BETA BLOCKER TOXICITY
MARC RICHARDS, AM REPORT, 5.11.10
OBJECTIVES
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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
Acebutolol
Atenolol
Betaxolol
Bisoprolol
Carteolol
Carvedilol
Esmolol
Labetalol
Metoprolol
Nadolol
Oxprenolol
Penbutolol
Pindolol
Propranolol
Sotalol
Timolol
Adrenergic
Receptor
Blocking
Activity
ß1
ß1
ß1
ß1
ß1, ß2
1, ß1, ß2
ß1
1, ß1, ß2
ß1
ß1, ß2
ß1, ß2
ß1, ß2
ß1, ß2
ß1, ß2
ß1, ß2
ß1, ß2
Intrinsic
Sympathomim
Lipid Solubility etic Activity
Low
Low
Low
Low
Low
High
Low
Moderate
Moderate
Low
High
High
Moderate
High
Low
Low to
moderate
Yes
No
No
No
Yes
No
No
Yes
No
No
Yes
Yes
Yes
No
No
No
Sodium
Channel
Blocking
Yes
No
Yes
No
No
No
No
No
No
No
Yes
No
No
Yes
No
No
Shepherd 2006
PROPANOLOL:
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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
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Sx within 6 hours of Ingestion
Hypotension
Bradycardia
SHOCK
Arrythmias
Neuro: sz, delirium, coma
Bronchospasm
Hypoglycemia
WORKUP:
• Get good ingestion history
• H&P
• LABS:
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BB screen/levels
Glucose
Chemistries
Other ingestion labs (APAP, ASA, etc)
• STUDIES:
• EKG
• CXR
TREATMENT: THE BASICS
1.
2.
3.
4.
5.
ABCs!!!!
Hypotension  IVF, Pressors (more on this in a minute)
Bradycardia  Atropine 0.5-1mg Q3-5min
Hypoglycemia  D50
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 Badrenergic 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!!!!!