BETA BLOCKER TOXICITY

M A R C R I C H A R D S , A M R E P O R T, 5 . 1 1 . 1 0
 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

Adrenergic Intrinsic
Receptor Sympathomimeti Sodium Channel
Agent Blocking Activity Lipid Solubility c Activity Blocking

Acebutolol ß1 Low Yes Yes

Atenolol ß1 Low No No
Betaxolol ß1 Low No Yes
Bisoprolol ß1 Low No No
Carteolol ß1, ß2 Low Yes No
Carvedilol 1, ß1, ß2 High No No
Esmolol ß1 Low No No
Labetalol 1, ß1, ß2 Moderate Yes No
Metoprolol ß1 Moderate No No
Nadolol ß1, ß2 Low No No
Oxprenolol ß1, ß2 High Yes Yes
Penbutolol ß1, ß2 High Yes No
Pindolol ß1, ß2 Moderate Yes No
Propranolol ß1, ß2 High No Yes
Sotalol ß1, ß2 Low No No
Timolol ß1, ß2 Low to moderate No 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 Q3-5min
4. Hypoglycemia  D50
5. 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:
 Charcoal
 Bicarb, Mg
 IABP
 CVVHD
 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!!!!!