Diazepam
Diazepam is a classic, long-acting **benzodiazepine** derivative widely utilized in veterinary medicine for its anxiolytic, muscle relaxant, hypnotic, appetite-stimulating, and anticonvulsant properties. **Clinical Pearls:** * **Seizure Management:** Diazepam is a first-line drug of choice for the emergency treatment of status epilepticus and cluster seizures. However, it is generally ineffective as a long-term maintenance anticonvulsant in dogs due to its short duration of action and the rapid development of tolerance. * **Feline Considerations:** While tolerance is less of an issue in cats, oral administration of diazepam is highly controversial due to the risk of idiosyncratic, potentially fatal **fulminant hepatic necrosis**. * **Formulation Quirk:** The injectable formulation contains **propylene glycol**, which can cause hypotension, bradycardia, and cardiotoxicity if administered too rapidly intravenously. It also readily adsorbs to PVC plastics, making it unsuitable for storage in plastic syringes or prolonged administration via standard IV fluid bags.
กลไกการออกฤทธิ์: Diazepam exerts its effects by binding to specific allosteric sites on **GABA-A receptors** in the central nervous system (primarily in the limbic system, thalamus, and hypothalamus). * Binding to the benzodiazepine site → enhances the affinity of the inhibitory neurotransmitter **gamma-aminobutyric acid (GABA)** for its receptor. * This facilitation → increases the frequency of chloride channel opening → influx of chloride ions → **neuronal hyperpolarization**. * The resulting hyperpolarization leads to profound CNS depression, producing anxiolytic, sedative, muscle relaxant, and anticonvulsant effects.
ขนาดยาตามชนิดสัตว์
- Urine marking and anxiety · 0.2-0.4 mg/kg (start at 0.2 mg/kg PO q12h) · PO · q12-24h
- Spraying · 1-2.5 mg per cat · PO · q8-12h · Sedation and ataxia should abate within several days.
- Fast-acting anxiolytic · 0.2-0.5 mg/kg · PO · prn
- Treatment of seizure disorders · 0.25-0.5 mg/kg · PO · q8-12h · Do not use if cat has been exposed to chlorpyrifos.
- Halt an ongoing seizure · 0.5-1 mg/kg · IV · prn · If cat has a history of receiving insulin, glucose may be more beneficial.
- Maintenance therapy for seizures · 0.2-1 mg/kg · PO · q12h · Use with caution; associated with fatal hepatic necrosis. Phenobarbital is preferred.
- Functional urethral obstruction/urethral sphincter hypertonus · 1-2.5 mg (total dose) · PO · q8h
- Functional urethral obstruction/urethral sphincter hypertonus · 2.5-5 mg (total dose) PO q8h or as needed, or 0.5 mg/kg IV · PO/IV · q8h or prn
- Short-term emergency control of severe epileptic seizures · Dose not specified in monograph · IV/Rectal · PRN · Short-term · Half-life is longer in cats; may be effective as maintenance, but oral use carries high risk of hepatic necrosis.
- Appetite stimulant · Dose not specified in monograph · PO/IV · PRN · Short-term · Use with extreme caution due to risk of liver injury.
วิธีการให้ยา
ข้อห้ามใช้
- Known hypersensitivity to benzodiazepines
- Cats exposed to chlorpyrifos (potentiates organophosphate toxicity)
- Significant liver disease (especially in cats)
- Intra-carotid artery injections (must be strictly avoided)
- CNS depression
- Respiratory depression
- Severe muscle weakness
- Hepatic impairment (may worsen hepatic encephalopathy)
- Long-term treatment of behavioural disorders (due to risks of disinhibition and interference with memory/learning)
อาการไม่พึงประสงค์
- Sedation and ataxia (most common)
- Dogs: Paradoxical CNS excitement/agitation (especially at doses >0.8 mg/kg)
- Dogs: Increased appetite
- Cats: Idiosyncratic hepatic failure (with oral use)
- Cats: Behavior changes (irritability, depression, aberrant demeanor)
- Horses: Muscle fasciculations, weakness, ataxia, recumbency (at doses >0.2 mg/kg)
- Hypotension and phlebitis (with rapid IV injection)
- Sedation
- Muscle weakness
- Ataxia
- Paradoxical excitation and aggression (especially with rapid IV injection or oral overdose in dogs)
- Pain and erratic absorption (IM injection)
- Fulminant hepatic necrosis (cats, repeated oral dosing)
- Thrombophlebitis (associated with propylene glycol injectable formulations)
อันตรกิริยาระหว่างยา
- Amitriptyline · May increase diazepam levels
- Antacids · May decrease oral diazepam absorption
- Azole Antifungals (itraconazole, ketoconazole) · May increase diazepam levels by inhibiting metabolism
- Cimetidine · May decrease metabolism of benzodiazepines · moderate
- CNS Depressants (barbiturates, narcotics, anesthetics) · Additive CNS depression effects may occur
- Dexamethasone · May decrease diazepam levels
- Digoxin · Diazepam may increase digoxin levels · moderate
- Erythromycin · May decrease the metabolism of benzodiazepines
- Mineral Oil · May decrease oral diazepam absorption
- Omeprazole · May inhibit the metabolism of diazepam and increase levels · moderate
- Phenobarbital · May decrease diazepam concentrations · moderate
- Phenytoin · May decrease diazepam concentrations
- Quinidine · May increase diazepam levels
- Rifampin · May induce hepatic microsomal enzymes and decrease the pharmacologic effects of benzodiazepines
การติดตาม
- Horses should be observed carefully after receiving this drug.
- Cats receiving oral diazepam must have baseline liver function tests. Repeat and discontinue drug if emesis, lethargy, inappetence, or ataxia develop.
- When used for seizure control in cats, obtain serum levels 5 days after beginning therapy (therapeutic goal: 200-700 ng/mL or 2500-700 nmol/L).
- Hepatic function (especially in cats)
- Respiratory rate and effort
- Level of CNS depression / sedation
- Seizure activity
การได้รับยาเกินขนาด
When administered alone, diazepam overdoses are generally limited to significant **CNS depression** (confusion, coma, decreased reflexes, etc.). Hypotension, respiratory depression, and cardiac arrest have been reported in human patients, but are quite rare. **Treatment:** * Standard protocols for removing and/or binding the drug in the gut if taken orally (e.g., emesis, activated charcoal). * Supportive systemic measures (fluids, respiratory support if needed). * The use of analeptic agents (CNS stimulants like caffeine) is generally **not recommended**. * **Flumazenil** (a specific benzodiazepine antagonist) may be considered for adjunctive treatment of severe overdoses.
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