Verapamil
Verapamil is a **non-dihydropyridine calcium channel blocker** and a **Class IV antiarrhythmic** agent. Unlike dihydropyridine calcium channel blockers (such as amlodipine) which primarily target vascular smooth muscle to cause vasodilation, verapamil has profound effects on the cardiac conduction system, specifically the atrioventricular (AV) node. **Key Clinical Uses:** * Primarily utilized in veterinary medicine to manage **supraventricular tachycardias (SVT)** in dogs and cats. * May be used for rate control in atrial flutter or atrial fibrillation. * **Clinical Pearl:** Verapamil is a known inhibitor of **P-glycoprotein (P-gp)**. Because of this mechanism, it is currently being investigated as an adjunctive treatment for pharmaco-resistant epilepsy to help prevent the efflux of antiepileptic drugs from the central nervous system.
Mecanismo: Verapamil exerts its effects by blocking the transmembrane influx of extracellular calcium ions through **L-type voltage-gated calcium channels** in myocardial cells and vascular smooth muscle cells. * **Cardiac Conduction (Primary Effect):** Blocks calcium channels in the SA and AV nodes → **decreases AV node conduction velocity** and increases the effective refractory period → slows ventricular response rate in supraventricular arrhythmias. * **Myocardial Contractility:** Exhibits a **negative inotropic effect** (decreases heart muscle contractility). * **Vascular Smooth Muscle:** Inhibits contractile mechanisms → causes vasodilation and decreases peripheral vascular resistance (though less potently than amlodipine). * **Neurological:** Inhibits **P-glycoprotein (MDR1/ABCB1)** at the blood-brain barrier → reduces the efflux of certain substrate drugs back into the systemic circulation.
Dosificación por especie
- Supraventricular tachycardia · Initial dose of 0.025 mg/kg IV slowly, can repeat every 5 minutes up to a total dose of 0.15-0.2 mg/kg; Oral Dose: 0.5-1 mg/kg PO q8h · IV/PO · q8h (for PO)
- Supraventricular tachyarrhythmias · 0.5-1 mg/kg · PO · q8h
- Supraventricular tachyarrhythmias (Acute) · 0.025 mg/kg · IV · once · over 5 minutes · Administer slowly with ECG monitoring. Up to 3 repeat IV administrations q5min if necessary.
- To control ventricular rate in atrial fibrillation · 0.025-0.05 mg/kg IV q 30 minutes; give less than 0.2 mg/kg total dose · IV · q 30 minutes · ARCI UCGFS CLASS 4 DRUG
- Cardiovascular disease · 0.25-0.5 mg (total dose per hamster) SC · SC · Hamsters
- Cardiovascular disease · 8-16 mg/kg PO + 0.5-2 mg/kg SC once daily (q24h) · PO/SC · q24h · Rabbits
- Supraventricular tachycardia · Initial dose of 0.05 mg/kg IV slowly, can repeat every 5 minutes up to a total dose of 0.15-0.2 mg/kg; Oral Dose: 0.5-2 mg/kg PO q8h · IV/PO · q8h (for PO)
- Treatment of hypertension · 1-5 mg/kg PO q8h · PO · q8h
Vías de administración
Contraindicaciones
- Cardiogenic shock
- Severe CHF (unless secondary to a supraventricular tachycardia amenable to verapamil)
- Hypotension (<90 mmHg systolic)
- Sick sinus syndrome
- 2nd or 3rd degree AV block
- Digoxin intoxication
- Hypersensitivity to verapamil
- Recent use (within a few hours) of IV beta-adrenergic blockers
- Hypotension
- Left ventricular dysfunction
- Heart failure
Efectos adversos
- Hypotension
- Bradycardia
- Tachycardia
- Exacerbation of congestive heart failure (CHF)
- Peripheral edema
- AV block
- Pulmonary edema
- Nausea
- Constipation
- Dizziness
- Headache
- Fatigue
- Precipitation or exacerbation of congestive heart failure
Interacciones farmacológicas
- ACE Inhibitors · May cause additive hypotensive effects
- Alpha-Adrenergic Blockers (e.g., prazosin) · May cause additive hypotensive effects
- Beta-Adrenergic Blockers (e.g., propranolol) · May cause additive negative cardiac inotrope and chronotrope effects; IV combination is contraindicated
- Doxorubicin · Verapamil may increase doxorubicin concentrations
- COPP Chemotherapy · May decrease oral absorption of verapamil
- Cyclosporine · Verapamil may increase cyclosporine levels
- Dantrolene · Cardiovascular collapse reported in animals when used with verapamil
- Digoxin · Verapamil may increase blood levels of digoxin; monitoring recommended · major
- Disopyramide · May cause additive effects and impair left ventricular function; concurrent use within 24-48 hours not recommended
- Diuretics · May cause additive hypotensive effects
- Erythromycin, Clarithromycin · May increase verapamil levels
- Flecainide · Possible additive effects; concurrent use is to be avoided in humans
- Neuromuscular Blockers · Effects of nondepolarizing muscle relaxants may be enhanced by verapamil
Monitoreo
- ECG
- Clinical signs of toxicity (hypotension, bradycardia, edema)
- Blood pressure (especially during acute IV therapy)
- Serum concentration (if efficacy or toxicity warrant; 100-300 ng/mL is considered therapeutic)
- ECG (especially during IV administration)
- Blood pressure
- Heart rate and rhythm
- Liver function (in patients with hepatic disease)
Sobredosis
**Clinical Signs of Overdose:** Bradycardia, hypotension, hyperglycemia, junctional rhythms, and 2nd or 3rd degree AV block. **Treatment:** * **Decontamination:** If secondary to recent oral ingestion, consider gut emptying and activated charcoal administration. * **Supportive Care:** Vigorously monitor cardiac and respiratory function. * **Negative Inotropy:** Intravenous calcium salts (1 mL of 10% solution per 10 kg of body weight) may treat negative inotropic signs, but may not adequately resolve heart block. * **Hypotension:** Fluid therapy and pressor agents (e.g., dopamine, norepinephrine) may be utilized. * **AV Block / Bradycardia:** Treat with isoproterenol, norepinephrine, atropine, or cardiac pacing. * **Rapid Ventricular Rate:** Patients developing rapid ventricular rate due to antegrade conduction in flutter/fibrillation with WPW syndrome have been treated with D.C. cardioversion, lidocaine, or procainamide.
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