メキシレチン
メキシレチンは、リドカインと非常に似た電気生理学的特性を持つ経口の**クラスIB抗不整脈薬**です。リドカインは初回通過効果が大きく経口投与できないため、メキシレチンは不整脈の慢性管理における「経口版リドカイン」としてよく利用されます。 獣医療では主に、犬の**心室性不整脈**（心室期外収縮［PVC］や心室頻拍など）の治療に使用されます。特に、不整脈源性右室心筋症（ARVC）のボクサーや、拡張型心筋症（DCM）のドーベルマンでの使用が顕著です。相乗効果を得るために、β遮断薬（アテノロールなど）やソタロールと併用されることがよくあります。 さらに、メキシレチンは、**先天性ミオトニー**（チャウチャウやミニチュア・シュナウザーに見られる）や**ミオキミア**（ジャック・ラッセル・テリアに見られる）などの特定のまれな遺伝性筋疾患の治療にも利用されます。
作用機序: Mexiletine is a **Class IB antiarrhythmic**. * **Mechanism**: It binds to and inhibits the inward **fast sodium channels (Na+)** in the myocardial cell membrane. * **Electrophysiologic Effects**: By blocking these channels, it reduces the rate of rise of the action potential (**Phase 0**). In Purkinje fibers, it decreases automaticity, shortens the action potential duration, and decreases the effective refractory period. * **Selectivity**: Like lidocaine, it is highly selective for diseased, ischemic, or rapidly firing myocardial tissue, making it effective at suppressing ventricular ectopic pacemakers without significantly depressing normal sinus node function or conduction (unless pre-existing abnormalities exist).
動物種別の用量
- Treating or assisting in treatment of ventricular arrhythmias · 5-8 mg/kg · PO · q8h
- Treating or assisting in treatment of ventricular arrhythmias · 4-10 mg/kg · PO · q8h
- Ventricular arrhythmias in Boxers · 5-7.5 mg/kg · PO · three times daily · Given with sotalol at 1.5-3 mg/kg twice daily; was successful in 7/8 dogs treated in study.
- Treating or assisting in treatment of ventricular arrhythmias · 4-8 mg/kg · PO · q8h · Combined with atenolol (0.5 mg/kg PO q12-24h).
- Familial arrhythmic cardiomyopathy of Boxers (ARVC) · 5-8 mg/kg · PO · q8h · Given with atenolol at 12.5 mg (total dose) q12h.
- Treating or assisting in treatment of ventricular arrhythmias · 5-6 mg/kg · PO · q8h · Always give with food to avoid nausea.
- Myotonia congenita or myokymia · 8.3 mg/kg · PO · q8h · Most studied in Chow Chows, miniature schnauzers, and Jack Russell terriers.
用量は獣医療従事者向けの臨床リファレンスです。必ず最新の添付文書と個々の患者で確認してください。
投与経路
禁忌
- Pre-existing 2nd or 3rd degree AV block (without a pacemaker)
- Cardiogenic shock
- Known hypersensitivity to mexiletine
有害事象
- Vomiting (very common)
- Nausea
- Trembling/Tremors
- Unsteadiness/Ataxia
- Dizziness
- Depression/Lethargy
- Shortness of breath
- Proarrhythmia (PVCs)
- Chest pain
- Seizures (rare)
- Agranulocytosis (rare)
- Thrombocytopenia (rare)
薬物相互作用
- Antacids (Aluminum-Magnesium) · May slow the absorption of mexiletine.
- Atropine · May reduce the rate of oral absorption.
- Cimetidine · May increase or decrease mexiletine blood levels.
- Griseofulvin · May accelerate the metabolism of mexiletine.
- Lidocaine · May cause additive adverse effects (especially CNS toxicity).
- Metoclopramide · May accelerate the absorption of mexiletine.
- Opiates · May slow the absorption of mexiletine.
- Phenobarbital · May accelerate the metabolism of mexiletine.
- Primidone · May accelerate the metabolism of mexiletine.
- Phenytoin · May accelerate the metabolism of mexiletine.
- Rifampin · May accelerate the metabolism of mexiletine.
- Theophylline · Mexiletine may reduce the metabolism of theophylline, potentially leading to theophylline toxicity.
- Urinary Acidifying Drugs (e.g., methionine, ammonium chloride) · May accelerate the renal excretion of mexiletine.
モニタリング
- Electrocardiogram (ECG) to assess antiarrhythmic efficacy and monitor for proarrhythmia
- Clinical signs of adverse effects (especially GI and CNS signs)
- Plasma concentrations (Therapeutic range in humans: 0.5-2 mcg/mL; note that toxicity may be noted even at therapeutic levels)
- Liver enzymes (AST may transiently increase in a small percentage of patients)
過量投与
Toxicity associated with overdosage can be significant and life-threatening. * **Clinical Signs**: In human case reports, **CNS signs (tremors, seizures, depression) always preceded cardiovascular signs** (hypotension, bradycardia, heart block). * **Treatment**: * Perform GI tract emptying protocols (emesis/gastric lavage) if indicated and safe. * Administer supportive therapy. * Acidification of the urine may be considered to enhance urinary excretion. * **Atropine** may be useful if severe hypotension or bradycardia occurs.
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。