A Review of Beta Antagonist Treatment for Infantile Hemangioma
July 2012 | Volume 11 | Issue 7 | Original Article | 826 | Copyright © 2012
Infantile hemangiomas are benign vascular neoplasms of childhood that often have implications on development, cosmesis, and comfort.
Traditional therapy has involved either observation or corticosteroids, depending on location and size. Recent studies have reported
the successful use of beta-adrenergic antagonists in treating infantile hemangiomas. This succinct review discusses the properties and
current applications of beta-adrenergic antagonists as well as the established treatments for infantile hemangioma.
J Drugs Dermatol. 2012;11(7):826-829.
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Recent studies have reported the successful use of beta- adrenergic blockers in treating infantile hemangiomas.1 In light of this new clinical application for betablockade in pediatric dermatology, this succinct review of the properties and current applications of available beta-adrenergic antagonists, as well as the established treatments for infantile hemangioma will serve as an overview for consideration of therapeutic options in managing infantile hemangiomas.
The sympathetic autonomic response is mediated by adrenergic receptors, the targets of intrinsic catecholamines. These receptors are divided into alpha and beta subgroups based upon their respective mechanisms of action and physiologic functions. Beta-adrenergic receptors are G-protein linked and mediate the adenylate cyclase cascade in targeted cells.2,3,4 These receptors are further divided into 3 subclasses.
Beta-1 adrenergic receptors have an important role in cardiac function. Stimulation yields positive inotropic and chronotropic effects, as well as increased cardiac conduction velocity. Secondary effects include activation of lipolysis pathways and secretion of renin from renal juxtaglomerular cells.1 Beta-2 adrenergic receptors primarily regulate smooth muscle and glandular function. Stimulation results in smooth muscle relaxation, leading to vasodilation, bronchodilation, tocolysis, down-regulation of gut motility, and decreased bladder tone. Gluconeogenesis, glycolysis, insulin secretion, and lipolysis are activated via the glandular effects.1 The role of beta-3 adrenergic receptors is not fully established. These receptors are found in gallbladder and brown adipose tissues.1
The majority of the available literature on beta receptor antagonists and infantile hemangiomas pertains to propranolol. Propranolol's efficacy is most probably attributable to its inhibition of vasodilation and angiogenesis—functions associated with beta-2 blockade.5 Individual beta-blockers have varying affinities for the receptor subclasses, leading to diverse physiologic effects. The majority of the beta-blockers with reported use in treating infantile hemangioma are nonspecific beta antagonists, with activity on both beta-1 and beta-2 receptor sites. The relative cardiospecificity of selective beta-1 antagonists renders them less likely candidates for dermatological application, though a recently published paper reports the successful replacement of propanolol therapy with atenolol in 2 patients.6 In the following section, the individual properties of available beta antagonists will be discussed.
DrugsAlprenolol is a nonspecific beta-adrenergic inhibitor with additional antagonist effects on serotonin 5HT-1a receptors. Currently, alprenolol has no formal FDA approved indications but is used off-label in adult hypertension, angina pectoris, anxiety, hyperthyroidism, and post-myocardial infarction. Pediatric safety and efficacy has not been established.7,8
Bucindolol is a nonspecific beta-adrenergic inhibitor with slight alpha-adrenergic antagonistic properties. Currently, bucindolol has no formal FDA approved indications but has been used off-label in adult congestive heart failure and hypertension. Pediatric safety and efficacy has not been established.9,10
Carteolol is a nonspecific beta-adrenergic inhibitor. FDA approved indications for its use include adult hypertension, adult ocular hypertension, and adult open-angle glaucoma. Carteolol is used off-label in angina, arrhythmia, congestive heart failure, post-myocardial infarction, anxiety, panic attacks, aggressive behavior, and neuroleptic-induced akathisia. Pediatric safety and efficacy has not been established. Carteolol is available as an ophthalamic solution or an oral tablet.11