antidotes dr. f.l. lau cos (aed) uch. effective antidotes are limited effective antidotes are...
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Antidotes
Dr. F.L. LauDr. F.L. Lau
COS (AED) UCHCOS (AED) UCH
Effective antidotes are limited Effective antidotes are limited Availability / stocking level variableAvailability / stocking level variable Some very expensive (expire before use)Some very expensive (expire before use)
Appropriate use can :Appropriate use can : reduce M&Mreduce M&M avoid unnecessary investigationavoid unnecessary investigation
Not without risk—poison itselfNot without risk—poison itself
UCH Antidotes Use (1999-2004)
Nalaxone NAC Flumazenil
NaHCO3 Calcium Physostigmine
Glucagon Atropine Antivenom
No Antidotes
AntidoteAntidote FrequencyFrequency
NaloxoneNaloxone 136 (7%)136 (7%)
N-acetylcysteineN-acetylcysteine 57 (3%)57 (3%)
FlumazenilFlumazenil 29 (2%)29 (2%)
NaHCONaHCO33 11 (1%)11 (1%)
CalciumCalcium 8 (0%)8 (0%)
PhysostigminePhysostigmine 3 (0%)3 (0%)
GlucagonGlucagon 1 (0%)1 (0%)
AtropineAtropine 1 (0%)1 (0%)
AntivenomAntivenom 1 (0%)1 (0%)
No AntidotesNo Antidotes 1648 (87%)1648 (87%)
Use of Antidote
Consider risk benefit ratioConsider risk benefit ratio Patients clinical status (e.g. Patients clinical status (e.g.
Benzodiazepine)Benzodiazepine) Appropriate laboratory result (Panadol)Appropriate laboratory result (Panadol) Expected pharmaceutical action of toxinExpected pharmaceutical action of toxin Possible adverse reactions of antidotePossible adverse reactions of antidote
Case1
F/30 mental patientF/30 mental patient Found unconscious in bed with suicidal Found unconscious in bed with suicidal
notenote RR 10/min, BP 100/80, pulse 60/minRR 10/min, BP 100/80, pulse 60/min Pupil small (E&R) SaOPupil small (E&R) SaO22: 98%: 98%
After initial stabilizationAfter initial stabilization What antidote will you use?What antidote will you use?
Drug induced coma
AA alcohols & anticonvulsantsalcohols & anticonvulsants
BB barbiturate & benzodiazepine & other barbiturate & benzodiazepine & other sedativessedatives
CC carbon monoxide & cyanidecarbon monoxide & cyanide
NN neurolepticsneuroleptics
OO opiates & oral hypoglycemicopiates & oral hypoglycemic
TT TCA & other tranquilizersTCA & other tranquilizers
Relative produce empty bags of Doloxene, Relative produce empty bags of Doloxene, Mogadon & SinequanMogadon & Sinequan
When would you giveWhen would you give Narcan?Narcan? Anexate?Anexate? NaHCONaHCO33??
Naloxone (Narcan)
IndicationsIndications
Reversal of CNS & respiratory depression in opioid poisoningReversal of CNS & respiratory depression in opioid poisoning
Also effective for clonidine +/- ethanol/benzo/valproic acidAlso effective for clonidine +/- ethanol/benzo/valproic acid
Diagnostic use for coma patientDiagnostic use for coma patient
Naloxone (Narcan)
Dosage:Dosage:
0.4-2mg I.V. bolus, can be repeated up to 10 mg0.4-2mg I.V. bolus, can be repeated up to 10 mg
For chronic user, titrate with low dose (0.1mg) upwardFor chronic user, titrate with low dose (0.1mg) upward
Infusion usually indicated (T ½ ~ 1 hour)Infusion usually indicated (T ½ ~ 1 hour)
-2/3 initial effective close hourly-2/3 initial effective close hourly
Caution:Caution:
Rapid reversion cause withdrawal seizureRapid reversion cause withdrawal seizure
Pulmonary edema & vent. fibrillationPulmonary edema & vent. fibrillation
Flumazenil (Anexate)
Pure competitive benzodiazepine receptor antagonistPure competitive benzodiazepine receptor antagonist
IndicationsIndications Post op or post procedure reversal of benzodiazepine Post op or post procedure reversal of benzodiazepine
sedationsedation Rapid reversal of benzodiazepine – induced coma & resp. Rapid reversal of benzodiazepine – induced coma & resp.
