPECTRUM I. BACTERIA Anaerobic bacteria Aerobic bacteria II. Protozoa III. Helminth **Primarily active against anaerobic bacteria  NITROIMIDAZOLES ANTIMICROBIAL SPECTRUM I. Anaerobic bacteria 1.Anaerobic gram positive bacilli Clostridium tetani Clostridium perfringens Clostridium difficiles Clostridium septicum Clostridium novyi Clostridium histolyticum Mobiluncus Eubacterium  NITROIMIDAZOLES ANTIMICROBIAL SPECTRUM 2. Anaerobic gram negative bacilli Fusobacterium Helicobacter pylori Bacteroides fragilis Prevotella 3. Anaerobic gram positive cocci Peptococcus Peptostreptococcus 4. Anaerobic gram negative cocci No significant Action  NITROIMIDAZOLES ANTIMICROBIAL SPECTRUM II. Aerobic bacteria 1. Aerobic gram negative bacilli Escherichia coli Klebsiella pneumoniae Haemophilus influenza Campylobacter jejuni No significant Action ON: Aerobic gram positive bacilli Aerobic gram negative cocci Aerobic gram positive cocci  NITROIMIDAZOLES ANTIMICROBIAL SPECTRUM III. Protozoa Entamoeba histolytica Giardia intestinalis Trichomonas vaginalis Balantidium coli Blastocystis hominis IV. Helminth Dracunculus medinesis (Guinea worm) NO ACTION ON: FUNGUS VIRUS  NITROIMIDAZOLES MECHANISM OF ACTION METRONIDAZOLE - PRO DRUG – requires activation of NITRO GROUP NITROREDUCTASE (Ferredoxin reduced Ferredoxin oxidized ) ACTIVE METABOLITE BIND TO DNA - FRAGMENTATION OF DNA INHIBIT PROTEIN SYNTHESIS  METRONIDAZOLE PHARMACOKINETICS COMPLETELY ABSORBED Wide distribution – Saliva, Semen, Liver, Vaginal fluids, CSF, Breast Milk, Placenta – good penetration. Gastro Intestinal Irritation – Taken along with food.  METRONIDAZOLE THERAPEUTIC USES: I. Dental Uses: Anaerobic Orodental Infections: – ANUG, CELLULITIS, PERICORONITIS, VINCENTS STOMATITIS, PERIODONTITIS, ACUTE APICAL INFECTIONS, ENDODONTIC INFECTIONS For aerobic & Facultative bacterial infectins - ++ Penicillin, Cephalosporins, Aminoglycosides or Macrolide antibiotics.  METRONIDAZOLE THERAPEUTIC USES: II. OTHER USES AMOEBIASIS – CHOICE DRUG TRICHOMONIASIS – CHOICE DRUG GIARDIASIS – CHOICE DRUG ANAEROBIC BACTERIAL INFECTIONS: A.Intraabdominal, Gynaecologic, Dermal, CNS, Bones & Joints Infections, Bacterial septicemia & Endocarditis.  METRONIDAZOLE THERAPEUTIC USES: II. OTHER USES – ANAEROBIC BACTERIAL INFECTIONS B.TETANUS C.Mixed aerobic & anaerobic infections D.Pseudomembranous enterocoliltis – suprainfection. Preferred over parenteral vancomycin. E. Helicobacter pylori INFECTIONS – triple drug regimen  METRONIDAZOLE THERAPEUTIC USES: II. OTHER USES 5. DRACUNCULASIS – GUINEA WORM INFESTATION 6. HIV SERONEGATIVE EOSINOPHILIC PUSTULAR FOLLICULITIS 7. ANTIBOTIC ASSOCIATED DIARRHOEA IN PREGNANCY 8. RELIEVES SYMPTOMS IN IRRITABLE BOWEL SYNDROME  NITROIMIDAZOLES TINIDAZOLE LONG HALF LIFE – SINGLE DAILY DOSE ORAL & IV INFUSION MORE POTENT THAN METRONIDAZOLE MORE RAPID CELLULAR PENETRATION & INHIBITION OF DNA HIGHER & PERSISTANT PLASMA CONCENTRATIONS.  METRONIDAZOLE ADVERSE DRUG EFFECTS COMMON: Headache, Nausea, Dry Mouth, Metallic taste Less Frequent: Diziness, vertigo, darkurine, stomatitis, parestesias, furred tongue (due to candida), Neutropeia Urticaria, Flushing, Pruritis Prononged treatment –Peripheral Neuritis & Seizures DRUG INTERACTION: DISULFIRAM LIKE EFFECT; DECREASE THE METABOLISM OR EXCRETION - WARFARIN, LITHIUM, PHENYTOIN, CYCLOSPORIN, 5 FLUOROURACIL.  METRONIDAZOLE ADVERSE DRUG EFFECTS DRUG INTERACTION: DISULFIRAM LIKE EFFECT; DECREASE THE METABOLISM OR EXCRETION - WARFARIN, LITHIUM, PHENYTOIN, CYCLOSPORIN, 5 FLUOROURACIL. SPECIAL PRECAUTION: MUTAGENIC & CARCINOGENIC & TERATOGENIC IN ANIMAL STUDIES