Antidotes
Dr. F.L. Lau
COS (AED) UCH

Effective antidotes are limited
 Availability / stocking level variable
 Some very expensive (expire before use)

Appropriate use can :
 reduce M&M
 avoid unnecessary investigation

Not without risk—poison itself
UCH Antidotes Use (1999-2004)
Nalaxone
NaHCO3
Glucagon
No Antidotes
NAC
Calcium
Atropine
Flumazenil
Physostigmine
Antivenom
Antidote
Frequency
Naloxone
136 (7%)
N-acetylcysteine
57 (3%)
Flumazenil
29 (2%)
NaHCO3
11 (1%)
Calcium
8 (0%)
Physostigmine
3 (0%)
Glucagon
1 (0%)
Atropine
1 (0%)
Antivenom
1 (0%)
No Antidotes
1648 (87%)
Use of Antidote
Consider risk benefit ratio
 Patients clinical status (e.g. Benzodiazepine)
 Appropriate laboratory result (Panadol)
 Expected pharmaceutical action of toxin
 Possible adverse reactions of antidote

Case1
F/30 mental patient
 Found unconscious in bed with suicidal
note
 RR 10/min, BP 100/80, pulse 60/min
 Pupil small (E&R) SaO2: 98%
 After initial stabilization
 What antidote will you use?

Drug induced coma
A
B
C
N
O
T
alcohols & anticonvulsants
barbiturate & benzodiazepine & other sedatives
carbon monoxide & cyanide
neuroleptics
opiates & oral hypoglycemic
TCA & other tranquilizers
Relative produce empty bags of Doloxene,
Mogadon & Sinequan
 When would you give
 Narcan?
 Anexate?
 NaHCO3?

Naloxone (Narcan)
Indications
Reversal of CNS & respiratory depression in opioid poisoning
Also effective for clonidine +/- ethanol/benzo/valproic acid
Diagnostic use for coma patient
Naloxone (Narcan)
Dosage:
0.4-2mg I.V. bolus, can be repeated up to 10 mg
For chronic user, titrate with low dose (0.1mg) upward
Infusion usually indicated (T ½ ~ 1 hour)
-2/3 initial effective close hourly
Caution:
Rapid reversion cause withdrawal seizure
Pulmonary edema & vent. fibrillation
Flumazenil (Anexate)
Pure competitive benzodiazepine receptor antagonist
Indications
 Post op or post procedure reversal of benzodiazepine
sedation
 Rapid reversal of benzodiazepine – induced coma & resp.
depression as a diagnostic aid or avoid intubation
Flumazenil (Anexate)
Cautions
 Oral benzodiazepine overdose never life-threatening
 In chronic user cause withdrawal & convulsion
 In polydrug overdose, removal of protective effective of
benzodiazepine unmask convulsion or arrhythmia of TCA
or cocaine
Dosage:
 Titrate with response starting 0.2mg I.V. over 30 sec
 Up to 3mg
Case1
F/30 mental patient
 Found unconscious in bed with suicidal
note
 RR 10/min, BP 100/80, pulse 60/min
 Pupil small (E&R) SaO2: 98%

Compatible with TCA poisoning?
NaHCO3
Indications
1.
Reverse sodium channel blockers overdose

TCA

Antiarrhythmic

1a: Quindine, procainamide & disopyramide

1c: Encainide & flecaimide

Propanolol

Propoxyphene (Doloxene)

Phenothiazines (melleril)

Diphenhydramine (benadryl)

Cocaine



Quinidine-like effect
 Myocardial depression – hypotension
 Reduce excitability – heart block
 Reduce conduction velocity – wide QRS
 Delay repolarization – prolong QTc
Sodium ion load & alkalaemia reverse membrane depressant effects
Indicated if QRS > 0.1 sec, hypotension & bradycardia
Dosage:
1-2mEq/Kg bolus repeated q 5-10 min till pH: 7.45-7.5 or QRS shorten to
normal
NaHCO3
2.
Urinary alkalinazation

