Diltiazem
Diltiazem is a **non-dihydropyridine calcium channel blocker** and **Class IV antiarrhythmic** agent used primarily in veterinary medicine to manage supraventricular tachycardias (SVTs), systemic hypertension, pulmonary hypertension, and hypertrophic cardiomyopathy (HCM), particularly in cats. * **Cardiovascular Effects:** It acts primarily by slowing conduction through the AV node and promoting vasodilation, making it highly effective for rate control in atrial fibrillation. * **Clinical Utility:** While historically a cornerstone for feline HCM, its use for this specific indication has decreased in recent years in favor of other therapies, though it remains a vital tool for tachyarrhythmias. * **Clinical Pearl:** Unlike dihydropyridines (e.g., amlodipine) which are potent peripheral vasodilators, diltiazem has more pronounced effects on cardiac conduction, making it superior for rhythm control but less potent for severe systemic hypertension.
Mecanismo: Diltiazem exerts its effects by binding to the alpha-1 subunit of **L-type voltage-gated calcium channels**. * **Mechanism:** Inhibits transmembrane influx of extracellular calcium ions → decreases intracellular calcium in myocardial cells and vascular smooth muscle. * **Cardiac Conduction:** Slows **AV node conduction** and prolongs refractory times (negative dromotropic effect). It rarely affects SA node conduction except in sick sinus syndrome. * **Vasodilation:** Relaxes vascular smooth muscle → dilates main systemic and coronary arteries → reduces total peripheral resistance, blood pressure, and cardiac afterload. * **Inotropy:** Can cause mild negative inotropic effects, though rarely of clinical significance compared to verapamil.
Dosificación por especie
- Treatment of hypertrophic cardiomyopathy (Option A) · 7.5 mg (total dose) PO q8-12h; Long-acting forms: Cardizem CD Capsules: 10 mg/kg once daily. Dilacor XR Capsules: 15-30 mg total dose q12-24h. · PO · q8-24h · Some cats tolerate 60 mg daily, but vomiting may be a problem.
- Treatment of hypertrophic cardiomyopathy (Option B) · 1.75-2.5 mg/kg PO q8h or sustained release (Dilacor) dosed at 30 mg (total dose) PO q12h · PO · q8-12h
- Treatment of hypertrophic cardiomyopathy (Option C) · 7.5-15 mg (total dose) per cat PO q8h. Alternatively, the sustainedrelease products Cardizem CD at 45 mg (total dose) PO q24h or Dilacor XR at 30 mg (total dose; 1/2 of one of the 60 mg tablets found within the capsule) PO q12h can be used. · PO · q8-24h
- Treatment of hypertrophic cardiomyopathy (Option D) · If using standard release formulations: 1-2.5 mg/kg PO q8h; if using sustained release formations: 30-60 mg (total dose per cat) q24h. · PO · q8-24h · Also indicated for supraventricular arrhythmias.
- Treatment of hypertrophic cardiomyopathy (Option E) · Dilacor XR 30 mg/cat PO q24h. · PO · q24h · If cat has minimal tachycardia and a loud S4 gallop, many prefer using diltiazem (over a beta blocker).
- Emergency treatment of supraventricular tachyarrhythmias · Initially, 0.25 mg/kg IV bolus given over 2 minutes; subsequent 0.25 mg/kg boluses may be repeated at 15 minute intervals until conversion occurs or to a maximum (total) dose of 0.75 mg/kg. · IV · q15min
- Acute management of supraventricular tachyarrhythmias · 0.125-0.35 mg/kg IV · IV · As directed
- Chronic management of supraventricular tachyarrhythmias · 7.5 mg (per cat) PO q8h · PO · q8h · Used in combination with digoxin for patients with CHF unless cat has hypertrophic cardiomyopathy and atrial fib, then digoxin not used.
Vías de administración
Contraindicaciones
- Severe hypotension (<90 mm Hg systolic)
- Sick sinus syndrome (unless functioning pacemaker is in place)
- 2nd or 3rd degree AV block (unless functioning pacemaker is in place)
- Acute myocardial infarction
- Radiographically documented pulmonary congestion
- Hypersensitivity to diltiazem
- Second or third degree AV block
- Marked hypotension
- Sick sinus syndrome
- Acute or decompensated congestive heart failure (relative contraindication)
Efectos adversos
- Dogs: Bradycardia (most prominent)
- Cats: Vomiting (especially with 60 mg sustained-release pellets)
- Lethargy
- Anorexia / GI distress
- Hypotension
- Heart block or rhythm disturbances
- CNS effects
- Skin rashes
- Elevations in liver enzymes
- Bradycardia (most common in dogs)
- Vomiting (most common in cats)
- AV block
Interacciones farmacológicas
- Anesthetics, General · May increase cardiac depressant effects of diltiazem.
- Benzodiazepines · Diltiazem may increase benzodiazepine levels.
- Beta-Blockers · May increase the likelihood of bradycardia, AV block, or CHF. Diltiazem may substantially increase the bioavailability of propranolol.
- Buspirone · Diltiazem may increase buspirone levels.
- Cisapride · Could potentially increase risk for increased QT intervals.
- Digoxin · Data conflicts regarding pharmacokinetic effects; diligent monitoring of digoxin serum concentrations is required. · moderate
- Cimetidine · May increase plasma diltiazem concentrations; increased monitoring warranted. · moderate
- Ranitidine · May affect diltiazem concentrations, but to a lesser extent than cimetidine.
- Cyclosporine · Diltiazem may increase cyclosporine serum concentrations; monitoring and dosage adjustments may be required.
- Rifampin · May decrease diltiazem levels.
- Quinidine · Diltiazem may increase quinidine serum concentrations; monitoring and dosage adjustments may be required.
- Beta-adrenergic blockers (e.g., propranolol) · Additive negative inotropic and chronotropic effects. Co-administration is not recommended. · major
Monitorización
- ECG / Heart rate
- Blood pressure
- Adverse effects (vomiting, lethargy)
- Heart rate and rhythm (ECG)
- Renal and hepatic function (periodically)
- Serum digoxin levels (if used concurrently)
Sobredosis
The oral LD50 in dogs is >50 mg/kg. * **Clinical Signs:** GI signs, heart block, severe bradycardia, hypotension, CNS depression, and heart failure. * **Treatment:** * Gut emptying protocols if recent ingestion. * **Bradycardia/AV Block:** Atropine. If unresponsive to vagal blockade, cautious use of isoproterenol. Fixed block may require temporary transvenous cardiac pacing. * **Hypotension/Heart Failure:** Inotropics (dobutamine, dopamine, isoproterenol) and pressors (norepinephrine). * **Antidote:** A slow intravenous calcium infusion (1 mL/10 kg body weight of 10% calcium gluconate) may be useful for severe acute toxicity.
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