MARC RICHARDS, AM REPORT, 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 ActivityLipid Solubility Intrinsic Sympathomim etic Activity Sodium Channel Blocking Acebutololß1ß1 LowYes Atenololß1ß1 LowNo Betaxololß1ß1 LowNoYes Bisoprololß1ß1 LowNo Carteololß 1, ß 2 LowYesNo Carvedilol 1, ß 1, ß 2 HighNo Esmololß1ß1 LowNo Labetalol 1, ß 1, ß 2 ModerateYesNo Metoprololß1ß1 ModerateNo Nadololß 1, ß 2 LowNo Oxprenololß 1, ß 2 HighYes Penbutololß 1, ß 2 HighYesNo Pindololß 1, ß 2 ModerateYesNo Propranololß 1, ß 2 HighNoYes Sotalolß 1, ß 2 LowNo Timololß 1, ß 2 Low to moderate 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 Bailey B. Glucagon in beta blocker and calcium channel blocker overdoses: a systematic review. Journal of Clinical Toxicology. 2003; 41 (5); Leppikangas, et al. Levosimendan as a rescue drug in experimental propanolol-induced myocardial depression: a randomized study. Ann Emerg Med Dec; 54(6):

MAZEL TOV!!!!!