勞拉西泮 (Lorazepam)
勞拉西泮 (Lorazepam) 是一種強效的中效**苯二氮平類藥物 (Benzodiazepine)**，在獸醫學中主要用作行為障礙的抗焦慮藥，以及作為地西泮 (Diazepam) 的替代品來治療**癲癇重積狀態**。 > **臨床重點：** 與地西泮不同，勞拉西泮直接進行葡萄糖醛酸結合反應，不會形成具活性的中間代謝物。這使其成為老年、肥胖或肝功能受損病患更安全的選擇。 - **給藥途徑多樣：** 可透過多種途徑給藥，包括鼻內、肌肉注射和舌下/頰內，使其在家庭或診所的緊急癲癇管理中具有高度靈活性。 - **作用時間：** 其療效似乎與地西泮相當，且可能具有更長的抗癲癇作用時間（儘管在犬隻中尚未被明確證實）。
作用機制: 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.
各物種劑量
- 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
給藥途徑
禁忌症
- Hypersensitivity to benzodiazepines
- Severe respiratory insufficiency (unless mechanically ventilated)
- Glaucoma
- Significant liver disease
- Significant kidney disease
- Pregnant animals
- Lactating animals
不良反應
- 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)
藥物相互作用
- 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
監測
- 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
過量
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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