Amlodipine is a dihydropyridine calcium-channel blocker. It is a peripheral and coronary vasodilator, but, unlike the calcium-channel blockers verapamil or diltiazem, has little or no cardiac conduction and negative inotropic activity is rarely seen at therapeutic doses.
Class
- Calcium Channel Blocker (CCB)
- Subclass : Dihydropyridine CCB
Mechanism of Action
Amlodipine selectively inhibits L-type calcium channels in vascular smooth muscle and myocardial cells , reducing calcium influx:
- ↓ Intracellular calcium → ↓ activation of myosin light chain kinase (MLCK) → ↓ myosin phosphorylation → vascular smooth muscle relaxation
- ↓ Peripheral vascular resistance → ↓ afterload & blood pressure
- ↑ Coronary artery dilation → ↑ myocardial oxygen supply
Unlike verapamil and diltiazem , amlodipine has minimal effects on cardiac conduction and contractility at therapeutic doses.
Pharmacological Effects
- Vasodilation (peripheral and coronary arteries)
- ↓ Afterload → beneficial in angina
- ↑ Coronary blood flow → relief of coronary vasospasm
- Reflex tachycardia may occur, especially at initiation
Clinical Uses
- Hypertension (HTN)
- Chronic Stable Angina
- Prinzmetal (Variant) Angina
- Coronary Artery Disease (CAD)
- Diabetic Nephropathy
- Left Ventricular Hypertrophy (LVH)
- Raynaud Phenomenon
- Silent Myocardial Ischemia
Pharmacokinetics
| Parameter | Description |
|---|---|
| Absorption | Oral bioavailability: 64–90% |
| Onset | 24–96 hours |
| Peak Plasma | 6–12 hours |
| Duration of Action | ~ 24 hours |
| Steady State | Reached in 7–8 days |
| Protein Binding | 93–98% |
| Volume of Distribution | ~ 21 L/kg |
| Metabolism | Hepatic (CYP3A4) to inactive pyridine analogs |
| Half-life | 30–50 hours |
| Excretion | Renal (10% unchanged; 60% metabolites) |
Dosing & Administration
For Hypertension
- Adults : 5 mg once daily (max: 10 mg/day)
- Elderly/Debilitated : Start at 2.5 mg/day
- Children ≥6 yrs : 2.5–5 mg/day (max: 5 mg)
- Children <6 yrs : 0.05–0.2 mg/kg/day (max: 0.3–0.6 mg/kg, up to 20 mg)
For Angina & CAD
- Adults : 5–10 mg once daily
- Elderly/Debilitated : 5 mg once daily
Hepatic Impairment
- Start with 2.5 mg for hypertension or 5 mg for angina
- Titrate based on response
Combination Therapies
- Amlodipine + Atorvastatin : HTN + hyperlipidemia
- Amlodipine + ACE inhibitors/ARBs : e.g., benazepril, perindopril, olmesartan
- Amlodipine + Aliskiren : direct renin inhibitor combo
Adverse Effects
Most effects are related to vasodilation and tend to resolve with time:
- Common : Edema (especially ankles), dizziness, flushing, headache, palpitations
- Others : Fatigue, nausea, abdominal pain, constipation
- Rare/Serious :
- Hypotension , Reflex tachycardia
- Angina exacerbation , Myocardial ischemia
- Gingival hyperplasia , Skin rash (e.g., erythema multiforme)
- Liver enzyme elevation , Jaundice
- Psychiatric symptoms : depression, anxiety
- Sexual dysfunction
Contraindications & Precautions
Contraindications
- Cardiogenic shock
- Severe aortic stenosis
- Unstable angina
- Recent myocardial infarction (with caution)
- Known hypersensitivity
Caution In
- Heart failure (may worsen symptoms)
- Severe hepatic impairment
- Elderly patients (lower starting dose recommended)
⚠️ Avoid sudden discontinuation → may cause rebound angina or hypertensive crisis.
Drug Interactions
- CYP3A4 inhibitors (e.g., azole antifungals, macrolides) ↑ amlodipine levels
- CYP3A4 inducers (e.g., rifampin, carbamazepine) ↓ effectiveness
- Enhanced hypotension with beta-blockers, nitrates, diuretics
- Diabetic patients : Monitor for altered insulin/glucose response
- NSAIDs : May attenuate antihypertensive effect
Special Considerations
- Once-daily dosing due to long half-life
- Suitable for use in asthma or COPD patients (unlike non-dihydropyridines)
- Safe in renal impairment (no dosage adjustment needed)
Mnemonic for Amlodipine Adverse Effects
"HEADache DAMPENed blood pressure"
- H eadache
- E dema
- A ltered flushing
- D izziness
- A ngina (worsening)
- M yalgia
- P alpitations
- E levated LFTs
- N ausea
- B lood pressure low
