Metronidazole
Metronidazole is a synthetic nitroimidazole antibacterial and antiprotozoal agent widely used in veterinary medicine. **Key Clinical Applications:** * **Antiprotozoal:** Highly effective against *Giardia*, *Trichomonas*, *Entamoeba histolytica*, and *Balantidium coli*. * **Anaerobic Antibacterial:** Excellent efficacy against obligate anaerobes (e.g., *Bacteroides*, *Clostridium*, *Fusobacterium*). It is frequently used for enteric and systemic anaerobic infections, including sepsis, peritonitis, and deep bite wounds. * **Gastrointestinal Modulator:** Frequently utilized in the management of Inflammatory Bowel Disease (IBD) and chronic colitis. **Clinical Pearl:** Beyond its antimicrobial properties, metronidazole is believed to have local immunomodulatory and anti-inflammatory effects in the GI tract, specifically by inhibiting cell-mediated immunity. **Important Considerations:** * Strictly **prohibited by the FDA for use in food-producing animals**. * Notorious for its extremely bitter, metallic taste, which can cause profound hypersalivation and dosing aversion, especially in cats. Compounded metronidazole benzoate is often preferred for feline patients as it is less soluble in saliva and therefore less bitter.
Mecanismo: Metronidazole is a concentration-dependent bactericidal agent. **Mechanism Pathway:** 1. **Entry:** The drug enters the cell of the organism via passive diffusion. 2. **Activation:** In obligate anaerobes and certain protozoa, the nitro group of metronidazole is reduced by electron-transport proteins (such as **ferredoxin**). 3. **DNA Disruption:** This reduction process creates highly reactive, short-lived cytotoxic intermediate compounds (free radicals) → These radicals bind to and disrupt **DNA and nucleic acid synthesis** → leading to rapid cell death. Because aerobic bacteria lack the specific electron-transport proteins required to reduce and activate the drug, metronidazole is virtually inactive against obligate aerobes.
Dosificación por especie
- Giardia · 15-25 mg/kg · PO · q12-24h · 5-7 days
- Giardia · 25 mg/kg · PO · q12h · 7 days
- Giardia · 22 mg/kg · PO · twice daily · 5 days · May be combined with fenbendazole
- Entamoeba histolytica or Pentatrichomas hominis · 25 mg/kg · PO · q12h · 8 days
- H. pylori · 10-15 mg/kg · PO · two times a day · 14 days · With clarithromycin 7.5 mg/kg PO BID and amoxicillin 20 mg/kg PO BID
- Sepsis · 15 mg/kg · IV · q12h
- Inflammatory bowel disease (mild to moderate large bowel) · 10-20 mg/kg · PO · two to three times a day
- Inflammatory bowel disease · 62.5 mg (total dose) · PO · once daily · 10-20 days · With a change of diet to 'hypoallergenic'
- Inflammatory bowel disease (moderate to severe) · 10-15 mg/kg · PO · q8-12h · Combine with prednisone
- Hepatic encephalopathy · 7.5 mg/kg · PO · q8-12h
- Helicobacter mustelae gastritis infections · 22 mg/kg · PO · 3 times daily · 3-4 weeks · Using triple therapy with amoxicillin 22 mg/kg and bismuth subsalicylate 17.6 mg/kg
Vías de administración
Contraindicaciones
- Hypersensitivity to metronidazole or other nitroimidazole derivatives
- Food-producing animals (FDA prohibited)
- Pregnancy (potential teratogen, especially in early pregnancy)
- Severe hepatic disease (requires dose reduction)
Efectos adversos
- Neurologic disorders (ataxia, nystagmus, seizures, head-tilt)
- Lethargy and weakness
- Neutropenia
- Hepatotoxicity
- Hematuria
- Anorexia, nausea, vomiting, and diarrhea
- Hypersalivation (especially in cats due to bitter taste)
- Vomiting
- CNS toxicity (nystagmus, ataxia, knuckling, head tilt, seizures)
- Haematuria
- Excessive salivation/foaming (especially in cats)
- Impaired sense of smell (reported in explosive detection dogs)
Interacciones farmacológicas
- Alcohol · May induce a disulfiram-like reaction (nausea, vomiting, cramps).
- Cimetidine · May decrease the metabolism of metronidazole, increasing the likelihood of dose-related side effects. · major
- Phenobarbital · May increase the metabolism of metronidazole, thereby decreasing blood levels. · moderate
- Phenytoin · May increase the metabolism of metronidazole, thereby decreasing blood levels. · moderate
- Warfarin · May prolong the prothrombin time (PT). Avoid concurrent use or intensify monitoring.
- Macrolide antibiotics · Should not be used concurrently with Spiramycin (in combination products) as the combination may be antagonistic. · moderate
Monitoreo
- Clinical efficacy (resolution of diarrhea, negative fecal tests)
- Adverse effects (especially neurologic signs like ataxia or nystagmus)
- Neurological signs (for early detection of CNS toxicity)
- Liver function tests (ALT, AST, Bilirubin) in patients with pre-existing hepatic disease
- Complete Blood Count (for neutropenia)
Sobredosis
Signs of intoxication in dogs and cats are primarily neurologic and include: * Anorexia and/or vomiting * Depression * Mydriasis (dilated pupils) * **Nystagmus** (rapid eye flicking, very common in dogs) * **Ataxia** (stumbling, uncoordinated gait) * Head-tilt, proprioceptive deficits, joint knuckling * Tremors, seizures, rigidity, and stiffness These effects may be seen with acute massive overdoses, or more commonly with chronic therapy at doses >60 mg/kg/day (though sometimes seen at 'recommended' doses like 30 mg/kg/day). **Treatment:** * Discontinue metronidazole immediately. Most dogs with mild to moderate signs improve rapidly within 1-2 days of stopping the drug. * **Diazepam** has been used successfully to rapidly decrease the CNS effects associated with metronidazole toxicity. * For acute massive ingestions, standard decontamination protocols (emesis, activated charcoal) apply, but use **extreme caution** before inducing vomiting if the patient is already showing CNS signs, due to aspiration risk.
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