ドキセピン
ドキセピンはジベンゾオキサゼピン誘導体の**三環系抗うつ薬（TCA）**であり、獣医療では主に不安要素を伴う心因性皮膚疾患の補助療法として使用されます。 抗うつ薬に分類されますが、極めて強力な**H1-抗ヒスタミン作用**を持ち、そう痒と行動の問題を管理するための二重の目的を持つ薬剤です。アトピー性皮膚炎に対する単独の抗ヒスタミン薬としての有効性には議論がありますが、そう痒が不安や強迫行動（肢端舐性皮膚炎、過剰なグルーミングなど）を悪化させる、あるいは引き起こす場合には非常に有用です。 > **臨床のポイント**: 抗不安作用と抗ヒスタミン作用を併せ持つため、アレルギー性皮膚疾患を患う神経質または興奮しやすい患者にしばしば選択されます。
作用機序: Doxepin exerts its effects through multiple receptor pathways: * **Monoamine Reuptake Inhibition:** In the central nervous system, doxepin blocks the presynaptic reuptake of **norepinephrine** (moderate inhibition) and **serotonin (5-HT)** (weak inhibition) → increasing their synaptic concentrations and prolonging their activity, which contributes to its antidepressant and anxiolytic effects. * **Receptor Antagonism:** It exhibits potent **H1-histamine receptor blockade** (providing anti-pruritic and sedative effects), as well as **anticholinergic (muscarinic)** and **alpha-1 adrenergic blocking** activity. These latter receptor affinities are largely responsible for its side effect profile (e.g., dry mouth, urinary retention, hypotension).
動物種別の用量
- Treatment of psychogenic dermatoses · 0.5-1 mg/kg PO q12-24h. Up to 25-50 mg (total dose) per cat. · PO · q12-24h · Allow 3-4 weeks for initial trial
- Excessive grooming · 0.5-1 mg/kg PO q12h. · PO · q12h
- Treatment of behavior problems (e.g., overgrooming, intercat aggression) · 0.5-1 mg/kg PO once to twice daily. · PO · SID to BID
- Treatment of anxiety, pruritus caused feather plucking in psittacines · 1-2 mg/kg PO q12h · PO · q12h
- Treatment of anxiety, pruritus caused feather plucking in psittacines · 0.5-1 mg/kg PO twice daily · PO · BID
- Treatment of psychogenic dermatoses · 3-5 mg/kg PO q12h; maximum dose is 150 mg (per dog) q12h · PO · q12h
- Treatment of psychogenic dermatoses · 3-5 mg/kg, PO q8-12h. Begin at 3 mg/kg PO q12h for 2 weeks, then increase by 1 mg/kg PO q12h for 2 weeks up to the maximum dosage as needed; if no clinical response after at least 3-4 weeks of therapy, decrease dosage by 1 mg/kg PO q12h for 2 weeks until at the initial dosage · PO · q8-12h · Titrated over weeks
- Antihistaminic effects in treatment of atopy · 2.2 mg/kg PO three times daily · PO · TID
- Antihistaminic effects in treatment of atopy · 3-5 mg/kg twice daily · PO · BID · Used especially if dog has anxiety or other behavioral condition
投与経路
禁忌
- Prior sensitivity to doxepin or other tricyclic antidepressants
- Concomitant use with Monoamine Oxidase Inhibitors (MAOIs) such as selegiline or amitraz (within 14 days)
- Urinary retention
- Glaucoma
- Severe cardiac disease
- History of seizures
- Concurrent use with MAOIs
有害事象
- Hyperexcitability (paradoxical)
- Gastrointestinal distress
- Lethargy and sedation
- Ventricular arrhythmias (particularly in overdose)
- Anticholinergic effects (dry mouth, urinary retention, constipation)
- Altered blood glucose levels
- Sedation
- Lethargy
- Dry mouth (xerostomia)
- Tachycardia
- Urinary retention
- Constipation
薬物相互作用
- Anticholinergic Agents · Additive anticholinergic effects; use cautiously. · moderate
- Cimetidine · May inhibit tricyclic antidepressant metabolism and increase the risk of toxicity. · moderate
- CNS Depressants · Additive CNS depression; use cautiously. · moderate
- Meperidine, Pentazocine, Dextromethorphan · Increased risk for serotonin syndrome.
- Monoamine Oxidase Inhibitors (MAOIs, e.g., amitraz, selegiline) · Concomitant use (within 14 days) is generally contraindicated due to high risk of serotonin syndrome.
- Quinidine · Increased risk for QTc interval prolongation and tricyclic adverse effects.
- 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 (MAOIs) · Risk of fatal serotonin syndrome · major
- Selective Serotonin Reuptake Inhibitors (SSRIs) · Increased risk of serotonin syndrome · major
モニタリング
- Efficacy (reduction in pruritus, anxiety, or compulsive behaviors)
- Adverse effects (GI distress, lethargy, hyperexcitability)
- ECG (if arrhythmias are suspected or in cases of overdose)
- Heart rate and rhythm
- Resolution of pruritus or behavioral signs
- Signs of excessive sedation or anticholinergic effects
過量投与
Overdosage with tricyclic antidepressants can be **life-threatening**. * **Clinical Signs:** Severe ventricular arrhythmias, cardiorespiratory collapse, profound CNS depression or seizures. * **Action:** Because the toxicities and therapies for treatment are complicated and controversial, it is highly recommended to contact an **animal poison control center** immediately 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。