depression as a diagnostic aid or avoid intubationdepression as a diagnostic aid or avoid intubation
Flumazenil (Anexate)
CautionsCautions Oral benzodiazepine overdose never life-threateningOral benzodiazepine overdose never life-threatening In chronic user cause withdrawal & convulsionIn chronic user cause withdrawal & convulsion In polydrug overdose, removal of protective effective of In polydrug overdose, removal of protective effective of
benzodiazepine unmask convulsion or arrhythmia of TCA benzodiazepine unmask convulsion or arrhythmia of TCA or cocaineor cocaine
Dosage:Dosage: Titrate with response starting 0.2mg I.V. over 30 secTitrate with response starting 0.2mg I.V. over 30 sec Up to 3mgUp to 3mg
Case1 F/30 mental patientF/30 mental patient Found unconscious in bed with suicidal Found unconscious in bed with suicidal
notenote RR 10/min, BP 100/80, pulse 60/minRR 10/min, BP 100/80, pulse 60/min Pupil small (E&R) SaOPupil small (E&R) SaO22: 98%: 98%
Compatible with TCA poisoning?Compatible with TCA poisoning?
NaHCO3
IndicationsIndications
1.1. Reverse sodium channel blockers overdoseReverse sodium channel blockers overdose TCATCA AntiarrhythmicAntiarrhythmic 1a: Quindine, procainamide & disopyramide1a: Quindine, procainamide & disopyramide 1c: Encainide & flecaimide1c: Encainide & flecaimide PropanololPropanolol Propoxyphene (Doloxene)Propoxyphene (Doloxene) Phenothiazines (melleril)Phenothiazines (melleril) Diphenhydramine (benadryl)Diphenhydramine (benadryl) CocaineCocaine
Quinidine-like effectQuinidine-like effect Myocardial depression – hypotensionMyocardial depression – hypotension Reduce excitability – heart blockReduce excitability – heart block Reduce conduction velocity – wide QRSReduce conduction velocity – wide QRS Delay repolarization – prolong QTcDelay repolarization – prolong QTc
Sodium ion load & alkalaemia reverse membrane depressant effectsSodium ion load & alkalaemia reverse membrane depressant effects Indicated if QRS > 0.1 sec, hypotension & bradycardiaIndicated if QRS > 0.1 sec, hypotension & bradycardia
Dosage:Dosage:
1-2mEq/Kg bolus repeated q 5-10 min till pH: 7.45-7.5 or QRS shorten to 1-2mEq/Kg bolus repeated q 5-10 min till pH: 7.45-7.5 or QRS shorten to
normalnormal
NaHCO3
2.2. Urinary alkalinazationUrinary alkalinazation Enhance elimination of salicylate & phenobarbitalEnhance elimination of salicylate & phenobarbital Prevent renal deposition of myoglobin after Prevent renal deposition of myoglobin after
rhadomyolysisrhadomyolysis 100 ml NaHCO3 in 1 litre of D5 in 0.25% saline at 100 ml NaHCO3 in 1 litre of D5 in 0.25% saline at
150ml/hour150ml/hour Adjust rate to maintain urine pH7-8Adjust rate to maintain urine pH7-8 Add 20 mEq/L of potassiumAdd 20 mEq/L of potassium
NaHCO3
3.Correction of Acidaemia3.Correction of Acidaemia
For poisoning ofFor poisoning of
methanol methanol
ethylene glycolethylene glycol
salicylatesalicylate
What if the patient taken a bottle of What if the patient taken a bottle of
industrial alcohol ?industrial alcohol ?
What antidote to use?What antidote to use?
