Download Management of overdose and poisoning

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Drugs & Chemicals
Poisoning
By Dr. Jamshidi
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Management of overdose
and
poisoning
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General- evaluation

Rcognition of poisoning

Identification of agents involved

Assessment of severity

Prediction of toxicity
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General- management

provision of supportive care

prevention of poison absorption


Enhancement of elimination of
poison
Administration of antidotes
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Supportive care

A: First, the airway should be cleared of
vomitus or any other obstruction and an oral
airway or endotracheal tube inserted if
needed.

B: Breathing should be assessed by
observation and oximetry and, if in doubt by
measuring arterial blood gases patients with
respiratory insufficiency should be intubated
and mechanically ventilated
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Supportive care
•
•
•
•
C:
Circulation should be assessed by continuous
monitoring of:
- pulse rate
- blood pressure
-urinary output
•
An intravenous line should be placed and blood drawn
fro serum glucose and other routine determinations
•
Dextrose to treat hypoglycemia (0.5gm/kg)
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Supportive care

Vital signs, mental status, and pupil size

Pulse oximetry, cardiac monitoring, ECG

Protect airway

Intravenous access

cervical immobilization if suspect trauma

Rule out hypoglycaemia

Naloxone for suspected opiate poisoning
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History
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Pill bottles
Alcohol
Drug history including access
Remember OTC drugs
Suicide note
National Poisons Information
Centre (09694)
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Examinations

Drug Physiologic excitation :
anticholinergic
sympathomimetic
central hallucinogenic agents
drug withdrawal

Physiologic depression
cholinergic (parasympathomimetic)
sympatholytic
opiate, or sedative-hypnotic agents, or alcohols

Mixed state –
polydrugs, hypoglycemic agents, tricyclic
antidepressants, salicylates, cyanide
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Drug detection
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Drug levels
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Preventing absorption
Gastric lavage

Not in unconscious patient unless intubated (risk
aspiration)

Flexible tube is inserted through the nose into the stomach

Stomach contents are then suctioned via the tube

A solution of saline is injected into the tube

Recommended for up to 2 hrs in TCA & up to 4hrs in
Salicylate OD
Induced Vomiting


Ipecac - Not routinely recommended
Risk of aspiration
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CONTRAINDICATION OF
EMESIS
Corrosives and volatile poisons
 Comatose patients
 Heart disease patients
 Pregnant women
 Kerosene : may cause aspiration
pneumonia
 Convulsant patients

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Preventing absorption
Activated charcoal
 Adsorbs toxic substances or irritants, thus
inhibiting GI absorption



Addition of sorbitol →laxative effect
Oral: 25-100 g as a single dose
Repetitive doses useful to enhance the
elimination of certain drugs:
-theophylline
-phenobarbital
- carbamazepine
- aspirin
-sustained-release products
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Preventing absorption
not effective for:
- cyanide
-mineral acids
-caustic alkalis
- organic solvents
-iron, ethanol, methanol poisoning,
lithium
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Elimination of poisons
Renal elimination

Medication to stimulate urination or defecation
may be given to try to flush the excess drug out
of the body faster
Forced alkaline diuresis
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Infusion of large amount of NS+NAHCO3
Used to eliminate acidic drug that mainly
excreted by the kidney eg salicylates
CAUTIONS
Serious fluid and electrolytes disturbance may
occur
Need expert monitoring
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
Elimination of poisons
Hemodialysis or haemoperfusion:



Reserved for severe poisoning
Drug should be dialyzable i.e. protein
bound with low volume of distribution
may also be used temporarily or as
long term if the kidneys are damaged
due to the overdose.
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Hemoperfusion
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Antidotes

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Does an antidote exist?
Does actual or predicted severity of
poisoning warrant its use?
Do expected benefits of therapy
outweigh its associated risk?
Are there contraindications?
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Specific overdoses
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Opiates

Opiat poisoning

Antidote – naloxone



MoA: Pure opioid antagonist competes
and displaces narcotics at opioid
receptor sites
I.V. (preferred), I.M., intratracheal,
SubQ: 0.4-2 mg every 2-3 minutes as
needed
Lower doses in opiate dependence
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Opiates

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Elimination half-life of naloxone is only
60 to 90 minutes
Repeated administration/infusion may
be necessary
Side Effects
BP changes; arrhythmias; seizures;
withdrawal syndrome
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Benzodiazepines
Benzodiazepine poisoning
Antidote – flumazenil
 MoA: Benzodiazepine antagonist

IV administration 0.2 mg over 15 sec to max 3mg

S/E : arrhythmias; convulsions

C/I concomitant TCAD; status epilepticus

Should not be used for making the diagnosis

Benzodiazepines may be masking/protecting against
other drug effects
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Tricyclic antidepressants

