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# Calcium Channel Blockers ## Overview Calcium channel blockers (CCBs) are a class of drugs that inhibit the influx of calcium ions into vascular smooth muscle and cardiac muscle cells. They are broadly categorized into dihydropyridines (DHPs) and non-dihydropyridines (non-DHPs), which have different primary effects on the heart and vasculature. ## Primary Indications * Hypertension * Angina Pectoris (stable and vasospastic) * Supraventricular Tachycardias (rate control) - primarily non-DHPs * Raynaud's Phenomenon ## Adult Dosing Dosing varies significantly by agent and indication. Specific examples: * **Amlodipine (DHP):** * Hypertension: 5-10 mg once daily. Maximum 10 mg daily. * Angina: 5-10 mg once daily. Maximum 10 mg daily. * **Nifedipine (DHP) - Extended Release:** * Hypertension: 30-60 mg once daily. Maximum 120 mg daily. (Immediate-release formulations are generally not recommended for hypertension due to risk of reflex tachycardia and hypotension). * **Verapamil (Non-DHP):** * Hypertension: 80-120 mg two to three times daily. Maximum 480 mg daily. * Angina: 80-120 mg two to three times daily. Maximum 480 mg daily. * Supraventricular Tachycardia (IV): 2.5-5 mg given over 2 minutes. May repeat with 5-10 mg after 15-30 minutes if response inadequate. Maximum 20 mg in 30 minutes. * **Diltiazem (Non-DHP):** * Hypertension: 180-300 mg once daily (extended-release). Maximum 360 mg daily. * Angina: 30-60 mg three to four times daily (immediate-release) or 180-300 mg once daily (extended-release). Maximum 360 mg daily for ER. * Supraventricular Tachycardia (IV): 0.25 mg/kg bolus over 2 minutes. May repeat with 0.35 mg/kg after 15 minutes. Continuous infusion: 5-15 mg/hr. ## Pediatric Dosing Pediatric dosing for CCBs is less established and often requires careful titration under specialist guidance. * **Amlodipine:** Hypertension: 0.05 mg/kg once daily, maximum 5 mg daily. * **Verapamil:** Supraventricular Tachycardia (IV): 0.1-0.3 mg/kg per dose. * **Diltiazem:** Supraventricular Tachycardia (IV): 0.1-0.25 mg/kg per dose. Dosing for other indications and agents in pediatrics is not universally established and depends on local protocols and expert consultation. ## Dose Adjustments * **Hepatic Impairment:** Reduce dose, especially for non-DHPs, as they undergo extensive hepatic metabolism. Non-DHPs are generally more affected than DHPs. * **Renal Impairment:** Generally, dose adjustments are not required for DHPs. For non-DHPs, caution and potential dose reduction may be necessary in severe renal impairment. ## Contraindications * Hypersensitivity to the drug or components. * Severe hypotension. * Cardiogenic shock. * Sick sinus syndrome (excluding patients with a functioning artificial pacemaker). * Second- or third-degree atrioventricular (AV) block (excluding patients with a functioning artificial pacemaker) - primarily non-DHPs. * Congestive heart failure with reduced ejection fraction (non-DHPs). * **Verapamil/Diltiazem:** Concurrent use of beta-blockers or digoxin (increased risk of bradycardia, AV block, heart failure). * **Immediate-release nifedipine:** Unstable angina, recent myocardial infarction. ## Adverse Effects * **Dihydropyridines:** Peripheral edema, headache, flushing, dizziness, reflex tachycardia, gingival hyperplasia. * **Non-dihydropyridines:** Constipation (especially verapamil), bradycardia, AV block, dizziness, headache, nausea, peripheral edema. * **Both:** Hypotension, fatigue, rash. ## Key Drug Interactions * **CYP3A4 Inhibitors/Inducers:** Many CCBs are substrates of CYP3A4. Inhibitors (e.g., grapefruit juice, azole antifungals, macrolides) can increase CCB levels and toxicity. Inducers (e.g., rifampin, phenytoin) can decrease CCB levels. * **Other Antihypertensives:** Additive hypotensive effects. * **Beta-blockers:** Increased risk of bradycardia, AV block, and heart failure, particularly with non-DHPs. * **Digoxin:** Increased digoxin levels and risk of toxicity, especially with non-DHPs. * **Simvastatin/Atorvastatin:** Increased risk of myopathy when co-administered with certain CCBs (e.g., amlodipine). Consult specific drug interaction resources for maximum recommended statin doses. * **Grapefruit Juice:** Can significantly increase plasma concentrations of amlodipine, felodipine, and verapamil. ## Monitoring * Blood pressure (seated and standing, if orthostasis is a concern). * Heart rate. * Signs of heart failure (dyspnea, edema, weight gain). * Renal function and electrolytes (especially in patients with hepatic or renal impairment). * For non-DHPs: ECG for heart rate and AV conduction. * For verapamil: Monitor for constipation. ## Clinical Pearls * Dihydropyridines are generally preferred for primary treatment of hypertension and angina due to their potent vasodilatory effects and less significant impact on cardiac contractility and conduction. * Non-dihydropyridines (verapamil, diltiazem) are more effective for rate control in supraventricular tachycardias and angina with associated supraventricular arrhythmias due to their cardiac depressant effects. * Non-dihydropyridines should be used with caution or avoided in patients with impaired cardiac conduction or systolic heart failure. * Non-dihydropyridines have a higher incidence of constipation, particularly verapamil, which may necessitate proactive management. * Long-acting formulations are preferred for hypertension and chronic angina to ensure consistent therapeutic levels and improve adherence. * Avoid co-administration of immediate-release CCBs with beta-blockers. *** **Disclaimer:** This information is intended for clinical use and does not replace a thorough review of the complete prescribing information. Always verify current drug information and local protocols before initiating or adjusting therapy.