アミノフィリン / テオフィリン
アミノフィリンおよびテオフィリンは、獣医学において主に強力な気管支拡張薬として利用される**メチルキサンチン誘導体**です。猫の喘息、馬の回帰性気道閉塞（RAO）、犬の気管支炎などの下気道疾患、気管虚脱の管理、および心原性肺水腫の補助療法として頻繁に使用されます。 > **臨床のポイント：** アミノフィリンは本質的にテオフィリンの水溶性塩であり、エチレンジアミンを付加することで生成されます。**100mgの含水アミノフィリンには約79mgの無水テオフィリンが含まれています。** 2つの形態間で切り替える場合は、用量換算を慎重に行う必要があります。 これらの薬剤は非常に有効ですが、**治療域が狭い（狭い治療指数）**という特徴があります。毒性は用量依存的ですが、犬や猫は一般的に人間よりも高い血清濃度に耐容性を示します。代謝における個体差が大きいため、特に肝疾患や心疾患を併発している患者では、治療薬物モニタリング（TDM）が強く推奨されます。
作用機序: The primary mechanism of action involves the competitive inhibition of **phosphodiesterase (PDE)** enzymes. * **PDE Inhibition** → Decreased breakdown of **cyclic AMP (cAMP)** → Elevated intracellular cAMP levels. * Increased cAMP → Enhanced release of endogenous **epinephrine** → Relaxation of bronchial and pulmonary vascular smooth muscle. * Elevated cAMP also inhibits the release of inflammatory mediators like **histamine** and slow-reacting substance of anaphylaxis (SRS-A) from mast cells. * **Intracellular Calcium Translocation:** Methylxanthines alter intracellular ionized calcium dynamics, contributing to increased diaphragmatic contractility (reducing respiratory fatigue) and weak positive inotropic/chronotropic effects on the heart. * **Additional Effects:** Induces mild diuresis, stimulates the central nervous system (CNS) and respiratory centers, and increases gastric acid secretion.
動物種別の用量
- Bronchodilation (Extended-Release) · 20 mg/kg PO once daily in the PM; using Slo-Bid: 25 mg/kg PO once daily in the PM · PO · q24h · Products Theo-Dur and Slo-Bid are no longer available in the USA. Cautious use of dog dose/products is a reasonable alternative.
- Bronchodilation · 6.6. mg/kg PO twice daily; using sustained release tablets (Theo-Dur): 25-50 mg (total dose) per cat PO in the evening · PO · q12h or q24h · Using aminophylline tablets or sustained release tablets
- Tracheal collapse (mild clinical signs, <50% collapse) · aminophylline: 5 mg/kg PO, two times daily. · PO · q12h
- Bronchoconstriction associated with fulminant CHF · Aminophylline 4-8 mg/kg SC, IM, IV q8-12h. · SC/IM/IV · q8-12h
- Cough · Aminophylline: 5 mg/kg PO twice daily · PO · q12h
- Bronchodilation · 4.25 mg/kg PO 2-3 times a day · PO · q8-12h
- Pulmonary edema · Aminophylline 2-7 mg/kg IV q6-12h; Theophylline 5-15 mg/kg PO q12h · IV/PO · q6-12h · IV aminophylline should be diluted in at least 100 mL of D5W or normal saline and administered slowly (not >25 mg/min).
- Pulmonary edema · 11 mg/kg PO or IV q8-12h. · PO/IV · q8-12h · To 'load' may either double the initial dose or give both oral and IV dose at the same time. IV infusion in ~1L fluids over 20-60 mins.
投与経路
禁忌
- Hypersensitivity to any xanthines (including theobromine or caffeine)
- Hypersensitivity to ethylenediamine (specific to aminophylline)
有害事象
- Nausea and vomiting
- Diarrhea
- Insomnia / Restlessness
- Polyphagia (increased appetite)
- Polydipsia and polyuria (increased thirst and urination)
- Tachycardia (rapid heart rate)
- Nervousness, excitability, and tremors (especially in horses)
- Diaphoresis (sweating in horses)
- Ataxia
- Seizures (in severe toxicity)
- Cardiac dysrhythmias (in severe toxicity)
薬物相互作用
- Phenobarbital · May decrease theophylline levels via hepatic enzyme induction.
- Fluoroquinolones (e.g., enrofloxacin, ciprofloxacin) · Can significantly increase theophylline levels. Consider reducing theophylline dose by 30% and monitor for toxicity.
- Macrolides (e.g., erythromycin, clindamycin, lincomycin) · Can increase theophylline levels.
- Cimetidine · Can increase theophylline levels by inhibiting hepatic metabolism.
- Ketamine · Concurrent use can cause an increased incidence of seizures.
- Halothane · Concurrent use may cause an increased incidence of cardiac dysrhythmias.
- Sympathomimetics (e.g., ephedrine, isoproterenol) · Toxic synergism; can lead to severe cardiac arrhythmias.
- Beta-blockers (non-selective, e.g., propranolol) · Can increase theophylline levels and antagonize bronchodilatory effects.
- Corticosteroids · Can increase theophylline levels.
モニタリング
- Therapeutic efficacy (improvement in breathing/cough)
- Clinical signs of toxicity (GI upset, CNS stimulation, tachycardia)
- Serum trough levels at steady state (Target: >8-10 mcg/mL in small animals; do not exceed 15 mcg/mL in horses. Human therapeutic range is 10-20 mcg/mL)
過量投与
Clinical signs of toxicity are usually associated with serum levels **greater than 20 mcg/mL** in humans, though dogs appear to tolerate higher levels. **Life-threatening signs:** * Tachycardia and severe cardiac arrhythmias * CNS effects including seizures and hyperthermia **Treatment is supportive:** * **Decontamination:** Empty the gut, administer activated charcoal and a cathartic if oral ingestion was recent. * **Seizures:** Maintain an adequate airway and treat with IV **diazepam**. * **Monitoring:** Continuous ECG monitoring for arrhythmias. Monitor and correct fluid/electrolyte imbalances. * **Symptomatic Care:** Hyperthermia may be treated with phenothiazines; severe tachycardia may be treated with **propranolol** if life-threatening.
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。