Document Detail

Pharmacology of combined alpha-beta-blockade. I.
MedLine Citation:
PMID:  6151889     Owner:  NLM     Status:  MEDLINE    
Several compounds of the chemical class arylethanolamines have been shown to possess combined alpha- or vasodilator and beta-adrenoceptor blocking properties. The first drug was labetalol (AH5158)[5-(1-hydroxy-2)1-methyl-3-phenylpropyl(amino)-ethyl (salicylamide)]. Others include medroxalol, bucindolol and YM-09538, which differ from labetalol either by the nature of the substitution on the primary benzene ring and/or on the terminal nitrogen. All of these drugs are non-selective beta-blockers, except for bucindolol whose selectivity has not been carefully defined. The rationale for the development of this group of drugs was the knowledge that blockade of one adrenoceptor subtype causes reflex stimulation of the other, i.e. vasoconstriction after nonspecific beta-blockade and tachycardia after alpha-blockade. Since both of these compensatory responses act to prevent a fall in blood pressure, a relatively weak blockade of both receptor types should act synergistically to produce a lowering of blood pressure with minimal physiological disturbance. Haemodynamic studies have confirmed that the additional alpha-blocking properties of labetalol produce a pattern of haemodynamic changes unlike that of propranolol and other simple beta-adrenoceptor blocking agents. Peripheral vascular resistance, which falls acutely during the initial administration of the drug, tends to fall further during prolonged administration and the pulse rate tends to remain only slightly lower than pretreatment levels. In addition, at normal dose levels cardiac output is maintained by a compensatory increase in stroke volume. Thus, blood pressure is lowered largely by a reduction in vascular resistance, and although the heart rate falls significantly during exercise, the cardiac output is maintained by an increase in stroke volume. This pattern of events is different to that seen with beta-blocking agents which consistently reduce cardiac output during exercise. Currently labetalol is the only member of this group of drugs which is in established clinical use. Its antihypertensive efficacy has been confirmed in many studies and it has been shown to be effective in the management of both hypertensive emergencies and in the long term management of severe hypertension. It is particularly valuable in allowing a reduction in the number of drugs required for adequate blood pressure control. The early theoretical prediction that postural hypotension would occur with high doses is now acknowledged to be labetalol's major dose-limiting side effect. Most of the available pharmacokinetic data on labetalol were derived from studies which utilised a fluorimetric assay.(ABSTRACT TRUNCATED AT 400 WORDS)
W J Louis; J J McNeil; O H Drummer
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Drugs     Volume:  28 Suppl 2     ISSN:  0012-6667     ISO Abbreviation:  Drugs     Publication Date:  1984  
Date Detail:
Created Date:  1985-03-28     Completed Date:  1985-03-28     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7600076     Medline TA:  Drugs     Country:  AUSTRALIA    
Other Details:
Languages:  eng     Pagination:  16-34     Citation Subset:  IM    
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MeSH Terms
Adrenergic alpha-Antagonists / pharmacology*
Adrenergic beta-Antagonists / pharmacology*
Biological Availability
Chemical Phenomena
Drug Interactions
Endocrine Glands / drug effects
Epinephrine / metabolism
Ethanolamines / pharmacology*
Hemodynamics / drug effects
Intestinal Absorption
Labetalol / metabolism,  pharmacology*
Lipids / blood
Norepinephrine / metabolism
Physical Exertion
Postpartum Period / drug effects
Pregnancy Complications, Cardiovascular / drug therapy
Protein Binding / drug effects
Receptors, Adrenergic / drug effects
Renin-Angiotensin System / drug effects
Tissue Distribution
Uterine Contraction / drug effects
Reg. No./Substance:
0/Adrenergic alpha-Antagonists; 0/Adrenergic beta-Antagonists; 0/Ethanolamines; 0/Lipids; 0/Receptors, Adrenergic; 36894-69-6/Labetalol; 51-41-2/Norepinephrine; 51-43-4/Epinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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