PHARMACOLOGY —

TCAs have several important cellular effects, including inhibition of:
-Presynaptic neurotransmitter reuptake
-Cardiac fast sodium channels
-Central and peripheral muscarinic acetylcholine receptors
-Peripheral alpha-1 adrenergic receptors
-Histamine (H1) receptors
-CNS GABA-A receptors
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TCAD overdose
clinical features

Arrhythmias
- widening of PR, QRS, and QT intervals;
- heart block
Hypotension

Anticholinergic toxicity
- hyperthermia
- flushing
-dilated pupils
-intestinal ileus
-urinary retention
- sinus tachycardia


Confusion, delirium, hallucinations
Seizures
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TCAD overdose Diagnosis

History

Blood/urine toxicology screen
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TCAD overdose -Treatment

many require intubation

Consider gastric lavage if taken < 2hrs

Activated charcoal
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Treatment of hypotension with isotonic saline


Sodium bicarbonate for cardiovascular toxicity
Alpha adrenergic vasopressors (norepinephrine )
Benzodiazepines for seizures
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Sodium Bicarbonate in TCA overdose

Hypertonic sodium bicarbonate
(NaHCO3)
- QRS widening >100 msec
-ventricular arrhythmias
-refractory hypotension

↑ serum pH promotes protein binding
and ↓ free drug concentrations
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Sodium Bicarbonate in TCA
overdose

reasonable goal pH is 7.50 to 7.55 then
taper dose
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S/E:
Volume overload
hypernatreamia
metabolic alkalosis
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Special Cautions in TCAD overdose

Class IA and IC antiarrhythmic agents are contraindicated
eg:

quinidine

Disopyramide
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Flecainide

propafenone

Class IB Lignocaine, phenytoin used

Phenytoin may precipitate arrhythmias
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Magnesium may be useful
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Flumazenil must not be given
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Salicylate overdose
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Aspirin (acetylsalicylic acid)
Methyl salicylate (Oil of Wintergreen)
5 ml = 7g salicylic acid
Herbal remedies
Fatal intoxication can occur after the
ingestion of 10 to 30 g by adults and
as little as 3 g by children
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Salicylate levels

-Rapidly absorbed

-peak blood levels usually occur within one
hour but delayed in overdose 6-35 hrs plasma
salicylate concentration

Measure @ 4 hrs post ingestion & every 2 hrs
until they are clearly falling

Most patients show signs of intoxication when
the plasma level exceeds 40 to 50 mg/dL (2.9
to 3.6 mmol/L)
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Salicylate overdose

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1- Inhibition of cyclooxygenase results in decreased
synthesis of prostaglandins, prostacyclin, and
thromboxanes
2- Stimulation of the chemoreceptor trigger zone in the
medulla causes:
nausea and vomiting
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3- Activation of the respiratory center of the medulla
results in:
tachypnea, hyperventilation, respiratory alkalosis
4- Uncoupled oxidative phosphorylation in the
mitochondria generates heat and may increase body
temperature
5- Interference with cellular metabolism leads to
metabolic acidosis
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Clinical features

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Early symptoms of aspirin toxicity include:
tinnitus

Fever
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Vertigo
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Nausea
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Hyperventilation
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Vomiting

diarrhoea
More severe intoxication can cause:
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altered mental status, coma
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non-cardiac pulmonary edema and death
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Metabolic abnormalities
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Stimulate the respiratory center directly, early fall in the
PCO2 and respiratory alkalosis
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An anion-gap metabolic acidosis then follows, due to the
accumulation of organic acids, including lactic acid and
ketoacids
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Mixed respiratory alkalosis and metabolic acidosis with ↑
anion gap
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Arterial Ph variable depending on severity
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Metabolic abnormalities

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Metabolic acidosis increases the
plasma concentration of protonated
salicylate
thus worsening toxicity by allowing
easy diffusion of the drug across cell
membranes
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Salicylate overdose - treatment

directed toward increasing systemic pH by
the administration of sodium bicarbonate

IV fluids +/- vasopressors
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Supplemental glucose (100 mL of 50 percent
dextrose in adults) to patients with altered
mental status regardless of serum glucose
concentration to:
overcome neuroglycopaenia
Hemodialysis
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Alkalinization of plasma and urine

Alkalemia from a respiratory alkalosis is not a
contraindication to sodium bicarbonate therapy
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A urine pH of 7.5 to 8.0 is desirable
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Blood gas analysis every two hours
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Avoid severe alkalemia (arterial pH >7.60)
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Haemodialysis - indications
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Altered mental status
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Pulmonary or cerebral edema
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Renal insufficiency that interferes with salicylate excretion
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Fluid overload that prevents the administration of sodium
bicarbonate
A plasma salicylate concentration >100 mg/dL
Clinical deterioration despite aggressive and appropriate
supportive care
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Paracetamol
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Widely available

