Physiology and Pathophysiology
slow conduction through SA and AV nodes - bradycardia and heart blocks
impairs myocardial contraction - decreased cardiac output
decreases vascular smooth muscle tone - vasodilation/ hypotension
overdose leads to bradycardia, high-degree AV block, poor myocardial contractility, vasodilation
other Beta2 effects include glycogenolysis, gluconeogenesis, release of free fatty acids, bronchodilation, uterine muscle relaxation
hyperglycemia
lactic acidosis secondary to hypoperfusion
the cardioselectivity, lipophilicity, membrane-satbilizing effects, intrinsic sympathomimetic effects vary among Beta-blockers and thus may have different toxic manifestations
extremely high doses can inhibit sodium channels and thus decrease upslope of phase 1 and widen QRS, this may rarely lead to seizures as well
Propranolol the most toxic of the Beta-blockers - its lipophilicity and membrane-stabilizing effects ( sodium channel blockade) means that it readily penetrates the CNS leading to obtundation, respiratory depression, and seizures. The "quinidine-like" membrane stabilizing effects can lead to impaired ventricular conduction with widened QRS and VT/ VF/ torsade.
Drugs with high intrinsic sympathomimetic activity like pindolol can cause sinus tachycardia in overdose
Clinical Manifestations of Beta-blocker Overdose ( in decreasing frequency)
Bradycardia
Hypotension
Unconsciousness
Respiratory depression
Hypoglycemia
Seizures ( common only with propranolol)
VT or VF
Mild hyperkalemia
Hepatotoxicity, mesenteric ischemia, renal failure
Treatment
Fluids - Increase preload to enhance contractility, Beta2 effects lead to vasodilation
Atropine - efficacy is limited, lasts several minutes only
- Give as pretreatment before vagal stimuli ( lavge, intubation)
Glucagon 3 to 10 mg iv, then 5 mg/hr infusion ( bolus lasts 15 - 20 minutes)
Does not depend on beta receptors for action
Ionotropic and chronotropic
Counteracts any hypoglycemia caused by BB overdose
Side effects are nausea, vomitind, hyperglycemia
Temporary pacer - TCP, TVP
Swan-Ganz directed choice of ionotropes
caution with isoproterenol ( may get predominantly Beta2 effects), may need large doses ( up to 200 mcg/min have been reported
Amrinone or milrinone ( theorectic benefit since bypasses beta receptor)
High dose insulin
Intra-aortic balloon pump or cardiopulmonary bypass as temporizing measures until drug is eliminated
Lidocaine for ventricular dysrhythmias - avoid type 1a, 1c
Disposition
Most patients who remain completely asymptomatic after 6 hours can be safely discharged to psychiatry.
Those who have ingested sustained release preparations should be observed for a minimum of 24 hours.
Hypotension, heart block, greater than first degree, hemodynamically significant dysrhythmias are indications for admission to ICU