1. Introduction of Amlodipine
Amlodipine is a long-acting dihydropyridine calcium channel blocker (CCB) widely used for the management of hypertension, chronic stable angina, and vasospastic (Prinzmetal’s) angina.
It belongs to the dihydropyridine (DHP) subclass of calcium antagonists, which primarily act on vascular smooth muscle to produce vasodilation and reduce blood pressure.
Because of its high vascular selectivity and long duration of action, amlodipine is one of the most frequently prescribed antihypertensive agents worldwide.
2. Chemical and Pharmacological Classification
| Parameter | Detail |
|---|---|
| Drug Name | Amlodipine besylate |
| Class | Calcium channel blocker (CCB) |
| Subclass | Dihydropyridine-type |
| Drug Category (ATC) | C08CA01 |
| Common Brand Names | Norvasc®, Amlocard®, Amlopres®, Istin® |
3. Mechanism of Action
Amlodipine selectively inhibits L-type voltage-gated calcium channels in vascular smooth muscle and cardiac muscle, resulting in:
- ↓ Calcium influx → ↓ Intracellular calcium
- ↓ Smooth muscle contraction → Vasodilation of arterioles
- ↓ Total peripheral resistance (TPR) → ↓ Blood pressure
Unlike non-dihydropyridine CCBs (verapamil, diltiazem), amlodipine has minimal effect on heart rate and atrioventricular conduction, making it safer for patients with conduction abnormalities.
4. Pharmacokinetics
| Parameter | Amlodipine |
|---|---|
| Absorption | 60–90% (well absorbed orally) |
| Bioavailability | ~64–80% |
| Protein Binding | ~98% |
| Time to Peak (Tmax) | 6–12 hours |
| Half-life (t½) | 30–50 hours (enables once-daily dosing) |
| Metabolism | Hepatic (CYP3A4) to inactive metabolites |
| Elimination | Renal (60%) and fecal (20%) |
| Onset of action | Gradual (6–12 hours) |
| Duration | >24 hours |
The long half-life allows steady control of blood pressure with low risk of rebound hypertension if a dose is missed.
5. Pharmacodynamics
- Vasodilatory effect: Reduces afterload and arterial tone.
- Coronary vasodilation: Increases oxygen delivery to cardiac tissue.
- No significant negative inotropic or chronotropic effect, unlike verapamil or diltiazem.
- Antihypertensive effect maintained for 24 hours post single dose.
6. Therapeutic Indications
| Condition | Mechanism / Rationale |
|---|---|
| Hypertension | Vasodilation → ↓ peripheral resistance → ↓ BP |
| Stable angina (effort angina) | ↓ Afterload → ↓ myocardial oxygen demand |
| Vasospastic (Prinzmetal’s) angina | Coronary artery dilation → Relieves spasm |
| Coronary artery disease (CAD) | Improves coronary flow |
| Raynaud’s phenomenon (off-label) | Peripheral vasodilation |
7. Dosage and Administration
| Population | Dose | Notes |
|---|---|---|
| Adults (Hypertension / Angina) | 5–10 mg once daily | Start at 5 mg, max 10 mg/day |
| Elderly / Hepatic Impairment | 2.5–5 mg once daily | Adjust for reduced clearance |
| Children (6–17 years) | 2.5–5 mg once daily | Limited data in <6 years |
Administer orally once daily, with or without food.
8. Combination Therapy
Amlodipine is often used in fixed-dose combinations for synergistic effect:
| Combination | Purpose |
|---|---|
| Amlodipine + Valsartan / Olmesartan / Telmisartan | Hypertension (dual vasodilation) |
| Amlodipine + Atorvastatin | Hypertension + Dyslipidemia |
| Amlodipine + Benazepril / Perindopril | Hypertension (ACE inhibitor + CCB combo) |
These combinations are clinically beneficial as they:
- Improve compliance
- Enhance blood pressure control
- Reduce dose-related side effects of individual drugs
9. Adverse Effects
Common (Dose-Dependent)
| Effect | Explanation |
|---|---|
| Peripheral edema (especially ankles) | Arteriolar dilation → capillary leakage |
| Flushing | Vasodilation |
| Headache | Cerebral vasodilation |
| Dizziness, fatigue | BP reduction |
| Palpitations | Reflex tachycardia (rare) |
Less Common / Rare
- Gingival hyperplasia
- Hypotension (rare with standard doses)
- Bradycardia (very rare)
- Hepatic enzyme elevation
- Rash, nausea
Peripheral edema is the most frequent side effect; may respond to combination with an ACE inhibitor or ARB.
