イミプラミン
イミプラミンは、獣医療において適応外使用される**三環系抗うつ薬（TCA）**です。主に分離不安などの行動学的問題に認識されていますが、そのユニークな受容体プロファイルにより非常に多用途です。 * **犬や猫**では、**尿失禁**や**情動脱力発作（カタプレキシー）**の治療に頻繁に使用されます。 * **馬の医療**では、**ナルコレプシー**の管理や薬理学的な射精の誘発に用いられます。 > **臨床のポイント：**イミプラミンは第3級アミンTCAであり、肝臓で急速に活性を持つ第2級アミン代謝物である**デシプラミン**に代謝されます。この二重の作用により、セロトニンとノルアドレナリンの両方の経路に影響を与え、薬理学的なスペクトルが広がります。
作用機序: Imipramine and its active metabolite, desipramine, exert their effects through a complex, multi-receptor pharmacologic profile: * **Monoamine Reuptake Inhibition**: Blocks the presynaptic amine pump, preventing the reuptake of **serotonin (5-HT)** and **norepinephrine (NE)** → increases neurotransmitter concentrations in the synaptic cleft → modulates mood, arousal, and pain pathways. * **Anticholinergic Activity**: Antagonizes **muscarinic receptors** centrally and peripherally. This mechanism is primarily responsible for its efficacy in treating urinary incontinence (facilitating urine storage by relaxing the detrusor muscle) and its common side effects (dry mouth, tachycardia). * **Alpha-Adrenergic Agonism/Antagonism**: Exhibits complex interactions at alpha receptors, which may contribute to increasing internal urethral sphincter tone. * **Antihistaminic (H1) Activity**: Contributes to its significant **sedative** properties.
動物種別の用量
- Urethral incompetence · 2.5-5 mg (total dose) · PO · q12h
- Adjunctive cancer pain treatment · 2.5-5 mg (total dose) · PO · q12h
- Anxiety, inappropriate urination · 0.5-1 mg/kg · PO · q12-24h
- Pharmacologic induced ejaculation · 2 mg/kg · IV · once · If imipramine alone does not induce erection and ejaculation in 10-15 minutes, give xylazine 0.2-0.3 mg/kg IV. (Note: ARCI UCGFS Class 2 Drug)
- Narcolepsy/cataplexy · 0.55 mg/kg IV or 250-750 mg (total dose) orally · IV, PO · once · PO administration produces inconsistent results.
- Urethral incompetence · 5-15 mg (total dose) · PO · q12h
- Urinary incontinence when other agents fail · 5-20 mg (total dose) · PO · q12h
- Cataplexy · 0.5-1 mg/kg · PO · q8h · Titrate dose based on clinical effect
- Adjunctive treatment of separation anxiety or other tricyclic antidepressant-responsive behavior disorders · 2.2-4.4 mg/kg · PO · once to twice daily
- Adjunctive cancer pain treatment · 0.5-1 mg/kg · PO · q8h
投与経路
禁忌
- Prior sensitivity to any tricyclic antidepressant
- Concomitant use with monoamine oxidase inhibitors (MAOIs) within 14 days
- Glaucoma
- History of seizures
- Urinary retention
- Severe liver disease
- Hypersensitivity to tricyclic antidepressants
有害事象
- Sedation
- Dry mouth
- Constipation
- Tachycardia
- Hyperexcitability
- Tremors
- Seizures (CNS stimulation)
- Bone marrow suppression
- Diarrhea
- Vomiting
- Diarrhoea
- Excitability
- Arrhythmias
- Hypotension
- Syncope
- Increased appetite
薬物相互作用
- Anticholinergic agents · Additive anticholinergic effects; use cautiously
- Cimetidine · May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity · major
- CNS Depressants · Additive CNS depressant effects; use cautiously
- Levodopa · Imipramine may decrease levodopa oral absorption
- Phenobarbital · May decrease tricyclic levels
- Quinidine · Increased risk for QTc interval prolongation and tricyclic adverse effects
- Rifampin · May decrease tricyclic blood levels
- SSRIs (e.g., fluoxetine, paroxetine, sertraline) · Increased risk for serotonin syndrome
- Sympathomimetic agents · May increase the risk of cardiac effects (arrhythmias, hypertension, hyperpyrexia)
- Monoamine Oxidase Inhibitors (including amitraz, selegiline) · Concomitant use (within 14 days) is generally contraindicated due to risk of serotonin syndrome
- Thyroid agents · May increase risk for cardiac arrhythmias
- Cisapride · Increased risk for prolonged QT interval
- Clonidine · Tricyclics may increase blood pressure
モニタリング
- Clinical efficacy
- Adverse effects
- ECG (Tricyclics can widen QRS complexes, prolong PR intervals, and invert or flatten T-waves)
- Blood Glucose (Tricyclics may increase or decrease blood glucose levels)
- Heart rate and rhythm (ECG) in susceptible patients
- Signs of serotonin syndrome (agitation, tremors, hyperthermia, tachycardia) if used with other serotonergic drugs
- Liver function tests (baseline and periodic)
過量投与
Overdosage with tricyclics can be **life-threatening**, leading to severe arrhythmias and cardiorespiratory collapse. Because the toxicities and therapies for treatment are complicated and controversial, it is highly recommended to **contact a poison control center** for further information in any potential overdose situation.
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。