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Toxicology Program Psychiatric drug poisoning

Toxicology Program Psychiatric drug poisoning. Dr HT Fung TMH AED 15 Jun 2005. F/18. Depression DO Confused BP 101/62 P 143 Pupils 5 mm NR. Poison DDx? Mechanism? Tx?. QRS 0.1 s QTc 0.58 s. BP 90/60, why?. -  conduction - inotropy -1 block NE depletion -Adenosine

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Toxicology Program Psychiatric drug poisoning

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  1. Toxicology ProgramPsychiatric drug poisoning Dr HT Fung TMH AED 15 Jun 2005

  2. F/18 • Depression • DO • Confused • BP 101/62 • P 143 • Pupils 5 mm NR

  3. Poison DDx? Mechanism? Tx?

  4. QRS 0.1 s QTc 0.58 s BP 90/60, why? • - conduction • - inotropy • -1 block • NE depletion • -Adenosine • -Nitric oxide

  5. Adenosine Kalkan 2004

  6. Nitric oxide Tuncok 2002

  7. BP 96/60 Tx?

  8. NaHCO3 • Na load,  pH, hypokalemia •  QRS,  BP • Till hypernatremia, pH > 7.55

  9. Alkalemia  mortality GP I: pH 7.48-7.55 GP II: pH >7.55 Anderson 1987

  10. If pH 7.56, Na 140, Tx? Hypertonic saline James 1998

  11. Hypertonic saline • NaHCO3 = HTS > HV in QRS & BP improvement in rats (Pentel 1984) • NaHCO3 > HTS in improving amplitude & conduction velocity of action potential of dogs’ cardiac fibers (Sasyniuk 1984) • Cases: 200 ml 7.5 % NaCl (Patrick 2003), 170 mM NaCl (Hoegholm 1991)

  12. If Na 151, pH 7.48, Tx? Hyperventilation Bessen 1985

  13. Hyperventilation • 2 cases: • Hyperventilation + NaHCO3 • pH 7.83 & 7.66 • pCO2 11 & 20 mmHg • Arrest • Keith 1992

  14. If QRS 0.8 s, BP 88/59, Na 146, pH 7.56, Tx? • Norepinephrine preferred to dopamine • ? Epinephrine preferred to norepinephrine

  15. E > NE in  survival Cummulative survival (%) Epinephrine Norepinephrine Control Time (min) Knudsen 1997

  16. E > NE in  QRS Norepinephrine Epinephrine Knudsen 1997

  17. Duration (min) in sinus rhythm: E > NE Knudsen 1997

  18. NE > E in  BP Norepinephrine Blood pressure (mmHg) Epinephrine Knudsen 1997 10 20 30 40 Time (min)

  19. Obsessive compulsive disorder Drug overdose Mute, dull, GCS 424 P 92, BP 138/86 Pupils 6 mm reactive Sweating ? Sympathomimmetic toxidrome Answer: Mirtazepine Block central 2 > 1, also 5HT, H1 Release 5HT, NE F / 30

  20. SSRI toxicity Isbister 2004

  21. Other atypical antidepressants • Multiple sites of action on 5HT, NE, D, etc • Receptor antagonists, reuptake inhibitors, release neurotransmitters • Drowsiness, anxiety, tachycardia • Could be seizures,  QRS / QTc, serotonin syndrome • Mirtazapine, venlafaxine, nefazodone

  22. Priapism • Trazodone, chlorpromazine, thioridazine, etc • Low flow • Painful • USG • Blood gas Priapus

  23. Priapism Tx • Aspiration • Epinephrine 1 in 1,000,000 1-10 ml • Methylene blue 50 mg • R-TPA 15 mg • Surgical shunt

  24. Thioridazine – the most cardiotoxic neuroleptic Buckley 1995

  25. Atypical antipsychotics – 5HT / D2 block (EPS) (--ve s/s) (Temp) (+ve s/s)

  26. Olanzapine overdose •  GCS 92% • Agitation 42% • Convulsion 4% • Tachycardia 23% • Hypotension 4% • QTc > 0.45 s 4% • Miosis 31% Palenzona 2004

  27. F / 36 • Depression, recently unemployed • Anxious, labile mood x 2/7 • Psychiatric opinion: acute stress reaction • While pending home: incoherent speech, irritable, sweating • Computer search: on long term psychiatric medications, attended another ED 3/7 ago x chronic LBP Dx? Serotonin syndrome?

