ロラゼパム
ロラゼパムは強力な中時間作用型**ベンゾジアゼピン系薬**であり、獣医療では主に行動障害に対する抗不安薬として、また**てんかん重積状態**の治療においてジアゼパムの代替薬として使用されます。 > **臨床のポイント：** ジアゼパムとは異なり、ロラゼパムは活性代謝物を形成せずに直接グルクロン酸抱合を受けます。そのため、高齢、肥満、または肝機能障害のある患者にとってより安全な選択肢となります。 - **多様な投与経路：** 経鼻、筋肉内、舌下/頬側など複数の経路で投与できるため、家庭やクリニックでの緊急のてんかん管理において非常に汎用性が高いです。 - **作用時間：** ジアゼパムと同等の効果があると考えられており、抗てんかん作用の持続時間がより長い可能性があります（ただし、犬では明確に証明されていません）。
作用機序: 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.
動物種別の用量
- 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
投与経路
禁忌
- Hypersensitivity to benzodiazepines
- Severe respiratory insufficiency (unless mechanically ventilated)
- Glaucoma
- Significant liver disease
- Significant kidney disease
- Pregnant animals
- Lactating animals
有害事象
- 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)
薬物相互作用
- 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
モニタリング
- 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
過量投与
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.
VetSheet の薬剤リファレンスは、獣医療従事者向けの臨床意思決定支援を目的としており、専門的判断やメーカーの最新添付文書に代わるものではありません。