Calcium channel blockers (CCBs) block L-type calcium channels. Less calcium enters the cells, so:
- Vascular smooth muscle relaxes → arteriolar dilation → ↓afterload and ↓BP; coronary arteries dilate (relieves vasospasm)
- Heart muscle contracts less forcefully (negative inotropy)
- SA and AV nodes fire and conduct more slowly (↓heart rate, ↑PR interval)
The two groups differ in where they act:
| Group | Drugs | Main site | Heart rate effect |
|---|
| Dihydropyridines (DHP) — "-dipine" | amlodipine (prototype), nifedipine, felodipine, nicardipine, clevidipine, nimodipine | Arterioles | May increase (reflex tachycardia) |
| Non-dihydropyridines (non-DHP) | verapamil, diltiazem | Heart (nodes and muscle) and vessels | Decrease — slow rate and AV conduction |
CCBs dilate arterioles, not veins, so they cause little orthostatic hypotension.
Direct vasodilators relax vascular smooth muscle by other routes:
- Hydralazine — arteriolar dilator (mechanism not fully defined)
- Minoxidil — opens potassium channels in arterioles
- Sodium nitroprusside — releases nitric oxide; dilates both arteries and veins; acts in seconds
- Nitrates — mainly venous (preload) dilators; covered in Antianginal Drugs
Arteriolar dilators trigger reflexes: sympathetic activation (tachycardia) and renin release (sodium and water retention). That is why hydralazine and minoxidil are usually given with a beta blocker and a diuretic.
Calcium channel blockers
| Drug (generic) | Key use | Key point |
|---|
| Amlodipine | Hypertension (first-line), chronic stable and vasospastic angina | Long half-life (once daily); ankle edema; safe in HFrEF when needed for BP or angina |
| Nifedipine (extended-release) | Hypertension, vasospastic angina, Raynaud phenomenon; hypertension in pregnancy | Use extended-release for chronic therapy; immediate-release capsules are not used for hypertension outside pregnancy protocols (abrupt BP fall, reflex tachycardia, ischemia). Never sublingual |
| Nicardipine (IV) | Hypertensive emergency, BP control in stroke and hemorrhage | Titrated infusion; headache, reflex tachycardia; change peripheral site every 12 hours per label to reduce phlebitis |
| Clevidipine (IV) | Hypertensive emergency, perioperative BP control | Ultra-short-acting lipid emulsion — contraindicated with soy or egg allergy and disorders of lipid metabolism; strict aseptic handling |
| Nimodipine (oral) | Aneurysmal subarachnoid hemorrhage — improves outcome from vasospasm | Oral or by feeding tube only — never IV (boxed warning: IV injection of capsule contents has caused cardiac arrest and death). Use the oral solution or draw capsule contents with an oral syringe |
| Diltiazem | Rate control in atrial fibrillation/flutter, SVT, angina, hypertension | IV bolus then infusion for AF (see Antiarrhythmic Drugs); oral extended-release forms — do not crush |
| Verapamil | Rate control, SVT, angina, hypertension, migraine prevention, hypertrophic cardiomyopathy | Constipation; most negative inotropic CCB |
Current guidance: long-acting dihydropyridine CCBs are one of the four first-line classes for hypertension (2025 AHA/ACC). An ACE inhibitor or ARB plus amlodipine is a common single-pill combination.
Direct vasodilators
| Drug (generic) | Key use | Key point |
|---|
| Hydralazine | IV/IM for severe hypertension in pregnancy; oral with isosorbide dinitrate in HFrEF (self-identified Black clients, or when RAAS inhibitors cannot be used); resistant hypertension | Reflex tachycardia, headache, fluid retention; drug-induced lupus with long-term higher doses. Look-alike name: hydrALAZINE vs hydrOXYzine |
| Minoxidil (oral) | Severe resistant hypertension | Boxed warning: pericardial effusion and tamponade, worsening angina; must be given with a beta blocker and a loop diuretic. Hair growth (hypertrichosis). Topical minoxidil for hair loss has minimal systemic effect |
| Sodium nitroprusside (IV) | Hypertensive emergency, acute HF with high BP, aortic dissection (with a beta blocker first) | Boxed warnings: not for direct injection (must be diluted); sudden severe hypotension; cyanide toxicity — at the maximum rate (10 mcg/kg/min), infuse no longer than 10 minutes. Given by pump with continuous arterial BP monitoring; protect from light |
Hypertensive emergency principles (severe BP with acute organ damage): ICU care with IV titratable drugs (nicardipine, clevidipine, labetalol, esmolol, nitroprusside, nitroglycerin). Lower BP by no more than about 25% in the first hour, then toward 160/100–110 mmHg over the next 2–6 hours, then gradually to normal over 24–48 hours. Exceptions: aortic dissection (faster, SBP below 120 mmHg during the first hour per ACC/AHA; some summaries say within about 20 minutes), acute stroke (specific limits), severe preeclampsia. Severe BP without organ damage is not treated with IV "bolus" drugs — oral therapy is adjusted (2025 AHA/ACC).
