Lorazepam
Lorazepam is a potent, intermediate-acting **benzodiazepine** utilized in veterinary medicine primarily as an anxiolytic for behavioral disorders and as an alternative to diazepam for the management of **status epilepticus**. > **Clinical Pearl:** Unlike diazepam, lorazepam undergoes direct glucuronidation without forming active intermediate metabolites. This makes it a significantly safer option for geriatric, obese, or hepatically compromised patients. - **Versatile Administration:** It can be administered via multiple routes, including intranasal, intramuscular, and sublingual/buccal, making it highly versatile for emergency seizure management at home or in the clinic. - **Duration:** It appears to be as effective as diazepam and may possess a longer duration of anticonvulsant action, though this is not definitively proven in dogs.
Mecanismo: Lorazepam acts as a **positive allosteric modulator** at the **GABA-A receptor**. - It binds to the benzodiazepine site on the GABA-A receptor complex → enhances the affinity of the receptor for the inhibitory neurotransmitter **gamma-aminobutyric acid (GABA)**. - This increases the frequency of chloride channel openings → influx of chloride ions → **hyperpolarization** of the neuronal membrane → decreased neuronal excitability. - This widespread CNS depression primarily affects the subcortical levels (limbic, thalamic, and hypothalamic), yielding anxiolytic, sedative, skeletal muscle relaxant, and anticonvulsant effects. - Other postulated mechanisms include antagonism of serotonin and diminished release or turnover of acetylcholine in the CNS.
Dosificación por especie
- Fears/anxiety · 0.03-0.08 mg/kg PO q12h · PO · q12h · The lowest dose and frequency that alleviate the fear should be used
- Fears, anxieties, phobias · 0.125 mg-0.25 mg total dose (¼-½ of a 0.5 mg tablet) once to twice a day · PO · q12-24h · May be used on an as needed basis
- Anxiolytic · 0.05-0.25 mg/kg PO q12-24h · PO · q12-24h
- Short-term management of anxiety disorders · 0.02-0.1 mg/kg · PO · q12-24h · Short-term · Start at the lower end of the dose range and gradually increase. Monitor closely for signs of hepatotoxicity.
- Status epilepticus (alternative to diazepam) · 0.2 mg/kg IV, IM or intranasal once · IV/IM/intranasal · once
- Status epilepticus · 0.2 mg/kg IV once, followed by a bolus IV loading dose of levetiracetam at 60 mg/kg · IV · once
- Fears, anxieties, phobias · 0.02-0.1 mg/kg PO once daily to three times a day · PO · q8-24h · May be used on an as needed basis
- Anxiolytic · 0.05-0.25 mg/kg PO q12-24h · PO · q12-24h
- Fears/anxiety · 0.02-0.5 mg/kg PO q8h · PO · q8h · The lowest dose and frequency that alleviate the fear should be used
- Fears, anxieties, phobias, aversions · 0.02-0.1 mg/kg q8-24h · PO · q8-24h · Minimally sedating, may require 4 weeks to peak effect
Vías de administración
Contraindicaciones
- Hypersensitivity to benzodiazepines
- Severe respiratory insufficiency (unless mechanically ventilated)
- Glaucoma
- Significant liver disease
- Significant kidney disease
- Pregnant animals
- Lactating animals
Efectos adversos
- Increased appetite
- Aggression
- Increased activity/excitement (paradoxical reaction)
- Vocalization
- Ataxia
- Somnolence
- Lethargy
- Disinhibition (potential emergence of aggression)
- Drowsiness
- Mild transient incoordination (ataxia)
- Tremor and inappetence (associated with acute withdrawal)
Interacciones farmacológicas
- CNS Depressants (opiates, barbiturates, sedatives, anticonvulsants) · Additive CNS effects
- Probenecid · Decreased renal clearance of lorazepam
- Scopolamine · Increased CNS depression, irrational behavior
- Theophylline · Decreased sedation from lorazepam
- Valproate · Increased lorazepam serum concentration
- Itraconazole · Inhibits the metabolism of lorazepam, potentially leading to increased plasma concentrations and prolonged sedation. · moderate
- Ketoconazole · May inhibit the metabolism of lorazepam, increasing the risk of toxicity. · moderate
- Other CNS Depressants · Additive CNS depression and sedation. · major
Monitoreo
- Clinical efficacy (seizure control or anxiety reduction)
- Adverse effects (CNS depression, paradoxical excitation, ataxia)
- Behavioral changes (watch for paradoxical aggression or extreme sedation)
- Liver enzymes (ALT, AST, ALP, Bilirubin), especially in cats
- Appetite and water intake
Sobredosis
Overdoses of lorazepam are generally limited to **CNS depression** (confusion, lethargy, somnolence, decreased reflexes). - **Severe Toxicity:** Very large overdoses can cause ataxia, hypotension, coma, and rarely death. - **Treatment:** Standard protocols for removing/binding the drug in the gut (if orally ingested) and supportive systemic measures. Forced diuresis with IV fluids/electrolytes and mannitol may enhance excretion in patients with normal renal function. - **Antidote:** **Flumazenil** may be considered for adjunctive treatment of serious overdoses, but it does not replace supportive therapy. *Caution: Flumazenil is not recommended in patients with seizure disorders as it may induce seizures.* - **Note:** Analeptic agents (CNS stimulants like caffeine) are generally not recommended.
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