beta adrenergic receptor antagonist (beta-blocker)

Introduction

A molecule/drug that blocks the effect of catecholamines on beta adrenergic receptors, producing a decrease in heart rate & oxygen demand in the myocardium.

Indications

• coronary artery disease
  • myocardial infarction*
  • angina pectoris, unstable angina
  • secondary prevention in patients with cardiovascular disease
• states of catecholamine excess
  • thyrotoxicosis
  • pheochromocytoma
  • may leave alpha adrenergic effects unopposed
• tachyarrhythmias
  • supraventricular tachycardia
    • atrial fibrillation
    • atrial flutter
    • sinus tachycardia
  • ventricular tachycardia (sotalol)
• congenital long QT syndrome (may prevent episodes of torsades de pointes)
• neurocardiogenic syncope
• hypertension#
• treatment of heart failure
  • left ventricular dysfunction
• hypertrophic cardiomyopathy
• dissecting aortic aneurysm
• mitral valve prolapse
• esophageal varices
• migraine prophylaxis
• treatment of anxiety
• increased intraocular pressure, glaucoma
• essential tremor
• use of beta-blockers is associated with less arthragias & less use of opioids & other analgesics for symptomatic large-joint osteoarthritis

* no advantage of beta-blockers for preventing myocardial infarction or death when used to treat hypertension or in patients with stable coronary artery disease or cardiovascular risk factors

# not 1st line for uncomplicated hypertension

Contraindications

• asthma, symptomatic reactive airways disease
• symptomatic bradycardia
  • high degree AV block
    • third degree AV block
• uncontrolled or unstable heart failure
  • cardiogenic shock
• severe peripheral vascular disease
• Raynaud's phenomenon
• pheochromocytoma
• likely OK in 1st trimester of pregnancy

Caution:

• when discontinuing beta blocker, taper over 1-2 weeks
• intermittent claudication
• may mask signs & symptoms of hypoglycemia
• use with caution in patients at risk for anaphylaxis
  • may inhibit effects or epinephrine & make anaphylaxis more severe & difficult to treat

Adverse effects

• bronchospasm
• bradycardia
• decreased cardiac output
• negative inotropic effects
• abrupt withdrawal may precipitate arrhythmia or angina
• may mask symptoms of hypoglycemia
• unopposed alpha adrenergic activity may potentiate coronary artery vasospasm
• lethargy
• confusion & diminished ability to concentrate
• impotence
• potentiation of Raynaud's phenomenon
• nightmares
• insomnia
• depression is, but is not, & might be an adverse effect of beta-blockers
• may diminish effect of sulfonylureas
• hyperkalemia (extracellular shift of K+)
• metabolic alkalosis
• increased triglycerides
• diminished HDL cholesterol
• may exacerbate psoriasis
• may increase risk of developing diabetes mellitus
• increased cardiovascular mortality directly correlates with magnitude of heart rate slowing when used to treat hypertension
• no fetal heart risk from Mom's beta-blocker usage

Overdose:

• supportive therapy:
  • IV access
  • continuous cardiac monitoring
• bradycardia
  • atropine generally not useful (not vagally mediated)
  • glucagon 2-4 mg IV over 1-2 minutes, then start infusion at 2-5 mg/hr (do not exceed 10 mg/hr);
    • may cause nausea/vomiting
    • monitor for vagally-mediated bradycardia
  • ventricular pacing
• hypotension
  • calcium gluconate 3-9 g IV through peripheral line
  • calcium chloride 1-2 g IV over 10 minutes through a central venous catheter is alternative (caution: sclerosing agent)
  • high-dose insulin euglycemia therapy
  • intra-aortic balloon pump

• 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

• alpha-1 adrenergic antagonists: orthostatic hypotension
• amiodarone: symptomatic bradycardia & sinus arrest
• sympathomimetics
• lidocaine serum levels may increase by 20-30%
• methacholine
• methyldopa (paradoxical hypertensive response to stress)
• NSAIDs may interfere with antihypertensive effect

• 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

• beta-blocker in hair
• beta-blocker in body fluid
• beta-blocker in blood
• beta-blocker in serum/plasma

Mechanism of action

• antagonism at beta-adrenergic receptor
  • some are specific for the beta-1 adrenergic receptor
  • beta-adrenergic receptor blockade leaves unbalanced alpha-adrenergic receptor activity (which tends to increase with age)
• polymorphism in the ADRB2 gene (C & G) alleles associated with different mortality when treated with beta-blocker after acute coronary syndrome

More general terms

• adrenergic receptor antagonist

More specific terms

• alprenolol
• beta-1 adrenergic receptor antagonist (beta-1 blocker)
• non-specific beta-adrenergic receptor antagonist (non-specific beta-blocker)
• oxprenolol (Coretal)
• vasodilating beta-blocker

Additional terms

• beta adrenergic receptor

Component of

• polypill (Polycap)