10. Contraindications
- Hypersensitivity to amlodipine or other dihydropyridines
- Severe hypotension (systolic BP <90 mmHg)
- Cardiogenic shock
- Severe aortic stenosis (may worsen obstruction)
11. Precautions
- Hepatic impairment: Reduce initial dose; clearance is reduced.
- Heart failure: Use cautiously in advanced cases (may worsen edema).
- Elderly: Start low, titrate slowly.
- Pregnancy (Category C): Use only if benefit outweighs risk.
- Lactation: Limited data; caution advised.
12. Drug Interactions
| Interacting Drug/Class | Effect / Mechanism |
|---|---|
| CYP3A4 inhibitors (ketoconazole, diltiazem, clarithromycin) | ↑ Plasma amlodipine levels |
| CYP3A4 inducers (rifampin, carbamazepine, phenytoin) | ↓ Amlodipine efficacy |
| Simvastatin | ↑ Risk of myopathy (limit simvastatin to ≤20 mg/day) |
| Antihypertensives | Additive BP-lowering effects |
| Grapefruit juice | Minor increase in drug concentration (usually not clinically significant) |
13. Overdose and Management
Overdose symptoms:
- Severe hypotension
- Reflex tachycardia
- Shock (rare)
Treatment:
- Supportive care and monitoring
- Activated charcoal if early ingestion
- IV fluids, vasopressors (norepinephrine)
- IV calcium gluconate (may reverse some effects)
14. Clinical Pearls
- Once-daily dosing improves compliance compared to short-acting CCBs.
- No need for dose adjustment in renal impairment — primarily hepatically cleared.
- Does not cause rebound hypertension upon withdrawal.
- Preferred in elderly hypertensive patients due to long safety record.
- Combination therapy reduces edema and enhances efficacy.
- Beneficial in hypertensive patients with angina or atherosclerosis.
15. Summary Table
| Property | Details |
|---|---|
| Drug Class | Dihydropyridine Calcium Channel Blocker |
| Main Action | Vascular smooth muscle relaxation (vasodilation) |
| Primary Indications | Hypertension, Angina |
| Half-life | 30–50 hours |
| Dose Range | 2.5–10 mg daily |
| Adverse Effect (Most Common) | Peripheral edema |
| Metabolism | CYP3A4 (hepatic) |
| Elimination | Renal and fecal |
| Pregnancy Category | C |
16. Clinical Importance
Amlodipine remains one of the most effective and well-tolerated first-line antihypertensive agents.
Its vascular selectivity, minimal cardiac depression, and once-daily dosing make it an ideal option for long-term therapy.
When combined with other antihypertensives, it helps achieve comprehensive blood pressure control with a favorable safety profile.
17. References
- Katzung BG, et al. Basic and Clinical Pharmacology. 16th Edition. McGraw-Hill, 2021.
- Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 14th Edition. McGraw-Hill, 2021.
- Messerli FH, et al. Vasodilatory edema: A common side effect of antihypertensive therapy. Am J Hypertens. 2002;15:982–988.
- Whelton PK, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS Hypertension Guideline. Hypertension. 2018;71:e13–e115.
- Neutel JM. Clinical pharmacokinetics of amlodipine. Clin Pharmacokinet. 1997;32(6):428–435.
External Reference Links
- Drugs.com – Amlodipine Monograph
- PubMed – Clinical Pharmacokinetics of Amlodipine
- FDA – Amlodipine Besylate Label Information
- Mayo Clinic – Amlodipine (Oral Route)
- National Center for Biotechnology Information (NCBI) – Amlodipine
- American Heart Association – Hypertension Treatment Guidelines
How does Amlodipine lower blood pressure?
It relaxes blood vessels, making it easier for the heart to pump blood. This lowers total peripheral resistance and decreases blood pressure.
When is the best time to take Amlodipine?
It can be taken any time of day, but taking it at the same time every day ensures consistent blood levels. Some people prefer taking it at night to reduce daytime dizziness.