Ethanol
Compete with methanol/ethylene glycolCompete with methanol/ethylene glycol Higher affinity for alcohol dehydrogenaseHigher affinity for alcohol dehydrogenase Allow toxic alcohol excreted avoiding toxic Allow toxic alcohol excreted avoiding toxic
metabolite production metabolite production
IndicationIndication Symptoms of toxicity/anion gap metabolic Symptoms of toxicity/anion gap metabolic
acidosis with history of ingestionacidosis with history of ingestion
Ethanol
Dosage:Dosage: Loading: 750 mg/kgLoading: 750 mg/kg Maintenance: 100-150 mg/kg/hr to keep Maintenance: 100-150 mg/kg/hr to keep
serum level 100mg/dL serum level 100mg/dL Increase rate with dialysisIncrease rate with dialysis
(Fomepizole : not A/V in HK)(Fomepizole : not A/V in HK)
Case II
M/30M/30 Well all alongWell all along Recent depression after diagnosis of T.B.Recent depression after diagnosis of T.B. Status epilepticus 1 hour after dinnerStatus epilepticus 1 hour after dinner Poor response to all anticonvulsantsPoor response to all anticonvulsants
What is your DDX?What is your DDX?
Drug induced convulsionStatus epilepticutsStatus epilepticuts
OOrganophosphaterganophosphate
TTricyclic antidepressantricyclic antidepressant AmoxopineAmoxopine
IIsoniazidsoniazid INAHINAH
SSympathomimeticympathomimetic
CCamphor, cocaineamphor, cocaine cocainecocaine
AAmphetaminesmphetamines AmphetaminesAmphetamines
MMethylxanthinesethylxanthines theophyllinetheophylline
PPhencyclidinehencyclidine
BBenzodiazepine withdrawalenzodiazepine withdrawal
EEthenol withdrawalthenol withdrawal ethanol withdrawalethanol withdrawal
LLithium, lidocaineithium, lidocaine
LLeadead LeadLead
TetramineTetramine
Pyridoxine (vit B6)
INAH inhibit brain pyridoxal phosphate INAH inhibit brain pyridoxal phosphate decrease GABA levels causing repeated seizure decrease GABA levels causing repeated seizure block liver metabolism causing lactate acidosisblock liver metabolism causing lactate acidosis High dose Pyridoxine control the convulsionHigh dose Pyridoxine control the convulsion Also correct the lactic acidosisAlso correct the lactic acidosis Adjunct therapy for ethylene glycol poisoningAdjunct therapy for ethylene glycol poisoning (Glyoxylic acid to glycine)(Glyoxylic acid to glycine)Dosage:Dosage: 1 gm pyridoxine per gram of INAH or empirically 5g 1 gm pyridoxine per gram of INAH or empirically 5g
I.V.I.I.V.I.
If no response, think of tetramineIf no response, think of tetramine
Especially ifEspecially if
no evidence of suicidal drug ingestionno evidence of suicidal drug ingestion
DMPS
Sodium dimercaptopropane sulfonate is Sodium dimercaptopropane sulfonate is related to BAL (dimercaprol) & succimer related to BAL (dimercaprol) & succimer (dimercaptosuccinic acid)(dimercaptosuccinic acid)
All are chelating agentsAll are chelating agents DMPS & succimer also useful for non-DMPS & succimer also useful for non-
metalic pesticide -Tetraminemetalic pesticide -Tetramine
HH HH
SS SS
R1R1 CC CC R2R2
HH HH
R2R2 R1R1 CompoundCompound
HH CH2OHCH2OH BALBAL
COOHCOOH COOHCOOH SuccimerSuccimer
CH2SO2NaCH2SO2Na HH DMPSDMPS
Mechanism of action unknown (? Dithiol group)Mechanism of action unknown (? Dithiol group) Proven in animal study control convulsion & Proven in animal study control convulsion &
mortalitymortality Many studies in China show effectivenessMany studies in China show effectiveness Study not vigorous Study not vigorous
Journal of China Clin Med 2002 ChengJournal of China Clin Med 2002 Cheng
KidsKids RxRx Death Death Disable Disable
2020 DMPS + ValiumDMPS + Valium 00 0 0
44 Luminal + ValiumLuminal + Valium 33 1 1
Henan Journ Pract Neuro Diseae: YeeHenan Journ Pract Neuro Diseae: Yee
10 DMPs10 DMPs 0 deaths0 deaths
11 control11 control 2 deaths2 deaths
Action within 30 min. reduce convulsionAction within 30 min. reduce convulsion Side effect mild: allergic reactions, vertigo Side effect mild: allergic reactions, vertigo
& weakness& weakness
Dosage
No standard protocol No standard protocol Na-DMPS 0.25 mg IMI (0.5 mg/kg for child), Na-DMPS 0.25 mg IMI (0.5 mg/kg for child),
response within 30 minsresponse within 30 mins Can be repeated 30-60 min. to max. 1gm/dayCan be repeated 30-60 min. to max. 1gm/day Then 2 doses on D2Then 2 doses on D2 Then 1 dose daily for 2-3 weeksThen 1 dose daily for 2-3 weeks
Adjunct therapy
Vit B6 0.5-1.5/D I.V.Vit B6 0.5-1.5/D I.V. plasmaphoresisplasmaphoresis
If taken huge dose of organophosphate,If taken huge dose of organophosphate,
what is the antidote?what is the antidote?
