1. BETA BLOCKER TOXICITY Marc richards, am report, 5.11.10

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

3. 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?

4. 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

5. 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

6. Beta blocker properties Shepherd 2006

7. 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

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

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

10. Treatment: The Basics • ABCs!!!! • Hypotension  IVF, Pressors(more on this in a minute) • Bradycardia  Atropine 0.5-1mg Q3-5min • Hypoglycemia  D50 • Seizures  Benzos

11. 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/hrgtt • 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

12. 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

13. 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

14. 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.

15. Mazel tov!!!!!