Nifedipine
Competitive antagonist
Generic Name
Competitive antagonist
Mechanism
- Competitive antagonist of voltage‑gated L‑type Ca²⁺ channels in vascular smooth muscle.
- Inhibits calcium influx → relaxation of arterial smooth muscle, reducing peripheral resistance.
- Rapid onset of vasodilation due to high affinity for the channel’s open state.
- No significant effect on myocardial contractility or conduction at therapeutic doses (minimal negative inotropy/no‑atrioventricular block).
Pharmacokinetics
| Parameter | Typical Value (oral, immediate‑release) | Comment |
| Absorption | Rapid; peak plasma 30–120 min | Food delays onset slightly |
| Bioavailability | 20–40 % (first‑pass hepatic metabolism) | High intra‑individual variability |
| Metabolism | CYP3A4‑mediated 3‑hydroxylation, glucuronidation | Shedding significant drug–drug interactions |
| Elimination | Renal (≥ 50 %) & biliary | Terminal half‑life 2–4 h (IR) |
| Protein binding | 90–95 % | Albumin and α1‑acid glycoprotein |
| Therapeutic window | Narrow; monitor BP closely |
> Key Point: Dosing must account for CYP3A4 modulators (e.g., ketoconazole ↑ Nifedipine, rifampin ↓).
Indications
- Hypertension – short‑acting oral ER or transdermal patches.
- Stable angina pectoris – oral or transdermal for early onset relief.
- Primal graft and organ perfusion – intraoperative vasodilatory infusion.
- Pre‑eclampsia / eclampsia – adjunct to magnesium sulfate for severe cases (ER or IV).
Contraindications
- Absolute Contraindications
- Severe hypotension (SBP < 90 mm Hg).
- Second‑degree block type III (Wolff–Parkinson‑White).
- Severe aortic stenosis.
- Relative Warnings
- First‑trimester pregnancy (category D).
- Concomitant use with strong CYP3A4 inhibitors.
- Uncontrolled heart failure.
- Bezold‑Jarisch reflex potential with rapid IV bolus.
Dosing
| Formulation | Initial Dose (Adult) | Maintenance | Notes |
| Oral Immediate‑Release (IR) | 10 mg 3–4 × day | 20–40 mg / day | Start low, titrate by 5 mg increments every 4–7 days. |
| Oral Extended‑Release (ER) | 30 mg once‑daily | 30–60 mg / day | Avoid dim light; acidic foods reduce absorption. |
| Transdermal Patch (12/2 mg/h) | 12 mg/h for 14 days | 12 mg/h @ 14‑day interval | Tilt 10° upward; avoid skin irritation. |
| IV (intra‑operative) | 0.1 mg/kg / min load, then 0.03 mg/kg / min infusion | 0.025–0.04 mg/kg / min | Requires 3‑lev heart monitor and rapid‑response team. |
> Tip: For ARBs or ACEIs, consider a “washout” period if switching.
Adverse Effects
- Common (≥ 10 %)
- Flushing, headache, dizziness.
- Peripheral edema, tachycardia.
- Nasal congestion.
- Serious (> 1 %)
- Hypotension, syncope.
- Severe bradycardia (rare).
- Cardiogenic shock if IV overloaded.
- Drug interactions: CYP3A4 inhibitors > platelet aggregation, e.g., *ketoconazole* → supra‑therapeutic levels.
Monitoring
- Blood pressure: Titrate to 10–15 % reduction in SBP; avoid > 20 % drop.
- Heart rate: Monitor for tachycardia > 100 bpm.
- Clinical signs: edema, skin reactions.
- Renal/liver function: Every 3–6 months (for chronic therapy).
- Drug interactions: Check for concurrent CYP3A4 inducers/inhibitors at every refill.
Clinical Pearls
- Transdermal vs Oral: Transdermal offers steady plasma levels and fewer GI side‑effects; ideal for nighttime BP control.
- Use in Pregnancy: Only in life‑threatening, uncontrolled hypertension when benefits outweigh fetal risks; otherwise, avoid.
- IV Nifedipine in angina: Rapid, short‑acting; may precipitate reflex tachycardia—consider beta‑blocker cover.
- Avoid 4‑hour IV bolus: Can cause Bezold‑Jarisch reflex and myocardial stunning.
- Patch removal position: Tilt patient 10° upward during removal to reduce pooling and systemic absorption.
- Titration schedule: Use 5‑mg daily increments at 4‑day intervals for oral ER; for IR, adjust after 1 week.
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• For a quick reference, keep this card handy when prescribing or reviewing nifedipine protocols.