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Toxicology Program Case presentation

Toxicology Program Case presentation. Dr. KK Lam TMH 23 rd March 2005. F / 53. Hypertension DO 4 hrs ago Drowsy. GCS 356 P 40 BP 54/36 RR 18 34.8 0 C H’stix 14. DDx?. Exact amount of drugs uncertain. Adalat retard Metoprolol (Betaloc) Natrilix. Progress & Treatment.

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Toxicology Program Case presentation

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  1. Toxicology ProgramCase presentation Dr. KK Lam TMH 23rd March 2005

  2. F / 53 • Hypertension • DO 4 hrs ago • Drowsy

  3. GCS 356 P 40 BP 54/36 RR 18 34.80C H’stix 14 DDx?

  4. Exact amount of drugs uncertain • Adalat retard • Metoprolol (Betaloc) • Natrilix

  5. Progress & Treatment

  6. AED I-stat results • Na 142 mmol/L • K 3.3 mmol/L • I-Ca 1.91 mmol/L • Hb 12.9 g/dL • pH 7.141 • pCO2 5.54 kPa • pO2 20.4 kPa • HCO314 mmol/L • BE –15 mmol/L • SO2 99%

  7. GCS 356 P 59 83 BP 67/40 109/67 CVP 23 15 34.80C 38.20C CaCl2 160 mg/h Glucagon 1 mg Isoprenaline 40 mcg/h Transvenous pacing AC 2 doses ICU D1

  8. GCS 356 P 80 BP 145/70 CVP 6 Stop CaCl2, Isoprenaline, pacing Phenylephrine 2 ml/h Alpha agonist AC 3 doses To Medical ICU D2

  9. Toxicology result • Metoprolol

  10. Ca++ flow through voltage sensitive channel Trigger opening of Ca++ releasing channel at sacroplasmic reticulum Ca++ induce Ca++ release phenomenon Ca++ bind to troponin, actin-myosin sliding Myocardial cell contraction

  11. Ca++ actively pump into sacroplasmic reticulum Ca-Na antiporter: passive transport– 3Na in, 1Ca out Ca++ATPase Fall intracellular Ca++ conc Ca++ release from troponin Myocardial cell relaxation

  12. Activation of beta adrenergic receptor Activate G-protein Increase cAMP Activate protein kinase Phosphorylation of phospholamban  increase Ca++ store in SR Increase Ca++ influx from voltage sensitive Ca++ channel Phosphorylation of troponin  facilitating unbinding of Ca++ Beta adrenergic agonist

  13. Characteristic of beta blocker • Membrane stabilizing • Inhibit fast Na channel • Propanolol, acebutolol • Lipid solubility • Cross BBB • Propanolol, metoprolol, labetalol • Instrinic sympathomimetic activity • acebutolol

  14. Characteristic of beta blocker • Beta1 selectivity • Acebutolol, metoprolol • Loss cardioselectivity in overdose • K+ channel blockage • Sotalol (anti-arrhythmic property) • Vasodilation (alpha antagonist activity) • labetalol

  15. Clinical features • Cardiogenic shock • hypotension, bradyarthymia, heart block • Hypoglycemia • common in child, uncommon in adult • Depressed mental state • Respiratory depression • Prolong QRS, QTc • Coma, confusion, convulsion • Slightly hyperkalemia • Bronchospasm (uncommon)

  16. Clinical features • All major symptoms develop within 6 hours • Except controlled release preparation • Except sotalol

  17. Overdose of: Beta-adrenergic antagonist Calcium channel blocker Digoxin Na channel blocker Anticholinerstase Alpha 1 agonist Alpha 2 agonist (e.g. clonidine) Opioids Sedative hypnotics GHB (gamma hydroxybutyrate) Coingestion P   Propranolol and other Beta-blockers, Poppies A  Anitcholinesterase C  Calcium channel blockers , clonidine E   Ethanol and other sedatives. D Digoxin DDX of Bradyarrthymia

  18. Treatments • General • ABC • Decontamination • IVF • Atropine

  19. Specific treatments • Glucagon • Calcium • Insulin • Inotropes • Phosphodiesterase inhibitor • Pacing • Extracorporeal removal • Mechanical pump

  20. Glucagon– glucagon receptor  increase cAMP Calcium – increase Ca++ influx during depolarization Phosphodiesterase inhibitor  increase cAMP Inotropes – beta adrenergic agnoist  increase cAMP

  21. Glucagon • First line after IVF and atropine • Adult:Initial 3-5mg IVI, up to 10mg • Child:50-150ug/kg • Followed by infusion • “response dose” per hour or • 2-5mg/hr • Up to 10mg/hr even glucagon is not responsive • Pedi: 50ug/kg/hr on to max adult dose • HA preparation NS as diluent (does not contain phenol

  22. Calcium • Adult • CaCl3 1-3g IVI, up to 5gm in adult • Children • Ca gluconate 10-20mg/kg IVI

  23. Insulin • Combined with glucose, maintain euglycemia (monitor glucose during and several hr after discontinuing insulin) • Effective in beta adrenergic antagonist and CCB overdose • May increase glucose utilization or Ca++ handling in myocardial cell • Delayed onset of response (15-30 minutes) • 0.5-1unit/kg/hr with glucose 1g/kg/hr • Frequent glucose monitoring

  24. Catecholamines (inotropes) • Isoproterenol • Epineprine • Unopposed alpha effect • Invasive monitor

  25. Phosphodiesterase inhibitor • Amrinone • Long half life • Vasodilatation • Invasive monitor

  26. Other treatments • Ventricular pacing • Extracorporeal removal • Water soluble drugs only e.g. atenolol • Difficult in bradycardia and hypotension • Intra-aortic balloon pump/ extracorporeal circulation

  27. Special conditions • Membrane stabilizing effect • NaHCO3 • Peripheral vasodilation effect • alpha adrenergic agonist • Sotalol • Correct electrolyte disturbance • Mg/ overdrive pacing for ventricular dysrrthymia

  28. Observation • ICU for all symptomatic • For regular-release preparation • Medically fit for discharge if adequate GI decontamination, asymptomatic, normal vital sign and ECG for 6-8 hours, • Sotalol overdose or extended release preparation -- 24 hours observation

  29. Summary • Beta adrenergic antagonist is one of commonest drugs cause hypotension and bradyarrthymia • Aggressive treatment should be initiated at AED • Glucogan is an antidote • All symptomatic cases should be managed amd monitored in ICU • Prolong observation for extended release preparation and sotalol

  30. Thank you

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