Amlodipine
Amlodipine
Generic Name
Amlodipine
Mechanism
- Amlodipine is a dihydropyridine calcium‑channel blocker (CCB) that selectively inhibits L‑type voltage‑dependent Ca²⁺ channels in vascular smooth muscle.
- It reduces intracellular Ca²⁺ influx, causing vasodilation of arteriolar beds ➜ ↓ systemic vascular resistance and arterial pressure.
- Minimal effect on cardiac conduction; at therapeutic doses it produces little change in heart rate or contractility.
- The drug’s high lipophilicity allows rapid endothelial access, but the onset of action is delayed by enterohepatic recirculation.
Pharmacokinetics
| Parameter | Typical Value |
| Absorption | Peak plasma ~1–2 h (diet ↓ bioavailability 25 %) |
| Bioavailability | 75–85 % (dietary fat decreases absorption) |
| Distribution | Large volume (≈3 L/kg), high protein binding (≈90 % to albumin & α1‑acid glycoprotein) |
| Metabolism | Predominantly hepatic CYP3A4/2C9 → O‑glucuronides (inactive) |
| Half‑life | 30–50 h; prolonged in liver disease |
| Elimination | Biliary excretion; minimal renal loss (≈10 %) |
| Drug–Drug Interactions | Strong CYP3A4 inhibitors (ketoconazole, erythromycin) ↑ plasma levels; inducers (rifampin) ↓ efficacy |
Indications
- Hypertension – oral once‑daily dosing reduces systolic/diastolic pressure.
- Stable and Unstable Angina Pectoris – improves exercise tolerance and reduces nitrate requirement.
- Variant (Prinzmetal) Angina – effective long‑term prophylaxis.
- Hypertrophic Cardiomyopathy – adjunct treatment to alleviate myocardial oxygen demand.
Contraindications
- Contraindications
- Hypersensitivity to amlodipine or dihydropyridines.
- Severe aortic stenosis (risk of heart failure decompensation).
- Acute decompensated heart failure (may worsen preload).
- Pregnancy – category C (avoid if possible).
- Severe hepatic impairment (CYP3A4 overload).
- Warnings
- Heart Failure – careful titration to prevent pulmonary edema.
- Pregnancy & Lactation – review risk‑benefit; minimal data available.
- Drug Interactions – avoid co‑administration with high‑potency CYP3A4 inhibitors unless closely monitored.
- Baseline ECG – assess QRS complex before initiating in patients with conduction abnormalities.
Dosing
| Condition | Starting Dose | Titration | Target Dose | Frequency |
| Hypertension | 5 mg PO QD | ↑ 5 mg every 2–4 weeks | 10–20 mg PO QD | Once daily |
| Angina (stable/variant) | 5 mg PO QD | ↑ 5 mg every 2–4 weeks | 10–15 mg PO QD | Once daily |
| Hypertrophic CM | 5 mg PO QD | ↑ 5 mg every 2–4 wk | 10 mg PO QD | Once daily |
• Administration Tips
• Take on an empty stomach for maximal absorption; food reduces peak concentration by ~25 %.
• Maintain consistent dosing time to avoid trough‑peak variations.
• Slow titration (≤5 mg every 2 weeks) reduces edema risk.
Adverse Effects
| Category | Examples |
| Common (≤10 %) | Peripheral edema (pre‑eclampsia), flushing, headache, dizziness, constipation, gastrointestinal upset |
| Less Common (1–10 %) | Tiredness, palpitations, arrhythmias, depression |
| Serious (≤1 %) | Severe angioedema (rare), heart failure exacerbation (in predisposed patients), severe hypotension, malignant hypertension during withdrawal |
| Drug‑Interaction–Related | Elevated LFTs with CYP3A4 inhibitors; increased QT prolongation risk with concurrent tricyclic antidepressants |
Monitoring
- Blood Pressure / Heart Rate – baseline, 2–4 weeks post‑dose adjustment.
- Weight / Central Obesity – monitor for fluid retention.
- Edema Assessment – distal extremities, pleural and pericardial.
- Liver Function Tests – baseline, then every 3–6 months in hepatic disease.
- Electrocardiogram – baseline in patients with conduction disease or heart failure.
- Drug Levels / Interaction Checks – if on strong CYP3A4 modulators.
Clinical Pearls
- Dose‑Delay Mechanism – Amlodipine’s delayed peak (~1–2 h) is mitigated by its long half‑life; thus a single daily dose suffices for 24‑hour control.
- Food Effect – Even though high lipophilicity reduces the factor, avoid taking amlodipine immediately after high‑fat meals; schedule it >2 h before or after food.
- Fixed‑Dose Combination – Amlodipine/valsartan or amlodipine/benazepril can enhance antihypertensive synergy while simplifying compliance and reducing cost‑related barriers.
- Peripheral Edema Management – Encourage leg elevation, avoid salt intake, and consider adding a diuretic (e.g., hydrochlorothiazide) when edema limits dose titration.
- Use in Women of Childbearing Potential – Counsel on effective contraception; store in a child‑proof container to avert inadvertent exposure.
- Rebound Hypertension – Abrupt withdrawal can precipitate severe hypertension; taper gradually if discontinuation is required.
- Drug Interaction Super‑Check – Use a verified CYP3A4 inhibitor‑checker tool so clinicians can preemptively adjust dosing or monitor plasma levels.
This concise, evidence‑based drug card equips students and clinicians to recall key pharmacologic facts, clinical protocols, and safety nuances regarding amlodipine.