MARC R ICHARDS , A M R E P O RT , 5 . 1 1 . 1 0

BETA BLOCKER TOXICITY

OBJECTIVES

• Review of Beta receptors• Epidemiology• Toxicology• Clinical S/Sx/WU• Treatment

BETA RECEPTORS

• B1:• Heart Muscle• inc. HR, contractility, AV conduction

• B2:• Smooth Muscle (lungs, peripheral vasculature), Heart• vasodilation, bronchodilation

• B3:• Adipose Tissue, Heart• cat. Thermogenesis?, dec. contractility?

EPIDEMIOLOGY

• 2006: • 9041 BB exposures reported to poison centers• 613 moderate-major adverse outcomes• 4 deaths

• Often associated with polyingestion• DDX: CaChB, Digoxin, Clonidine, Cholinergics

PATHOPHYSIOLOGY

• Direct Beta Blockade• All BBs

• Membrane Stabilizing Activity (MSA):• Propanolol, Acebutolol• Fast Na Channel Inhibition (Heart) wide QRS

• Lipophilicity:• Propanolol• Cross BBB into CNS sz, delirium

• Intrinsic Sympathomimetic Activity (ISA):• Partial B agonist activity less pronounced Sx

BETA BLOCKER PROPERTIES

Agent

Adrenergic Receptor Blocking Activity

Lipid Solubility

Intrinsic Sympathomi

metic Activity

Sodium Channel Blocking

Acebutolol ß1 Low Yes YesAtenolol ß1 Low No NoBetaxolol ß1 Low No YesBisoprolol ß1 Low No NoCarteolol ß1, ß2 Low Yes NoCarvedilol 1, ß1, ß2 High No NoEsmolol ß1 Low No NoLabetalol 1, ß1, ß2 Moderate Yes NoMetoprolol ß1 Moderate No NoNadolol ß1, ß2 Low No NoOxprenolol ß1, ß2 High Yes YesPenbutolol ß1, ß2 High Yes NoPindolol ß1, ß2 Moderate Yes NoPropranolol ß1, ß2 High No YesSotalol ß1, ß2 Low No NoTimolol ß1, ß2 Low to

moderateNo No

Shepherd 2006

PROPANOLOL:

• Nonselective beta blocker• High MSA• Lipophilic• Rec. Dose in Thyroid Storm: 1-3mg IVP x1• Rec. Dose for Tachyarrythmia: 1-3mg IVP, MR x1• Half Life: 3-6hr, Duration 6-12hr• Metabolism: Liver

CLINICAL MANIFESTATIONS

• Sx within 6 hours of Ingestion• Hypotension• Bradycardia• SHOCK• Arrythmias• Neuro: sz, delirium, coma• Bronchospasm• Hypoglycemia

WORKUP:

• Get good ingestion history• H&P• LABS:• BB screen/levels• Glucose• Chemistries• Other ingestion labs (APAP, ASA, etc)

• STUDIES:• EKG• CXR

TREATMENT: THE BASICS

1. ABCs!!!!2. Hypotension IVF, Pressors (more on this in a minute)

3. Bradycardia Atropine 0.5-1mg Q3-5min4. Hypoglycemia D505. Seizures Benzos

TREATMENT: BEYOND THE BASICS

GLUCAGON• Activates adenylyl cyclase increased CAMP increased

Ca available for muscle contraction• 5mg IV x1, MR x1 to assess for VS improvement• If successful, start a 2-5mg/hr gtt• SE: Vomiting• NO GOOD DATA IN PEOPLE (just some in animals)

CALCIUM• CaCl 1g IVP (max: 3g) OR CaGlc 1g IV (max: 3g)• Increase inotropy• DATA: Case reports only

TREATMENT: BEYOND THE BASICS II

PRESSORS:• Stimulate receptors to increase CAMP inotropy• No good data, but recommended if necessary to maintain

MAPs• Competitive Inhibition

PDE INHIBITORS:• Milrinone, Inamrinone• Inhibit CAMP breakdown by PDE• Data: isolated case reports only (although our patient did

well!!)• SE: GI, Hypotension, Arrythmias

TREATMENT: BEYOND THE BASICS III

HDIDK (high dose insulin w/ dextrose and K):• Last line of defense at this point as data is preliminary

(some good data with CaChB overdose)• BBs inhibit pancreatic insulin release less glucose

available in muscle cells for energy extraction• Correct hypoglycemia first!!!

MISCELLANEOUS:CharcoalBicarb, MgIABPCVVHD

REFERENCES:

• UpToDate- Beta Blocker Poisoning, Thyroid Storm, Beta Blockers in Management of Hyperthyroidism

• Shepherd et, al. “Treatment of poisoning caused by B-adrenergic and calcium-channel blockers”. Am J Health Syst. Pharm- Vol 63. Oct 1 2006.

• Bailey B. Glucagon in beta blocker and calcium channel blocker overdoses: a systematic review. Journal of Clinical Toxicology. 2003; 41 (5); 595-602.

• Leppikangas, et al. Levosimendan as a rescue drug in experimental propanolol-induced myocardial depression: a randomized study. Ann Emerg Med. 2009 Dec; 54(6): 811-817.

MAZEL TOV!!!!!