labetalol (Trandate, Normodyne, Ibidomide, Dilevolol)
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Introduction
Tradenames: Trandate, Normodyne.
Indications
- hypertension, including hypertensive crisis
- short-term management of tachycardia
- treatment of aortic dissection
- adjunct 1st line agent
- concomitant use with sodium nitroprusside generally results in BP homeostasis & reductions in aortic wall shear forces
- may be of particular benefit in states of adrenergic excess
- antihypertensive agent of choice in association with stroke
- neglible effect on intracranial pressure
- angina pectoris[7]
Contraindications
- absolute
- cardiogenic shock
- overt heart failure
- bradycardia
- moderate to severe asthma
- relative
- asthma (asymptomatic)
- COPD
- CHF (stable)
- 2nd degree heart block
Dosage
- 20-80 mg IV every 10 min up to 300 mg.
- IV infusion 2-4 mg/min.
- PO start 100 mg BID, maximum 2400 mg/day.
Tabs: 100, 200, 300 mg.
Pharmacokinetics
- extensive 1st pass metabolism in liver
- oral bioavailablity is 25%
- 50% bound to plasma proteins
- onset of action following IV administration is 5-15 minutes
- duration of action is 2-4 hours
- elimination 1/2life
- 6-8 hours following oral administration
- 5.5 hours following IV administration
- since the 1/2 life of labetalol is 5-8 hours, intermittent IV bolus dosing may be preferable to IV infusion
- IV infusion may be discontinued 5-8 hours before beginning oral labetalol
- formulation contains equal proportions of 4 optical isomers
- RR & SR isomers produce most of the beta & alpha adrenergic blockade, respectively
elimination via liver
elimination via kidney
1/2life = 4-8 hours
protein binding = 50 %
Monitor
- liver function test annually
Adverse effects
- not common (1-10%)
- impotence, bronchospasm, heart failure, heart block, depression, reduced peripheral circulation, taste disturbance, dizziness, drowsiness, itching, nausea/vomiting, numbness of skin, dyspepsia, nasal congestion, weakness/fatigue
- uncommon (< 1%)
- other
- hypotension:
- symptomatic postural hypotension may occur with IV use
- treat with patients in a supine position
- scalp tingling
- headache
- paradoxical pressor response
- nightmares
- elevated serum transaminases
- tolerance may develop with prolonged use
- hypotension:
- 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
- labetalol blunts the bronchodilator effect of beta- adrenergic agonists
- cimetidine increases bioavailability of oral labetolol
- halothane in combination results in synergistic adverse effects on cardiovascular hemodynamics, resulting in significant myocardial depression
- labetalol may not be effective in patients receiving other alpha or beta adrenergic receptor antagonists
- phenothiazines increase plasma labetolol concentrations
- 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 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
Mechanism of action
- alpha-1 adrenergic receptor antagonist
- non-selective beta adrenergic receptor antagonist
- beta adrenergic receptor antagonism following oral administration is 7 times more potent than alpha-1 adrenergic antagonism
- neglibible effect on intracranial pressure
More general terms
Component of
References
- ↑ The Pharmacological Basis of Therapeutics, 8th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1990 pg 230
- ↑ Manual of Medical Therapeutics, 28th ed., GA Ewald & CR McKenzie (eds), Little, Brown & Co. Boston, 1995 pg 77
- ↑ Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, American College of Physicians, Philadelphia 1998
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 7.0 7.1 Deprecated Reference
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3869
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=71412
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=134043
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=134044
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657196