Atropine
For organophosphate or carbamate For organophosphate or carbamate poisoningpoisoning
Anti-muscarinic effect & central effectAnti-muscarinic effect & central effect Will not reverse nicotinic effectsWill not reverse nicotinic effects Dosage: 1mg I.V. titrated as neededDosage: 1mg I.V. titrated as needed May need huge dosesMay need huge doses Endpoint: drying of secretions and lung Endpoint: drying of secretions and lung
clearclear
Pralidoxime
Reverse cholinesterase inhibitionReverse cholinesterase inhibition Reactivate phosphorylated cholinesterase Reactivate phosphorylated cholinesterase
enzyme (before it aged) enzyme (before it aged) Most pronounced with organophosphate Most pronounced with organophosphate Also in carbamate with nicotinic toxicityAlso in carbamate with nicotinic toxicity May precipitate myasthenic crisis May precipitate myasthenic crisis Rapid infusion : tachycardia, laryngospasm,Rapid infusion : tachycardia, laryngospasm,
muscle rigiditymuscle rigidity
Pralidoxime
Dosage:Dosage: 1-2 gm IV over 30 min 1-2 gm IV over 30 min Repeat the dose if muscle weakness not improvedRepeat the dose if muscle weakness not improved Followed by infusion 200-500 mg/hrFollowed by infusion 200-500 mg/hr May need several days (for fat soluble one, avoid May need several days (for fat soluble one, avoid
intermediate syndrome)intermediate syndrome)
Patient was on TCA, which is known to have Patient was on TCA, which is known to have
anticholinergic propertyanticholinergic property
What is the antidote for What is the antidote for
anticholingergic poisoning?anticholingergic poisoning?
Should we use it?Should we use it?
Physostigmine Reversible inhibitor of acetyl cholinesteraseReversible inhibitor of acetyl cholinesterase Tertiary amine cross BBB exerting central Tertiary amine cross BBB exerting central
cholinergic effectscholinergic effects Onset of action a few minute & half life ~ 30 minOnset of action a few minute & half life ~ 30 min Non-specific arousal reticular activating systemNon-specific arousal reticular activating system
Physostigmine
IndicationIndication Severe anticholinergic poisoning – agitated Severe anticholinergic poisoning – agitated
delirium, seizure delirium, seizure ++ (coma, severe hypertension, (coma, severe hypertension, arrhythmia and hypothermia).arrhythmia and hypothermia).
Sometimes diagnostic test for delirium Sometimes diagnostic test for delirium (functional/anticholinergic)(functional/anticholinergic)
Physostigmine
ContraindicationsContraindications Not for TCA poisoningNot for TCA poisoning
Aggravate arrhythmia & induce convulsionAggravate arrhythmia & induce convulsion Not for non-specific comaNot for non-specific coma
Unless pure anticholinergic toxidromeUnless pure anticholinergic toxidrome Not with depolarizing NM blockers Not with depolarizing NM blockers
(scoline)(scoline)
Dosage
Diagnostic trial 1mg IV slowly over 5 minDiagnostic trial 1mg IV slowly over 5 min Therapeutic 0.5mg I.V. repeated every 5 Therapeutic 0.5mg I.V. repeated every 5
min till 2mg or desired effectmin till 2mg or desired effect Atropine standby to reverse excessive Atropine standby to reverse excessive
muscarinic stimulationmuscarinic stimulation
Case III
M/30M/30 Worker caught in factory fireWorker caught in factory fire No burn nor smoke inhalation, SaONo burn nor smoke inhalation, SaO22 90% 90%
Persistent hypotension, acidosisPersistent hypotension, acidosis
What antidote to use?What antidote to use?
