卡維地洛
卡維地洛（Carvedilol）是一種獨特的第三代**非選擇性β受體阻斷劑**，同時具有**α-1腎上腺素受體阻斷**特性。在獸醫學中，主要被研究作為**犬擴張性心肌病 (DCM)** 及慢性心臟衰竭的輔助治療。 * **雙重作用：** 與傳統的β受體阻斷劑（如阿替洛爾）不同，卡維地洛提供額外的血管擴張作用，從而降低心臟後負荷。 * **具爭議性的使用：** 其在獸醫心臟病學中的應用仍具爭議。雖然在人類心臟衰竭中已證實能降低死亡率，但在犬隻的研究中，標準劑量對於改善神經賀爾蒙活化或心室重塑的療效結果不一。 * **臨床要點：** 卡維地洛具有強烈的負性肌力作用。它可能會導致晚期或症狀嚴重的心臟衰竭患畜出現急性代償失調。必須極度謹慎且緩慢地向上滴定劑量，且最好在症狀輕微的患畜中開始使用。
作用機制: Carvedilol exerts its cardiovascular effects through multiple mechanisms: * **Non-selective Beta-Adrenergic Blockade (β1 and β2):** Heart failure leads to chronic sympathetic nervous system (SNS) activation → tachycardia, renin-angiotensin-aldosterone system (RAAS) activation, beta-receptor downregulation, and myocyte necrosis. Carvedilol blocks these receptors → **reverses/diminishes SNS toxicity**, reduces heart rate, and decreases myocardial oxygen demand. * **Selective Alpha-1 Adrenergic Blockade:** Blocks peripheral α1-receptors → **vasodilation** → reduces systemic vascular resistance and cardiac afterload. * **Antioxidant Properties:** Carvedilol and its metabolites act as potent scavengers of reactive oxygen species (ROS) and inhibit lipid peroxidation, protecting the myocardium from oxidative stress. * **Antidysrhythmic Effects:** Secondary to its beta-blocking and membrane-stabilizing properties.
各物種劑量
- Heart failure (adjunctive therapy) · ¼-½ of a 3.125 mg tablet PO twice daily · PO · twice daily · Usual starting dose. Start at the low end of the dosing range and gradually titrate upward carefully watching to avoid negative inotropic effects.
- Early/mild heart failure or later stages of CHF · 0.2 mg/kg PO twice daily initially with slow titration upwards towards a dose of 0.8 mg/kg twice daily · PO · twice daily · Beta blockers are best employed in dogs that are minimally symptomatic. Many dogs with CHF will not tolerate this upward titration.
- Heart failure (target plasma concentration) · 0.5 mg/kg PO twice daily · PO · twice daily · Should result in beta-blockade, but maximum beta-blockade may require doses of >0.7-0.9 mg/kg. Because of bioavailability variations, plasma monitoring, clinical trials and uptitration protocols may be beneficial.
- Dilated cardiomyopathy · 0.3 mg/kg PO q12h · PO · q12h · 3 months · Did not produce any significant improvements in neurohormonal activation, heart size, or owner-perceived quality of life. Doses >0.3 mg/kg q12h are likely to be required to effect changes in ventricular remodeling and function.
- Chronic heart failure / Dilated Cardiomyopathy (DCM) · Start at 0.05-0.1 mg/kg, gradually increase at 2-week intervals to target dose of 0.3-0.4 mg/kg · PO · q12h · Long-term · Increase dose only if tolerated.
- ACVIM stage B2 degenerative mitral valve disease · 0.3 mg/kg, increased at intervals up to 1.1 mg/kg · PO · q12h · Long-term · For cardiac remodelling with no signs of cardiac failure.
劑量為持牌獸醫專業人員的臨床參考。請務必對照最新藥品說明書及個別病患確認。
給藥途徑
禁忌症
- Class IV decompensated heart failure
- Bronchial asthma
- 2nd or 3rd degree AV block
- Sick sinus syndrome (unless artificially paced)
- Severe bradycardia
- Cardiogenic shock
- Hypersensitivity to the drug
不良反應
- Inappetence
- Lassitude (lethargy/fatigue)
- Hypotension
- Decompensation of heart failure (if titrated too rapidly)
- Bronchospasm (reported in humans)
- Mild hepatocellular injury (rare)
藥物相互作用
- Beta-Blockers (other) · Use with carvedilol may cause additive effects
- Calcium Channel Blockers (e.g., diltiazem, verapamil) · May rarely cause hemodynamic compromise
- Cimetidine · May decrease metabolism and increase AUC of carvedilol
- Clonidine · Carvedilol may potentiate the cardiovascular effects of clonidine
- Cyclosporine · Carvedilol may increase cyclosporine levels
- Digoxin · Can increase digoxin plasma concentrations by approximately 15% · major
- Fluoxetine, Paroxetine, Quinidine · May increase R(+)carvedilol concentrations and increase alpha-1 blocking effects (vasodilation)
- Insulin / Oral Antidiabetic Agents · Carvedilol may enhance the blood glucose lowering effects of insulin or other antidiabetic agents
- Rifampin · Can decrease carvedilol plasma concentrations by as much as 70% · moderate
- Reserpine · Can cause increased bradycardia and hypotension in patients taking carvedilol
- Anaesthetic agents · Enhanced hypotensive effect and myocardial depression · major
- Phenothiazines · Enhanced hypotensive effect · moderate
監測
- Clinical efficacy (improvement in heart failure signs)
- Adverse effects (lethargy, inappetence, hypotension, worsening heart failure)
- Plasma drug levels (Target: 50-100 nanograms/mL)
過量
The acute oral LD50 in healthy rats and mice is greater than 8 grams/kg. **Clinical Signs of Overdose:** * Severe hypotension * Cardiac insufficiency * Bradycardia * Cardiogenic shock * Death due to cardiac arrest **Treatment:** * Gut emptying protocols should be considered if ingestion was recent. * **Bradycardia:** Treat with atropine. * **Cardiovascular Support:** Support function with glucagon and sympathomimetics (e.g., dobutamine, epinephrine). * Contact an animal poison control center for specific information.
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