Toxicology Program Psychiatric drug poisoning Dr HT Fung TMH AED 15 Jun 2005.
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Transcript of Toxicology Program Psychiatric drug poisoning Dr HT Fung TMH AED 15 Jun 2005.
Toxicology ProgramPsychiatric 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
- conduction
- inotropy
-1 block
-NE depletion
-Adenosine
-Nitric oxide
BP 90/60, why?
Adenosine
Kalkan 2004
Nitric oxide
Tuncok 2002
BP 96/60
Tx?
NaHCO3
• Na load, pH, hypokalemia QRS, BP
• Till hypernatremia, pH > 7.55
GP I: pH 7.48-7.55
GP II: pH >7.55
Anderson 1987
Alkalemia mortality
Hypertonic saline
QRS (ms) SBP (mmHg)
Control 144 54
HTS (15 mmol/kg)
80 134
NaHCO3
(3 mmol/kg)
105 85
HV (pH 7.5-7.6) 125 60
James 1998
If pH 7.56, Na 140, Tx?
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)
HyperventilationCase 1 Case 2 Case 3
pH 7.65 7.46 7.61
pCO2 14 mmHg 28 mmHg 23 mmHg
QRS Pre-Tx 0.2 s 0.146 s 0.136 s
Post-Tx 0.14 s
at 90 min
0.117 s
at 25 min
0.115 s
at 4.5 h
Bessen 1985
If Na 151, pH 7.48, Tx?
Hyperventilation
• 2 cases:
• Hyperventilation + NaHCO3
• pH 7.83 & 7.66
• pCO2 11 & 20 mmHg
• Arrest
• Keith 1992
If QRS 0.8 s, BP 88/59, Na 146, pH 7.56, Tx?
• Norepinephrine preferred to dopamine
• ? Epinephrine preferred to norepinephrine
E > NE in survival
Epinephrine
Norepinephrine
Control
Time (min)
Cu
mm
ulat
ive
surv
ival
(%
)
Knudsen 1997
E > NE in QRS
Norepinephrine
Epinephrine
Knudsen 1997
Duration (min) in sinus rhythm: E > NE
0
5
10
15
20
25
Control
Norepinephrine
Epinephrine
Knudsen 1997
NE > E in BP
Time (min)
10 20 30 40
Blo
od p
ress
ure
(mm
Hg)
Norepinephrine
Epinephrine
Knudsen 1997
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 > 1,
also 5HT, H1• Release 5HT, NE
SSRI toxicity
Setraline Paroxe-tine
Fluvoxa-mine
Fluoxe-tine
Citalo-pram
Seizures (%)
2 2 1 1 2
QTc (%) 40 40 24 36 68
Serotonin syndrome (%)
20 18 17 1 9
Isbister 2004
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
Priapism
• Trazodone, chlorpromazine, thioridazine, etc
• Low flow• Painful• USG• Blood gas
Priap
us
Priapism Tx
• Aspiration• Epinephrine 1 in
1,000,000 1-10 ml• Methylene blue 50 mg• R-TPA 15 mg• Surgical shunt
Thioridazine – the most cardiotoxic neuroleptic
QTc > O.45 s QRS > 0.1 s Arrhythmias
Thioridazine 60% 23% 5%
Chlorpromazine 34% 15% 0%
Other neuroleptics
19% 6% 0%
Buckley 1995
Atypical antipsychotics – 5HT / D2 block
(EPS)
(+ve s/s)(Temp)
(--ve s/s)
Olanzapine overdose
GCS 92%
• Agitation 42%
• Convulsion 4%
• Tachycardia 23%
• Hypotension 4%
• QTc > 0.45 s 4%
• Miosis 31%
Palenzona 2004
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?
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?
Sternbach criteria
• Serotonergic agent• No neuroleptics• Rule out others• > 3 of: - mental changes - shivering - agitation - tremor - myoclonus - diarrhea - hyperreflexia - incoordination - diaphoresis - fever
Sternbach 1991
Hunter criteria
• Serotonergic agent
• Any 1 of:• Inducible clonus & agitation or diaphoresis• Ocular clonus & agitation or diaphoresis• Tremor & hyperreflexia• Hypertonic & > 380C & ocular clonus or induci
ble clonus
Dunkley 2003
Levenson JL
• 3 major, or 2 major & 4 minor• Major: fever, rigidity, CK• Minor: HR, abnormal BP, RR, GCS, diaph
oresis, WBC
• Neuroleptic use
• Rule out others
Levenson 1985
DSM IV
• Fever & rigidity & > 2 of:
• Diaphoresis, dysphagia, tremor, incontinence, GCS, HR, BP changes, CK, WBC
S.S. N.M.S.Rapid onset ++ --Rigidity + +++ CK + +++ HR + ++ RR + ++ WBC +++ +Behavior +++ ++Clonus / shivering / tremor / reflex
+++ --
Fever / GCS ++ ++
Wappler 2001
L-tryptophan
MAOI
SSRI
Li
Amphatemines
5-HT agonistsSer
oton
in s
yndr
ome
D2 receptors X by neuroleptics
Sudden withdrawal of L-dopa NMS
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
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
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
Taken 10 more tablets of Li2CO3 in last 2 days
• Serum Li 3.6 mmol/L• Tremor gets coarse, a
taxia, hypertonic• Tx?
• WBI• NS IV• Na polystyrene sulpho
nate• HD• CAVHDF• CVVHDF
Na polystyrene sulphonate
• Case:• Acute on chronic Li overdose• Na polystyrene sulphonate 150 g/d• Li t½ 12 h
• Hypokalemia
• No rebound
Roberge 1993
Carbamazepine
• Anticholinergic - anticholinergic & delayed s/s, seizures• Membrane stabilization - QRS• Adenosine A1 / A2 - seizures• Active metabolites - prolonged s/s• MDAC• HP, HD
Carnitine
Carnitine
CoAAcyl-CoA
Acetyl-CoA
Kreb’s cycle Carbamyl phosphate synthetase
NH3 accumulation
Glutamate synthesis
Ketoglutarate depletion
oxidation
VA
4-en-VA
VA
Cyt
opl a
smM
itoc
hond
ria
Inhibit
VALPROIC ACID TOXICITY
X
X
XX
X
Tx of VA poisoning
• L-carnitine 50 mg/kg Q 3-4 h
• Naloxone 2 mg • Displace GABA• Enkephalin antagonist
• MDAC
• HP
• HD, CVVHDF
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
TCM
• 甘逐 – ‘ laxative’
• 天南星 – ‘ mucolytic’
• 朱砂 – ‘ sedative’