Oxygen
100% 100% or hyperbaricor hyperbaric For possible carbon monoxide poisoningFor possible carbon monoxide poisoning Also for :Also for :
hypoxaemia from toxic lung injuryhypoxaemia from toxic lung injury Cellular respiration inhibitor (cyanide & H2S)Cellular respiration inhibitor (cyanide & H2S)
Use with care in paraquat poisoning aggravate Use with care in paraquat poisoning aggravate lipid peroxidation in lung resulting in fibrosis)lipid peroxidation in lung resulting in fibrosis)
Co-oximetry:Co-oximetry:
COHb level: 10%COHb level: 10%
What antidote to use?What antidote to use?
Cyanide Kit
Sodium nitrite (Amyl nitrite)Sodium nitrite (Amyl nitrite) Produce cyanide – scavenging methemoglobinProduce cyanide – scavenging methemoglobin 1 dose produce 20-30% met Hb1 dose produce 20-30% met Hb C/1 pre-existing methemoglobinaemia > 40% C/1 pre-existing methemoglobinaemia > 40%
hypotension & concurrent CO poisoninghypotension & concurrent CO poisoning
Dosage:Dosage: NaNO2 300mg I.V. over 3-5minNaNO2 300mg I.V. over 3-5min Half dose can be repeated if no response within 30 minHalf dose can be repeated if no response within 30 min
Sodium thiosulphate
Sulfur donor that promote convertion of cyanide to Sulfur donor that promote convertion of cyanide to thiocyanatethiocyanate
Non-toxic can be used empiricallyNon-toxic can be used empirically Also for prophylaxis during Nitroprusside infusionAlso for prophylaxis during Nitroprusside infusion Cause burning sensation, muscle clamping & Cause burning sensation, muscle clamping &
twitchingtwitching
Dosage:Dosage:12.5g IV at 5ml/min12.5g IV at 5ml/minHalf dose can be repeated after 30-60 minHalf dose can be repeated after 30-60 min
Hydroxocohalamin
Synthetic form of Vit B12Synthetic form of Vit B12 Exchange with plasma cyanide to give non-toxic Exchange with plasma cyanide to give non-toxic
cyanocobalamincyanocobalamin Minimal adverse effectMinimal adverse effect Brown coloration of body fluid (interfere lab test)Brown coloration of body fluid (interfere lab test) Nausea/vomitingNausea/vomiting Muscle twitching & spasmMuscle twitching & spasm
Dosage:Dosage: Give 50 times of cyanide exposed or empirically 4gmGive 50 times of cyanide exposed or empirically 4gm
Other antidotesOther antidotes
MethanolMethanol EthanolEthanol
Ethylene glycolEthylene glycol Fomepizole*Fomepizole*
PanadolPanadol AcetylcysteineAcetylcysteine
Calcium channel blockerCalcium channel blocker Ca clCa cl
Hydrogen florideHydrogen floride Ca gluconateCa gluconate
Oral hypoglycaemicOral hypoglycaemic D50D50
InsulinInsulin OctreotideOctreotide
Arseric, Hg, LeadArseric, Hg, Lead Dimercaprol, Succimer*Dimercaprol, Succimer*
Beta blockersBeta blockers GlucagonGlucagon
MethaemoglobinaemiaMethaemoglobinaemia Methylene blueMethylene blue
WarfarinWarfarin Vit K1Vit K1
IronIron DeferoxamineDeferoxamine
Other antidotesOther antidotes
HeparinHeparin Protamine sulphateProtamine sulphate
Methotrexate, MethanolMethotrexate, Methanol Folinic acid*Folinic acid*
Valproic acidValproic acid carnitine*carnitine*
DigoxinDigoxin Digoxin-specific antibodies (digibind)Digoxin-specific antibodies (digibind)
Stone fish stingStone fish sting Stone fish antivenomStone fish antivenom
Bamboo snakeBamboo snake specific antiveninspecific antivenin
Russell riperRussell riper
Chinese CobraChinese Cobra
King CobraKing Cobra
Banded KraitBanded Krait
BotulismBotulism Botulinum antitoxin*Botulinum antitoxin*
Minimal Stocking Level
AEDAED HospitalHospital Know where to get at odd hourKnow where to get at odd hour Need a central station (PCC?)Need a central station (PCC?) Stock taking in all AEDs/Hospital PharmaciesStock taking in all AEDs/Hospital Pharmacies
Thank you