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propranolol (Inderal, InnoPran)

Tradename: Inderal, InnoPran XL. Indications: - hypertension - chronic stable angina - secondary prevention in patients with cardiovascular disease [11] - supraventricular arrhythmia, especially caused by: - catecholamines - cardiac glycosides - Wolff-Parkinson-White (WPW) syndrome - long QT syndrome [11] - mitral valve prolapse [11] - hypertrophic subaortic stenosis - adjunctive therapy for pheochromocytoma - used with alpha adrenergic receptor antagonist - migraine prophylaxis - hemodynamically stable post-myocardial infarction - essential tremor - anxiety - tardive dyskinesia - antipsychotic induced akathisia - thyrotoxicosis Contraindications: 1) asthma 2) overt heart failure 3) cardiogenic shock 4) bradycardia Dosage: 1) hypertension b) gradually increase at 3-7 day intervals until optimal blood pressure is achieved c) range: 160-240 mg/day 2) angina: a) start 10-20 mg TID-QID b) gradually increase at 3-7 day intervals until symptoms are controlled c) range: 160-240 mg/day 3) cardiac arrhythmias: 10-40 mg TID-QID 4) hypertrophic subaortic stenosis: 10-40 mg TID-QID 5) pheochromocytoma a) 60 mg/day in divided doses in combination with an alpha adrenergic receptor antagonist for 3 days prior to surgery b) for inoperable conditions, 30 mg/day in divide doses in combination with an alpha adrenergic receptor antagonist 6) migraine a) start 20-80 mg/day in divided doses b) titrate to 160-240 mg/day c) discontinue if adequate response is not obtained with maximum dose in 4-6 weeks 7) akathisia/tardive dyskinesia a) start 10 mg PO BID-TID b) maintenance: 20-40 mg BID-TID 8) essential tremor a) start 10 mg PO BID-TID b) maintenance: 20-40 mg BID-TID 9) anxiety: 10 mg QD or BID 10) thyrotoxicosis: 1-40 mg every 6 hours 11) maximum dose: 640 mg/day Tablets: 10, 20, 40, 60, 80, 90 mg. Solution: 4 & 8 mg/mL. Sustained release (Inderol LA): 1) start 80 mg PO QD, max 320 mg/day. 2) Capsule (sustained action): 60, 80, 120, 160 mg. InnoPran XL: QD evening dosing [9] IV: 1 mg increments every 2 min. Injection: 1 mg/mL (1 mL). Pharmacokinetics: 1) rapidly absorbed following oral administration -> absorption is increased by food [6] 2) undergoes extensive 1st pass metabolism a) principal metabolite 4-OH-propranolol with equal beta-blocking activity b) metabolized by cyt P450 1A2 & cyt P450 2D6 3) onset of action: a) oral: within 1-2 hours b) IV: within 2 minutes 4) duration of action: a) oral (except sustained release): 6 hours b) IV: 3-6 hours 5) 90% is bound to plasma proteins 6) crosses blood-brain barrier [10] 7) elimination 1/2life is 3-6 hours Adverse effects: 1) common (> 10%) - bradycardia, depression, sexual dysfunction 2) less common (1-10%) - rash, wheezing, confusion, congestive heart failure, hallucinations, reduced peripheral circulation, diarrhea, dizziness, nausea/vomiting, epigastric discomfort, insomnia, weakness, tiredness 3) uncommon (< 1%) - chest pain, dermatitis, leukopenia, thrombocytopenia, agranulocytosis, nightmares, vivid dreams, hypotension, lethargy, hypoglycemia, cold extremities 4) other - fatigue - drowsiness - headache - orthostatic hypotension - increased serum transaminases - increased lipid levels - eosinophilia - worsening of AV conduction disturbances - impaired myocardial contractility - bronchospasm Drug interactions: 1) beta adrenergic agonists: blunted bronchodilator effect 2) sulfonylureas: propranolol may impair glucose tolerance 3) lidocaine: increased lidocaine levels due to decreased metabolism 4) neuromuscular blocking agents: effect may be potentiated secondary to propranolol's interference at post-junctional membranes 5) barbiturates may enhance propranolol metabolism 6) any drug which inhibits cyt P450 1A2 or cyt P450 2D6 can increase propranolol levels 7) any drug which induces cyt P450 1A2 can diminish propranolol levels Laboratory: 1) specimen: a) serum, plasma (heparin, EDTA) b) stable at room temperature for 1 week c) addition of sodium metabisulfite stabilizes labile 4-OH-metabolite 2) methods: HPLC, GLC, fluorometry, RIA 3) no good correlation of plasma level with therapeutic effect Mechanism of action: 1) highly lipophilic, non-selective beta adrenergic antagonist 2) decreases heart rate, myocardial contractility, cardiac output & conduction through the SA node & AV node 3) increases systolic ejection time & cardiac volume 4) initially, causes an increase in peripheral vascular resistance, but with long-term use, peripheral vascular resistance decreases 5) lowers myocardial oxygen demand 6) blocks renin

Interactions

drug interactions drug adverse effects (more general classes)

Related

cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2) cytochrome P450 2D6 (cytochrome P450 2D, cytochrome P450 DB1, debrisoquine-4-hydroxylase, CYP2D6)

General

antiarrhythmic agent, Group II non-specific beta-adrenergic receptor antagonist (non-specific beta-blocker) propanolamine

Properties

MISC-INFO: elimination route LIVER 1/2life 4-6 HOURS 4-6 HOURS therapeutic-range 50-100 NG/ML protein-binding 90-95% elimination by hemodialysis - pregnancy-category C safety in lactation +

Database Correlations

PUBCHEM correlations

References

  1. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
  2. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  4. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  5. Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
  6. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 470
  7. Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  8. Physician's Desk Reference (PDR) 56th ed, 2002
  9. Prescriber's Letter 10(4):21 2003
  10. Alessi C In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  11. Deprecated Reference

Component-of

hydrochlorothiazide/propranolol; HCTZ/propranolol (Inderide)