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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 cardiac and vascular smooth muscle cells. This leads to vasodilation and/or decreased myocardial contractility and heart rate. CCBs are categorized into two main groups: dihydropyridines (DHPs) and non-dihydropyridines (non-DHPs).
## Primary Indications
* Hypertension
* Angina pectoris (stable and vasospastic)
* Supraventricular tachyarrhythmias (primarily non-DHPs for rate control)
* Raynaud's phenomenon
## Adult Dosing
**Dihydropyridines (DHPs)** - Primarily for hypertension and angina.
* **Amlodipine:** Start at 5 mg once daily. Titrate up to a maximum of 10 mg once daily.
* **Nifedipine (extended-release):** Start at 30 mg once daily. Titrate up to a maximum of 120 mg once daily. (Note: Immediate-release nifedipine is generally avoided due to risk of rapid BP drops and reflex tachycardia).
* **Felodipine:** Start at 5 mg once daily. Titrate up to a maximum of 10 mg once daily.
* **Nicardipine (extended-release):** Start at 30 mg twice daily. Titrate up to a maximum of 60 mg twice daily.
**Non-Dihydropyridines (Non-DHPs)** - Primarily for angina and supraventricular tachyarrhythmias.
* **Verapamil:**
* Angina: Start at 80 mg three times daily. Usual dose 160-480 mg/day divided into 3 doses.
* Arrhythmia (rate control): Start at 40-80 mg three times daily. Usual dose 240-480 mg/day divided into 3 doses.
* **Diltiazem:**
* Angina (immediate-release): Start at 30 mg four times daily. Usual dose 120-360 mg/day divided into 3-4 doses.
* Angina/Hypertension (extended-release): Start at 60-120 mg twice daily. Usual dose 240-360 mg/day divided into 2 doses. Maximum 480 mg/day.
* Arrhythmia (rate control, extended-release): Start at 120 mg twice daily. Usual dose 240-360 mg/day divided into 2 doses. Maximum 480 mg/day.
## Pediatric Dosing
Pediatric dosing for CCBs is not well-established and is often based on expert consensus or limited studies. Doses vary significantly by age and indication. Consultation with a pediatric specialist is recommended.
* **Amlodipine:** Typically initiated at 0.05 mg/kg/day, not to exceed 0.3 mg/kg/day or adult maximum.
* **Verapamil:** For supraventricular tachycardia, IV dose is 0.1-0.2 mg/kg/dose (max 10 mg). Oral doses are generally extrapolated from adult data and require careful titration.
* **Diltiazem:** IV dose for supraventricular tachycardia is 0.25 mg/kg/dose (max 20 mg). Oral doses require careful titration.
## Dose Adjustments
* **Hepatic Impairment:** Doses should be reduced and titrated carefully due to extensive hepatic metabolism. Non-DHPs often require more significant reduction than DHPs.
* **Renal Impairment:** Generally, dose adjustments are not required for DHPs or for non-DHPs unless there is severe impairment or significant fluid retention. However, caution is advised.
## Contraindications
* Severe hypotension (SBP < 90 mmHg)
* Cardiogenic shock
* Acute myocardial infarction (especially with mechanical complications)
* Severe left ventricular dysfunction (systolic failure)
* Sick sinus syndrome, AV block (2nd or 3rd degree) without a pacemaker (especially for non-DHPs)
* Porphyria (for some agents, consult specific drug monograph)
* Known hypersensitivity to the drug or its components
## Adverse Effects
* **Common:** Peripheral edema, headache, flushing, dizziness, constipation (especially with verapamil), nausea, fatigue.
* **DHP-specific:** Reflex tachycardia, gingival hyperplasia.
* **Non-DHP-specific:** Bradycardia, AV block, constipation (verapamil), worsening heart failure.
## Key Drug Interactions
* **Beta-blockers:** Additive effects on AV conduction and negative inotropy, increasing risk of bradycardia, AV block, and heart failure. Non-DHPs with beta-blockers are generally avoided.
* **Digoxin:** CCBs (especially verapamil) can increase digoxin levels by reducing renal and non-renal clearance.
* **CYP3A4 Inhibitors/Inducers:** Many CCBs are substrates of CYP3A4. Concomitant use with strong inhibitors (e.g., grapefruit juice, ritonavir, ketoconazole) can increase CCB levels. Strong inducers (e.g., rifampin, carbamazepine) can decrease CCB levels.
* **Statins:** Some statins (simvastatin, atorvastatin) are CYP3A4 substrates. Concomitant use with CCBs that inhibit CYP3A4 may increase statin levels and risk of myopathy.
* **Antihypertensives:** Additive hypotensive effects.
## Monitoring
* Blood pressure (seated and standing if indicated)
* Heart rate and rhythm (especially with non-DHPs)
* Signs of heart failure (edema, dyspnea, weight gain)
* Renal function and electrolytes (especially in patients with hepatic impairment or risk factors)
* Signs of constipation (especially with verapamil)
* ECG for bradycardia or AV block (particularly with non-DHPs)
## Clinical Pearls
* DHPs are generally preferred for hypertension due to less impact on cardiac function.
* Non-DHPs are preferred for rate control in atrial fibrillation/flutter and for vasospastic angina.
* Non-DHPs should be used with extreme caution, or avoided, in patients with heart failure with reduced ejection fraction.
* Dihydropyridine-induced peripheral edema is dose-dependent and may not be responsive to diuretics alone.
* Immediate-release nifedipine should be avoided for chronic management of hypertension due to risk of adverse events.
* Grapefruit juice can significantly increase serum concentrations of amlodipine, felodipine, and verapamil.
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*This information is intended for healthcare professionals and is not a substitute for professional medical advice. Always consult the most current prescribing information and relevant guidelines before making any treatment decisions. Local protocols may vary.*
