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Antidotes for cardiovascular drug poisoning. David H. Jang Assistant Professor Masters of Science Degree in Clinical Investigation (K30) Clinical and Translational Science Institute (CTSI). New York University Department of Emergency Medicine/Medical Toxicology.
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Antidotes for cardiovascular drug poisoning David H. Jang Assistant Professor Masters of Science Degree in Clinical Investigation (K30) Clinical and Translational Science Institute (CTSI) New York University Department of Emergency Medicine/Medical Toxicology *Funded by the American Academy of Clinical Toxicology Junior Investigator Research Grant and also supported in part by grant 1UL1RR029893 from the National Center for Research Resources, National Institutes of Health.
Case • 44 year-old man presents with a “overdose” after an argument with his mother • Patient obtained these medications from his mother who he still lives with in her basement
Case • Vitals on presentation: • Blood pressure: 140/90 mmHG • Heart rate: 90 BPM • Respiratory rate: 12 • Temperature: 98.6 • Oxygen saturation: 100% RA
Case 6 hours later…
Case • Repeat Vitals: • Blood pressure: 85/40 mmHG • Heart rate: 40 BPM • Respiratory rate: 20 • Temperature: 98.6 • Oxygen saturation: 100% RA
Intubated Hemodynamic support On norepinephrine On dopamine On epinephrine Still hypotensive… Case
Cardiovascular drug class • Antihypertensives • Imidazolines • Beta-blockers • Calcium channel blockers • ACE-Is and ARBs • Cardioactive steroids • Digoxin • Antidysrhythmics • Flecainide
Cardiovascular drug class • Antihypertensives • Imidazolines • Beta-blockers • Calcium channel blockers • ACE-Is and ARBs • Cardioactive steroids • Digoxin • Antidysrhythmics • Flecainide
Beta-blockers • Non-selective • Carvedilol • B1-selective • Atenolol • Esmolol • Intrinsic sympathomimetic • Pindolol
Beta-blockers • Potassium channel blockers • Sotalol • Membrane-stabilizing • Propanolol
Calcium channel blockers • Phenylalkylamine • Verapamil • Benzothiazepine • Diltiazem • Dihydropyridines • Nifedipine • Amlodipine • Nicardipine
Beta and calcium channel blocker poisoning • Clinical Features • Bradycardia • Hypotension • Management • Isotonic fluids • Glucagon • Inotropes/Pressors • High-insulin • Lipid emulsion
Beta and calcium channel blocker poisoning • Clinical Features • Bradycardia • Hypotension • Management • Isotonic fluids • Glucagon • Inotropes/Pressors • High-insulin • Lipid emulsion
Beta and calcium channel blocker poisoning • Clinical Features • Bradycardia • Hypotension • Management • Isotonic fluids • Glucagon • Inotropes/Pressors • High-insulin • Lipid emulsion
Historical use • Glucose-insulin-potassium (GIK) • Acute myocardial infarction • Heart failure Myocardium
Background • Hallmark of BB and CCB poisoning • Bradycardia • Vasodilation • Decreased contractility
Background • Altered myocardial physiology • Hyperglycemia (pancreas/liver) • Altered myocardial substrate use • Inhibition of lactate oxidation
Mechanism of action • Alters ions homeostasis (potassium/calcium/sodium) • Metabolic support • Increase lactate uptake • Epi and glucagon promote FFA use (increase energy)
Experimental evidence Groups 1. Control: (0/6) 2. Epi: (4/6)(2/4) 3. HIE: (6/6)(6/6) 4. Glucagon: (3/6)(0/3)
Experimental evidence Groups 1. Control: (0/6) 2. Epi: (4/6)(2/4) 3. HIE: (6/6)(6/6) 4. Glucagon: (3/6)(0/3)
Adverse events • Hypoglycemia • Hypokalemia
Background • Triglycerides and phospholipids • Primary triglycerides composed of linoleic, linolenic, and stearic acid • pH 8, isotonic, various concentrations availiable (20% is primarily used)
Mechanism of action 1. Modulation of intracellular metabolism 2. Lipid sink 3. Activation of ion channels
Treatment guidelines www.lipidrescue.org
Consider HIE early for suspected CCB poisoning Consider lipid emulsion when a patient is perimortem with suspected lipid-soluble medication Summary
Methylene blue • Sentinel node detection • Acquired methemoglobinemia • Vasodilatory shock • Anaphylaxis • Sepsis