Enhance elimination of salicylate & phenobarbital

Prevent renal deposition of myoglobin after
rhadomyolysis

100 ml NaHCO3 in 1 litre of D5 in 0.25% saline at
150ml/hour

Adjust rate to maintain urine pH7-8

Add 20 mEq/L of potassium
NaHCO3
3.Correction of Acidaemia
For poisoning of
methanol
ethylene glycol
salicylate
What if the patient taken a bottle of
industrial alcohol ?
What antidote to use?
Ethanol



Compete with methanol/ethylene glycol
Higher affinity for alcohol dehydrogenase
Allow toxic alcohol excreted avoiding toxic
metabolite production
Indication
 Symptoms of toxicity/anion gap metabolic
acidosis with history of ingestion
Ethanol
Dosage:
 Loading: 750 mg/kg
 Maintenance: 100-150 mg/kg/hr to keep
serum level 100mg/dL
 Increase rate with dialysis

(Fomepizole : not A/V in HK)
Case II
M/30
 Well all along
 Recent depression after diagnosis of T.B.
 Status epilepticus 1 hour after dinner
 Poor response to all anticonvulsants

What is your DDX?
Drug induced convulsion
Status epilepticuts
Organophosphate
Tricyclic antidepressant
Isoniazid
Sympathomimetic
Amoxopine
INAH
Camphor, cocaine
cocaine
Amphetamines
Methylxanthines
Phencyclidine
Benzodiazepine withdrawal
Ethenol withdrawal
Lithium, lidocaine
Lead
Amphetamines
theophylline
ethanol withdrawal
Lead
Tetramine
Pyridoxine (vit B6)
INAH inhibit brain pyridoxal phosphate
 decrease GABA levels causing repeated seizure
 block liver metabolism causing lactate acidosis
 High dose Pyridoxine control the convulsion
 Also correct the lactic acidosis
 Adjunct therapy for ethylene glycol poisoning
(Glyoxylic acid to glycine)
Dosage:
 1 gm pyridoxine per gram of INAH or empirically
5g I.V.I.

If no response, think of tetramine
Especially if
no evidence of suicidal drug ingestion
DMPS
Sodium dimercaptopropane sulfonate is
related to BAL (dimercaprol) & succimer
(dimercaptosuccinic acid)
 All are chelating agents
 DMPS & succimer also useful for nonmetalic pesticide -Tetramine

R1
H
S
C
H
S
C
H
H
R2
R2
R1
Compound
H
CH2OH
BAL
COOH
COOH
Succimer
CH2SO2Na
H
DMPS




Mechanism of action unknown (? Dithiol group)
Proven in animal study control convulsion &
mortality
Many studies in China show effectiveness
Study not vigorous
Journal of China Clin Med 2002 Cheng
Kids
Rx
Death
Disable
20
DMPS + Valium
0
0
4
Luminal + Valium
3
1
Henan Journ Pract Neuro Diseae: Yee
10 DMPs
0 deaths
11 control
2 deaths
Action within 30 min. reduce convulsion
 Side effect mild: allergic reactions, vertigo
& weakness

Dosage





No standard protocol
Na-DMPS 0.25 mg IMI (0.5 mg/kg for child),
response within 30 mins
Can be repeated 30-60 min. to max. 1gm/day
Then 2 doses on D2
Then 1 dose daily for 2-3 weeks
Adjunct therapy
Vit B6 0.5-1.5/D I.V.
 plasmaphoresis

If taken huge dose of organophosphate,
what is the antidote?
Atropine






For organophosphate or carbamate
poisoning
Anti-muscarinic effect & central effect
Will not reverse nicotinic effects
Dosage: 1mg I.V. titrated as needed
May need huge doses
Endpoint: drying of secretions and lung
clear
Pralidoxime



