Propranolol
Propranolol
Generic Name
Propranolol
Brand Names
Inderal, Propranol, Dasa‑Inda) is a non‑selective β‑adrenergic receptor antagonist widely used in cardiovascular, neurological, and endocrinological disorders.
Mechanism
- β‑Adrenergic Receptor Blockade
- Blocks both β1‑ and β2‑adrenergic receptors, decreasing sympathetic tone.
- ↓Heart rate (chronotropic effect), ↓cardiac contractility (inotropic effect).
- Receptor‑Crossing Effects
- Lipophilic; penetrates the blood–brain barrier → central β‑blockade → ↓central catecholamine release.
- Other Effects
- Inhibits renin release → ↓angiotensin–converting enzyme (ACE) activation.
- Downregulates β2‑mediated vasodilatory pathways → modest vasoconstriction in peripheral vessels.
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Pharmacokinetics
| Property | Detail |
| Route | Oral, intramuscular (IM), intravenous (IV) |
| Absorption | Rapid; peak plasma ~1–2 h after oral dosing |
| Bioavailability | ~15–25 % (first‑pass hepatic metabolism) |
| Metabolism | Hepatic CYP2D6 → inactive metabolites |
| Elimination | Renal (≈60 %) and fecal (≈30 %) |
| Half‑life | 2–3 h (short‑acting); chronic dosing leads to a cumulative effect |
| Protein Binding | ~90 % (primarily to albumin) |
| Special Populations |
• Renal impairment: ↓clearance, ↑dose interval • Hepatic impairment: ↑systemic exposure • Elderly: ↓clearance, ↑sensitivity |
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Indications
*Cardiovascular*
• Hypertension
• Chronic stable angina
• Post‑myocardial infarction (heart‑failure prevention)
• Symptomatic ventricular arrhythmias (e.g., SVT)
• Atrial fibrillation (rate control, especially mild EHFs)
*Neurological & Endocrine*
• Migraine prophylaxis (2–4 x daily)
• Essential tremor (≤ 2 mg/kg/day)
• Pheochromocytoma (pre‑operative β‑blockade)
• Anxiety & performance‑related tremor
*Other*
• Hyperthyroidism (symptomatic control)
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Contraindications
| Category | Details |
| Absolute |
• Severe bradycardia or heart block (≥ 2nd degree) • Severe asthma, COPD, or reactive airway disease • Decompensated heart failure |
| Relative |
• Aortic stenosis • Decreased hepatic reserve • Diabetes mellitus (masking hypoglycemia) |
| Warnings |
• Hypoglycemia in diabetics, especially insulin/secretagogue users • Bronchospasm in predisposed individuals • Fluid retention / peripheral edema • CNS side‑effects (sleep disturbance, depression) |
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Dosing
| Indication | Typical Oral Doses | Frequency | Special Notes |
| Hypertension | 40–320 mg/day | 1–3 times daily, or 80‑210 mg bid (titrated) | Start low, increase gradually |
| Angina / Post‑MI | 40–80 mg/d *or* 80‑210 mg bid | 1–3 times daily | Avoid abrupt withdrawal |
| Arrhythmias (SVT, AF) | 10 mg bid for rate control | 8–10 mg bid | May require IV for acute control |
| Migraine Prophylaxis | 40–80 mg 4‑5 × daily or 80‑200 mg bid | 4×/day | Pain tolerance determines frequency |
| Essential Tremor | 1‑2 mg/kg/day (≈ 80–120 mg) | 1–3 x daily | Titrate to benefit/side‑effects |
| Pheochromocytoma | 40 mg 2–4 × daily | 3–4 x daily | Add α‑blocker after β‑blockade |
| Acute AF / Tachycardia (IV) | 0.5–1 mg/kg over 5–10 min | 1–2 × | Monitor BP/HR closely |
| Acute Migraine (IM) | 10–20 mg/0.5 mg/kg | 1–2 × | For severe attacks |
Titration: Increase by 20 mg increments every 3–5 days until desired objective or side‑effect threshold.
Tapering: Discontinue over 3–5 days to avoid rebound hypertension/bradycardia.
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Adverse Effects
Common
• Bradycardia / hypotension
• Fatigue, dizziness, fatigue
• Cold extremities, orthostatic hypotension
• Gastro‑intestinal upset (nausea, abdominal pain)
• Visual disturbances (blurry vision, near‑sightedness)
Serious
• Bronchospasm, airway obstruction (especially in asthma/COPD)
• Heart failure exacerbation or decompensation
• Severe hypoglycemia (diabetic patients)
• Neuropsychiatric disorders: depression, insomnia, nightmares
• Reye‑like syndrome in children < 5 yrs (rare, use with caution)
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Monitoring
- Baseline: BP, HR, ECG, renal & hepatic panel, fasting glucose.
- During Therapy:
- BP & HR: every 2–4 weeks during titration.
- ECG: at baseline and if symptomatic changes occur.
- Fasting glucose: monthly for diabetics.
- Liver enzymes & creatinine: every 3 months or if clinically indicated.
- Special Populations:
- Elderly: monitor for orthostatic hypotension.
- Renal impairment: dose interval adjustments.
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Clinical Pearls
1. Avoid Abrupt Discontinuation
– Rapid withdrawal can precipitate rebound hypertension, arrhythmias, or anxiety. Taper over 3–5 days, monitoring BP/HR.
2. Additive CNS Penetration
– Propranolol crosses the blood–brain barrier → useful for performance anxiety and menstrual migraine prophylaxis.
3. Use with Caution in Diabetes
– β‑blockade blunts tachycardia and tremulousness associated with hypoglycemia. Pair with glucose‑monitoring devices or consider cardio‑selective blocker if needed.
4. Second‑Degree AV Block Hazard
– Contraindicated in patients with Mobitz II or recent AF history with rapid ventricular response.
5. Low‑Dose Regimens for Essential Tremor
– A “no‑extra‑drug” approach: start 40 mg 3 × week, increase to 80 mg/weekly if inadequate.
6. Combine with α‑Blocker in Pheochromocytoma
– Initiate propranolol first to prevent “unopposed α” crisis, then add phenoxybenzamine later.
7. Use Propranolol for Post‑MI
– Early initiation (within 48 h) reduces mortality when combined with ACE inhibitors and antiplatelet therapy.
8. Avoid Use in Severe Asthma
– Non‑selective β1/β2 blocking destabilizes bronchial response; consider cardio‑selective alternatives (e.g., metoprolol).
9. Administer with Food?
– Oral bioavailability is lower; may deliberately give with meals to reduce GI upset, but avoid doses > 2 h after meals to maintain therapeutic levels for arrhythmia control.
10. Use for Migraine Prophylaxis
– Cost‑effective compared to newer agents; watch out for worsening of depression or insomnia.
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• *Propranolol* remains a cornerstone beta‑blocker, but its non‑selectivity mandates vigilant monitoring, especially in patients with pulmonary disease, diabetes, or cardiac conduction abnormalities.