Key Facts

CCBs are widely used antihypertensives and antianginals. The distinction between dihydropyridine and non-dihydropyridine subclasses is clinically critical, as they have fundamentally different effects and drug interaction profiles.

Pharmacology

• L-type calcium channels: found in cardiac myocytes, vascular smooth muscle, and AV/SA node
• Blocking calcium entry → reduced intracellular calcium → reduced contraction
• Dihydropyridines: preferentially act on vascular smooth muscle → vasodilation → ↓ SVR → ↓ BP; reflex sympathetic activation → ↑ HR
• Non-dihydropyridines: preferentially act on cardiac tissue → ↓ HR (chronotropy), ↓ AV conduction (dromotropy), ↓ contractility (inotropy); minimal reflex tachycardia

Pathophysiology

• Hypertension: CCBs reduce SVR through arteriolar vasodilation
• Angina: reduce myocardial oxygen demand (↓ afterload, ↓ HR with non-DHP) and improve coronary flow (vasodilation)
• Arrhythmias (non-DHP): slow AV nodal conduction → control ventricular rate in AF/atrial flutter

Indications

• Hypertension: amlodipine/nifedipine MR — first-line in ≥55 or Black heritage; Step 1 NICE NG136
• Stable angina: amlodipine (if beta-blocker contraindicated/insufficient) or diltiazem
• Prinzmetal (vasospastic) angina: CCBs are treatment of choice — coronary vasodilation
• AF rate control: verapamil or diltiazem — alternative to beta-blocker (not combined)
• Raynaud's phenomenon: nifedipine MR 10–20 mg BD
• Hypertension in pregnancy: nifedipine MR (alongside labetalol)

Side Effects

• Amlodipine: ankle oedema (~10%), flushing, headache, dizziness, gingival hyperplasia
• Nifedipine: ankle oedema, flushing, headache, tachycardia
• Verapamil: constipation (common and dose-dependent), bradycardia, heart block, heart failure exacerbation
• Diltiazem: bradycardia, ankle oedema (less than amlodipine), constipation

Red Flags

• Verapamil + beta-blocker: CONTRAINDICATED — complete heart block, asystole
• Diltiazem + beta-blocker: generally avoid (high-risk combination; specialist use only)
• Verapamil/diltiazem in HFrEF: negative inotropy → worsening heart failure
• Severe ankle oedema on amlodipine: switch to alternative; diuretics are NOT effective (precapillary vasodilation, not fluid overload)
• Grapefruit juice + nifedipine/amlodipine: CYP3A4 inhibition → increased drug levels

Before Starting

• Heart rate and BP: baseline
• ECG: exclude heart block before non-DHP CCB; assess for LVH
• Echocardiogram: if heart failure suspected (avoid non-DHP in HFrEF)

Monitoring

• BP: at each dose change; target per NICE NG136
• Heart rate: if on non-DHP CCB (verapamil/diltiazem) — avoid excessive bradycardia
• Ankle oedema: common — reassure if mild; switch if troublesome
• LFTs: rarely, CCBs can cause hepatitis

Special Tests

• Drug interaction check: non-DHP CCBs interact with many drugs via CYP3A4 (simvastatin, ciclosporin)
• Verapamil + digoxin: verapamil increases digoxin levels — reduce digoxin dose by ~50%

Hypertension

• Amlodipine 5 mg OD → 10 mg OD: first-choice CCB
• Nifedipine MR 20 mg OD → 60 mg OD: alternative
• Used as Step 1 (≥55 or Black heritage) or Step 2 (add to ACE-i/ARB)

Angina

• Amlodipine 5–10 mg OD: if beta-blocker contraindicated or insufficient alone
• Diltiazem MR 120–360 mg OD: alternative to beta-blocker for angina (do NOT combine with beta-blocker routinely)

AF Rate Control

• Diltiazem or verapamil: alternative to beta-blocker when beta-blocker contraindicated
• Verapamil dose: 40–120 mg TDS (or SR preparations)

Raynaud's

• Nifedipine MR 10–20 mg BD: vasodilation improves digital blood flow

Overdose

• Hypotension, bradycardia, heart block, cardiac arrest
• Treatment: IV calcium gluconate 10% (10–20 mL over 5 min), IV fluids, atropine (bradycardia), high-dose insulin-glucose therapy (calcium channel blocker overdose protocol)

Referral Criteria

• Cardiology: angina management, AF rate control, complex hypertension
• Toxicology: CCB overdose (potentially lethal)

• Amlodipine-based BP control: superior outcomes vs atenolol-based (ASCOT-BPLA)
• CCBs in hypertension: reduce stroke risk by ~40%
• Non-DHP CCBs: effective for rate control and angina
• Ankle oedema: dose-dependent; manageable by switching to alternative or adding RAAS inhibitor
• CCB overdose: potentially fatal — aggressive treatment needed

DHP vs Non-DHP CCBs

Key Drug Interactions (Non-DHP)