| Drug group | Key adverse effects |
|---|
| DHP CCBs | Headache, flushing, dizziness, peripheral (ankle) edema — caused by arteriolar dilation, not fluid overload, so diuretics help little; reflex tachycardia (short-acting forms); gingival hyperplasia |
| Verapamil | Constipation, bradycardia, AV block, hypotension, worsening HF |
| Diltiazem | Bradycardia, AV block, hypotension, edema, worsening HF; IV — hypotension |
| Hydralazine | Headache, palpitations, reflex tachycardia, angina, fluid retention, lupus-like syndrome (joint pain, fever, rash, positive ANA), peripheral neuropathy (rare) |
| Minoxidil | Fluid retention, reflex tachycardia, pericardial effusion, hair growth, ECG T-wave changes |
| Nitroprusside | Profound hypotension; cyanide toxicity (metabolic acidosis, rising lactate, confusion, high venous oxygen saturation, cardiovascular collapse); thiocyanate toxicity with prolonged use or kidney failure (tinnitus, blurred vision, delirium, seizures); methemoglobinemia |
Contraindications
- Non-DHP CCBs (verapamil, diltiazem): HFrEF, sick sinus syndrome or second- or third-degree AV block without a pacemaker, hypotension, cardiogenic shock, pre-excited atrial fibrillation (Wolff–Parkinson–White) — AV-node blockade can speed conduction down the accessory pathway and cause VF; IV verapamil with an IV beta blocker
- DHP CCBs: cardiogenic shock, severe aortic stenosis (caution), unstable angina with immediate-release nifedipine
- Clevidipine: soy or egg allergy, abnormal lipid metabolism
- Nitroprusside: compensatory hypertension (e.g., coarctation), inadequate cerebral circulation, pregnancy (fetal cyanide risk — listed among drugs to avoid in the 2025 hypertension guideline), congenital optic atrophy
- Minoxidil: pheochromocytoma; caution after recent MI
- Hydralazine: coronary artery disease without beta blockade (reflex tachycardia can trigger angina), mitral valve rheumatic disease
Pregnancy and lactation: nifedipine (oral) and hydralazine (IV) are standard for hypertension in pregnancy. Verapamil and diltiazem have limited human pregnancy data (diltiazem caused fetal harm in animal studies) — use only when clearly needed, such as for a maternal dysrhythmia under specialist care. Nifedipine and diltiazem are generally compatible with breastfeeding.
Major interactions
- Beta blockers, digoxin, amiodarone, ivabradine + verapamil/diltiazem → bradycardia, heart block, HF
- Verapamil and diltiazem inhibit CYP3A4 and P-glycoprotein → raise levels of simvastatin and lovastatin (dose limits apply — myopathy risk), digoxin, cyclosporine, tacrolimus, apixaban, rivaroxaban, carbamazepine, and some benzodiazepines
- Grapefruit juice raises levels of felodipine, nifedipine, and verapamil (amlodipine is affected little)
- Strong CYP3A4 inhibitors (clarithromycin, azole antifungals, ritonavir) → excessive hypotension with CCBs; inducers (rifampin, carbamazepine, St. John's wort) → loss of effect
- Dantrolene + verapamil/diltiazem → hyperkalemia and cardiovascular collapse (malignant hyperthermia treatment)
- Magnesium sulfate + nifedipine → additive hypotension (monitor in preeclampsia)
- Other antihypertensives, alcohol, PDE-5 inhibitors → additive hypotension
Listed in priority order.
