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labetalol (Trandate, Normodyne, Ibidomide, Dilevolol)
Tradenames: Trandate, Normodyne.
Indications:
1) hypertension, including hypertensive crisis
2) short-term management of tachycardia
3) treatment of aortic dissection
a) adjunct 1st line agent
b) concomitant use with sodium nitroprusside generally results in BP homeostasis & reductions in aortic wall shear forces
4) may be of particular benefit in states of adrenergic excess
a) pheochromocytoma
b) monoamine oxidase inhibitor toxicity
c) clonidine withdrawal
d) cocaine intoxication
e) post-coronary bypass grafting
5) antihypertensive agent of choice in association with stroke
- neglible effect on intracranial pressure
6) angina pectoris [7]
Contraindications:
1) absolute
a) cardiogenic shock
b) overt heart failure
c) bradycardia
d) moderate to severe asthma
2) relative
a) asthma (asymptomatic)
b) COPD
c) CHF (stable)
d) 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.
Injection: 5 mg/mL (20 mL)
Pharmacokinetics:
1) extensive 1st pass metabolism in liver
2) oral bioavailablity is 25%
3) 50% bound to plasma proteins
4) onset of action following IV administration is 5-15 minutes
5) duration of action is 2-4 hours
6) elimination 1/2life
a) 6-8 hours following oral administration
b) 5.5 hours following IV administration
7) since the 1/2 life of labetalol is 5-8 hours, intermittent IV bolus dosing may be preferable to IV infusion
8) IV infusion may be discontinued 5-8 hours before beginning oral labetalol
9) formulation contains equal proportions of 4 optical isomers
-> RR & SR isomers produce most of the beta & alpha adrenergic blockade, respectively
Monitor:
- liver function test annually
Adverse effects:
1) 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
2) uncommon (< 1%)
- rash, joint pain, bradycardia, chest pain, hepatotoxicity, diarrhea, dry eyes
3) 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
Drug interactions:
1) labetalol blunts the bronchodilator effect of beta- adrenergic agonists
2) cimetidine increases bioavailability of oral labetolol
3) halothane in combination results in synergistic adverse effects on cardiovascular hemodynamics, resulting in significant myocardial depression
4) labetalol may not be effective in patients receiving other alpha or beta adrenergic receptor antagonists
5) phenothiazines increase plasma labetolol concentrations
Laboratory:
1) specimen: serum, plasma (EDTA, heparin)
2) methods: HPLC, fluorometry
Mechanism of action:
1) alpha-1 adrenergic receptor antagonist
2) non-selective beta adrenergic receptor antagonist
3) beta adrenergic receptor antagonism following oral administration is 7 times more potent than alpha-1 adrenergic antagonism
4) neglibible effect on intracranial pressure
Interactions
drug interactions
drug adverse effects (more general classes)
General
ethanolamine
non-specific beta-adrenergic receptor antagonist (non-specific beta-blocker)
Properties
MISC-INFO: elimination route LIVER
KIDNEY
onset-of-action 3-5 MIN {IV}
1/2life 4-8 HOURS
protein-binding 50%
pregnancy-category C
+ [
safety in lactation ?]
Database Correlations
PUBCHEM correlations
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
- Deprecated Reference
Component-of
hydroxyzine/labetalol