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

Reverse cholinesterase inhibition
Reactivate phosphorylated cholinesterase
enzyme
(before it aged)
Most pronounced with organophosphate
Also in carbamate with nicotinic toxicity
May precipitate myasthenic crisis
Rapid infusion : tachycardia, laryngospasm,
muscle rigidity
Pralidoxime
Dosage:
 1-2 gm IV over 30 min
 Repeat the dose if muscle weakness not improved
 Followed by infusion 200-500 mg/hr
 May need several days (for fat soluble one, avoid
intermediate syndrome)
Patient was on TCA, which is known to have
anticholinergic property
What is the antidote for
anticholingergic poisoning?
Should we use it?
Physostigmine




Reversible inhibitor of acetyl cholinesterase
Tertiary amine cross BBB exerting central
cholinergic effects
Onset of action a few minute & half life ~ 30 min
Non-specific arousal reticular activating system
Physostigmine
Indication
 Severe anticholinergic poisoning – agitated
delirium, seizure + (coma, severe hypertension,
arrhythmia and hypothermia).
 Sometimes diagnostic test for delirium
(functional/anticholinergic)
Physostigmine
Contraindications
 Not for TCA poisoning


Not for non-specific coma


Aggravate arrhythmia & induce convulsion
Unless pure anticholinergic toxidrome
Not with depolarizing NM blockers (scoline)
Dosage
Diagnostic trial 1mg IV slowly over 5 min
 Therapeutic 0.5mg I.V. repeated every 5
min till 2mg or desired effect
 Atropine standby to reverse excessive
muscarinic stimulation

Case III
M/30
 Worker caught in factory fire
 No burn nor smoke inhalation, SaO2 90%
 Persistent hypotension, acidosis

What antidote to use?
Oxygen




100% or hyperbaric
For possible carbon monoxide poisoning
Also for :
 hypoxaemia from toxic lung injury
 Cellular respiration inhibitor (cyanide & H2S)
Use with care in paraquat poisoning aggravate
lipid peroxidation in lung resulting in fibrosis)
Co-oximetry:
COHb level: 10%
What antidote to use?
Cyanide Kit




Sodium nitrite (Amyl nitrite)
Produce cyanide – scavenging methemoglobin
1 dose produce 20-30% met Hb
C/1 pre-existing methemoglobinaemia > 40%
hypotension & concurrent CO poisoning
Dosage:
 NaNO2 300mg I.V. over 3-5min
 Half dose can be repeated if no response within 30 min
Sodium thiosulphate




Sulfur donor that promote convertion of cyanide
to thiocyanate
Non-toxic can be used empirically
Also for prophylaxis during Nitroprusside infusion
Cause burning sensation, muscle clamping &
twitching
Dosage:
12.5g IV at 5ml/min
Half dose can be repeated after 30-60 min
Hydroxocohalamin






Synthetic form of Vit B12
Exchange with plasma cyanide to give non-toxic
cyanocobalamin
Minimal adverse effect
Brown coloration of body fluid (interfere lab test)
Nausea/vomiting
Muscle twitching & spasm
Dosage:
 Give 50 times of cyanide exposed or empirically 4gm
Other antidotes
Methanol
Ethanol
Ethylene glycol
Fomepizole*
Panadol
Acetylcysteine
Calcium channel blocker
Ca cl
Hydrogen floride
Ca gluconate
Oral hypoglycaemic
D50
Insulin
Octreotide
Arseric, Hg, Lead
Dimercaprol, Succimer*
Beta blockers
Glucagon
Methaemoglobinaemia
Methylene blue
Warfarin
Vit K1
Iron
Deferoxamine
Other antidotes
Heparin
Protamine sulphate
Methotrexate, Methanol
Folinic acid*
Valproic acid
carnitine*
Digoxin
Digoxin-specific antibodies (digibind)
Stone fish sting
Stone fish antivenom
Bamboo snake
specific antivenin
Russell riper
Chinese Cobra
King Cobra
Banded Krait
Botulism
Botulinum antitoxin*
Minimal Stocking Level
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AED
Hospital
Know where to get at odd hour
Need a central station (PCC?)
Stock taking in all AEDs/Hospital Pharmacies
Thank you