Potential toxicity underestimated
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Toxicity unlikely to result from a single dose of less than
150 mg/kg in child or 7.5 to 10 g for adult
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Toxicity is likely with single ingestions greater than 250
mg/kg or those greater than 12 g over a 24-hour period
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Virtually all patients who ingest doses in excess of 350
mg/kg develop severe liver toxicity unless appropriately
treated
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Factors influencing toxicity

Dose ingested

Excessive cytochrome P450 activity due to induction
by chronic alcohol or other drug use eg
carbamazepine, phenytoin, isoniazid, rifampin

Decreased capacity for glucuronidation or sulfation

Depletion of glutathione stores due to malnutrition or
chronic alcohol ingestion
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Acute alcohol ingestion is not a risk factor for
hepatotoxicity and may even be protective by
competing with acetaminophen for CYP2E1
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Clinical features

Stage I (0.5 to 24 hours)
No symptoms

Stage II (24 to 72 hours)
Subclinical elevations of hepatic aminotransferases (AST, ALT)
-right upper quadrant pain
-liver enlargement and tenderness
-Elevations of prothrombin time (PT)
-oliguria and renal function abnormalities may become evident
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Clinical features
Stage III (72 to 96 hours)
-Jaundice
-confusion (hepatic encephalopathy)
-marked elevation in hepatic enzymes
-hyperammonemia
lactic acidosis- renal failure 25%
- death
 Stage IV (4 days to 2 weeks)
Recovery phase that usually begins by day 4 and is
complete by 7 days after overdose
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Paracetamol overdose
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The risk of toxicity is best predicted by relating the time of
ingestion to the serum paracetamol concentration
Peak serum concentrations reached within 4 hrs following
overdose of immediate-release preparations
May be delayed with extended releases preparations or drugs
that delay gastric emptying (eg, opiates, anticholinergic
agents) are coingested
Check level at >= 4 hrs
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Paracetamol overdose treatment

Activated charcoal within four hours of
ingestion
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May reduce absorption by 50 to 90 percent
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Single oral dose of one gram per kilogram
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Inhibits absorption of oral methionine
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Activated Charcoal
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N-acetylcysteine
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Antidote – MOA: a glutathione precursor

Limits the formation and accumulation of NAPQI
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Powerful anti-inflammatory and antioxidant effects

IV infusion or oral tablets (also oral methionine)
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150mg/Kg over 15 min; 50mg/Kg over next 4 hrs;
100mg/kg over next 16 hrs up to 36hrs
Beyond 8 hours, NAC efficacy progressively decreases
S/Es nausea, flushing, urticaria, bronchospasm,
angioedema, fever, chills, hypotension, hemolysis and
rarely, cardiovascular collapse
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Paracetamol overdose treatment
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At the end of NAC infusion, a blood sample should be taken
for determination of the INR, plasma creatinine and ALT.
If any is abnormal or the patient is symptomatic, further
monitoring is required and advice sought from the NPIS
Patients with normal INR, plasma creatinine and ALT and
who are asymptomatic may be discharged from medical
care.
They should be advised to return to hospital if vomiting or
abdominal pain develop or recur
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Indications for liver
transplantation
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Liver transplantation is life-saving for fulminant hepatic
necrosis
The indications for liver transplantation are:
1 - Acidosis (pH < 7.3), or
2 - PT > 100 sec
3 - Creatinine > 300 mcg/l
4 - Grade 3 encephalopathy (or worse)
It is better to contact the local liver transplant centre earlier
than this.
Grossly abnormal prothrombin times should trigger referral:
PT > 20 sec at 24 hr
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PT > 40 sec at 48 hr
Alcohol poisoning

Clinical features of acute alcohol poisoning include:

Ataxia and anaesthesia leading to accidental injury

Dysarthria and nystagmus
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Drowsiness which may progress to coma

Inhalation of vomit which can be fatal & should be
prevented

Hypoglycaemia in children and some adults

Check BG TEST and give 50% glucose i.v. if required
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Coma (alcohol induced)

1.
2.
3.
4.
5.
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In cases of alcohol induced coma exclude:
Coincident head injury
Hepatic failure
Meningitis
Wernicke’s encephalopathy
Other associated drug ingestion
A blood test will confirm substantial levels of alcohol
Rule out alcoholic hypoglycaemia
The airway and circulation must be maintained
But glucose- containing fluids may precipitate Wernicke's
encephalopathy
Thiamine should given to all
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Intravenous naloxone has reversed coma in a proportion of
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