  28. M / 65 • Depression, dementia, parkinsonism • R AMA x # NOF • Post-op D2, 38.50C, GCS 14/15, limbs rigid, some abdominal rigidity Dx? Neuroleptic malignant syndrome?

  29. Sternbach criteria • Serotonergic agent • No neuroleptics • Rule out others • > 3 of: - mental changes - shivering - agitation - tremor - myoclonus - diarrhea - hyperreflexia - incoordination - diaphoresis - fever Sternbach 1991

  30. Hunter criteria • Serotonergic agent • Any 1 of: • Inducible clonus & agitation or diaphoresis • Ocular clonus & agitation or diaphoresis • Tremor & hyperreflexia • Hypertonic & > 380C & ocular clonus or inducible clonus Dunkley 2003

  31. Levenson JL • 3 major, or 2 major & 4 minor • Major: fever, rigidity,  CK • Minor:  HR, abnormal BP,  RR,  GCS, diaphoresis,  WBC • Neuroleptic use • Rule out others Levenson 1985

  32. DSM IV • Fever & rigidity & > 2 of: • Diaphoresis, dysphagia, tremor, incontinence,  GCS,  HR, BP changes,  CK,  WBC

  33. Wappler 2001

  34. L-tryptophan MAOI Serotonin syndrome SSRI Amphatemines 5-HT agonists Li

  35. Sudden withdrawal of L-dopa NMS D2 receptors X by neuroleptics

  36. Tx of serotonin syndrome • Cyproheptadine 4 mg up to 0.5 mg/kg/d • Methylsergide 2 mg up to 6 mg/d • Propanolol 1 mg IV + repeat • Chlorpromazine 25 – 100 mg IM + repeat • Benzodiazepine • Dentrolene

  37. Tx of NMS • Bromocriptine 7.5 mg/d – 45 mg/d, faster resolution, effect after h – 1 d • Dentrolene 2 – 3 mg/kg Q 10 min up to 10 mg/kg/d, faster resolution • ECT 84% good response • Carbidopa / levodopa • Benzodiazepine

  38. Schizoaffective disorder, hypertension On Li2CO3, lisinopril Tremor, nausea x 2/7 Causes of s/s? Side effects Acute poisoning Acute on chronic poisoning Chronic poisoning Drug interaction M / 42

  39. Serum Li 3.6 mmol/L Tremor gets coarse, ataxia, hypertonic Tx? WBI NS IV Na polystyrene sulphonate HD CAVHDF CVVHDF Taken 10 more tablets of Li2CO3 in last 2 days

  40. Na polystyrene sulphonate • Case: • Acute on chronic Li overdose • Na polystyrene sulphonate 150 g/d • Li t½ 12 h • Hypokalemia • No rebound Roberge 1993

  41. Carbamazepine • Anticholinergic - anticholinergic & delayed s/s, seizures • Membrane stabilization -  QRS • Adenosine A1 / A2 - seizures • Active metabolites - prolonged s/s • MDAC • HP, HD

  42. Cytoplasm VALPROIC ACID TOXICITY Carnitine  Ketoglutarate depletion Mitochondria  Glutamate synthesis VA Carnitine X Acyl-CoA VA CoA X NH3 accumulation Inhibit X  oxidation X 4-en-VA  Carbamyl phosphate synthetase Acetyl-CoA X Kreb’s cycle

  43. Tx of VA poisoning • L-carnitine 50 mg/kg Q 3-4 h • Naloxone 2 mg • Displace GABA • Enkephalin antagonist • MDAC • HP • HD, CVVHDF

  44. St. John’s Wort • Hyperforin inhibits reuptake of D, 5HT, NE • Hyperricin inhibits MAO • ? Risk if together with atypical antidepressants, MAOI & noradrenergic agents • No reports of overdose

  45. TCM • 甘逐– ‘laxative’ • 天南星– ‘mucolytic’ • 朱砂– ‘sedative’

  46. 謝謝! Thank you!

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