Nadolol
Nadolol
Generic Name
Nadolol
Mechanism
- Competitive inhibition of β₁
- and β₂-adrenergic receptors in cardiac, vascular, and bronchial tissues.
- ↓ Sympathetic stimulation → ↓ heart rate, contractility, and renin release.
- → ↓ Systemic vascular resistance and blood pressure.
- Inhibition of β₂ receptors in the lungs explains its bronchoconstrictive potential, especially in asthmatic or COPD patients.
Pharmacokinetics
| Parameter | Details | Clinical Notes |
| Absorption | ~100 % oral bioavailability; peak plasma conc. 60–90 min post dose. | Rapid onset, but higher dosing frequency is needed. |
| Distribution | Highly hydrophilic; limited lipophilicity → poor blood‑brain barrier penetration. | Fewer CNS side effects (e.g., insomnia). |
| Metabolism | Minimal hepatic metabolism; mainly converted to inactive metabolites. | Low potential for drug–drug interactions via CYP450. |
| Elimination | Renal excretion unchanged in urine (≈60 % as parent; remainder as metabolites). | Dose adjustment required in moderate‑to‑severe renal impairment. |
| Half‑life | 7–12 h (varies with renal function). | BID dosing recommended for most indications. |
Indications
- Hypertension – Best for patients requiring a non‑selective agent and when renal excretion is preferred.
- Angina pectoris – Reduces myocardial oxygen demand.
- Supraventricular arrhythmias – Controls ventricular rate in atrial fibrillation/flutter.
- Pre‑operative β‑blockade – Useful when immediate β‑blockade is needed prior to surgery.
- Migraine prophylaxis – ⅕–⅑ efficacy in chronic migraine patients.
- Essential tremor – Low‑dose therapy may reduce tremor amplitude.
Contraindications
- Absolute
- History of severe bronchospastic disease (asthma, COPD).
- Severe bradycardia (HR 3 × ULN) – limited data on safety.
- Relative
- Renal impairment (CrCl < 30 mL/min) – dose reduction or avoidance.
- Severe peripheral vascular disease (risk of ischemia).
- Diabetes mellitus – mask hypoglycemia symptoms (palpitations, tremor).
- Post‑CABG patients – careful titration to avoid heart block.
Dosing
| Condition | Adult Dose | Frequency | Notes |
| Hypertension | 20–80 mg PO daily (titrated) | BID | Start 20 mg BID; increase by 20 mg per week as needed. |
| Angina | 20–40 mg PO daily | BID | May add with nitrates; monitor BP/HR. |
| Supraventricular arrhythmia | 40–80 mg PO daily | BID | Initiate at 20 mg BID; target HR < 80 bpm. |
| Pre‑operative | 40–80 mg PO | BID | Ensure adequate plasma levels 4–6 h before surgery. |
| Migraine prophylaxis | 20–40 mg PO daily | BID | Start 20 mg BID; increase to 40 mg BID after 4 weeks. |
| Pediatric | 0.2–1.0 mg/kg/d (≤ 40 mg) | BID | Adjust based on response & renal function. |
Administration Tips
• Take with or after meals to enhance absorption.
• Do not abruptly discontinue; taper over 1–2 weeks to avoid rebound hypertension.
Adverse Effects
Common (≤ 10 %):
• Fatigue, dizziness, headache.
• Cold extremities, diminished exercise tolerance.
• Rebound tachycardia if stopped abruptly.
Serious (≤ 1 %):
• Severe bronchospasm (especially in asthmatics).
• AV conduction delay or heart block.
• Severe hypotension or syncope.
• Masking of hypoglycemia in diabetics.
Rare (≤ 0.1 %):
• Depression/anxiety, sexual dysfunction.
• QT prolongation (combine cautiously with other QT‑prolonging drugs).
Monitoring
| Parameter | Frequency | Rationale |
| Blood pressure & heart rate | Baseline, 3–5 days after dose change, then monthly | Detect bradyarrhythmia or hypotension early. |
| Renal function (CrCl) | Baseline, every 6–12 months (or sooner in CKD) | Adjust dose as needed. |
| Electrolytes (K⁺, Mg²⁺) | Baseline, if symptomatic or heart failure | Prevent arrhythmias. |
| Pulmonary function | Baseline in at-risk pts; repeat if dyspnea | Avoid bronchospasm. |
| Blood glucose | Continuous for diabetic patients | Detect hypoglycemia slip. |
| Drug interactions | Review all concomitant polypharmacy | Avoid synergistic bradycardic or hypotensive effects. |
Clinical Pearls
- Nadolol is the only β‑blocker that is entirely renally excreted unchanged, so it is especially useful when hepatic metabolism is contraindicated or when avoiding CYP450 interactions.
- Its lack of CNS penetration translates into fewer insomnia or depression reports compared with lipophilic β‑blockers (e.g., propranolol).
- Because it blocks both β₁ and β₂ receptors, ballooning diuretics (e.g., furosemide) can be combined to offset potassium loss while still benefiting from β‑blockade.
- In diabetic patients, Nadolol does not cause lipid‑000 but does mask hypoglycaemic symptoms; use with continuous glucose monitoring if routine ketogloss.
- Dose adjustment: Reduce to 10 mg BID when CrCl is 30–50 mL/min; avoid if < 30 mL/min unless there are no alternatives.
- For hypertensive emergencies or rapid post‑CABG control, a IV formulation is not available; rely on oral dosing or switch temporarily to a different β‑blocker.
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• *End of Nadolol drug card. Use for quick reference in student notes, clinical rounds, or pharmacy prep.*