Diltiazem
Nonspecific L‑type calcium channel blocker
Generic Name
Nonspecific L‑type calcium channel blocker
Mechanism
- Nonspecific L‑type calcium channel blocker that competitively inhibits the influx of Ca²⁺ into cardiac and vascular smooth‑muscle cells.
- ↓ intracellular Ca²⁺ → decreased myocardial contractility (negative inotropy) and relaxation of arterial smooth muscle → ↓ systemic vascular resistance.
- Slows AV‑nodal conduction → increases cardiac refractory period and diminishes heart rate.
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Pharmacokinetics
| Parameter | Typical Value (IV) | Typical Value (PO) |
| Absorption | Rapid; ~80 % bioavailability | Rapid, but first‑pass metabolism reduces AUC |
| Distribution | 2–3 L/kg (high protein binding 80 %) | 2–3 L/kg, highly protein‑bound |
| Metabolism | Hepatic by CYP2C8, CYP3A4 | Mainly hepatic; extensive first‑pass |
| Elimination | ~30 % renal, 70 % hepatic | ~30 % urinary, remainder biliary |
| Half‑life | IV: 1–2 h | PO: 3–5 h (modified‑release 24‑h formulation) |
| Steady‑state | ~4 h IV | ~5–6 days for PO to reach steady state |
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Indications
| Condition | Preferred Form |
| Angina pectoris (stable or variant) | Oral sustained‑release |
| Atrial fibrillation/sinus tachycardia with rapid ventricular response | Oral or IV for rate control |
| Hypertension (especially when combined with β‑blockers) | Oral |
| Hypertrophic obstructive cardiomyopathy | Oral |
| Pre‑operative preload reduction (short‑acting) | IV |
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Contraindications
- Absolute:
- Severe left ventricular systolic dysfunction (EF < 35 %)
- Cardiogenic shock / acute heart failure
- Aortic stenosis with high gradient
- Premature atrial or ventricular contractions as sole rhythm
- Relative:
- Severe bradycardia or sinus node dysfunction
- Untreated bundle‑branch block
- Bradyarrhythmias requiring pacing
- Pregnancy (Category C; use only if benefit outweighs risk)
- Concerns in elderly or renal/hepatic impairment
Warnings
• Hypotension (especially with IV) → monitor systolic BP.
• Negative inotropy → caution in patients with post‑infarction or ischemic cardiomyopathy.
• Drug interactions: potent CYP3A4 inhibitors (ketoconazole, ritonavir) ↑ diltiazem levels; β‑blockers + diltiazem → additive rate‑control → bradycardia.
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Dosing
| Form | Adult Dose | Pediatric Dose | Notes |
| Oral (Extended‑Release) | 90 mg TID (≈ 270 mg/day) or 120 mg QD | 0.5–2 mg/kg/day | Initiate at lower dose in renal/hepatic impairment. |
| Oral (Soluble) | 30 mg BID as needed | 0.5 mg/kg IV bolus | Use PRN for acute angina or rate control. |
| IV | 5–10 mg IV push over 2 min, repeat every 5‑10 min up to 50 mg/24 h | 1 mg/kg IV bolus (max 10 mg) | Use in acute arrhythmia or uncontrolled hypertension. |
| IV Continuous Infusion | 80–250 µg/kg/min (max 15 mg/hr) | 30–40 µg/kg/min (max 15 mg/hr) | For peri‑operative preload reduction or severe tachycardia. |
• Titration: Slow titration over 2–4 weeks to avoid abrupt BP drop or bradycardia.
• Discontinuation: Abrupt cessation can precipitate rebound tachycardia or angina.
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Adverse Effects
| Common (≥5 %) | Serious (≤1 %) |
| Headache, dizziness, flushing | Severe hypotension |
| Bradycardia, AV nodal block | Worsening heart failure |
| Peripheral edema | QT prolongation (rare) |
| Constipation | Arrhythmogenic events in predisposed patients |
| Rash, pruritus | Liver injury (elevated ALT/AST) |
| Increased intra‑ocular pressure (rare) |
> Serious adverse reactions warrant immediate consultation and potential discontinuation.
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Monitoring
- Baseline: BP, HR, ECG, LVEF (if known).
- During therapy:
- BP & HR 5–10 min after IV infusion, then 30 min, 1 h, 4 h, 8 h, 12 h, 24 h.
- ECG if symptoms or PR prolongation > 180 ms.
- Periodic:
- CBC, BMP (especially electrolytes).
- LFTs if long‑term use or hepatic impairment.
- Renal function if dose adjustment needed.
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Clinical Pearls
- Pre‑operative preload reduction: IV diltiazem (1 mg/kg bolus + infusion) provides a rapid, reversible drop in preload—ideal for patients with LV dysfunction undergoing cardiac surgery.
- Rate control in atrial fibrillation: Compared to β‑blockers, diltiazem has less negative inotropic effect in patients with preserved EF but should be avoided in severe LV dysfunction.
- Dosing in CKD: While diltiazem is largely hepatically cleared, caution is still warranted; monitor BP/HR closely and consider lower initial doses.
- Drug–drug synergy: Combining diltiazem with β‑blockers can synergistically blunt AV conduction—use minimal effective doses to avoid bradycardia.
- Patient education: Advise patients to report dizziness or fainting promptly; carry a pre‑filled emergency dose of β‑blocker if bradycardia may occur.
- Sustained‑release formulation: Delivers 75–85 % of the total bioavailability over 24 h, making it suitable for once‑daily dosing in stable angina; avoid abrupt switching to soluble form without overlap to prevent rebound.
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