propranolol (Inderal, InnoPran)
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Introduction
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
Dosage
- hypertension
- gradually increase at 3-7 day intervals until optimal blood pressure is achieved
- range: 160-240 mg/day
- angina:
- cardiac arrhythmias: 10-40 mg TID-QID
- hypertrophic subaortic stenosis: 10-40 mg TID-QID
- pheochromocytoma
- 60 mg/day in divided doses in combination with an alpha adrenergic receptor antagonist for 3 days prior to surgery
- for inoperable conditions, 30 mg/day in divide doses in combination with an alpha adrenergic receptor antagonist
- migraine
- akathisia/tardive dyskinesia
- essential tremor
- anxiety: 10 mg QD or BID
- thyrotoxicosis: 1-40 mg every 6 hours
- maximum dose: 640 mg/day
Tablets: 10, 20, 40, 60, 80, 90 mg.
Solution: 4 & 8 mg/mL.
Sustained release (Inderol LA):
- start 80 mg PO QD, max 320 mg/day.
- Capsule (sustained action): 60, 80, 120, 160 mg.
InnoPran XL: QD evening dosing[9]
IV: 1 mg increments every 2 min.
Pharmacokinetics
- rapidly absorbed following oral administration
- absorption is increased by food[6]
- undergoes extensive 1st pass metabolism
- principal metabolite 4-OH-propranolol with equal beta-blocking activity
- metabolized by cyt P450 1A2 & cyt P450 2D6
- onset of action:
- oral: within 1-2 hours
- IV: within 2 minutes
- duration of action:
- oral (except sustained release): 6 hours
- IV: 3-6 hours
- 90% is bound to plasma proteins
- crosses blood-brain barrier[10]
- elimination 1/2life is 3-6 hours
elimination via liver
1/2life = 4-6 hours adult
1/2life = 4-6 hours child
protein binding = 90-95 %
elimination by hemodialysis = -
Adverse effects
- common (> 10%)
- less common (1-10%)
- uncommon (< 1%)
- other
- fatigue
- drowsiness
- headache
- orthostatic hypotension
- increased serum transaminases
- increased lipid levels
- eosinophilia
- worsening of AV conduction disturbances
- impaired myocardial contractility
- bronchospasm
- drug adverse effects of beta-adrenergic receptor antagonists
- drug adverse effects of renin-angiotensin-aldosterone system inhibitors (RAAS inhibitors)
- drug adverse effects of antihypertensive agents
Drug interactions
- beta adrenergic agonists: blunted bronchodilator effect
- sulfonylureas: propranolol may impair glucose tolerance
- lidocaine: increased lidocaine levels due to decreased metabolism
- neuromuscular blocking agents: effect may be potentiated secondary to propranolol's interference at post-junctional membranes
- barbiturates may enhance propranolol metabolism
- any drug which inhibits cyt P450 1A2 or cyt P450 2D6 can increase propranolol levels
- any drug which induces cyt P450 1A2 can diminish propranolol levels
- drug interaction(s) of antiarrhythmic agents in combination with diuretics
- drug interaction(s) of beta-2 adrenergic receptor agonists with beta adrenergic receptor antagonists
- drug interaction(s) of renin-angiotensin-aldosterone inhibitors with trimethoprim-sulfamethoxazole
- drug interaction(s) of beta-adrenergic receptor antagonists with thyroid hormone
- drug interaction(s) of beta-adrenergic receptor antagonists with sulfinpyrazone
- drug interaction(s) of beta-adrenergic receptor antagonists with salicylate
- drug interaction(s) of beta-adrenergic receptor antagonists with rifampin
- drug interaction(s) of beta-adrenergic receptor antagonists with ampicillin
- drug interaction(s) of beta-adrenergic receptor antagonists with colestipol
- drug interaction(s) of beta-adrenergic receptor antagonists with cholestyramine
- drug interaction(s) of beta-adrenergic receptor antagonists with barbiturates
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium salts
- drug interaction(s) of beta-adrenergic receptor antagonists with aluminum carbonate
- drug interaction(s) of beta-adrenergic receptor antagonists with aluminum hydroxide
- drug interaction(s) of beta-adrenergic receptor antagonists with prazosin
- drug interaction(s) of beta-adrenergic receptor antagonists with lidocaine
- drug interaction(s) of beta-adrenergic receptor antagonists with ergot alkaloids
- drug interaction(s) of beta-adrenergic receptor antagonists with clonidine
- drug interaction(s) of propranolol with warfarin
- drug interaction(s) of beta-adrenergic receptor antagonists with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists (except atenolol) with benzodiazepines
- drug interaction(s) of beta-adrenergic receptor antagonists with quinolones
- drug interaction(s) of beta-adrenergic receptor antagonists with quinidine
- drug interaction(s) of beta-adrenergic receptor antagonists with propafenone
- drug interaction(s) of beta-adrenergic receptor antagonists with phenothiazines
- drug interaction(s) of beta-adrenergic receptor antagonists with MAO inhibitors
- drug interaction(s) of beta-adrenergic receptor antagonists with loop diuretics
- drug interaction(s) of beta-adrenergic receptor antagonists with hydralazine
- drug interaction(s) of beta-adrenergic receptor antagonists with histamine H2 receptor antagonists
- drug interaction(s) of beta-adrenergic receptor antagonists with haloperidol
- drug interaction(s) of beta-adrenergic receptor antagonists with flecainide
- drug interaction(s) of beta-adrenergic receptor antagonists with oral contraceptives
- drug interaction(s) of beta-adrenergic receptor antagonists with calcium channel blockers
- drug interaction(s) of beta-adrenergic receptor antagonists with sulfonylureas
- drug interaction(s) of beta blockers with ACE inhibitors
- drug interaction(s) of spironolactone with beta blockers
- drug interaction(s) of NSAIDs with beta blockers
- drug interaction(s) of NSAIDs & antihypertensives
Laboratory
- specimen:
- methods: HPLC, GLC, fluorometry, RIA
- no good correlation of plasma level with therapeutic effect
Mechanism of action
- highly lipophilic, non-selective beta adrenergic antagonist
- decreases heart rate, myocardial contractility, cardiac output & conduction through the SA node & AV node
- increases systolic ejection time & cardiac volume
- initially, causes an increase in peripheral vascular resistance, but with long-term use, peripheral vascular resistance decreases
- lowers myocardial oxygen demand
- blocks renin
More general terms
Additional terms
- 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)
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (ed), Companion Handbook, McGraw Hill, NY, 1994
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, NW Tietz (ed) 3rd ed, WB Saunders, Philadelpha 1995
- ↑ 6.0 6.1 Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 470
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Physician's Desk Reference (PDR) 56th ed, 2002
- ↑ 9.0 9.1 Prescriber's Letter 10(4):21 2003
- ↑ 10.0 10.1 Alessi C In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 11.0 11.1 11.2 11.3 Deprecated Reference
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4946
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=21138
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=105109
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=66366
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=62882