Toxicology Program Psychiatric drug poisoning

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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

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Poison DDx? Mechanism? Tx?
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QRS 0.1 s QTc 0.58 s
BP 90/60, why?

• -? conduction
• -? inotropy
• -?1 block
• NE depletion
• -Adenosine
• -Nitric oxide

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Adenosine
Kalkan 2004
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Nitric oxide
Tuncok 2002
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BP 96/60 Tx?
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NaHCO3

• Na load, ? pH, hypokalemia
• ? QRS, ? BP
• Till hypernatremia, pH gt 7.55

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Alkalemia ? mortality
GP I pH 7.48-7.55 GP II pH gt7.55
Anderson 1987
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Hypertonic saline
If pH 7.56, Na 140, Tx?
James 1998
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Hypertonic saline

• NaHCO3 HTS gt HV in QRS BP improvement in rats
  (Pentel 1984)
• NaHCO3 gt 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)

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

• 2 cases
• Hyperventilation NaHCO3
• pH 7.83 7.66
• pCO2 11 20 mmHg
• Arrest
• Keith 1992

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If QRS 0.8 s, BP 88/59, Na 146, pH 7.56, Tx?

• Norepinephrine preferred to dopamine
• ? Epinephrine preferred to norepinephrine

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E gt NE in ? survival
Cummulative survival ()
Epinephrine
Norepinephrine
Control
Time (min)
Knudsen 1997
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E gt NE in ? QRS
Norepinephrine
Epinephrine
Knudsen 1997
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Duration (min) in sinus rhythm E gt NE
Knudsen 1997
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NE gt E in ? BP
Norepinephrine
Blood pressure (mmHg)
Epinephrine
Knudsen 1997
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20
30
40
Time (min)
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F / 30

• 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 gt ?1, also 5HT, H1
• Release 5HT, NE

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SSRI toxicity
Isbister 2004
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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

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Priapism

• Trazodone, chlorpromazine, thioridazine, etc
• Low flow
• Painful
• USG
• Blood gas

Priapus
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Priapism Tx

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

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Thioridazine the most cardiotoxic neuroleptic
Buckley 1995
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Atypical antipsychotics 5HT / D2 block
(EPS)
(--ve s/s)
(Temp)
(ve s/s)
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Olanzapine overdose

• ? GCS 92
• Agitation 42
• Convulsion 4
• Tachycardia 23
• Hypotension 4
• QTc gt 0.45 s 4
• Miosis 31

Palenzona 2004
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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?
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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?
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Sternbach criteria

• Serotonergic agent
• No neuroleptics
• Rule out others
• gt 3 of
• - mental changes - shivering
• - agitation - tremor
• - myoclonus - diarrhea
• - hyperreflexia -
  incoordination
• - diaphoresis - fever

Sternbach 1991
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Hunter criteria

• Serotonergic agent
• Any 1 of
• Inducible clonus agitation or diaphoresis
• Ocular clonus agitation or diaphoresis
• Tremor hyperreflexia
• Hypertonic gt 380C ocular clonus or inducible
  clonus

Dunkley 2003
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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
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DSM IV

• Fever rigidity gt 2 of
• Diaphoresis, dysphagia, tremor, incontinence, ?
  GCS, ? HR, BP changes, ? CK, ? WBC

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Wappler 2001
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L-tryptophan
MAOI
Serotonin syndrome
SSRI
Amphatemines
5-HT agonists
Li
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Sudden withdrawal of L-dopa
NMS
D2 receptors X by neuroleptics
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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

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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

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M / 42

• 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

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Taken 10 more tablets of Li2CO3 in last 2 days

• Serum Li 3.6 mmol/L
• Tremor gets coarse, ataxia, hypertonic
• Tx?

• WBI
• NS IV
• Na polystyrene sulphonate
• HD
• CAVHDF
• CVVHDF

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Na polystyrene sulphonate

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

Roberge 1993
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Carbamazepine

• Anticholinergic
• - anticholinergic delayed s/s, seizures
• Membrane stabilization
• - ? QRS
• Adenosine A1 / A2
• - seizures
• Active metabolites
• - prolonged s/s
• MDAC
• HP, HD

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Cytoplasm
VALPROIC ACID TOXICITY
Carnitine
? Ketoglutarate depletion
Mitochondria
? Glutamate synthesis
VA
Carnitine
X
Acyl-CoA
CoA
VA
X
NH3 accumulation
Inhibit
X
? oxidation
X
4-en-VA
? Carbamyl phosphate synthetase
Acetyl-CoA
Krebs cycle
X
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Tx of VA poisoning

• L-carnitine 50 mg/kg Q 3-4 h
• Naloxone 2 mg
• Displace GABA
• Enkephalin antagonist
• MDAC
• HP
• HD, CVVHDF

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St. Johns Wort

• Hyperforin inhibits reuptake of D, 5HT, NE
• Hyperricin inhibits MAO
• ? Risk if together with atypical antidepressants,
  MAOI
• noradrenergic agents
• No reports of overdose

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TCM

• ?? laxative
• ??? mucolytic
• ?? sedative

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??!
Thank you!