- IV antihypertensives (nitroprusside, nicardipine, clevidipine)
- Continuous arterial BP and ECG; titrate per protocol to the ordered target; never lower BP faster than ordered (stroke, MI, kidney injury from underperfusion)
- Infusion pump, dedicated line, independent double check (high-alert drugs)
- Nitroprusside: wrap the bag in opaque material; monitor acid–base status and lactate, mental status, and kidney function; report metabolic acidosis, confusion, or rising doses needed (possible cyanide toxicity); monitor thiocyanate with prolonged use or kidney impairment
- Before oral doses
- BP and apical pulse; for non-DHP CCBs commonly hold for HR < 60/min or SBP < 90 mmHg per order
- ECG: PR interval and AV block with verapamil and diltiazem
- Heart failure signs — weight, edema, crackles, dyspnea (non-DHP in any client with reduced EF)
- Edema — distinguish CCB ankle edema (no weight gain or crackles) from fluid overload; report to the prescriber
- Nimodipine — confirm the oral or enteral route; label oral syringes; check BP before each dose every 4 hours; hold and notify for hypotension
- Hydralazine and minoxidil — heart rate, weight, edema; minoxidil — listen for pericardial friction rub, monitor for JVD and muffled heart sounds; hydralazine long-term — ANA and joint symptoms
- Bowel function with verapamil — fiber, fluids, stool softener as ordered
- Take as prescribed even when you feel well; do not stop suddenly
- Do not crush or chew extended-release tablets (nifedipine, diltiazem, verapamil ER); an empty tablet shell may appear in stool with some nifedipine products — this is normal
- Avoid grapefruit and grapefruit juice with felodipine, nifedipine, and verapamil
- Check your pulse and BP at home if taught; report a pulse below 60/min (or your given number), fainting, or dizziness
- Ankle swelling, headache, and flushing are common with amlodipine or nifedipine; elevate the legs and report swelling that is new, worsening, or comes with weight gain or breathlessness
- Verapamil: increase fiber and fluids to prevent constipation
- Brush and floss carefully and keep dental visits (gum overgrowth)
- Rise slowly; limit alcohol
- Tell all prescribers and pharmacists you take verapamil or diltiazem — many drugs, including some statins, interact
- Hydralazine: report joint pain, fever, or rash. Minoxidil: report weight gain of 2–3 lb (about 1 kg) in a day, chest pain, or breathlessness; expect increased body hair
CCB overdose is one of the most dangerous cardiovascular overdoses: hypotension, bradycardia, heart block, cardiogenic shock, and hyperglycemia (insulin release is calcium-dependent). Mental status may stay clear until late. Extended-release products cause delayed and prolonged toxicity — admit and monitor even if the client looks well.
Management (priority order)
- Airway, breathing, circulation; continuous ECG; IV access; glucose and potassium
- IV fluids; atropine for bradycardia (often weak effect). Glucagon is not recommended for CCB poisoning (2017 expert consensus) — unlike beta-blocker overdose
- First-line: IV calcium (calcium chloride through a central line, or calcium gluconate peripherally) per protocol
- High-dose insulin with dextrose — a key therapy; monitor glucose and potassium closely
- Vasopressors (norepinephrine, epinephrine); pacing
- Lipid emulsion or extracorporeal support in refractory cases; whole-bowel irrigation for extended-release ingestions per toxicology advice
Nitroprusside cyanide toxicity: stop the infusion; hydroxocobalamin (turns skin and urine red and interferes with some lab tests) or sodium thiosulfate per protocol; supportive care. Thiocyanate toxicity: stop the drug; hemodialysis.
Excessive BP drop from any vasodilator: stop or reduce the infusion, place supine with legs raised, IV fluids, notify.
- DHP ("-dipine") = vessels → headache, flushing, ankle edema, reflex tachycardia; non-DHP (verapamil, diltiazem) = heart → bradycardia, AV block, HF
- Verapamil → constipation
- Avoid verapamil and diltiazem in HFrEF, AV block, and pre-excited AF
- Hold parameters: commonly HR < 60/min or SBP < 90 mmHg per order
- Grapefruit raises felodipine, nifedipine, verapamil levels; verapamil/diltiazem raise statins and digoxin
- Nimodipine: oral only, never IV
- Nifedipine ER and IV hydralazine/labetalol are used for hypertension in pregnancy
- Nitroprusside: arterial line, protect from light, cyanide toxicity (metabolic acidosis) → hydroxocobalamin
- Hypertensive emergency: lower ≤ 25% in the first hour
- CCB overdose: calcium, high-dose insulin, vasopressors; watch for delayed toxicity with ER products
Country Notes
United States
- Hydralazine appears on the ISMP list of confused drug names (hydrALAZINE vs hydrOXYzine); tall-man lettering is used in electronic systems.
- Clevidipine and nicardipine are common ICU and emergency department choices for hypertensive emergency.
Philippines
- Amlodipine and losartan are among the most widely prescribed antihypertensives; reinforce once-daily adherence and home BP checks.
- High dietary sodium (fish sauce, soy sauce, dried fish, instant noodles) reduces the effect of all antihypertensives; pair drug teaching with salt reduction.