Inderal
Inderal
Generic Name
Inderal
Mechanism
- Competitive antagonist of β₁‑ and β₂‑adrenergic receptors
- ↓ Sympathetic tone → ↓ heart rate, contractility, and myocardial oxygen demand
- ↓ β₂‑mediated vasodilatory tone → modest vasoconstriction, improving hemodynamic control
- Inhibits renin release from juxtaglomerular cells → lowers angiotensin‑II production, contributing to antihypertensive effects
- Reduces catecholamine‑triggered trigeminal nerve activation → prevents migraine aura and pain pathways
Pharmacokinetics
- Absorption: Oral, ~80 % bioavailability; first‑pass effect (~35–55 %)
- Distribution: Lipophilic → high tissue penetration; protein binding ~30 %
- Metabolism: Hepatic CYP2D6, CYP1A2; extensive oxidation, glucuronidation
- Elimination: Urinary (≈60 %) and fecal; terminal half‑life 3–6 h (up to 12 h in hepatic impairment)
- Drug interactions: Strong CYP2D6 inhibitor (cimetidine) ↑ plasma levels; CYP2D6 inhibitors (fluoxetine, paroxetine) ↑ risk of bradycardia/hypotension
Indications
- Cardiac
- Hypertension (adjunct or monotherapy)
- Stable angina (reduction of myocardial oxygen demand)
- Post‑myocardial infarction (reduced mortality when combined with ACE inhibitors)
- Arrhythmias: supraventricular tachycardia, atrial fibrillation (rate control)
- Neuro‑Psychiatric/Other
- Migraine prophylaxis (reduces frequency/duration)
- Essential tremor (dose‑dependent)
- Sympathetic hyperactivity: hyperthyroidism (symptoms), pheochromocytoma (pre‑operative)
- Anxiety disorders (sub‑therapeutic doses)
- Acute cardiac arrhythmia post‑AMI, ventricular arrhythmias
Contraindications
- Absolute contraindications
- Sinus bradycardia, second‑ or third‑degree AV block (unless pacer)
- Severe heart failure (decompensated)
- Uncontrolled asthma or COPD (β₂ blockade)
- Severe peripheral vascular disease
- Relative contraindications/precautions
- Diabetes (unmask hypoglycemia, delay detection)
- Chronic obstructive pulmonary disease
- Hepatic or renal impairment (adjust dosing)
- Elderly: higher sensitivity, risk of orthostatic hypotension
- Warnings
- Hypotension: monitor BP; avoid rapid titration
- Coronary artery disease: risk of silent ischemia in patients with impaired autonomic regulation
- Sleep disturbance: nightmares, insomnia at high doses
- Drug‑drug interactions: potentiation with nitrates, calcium channel blockers, digoxin
Dosing
| Indication | Initial Dose | Titration | Max Dose |
| Hypertension | 40 mg BID | ↑ 40 mg every 2–3 days | 320 mg/day |
| Angina | 10 mg TID | ↑ 10 mg weekly | 320 mg/day |
| Migraine | 20 mg BID (oral) or 2.5 mg/kg BID (IV) | Maintain | 80 mg BID (oral) |
| Essential tremor | 20 mg BID | ↑ 10–20 mg weekly | 80 mg BID |
• Route: Oral; IV form for acute arrhythmia or migraine (not for chronic use)
• Co‑administration: With food or antacids, absorption ↓; advised to take on empty stomach (30 min before food)
• Compliance: Teach patients to take consistently to maintain therapeutic levels
Adverse Effects
| Common (≤10 %) | Serious (≤1 %) |
| Bradycardia, fatigue, dizziness, insomnia, mild GI upset | Hypotension, heart block, severe bronchospasm |
| Cold extremities (Raynaud’s), edema, headache, nausea | Severe hypoglycemia (diabetics) |
| Sexual dysfunction, vivid dreams | Severe allergic reactions (rare) |
| Rash, pruritus (rarely) | Cardiac arrhythmias in vulnerable patients |
| ↓ Exercise tolerance | Long‑term bone density loss (very low risk) |
• Watch for: early signs of asthma exacerbation; bradycardia; orthostatic hypotension
Monitoring
- Baseline & follow‑up: Blood pressure, heart rate, ECG, renal & liver panel
- Post‑initiation: Check BP/HR after first 24 h, then weekly until stable
- Diabetes: SMBG or HbA1c at 4‑6 week intervals
- Cardiac status: Exercise tolerance tests (if indicated), Holter monitor in arrhythmia patients
- Drug levels: Not routinely required; check if toxicity suspected
Clinical Pearls
- Beta‑blocker “challenge”: For patients with beta‑blocker intolerance, a low‑dose (e.g., 10 mg twice daily) prodrugs (e.g., carvedilol) can be trialed before escalating Inderal.
- Migraine prophylaxis dosing: A split‑dose strategy (10 mg at night, 10 mg first thing next morning) maximizes serum troughs, reducing breakthrough migraines.
- Combining with ACE inhibitors: Start Inderal at 20 mg AM, titrate while adding lisinopril to synergistically reduce mortality post‑MI.
- Peri‑operative care: Withhold Inderal 24 h before elective surgery to avoid intra‑operative hypotension, but continue in cases of pheochromocytoma to blunt catecholamine surges.
- Non‑cardiovascular: Use Inderal 20–40 mg BID in essential tremor; its central β₂ blockade dampens tremor amplitude, making it a first‑line therapy for patients intolerant to anticonvulsants.
*Remember:* Inderal’s non‑selectivity makes it powerful but also demands vigilant monitoring for respiratory, metabolic, and cardiovascular adverse effects.