Calcium Channel Blockers

# Calcium channel blockers ## Overview - **Classification**: Anti-hypertensive, Anti-anginal, Anti-arrhythmic (Non-DHP) - **Mechanism**: Block influx of calcium ions into vascular smooth muscle and myocardial cells. - **Dihydropyridines (DHP)**: Primarily vascular smooth muscle (vasodilation). E.g., amlodipine, nifedipine. - **Non-dihydropyridines (Non-DHP)**: Primarily cardiac muscle and conduction system (rate/contractility reduction). E.g., diltiazem, verapamil. ## Primary Indications 1. **Hypertension**: Lower blood pressure (all CCBs; DHP often preferred). 2. **Angina Pectoris**: Reduce myocardial oxygen demand (all CCBs). 3. **Supraventricular Tachyarrhythmias**: Ventricular rate control in AF/AFlutter, PSVT (Non-DHP only). 4. **Raynaud's Phenomenon**: Reduce vasospasm (DHP, e.g., nifedipine). ## Adult Dosing ### Standard Dosing **Amlodipine (Dihydropyridine)** **Hypertension / Chronic Stable Angina** - **Dose**: Start **2.5-5 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **10 mg** once daily - **Special Considerations**: Titrate dose over 7-14 days. **Diltiazem (Non-Dihydropyridine)** **Chronic Stable Angina / Hypertension (Extended Release)** - **Dose**: Start **120-240 mg** - **Frequency**: Once daily (ER formulations) - **Route**: Oral - **Maximum**: **540 mg** once daily - **Special Considerations**: Dose based on clinical response and tolerability. **Diltiazem (Non-Dihydropyridine)** **Atrial Fibrillation/Flutter (IV, Rate Control)** - **Dose**: Initial **0.25 mg/kg** (typical **15-20 mg**) over 2 min - **Frequency**: May repeat **0.35 mg/kg** (typical **20-25 mg**) once after 15 min - **Route**: Intravenous (IV push) - **Maintenance Infusion**: **5-15 mg/hour** continuous IV - **Maximum**: Total bolus **50 mg**; Infusion **15 mg/hour**. ### Dose Adjustments - **Renal Impairment**: - **Amlodipine**: No routine adjustment. Use with caution in severe impairment. - **Diltiazem**: Use with caution. No specific adjustment, but monitor for adverse effects. - **Hepatic Impairment**: - **Amlodipine**: Reduce starting dose to **2.5 mg** once daily. Titrate slowly. - **Diltiazem**: Reduce dose. Monitor for increased drug levels and effects. - **Elderly Patients**: Start at lower end of dosing range. Titrate slowly due to increased sensitivity. ## Pediatric Dosing (Examples: Amlodipine, Diltiazem) ### Neonates (0-28 days) - **Amlodipine**: Not recommended. Safety and efficacy not established. - **Diltiazem**: Not recommended due to significant cardiac depressant effects. Avoid unless under extreme specialist guidance for refractory conditions. ### Infants (1-12 months) - **Amlodipine**: Not recommended. Safety and efficacy not established. - **Diltiazem**: Not recommended for routine use. Avoid due to cardiac effects. Specialist use only for refractory arrhythmias. ### Children (1-12 years) - **Amlodipine (6-17 years for Hypertension)** - **Dose**: Start **2.5 mg** - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **5 mg** once daily - **Special Notes**: Titrate after 4 weeks based on BP. Not for children <6 years. - **Diltiazem (Off-label for Hypertension/SVT)** - **Dose (Oral)**: **0.5-3.5 mg/kg/day** - **Frequency**: Divided 3-4 times daily - **Route**: Oral - **Maximum**: **360 mg/day** (or adult max for older children). - **Special Notes**: Highly specialized use for refractory conditions. IV use very rare. ### Adolescents (13-18 years) - **Amlodipine (Hypertension)** - **Dose**: Follow adult dosing, start **2.5 mg** once daily. - **Frequency**: Once daily - **Route**: Oral - **Maximum**: **5 mg** once daily (up to **10 mg** for >12 years if needed). - **Special Notes**: Monitor closely for efficacy and adverse effects. - **Diltiazem (Oral for Hypertension, IV for SVT)** - **Dose (Oral ER)**: **120-180 mg** once daily - **Dose (IV for SVT)**: **0.25 mg/kg** (max **20 mg**) over 2 min; may repeat **0.35 mg/kg** (max **25 mg**) once. Infusion: **5-15 mg/hour**. - **Frequency**: Once daily (oral ER), PRN (IV bolus), continuous (IV infusion). - **Route**: Oral, Intravenous - **Maximum**: Oral **540 mg/day**, IV bolus **50 mg**, IV infusion **15 mg/hour**. - **Special Notes**: Monitor for bradycardia, hypotension. ## Safety Information ### Contraindications - **Absolute**: Hypersensitivity to CCBs. - **Absolute (Non-DHP only)**: Severe hypotension (SBP <90 mmHg), Cardiogenic shock. - **Absolute (Non-DHP only)**: Acute MI with pulmonary congestion. - **Absolute (Non-DHP only)**: Sick sinus syndrome (without pacemaker), 2nd/3rd degree AV block (without pacemaker). - **Absolute (Non-DHP only)**: WPW or LGL syndrome with AF/AFlutter (risk of accelerated conduction). - **Relative**: Severe aortic stenosis (DHP). ### Common Adverse Effects - **Very Common (>10%)**: Headache, peripheral edema (DHP esp. amlodipine), dizziness, flushing (DHP). - **Common (1-10%)**: Fatigue, nausea, abdominal pain, palpitations, bradycardia (Non-DHP), constipation (verapamil). - **Serious but Rare**: Severe hypotension, syncope, exacerbation of angina, MI, heart failure (Non-DHP), severe bradycardia, AV block (Non-DHP), gingival hyperplasia. ### Key Drug Interactions - **Beta-blockers (Non-DHP)**: Increased risk of bradycardia, AV block, myocardial depression. Avoid concurrent IV use. - **Grapefruit Juice (DHP)**: Increases CCB levels, enhances effects (hypotension). Avoid or limit consumption. - **Strong CYP3A4 Inhibitors (e.g., ketoconazole, clarithromycin, ritonavir)**: Increase CCB levels. Monitor for toxicity (esp. DHP). - **Strong CYP3A4 Inducers (e.g., rifampin, phenytoin)**: Decrease CCB levels. May reduce efficacy. - **Digoxin (Non-DHP, esp. verapamil)**: Increases digoxin levels. Monitor digoxin levels. - **Statins (e.g., simvastatin)**: Amlodipine can increase simvastatin levels. Limit simvastatin to **20 mg/day**. ## Monitoring & Follow-up - **Before Treatment**: Baseline BP, HR, ECG (for Non-DHP). Liver/renal function. - **During Treatment**: BP (regularly), HR (Non-DHP, regularly), peripheral edema (DHP). - **Clinical Signs**: Dizziness, fainting, excessive swelling, new chest pain, shortness of breath, severe fatigue. ## Clinical Pearls - 💡 **DHP vs. Non-DHP**: DHP mainly for BP/angina via vasodilation. Non-DHP for rate control/angina via cardiac effects. - 💡 **Peripheral Edema**: Common with DHPs, dose-dependent. Not usually responsive to diuretics. Consider lowering dose, switching DHP, or adding ACEi/ARB. - 💡 **Nifedipine IR**: Avoid for chronic hypertension or acute BP drops due to rapid onset and unpredictable effects. - 💡 **Non-DHP Caution**: Avoid in patients with reduced left ventricular (systolic) heart failure due to negative inotropic effects. - 💡 **Constipation**: More common with verapamil; advise increased fluid/fiber intake. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.