Management of

overdose and
poisoning
Paula Jerrard-Dunne

Pharmacology & Therapeutics

2006

General- evaluation

recognition of poisoning
identification of agents involved
assessment of severity
prediction of toxicity

General- management

provision of supportive care

prevention of poison absorption
enhancement of elimination of
poison
administration of antidotes

Supportive care

ABC
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

History

Pill bottles
Alcohol
Drug history including access
Remember OTC drugs
Suicide note
National Poisons Information
Centre *

Examination

Physiologic excitation
anticholinergic, sympathomimetic, or 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

Drug detection

Drug levels

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

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 (eg, theophylline, phenobarbital,
carbamazepine, aspirin, sustained-release products)
not effective for cyanide, mineral acids, caustic alkalis,
organic solvents, iron, ethanol, methanol poisoning,
lithium

Elimination of poisons
Renal elimination

Medication to stimulate urination or defecation may be given t

try to flush the excess drug out of the body faster.

Forced alkaline diuresis

Infusion of large amount of NS+NAHCO3

Used to eliminate acidic drug that mainly excreted by the kidn
eg salicylates
Serious fluid and electrolytes disturbance may occur
Need expert monitoring

Hemodialysis or haemoperfusion:

Reserved for severe poisoning

Drug should be dialyzable i.e. protein bound with low volume o
distribution
may also be used temporarily or as long term if the kidneys are
ar
damaged due to the overdose.

Antidotes

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?

Specific overdoses

Opiates

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

Elimination half-life of naloxone is only 60 to 90

minutes

Repeated administration/infusion may be necessary

S/E BP changes; arrhythmias; seizures; withdrawal

Benzodiazepines

Antidote flumazenil

MOA: Benzodiazepine antagonist

IV administration 0.2 mg over 15 sec to max

3mg

S/E N&V; 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

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

TCAD overdose
clinical features

Arrhythmias
- widening of PR, QRS, and QT intervals;
heart block; VF/VT

Hypotension

Anticholinergic toxicity
- hyperthermia, flushing, dilated pupils,
intestinal ileus, urinary retention, sinus tachycardia

Confusion, delirium, hallucinations

Seizures

Diagnosis

History

Blood/urine toxicology screen

Levels not clinically useful

TCAD overdose -Treatment

ABC many require intubation

Consider gastric lavage if taken < 2hrs
Activated charcoal
Treatment of hypotension with isotonic saline
Sodium bicarbonate for cardiovascular toxicity
Alpha adrenergic vasopressors (
norepinephrine ) for hypotension refractory to
aggressive fluid resuscitation and bicarbonate
infusion
Benzodiazepines for seizures

Sodium Bicarbonate in TCA

overdose

Hypertonic sodium bicarbonate (NaHCO3)

- QRS widening >100 msec; ventricular
arrhythmias, and/or refractory hypotension

serum pH promotes protein binding and free drug

concentrations; narrows the QRS complex, systolic blood
pressure, and controls ventricular arrhythmias

1 to 2 meq/kg (two to three 100 mL ampules of 8.4 percent

NaHCO3) rapid IV push large bore IV then infusion if working

reasonable goal pH is 7.50 to 7.55 then taper dose

S/E Volume overload, hypernatreamia, and metabolic alkalosis

Special Cautions in TCAD

overdose

Class IA and IC antiarrhythmic agents are

contraindicated eg quinidine;disopyramide,
flecainide; propafenone

Class IB Lignocaine, phenytoin used

Phenytoin may precipitate arrhythmias

Magnesium may be useful

Flumazenil must not be given

Salicylate overdose

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

Salicylate levels

Plasma salicylate concentration

Rapidly absorbed; peak blood levels usually occur

within one hour but delayed in overdose 6-35 hrs

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)

Salicylate overdose

Inhibition of cyclooxygenase results in decreased synthesis of

prostaglandins, prostacyclin, and thromboxanes
Stimulation of the chemoreceptor trigger zone in the medulla
causes nausea and vomiting
Direct toxicity of salicylate species in the CNS, cerebral edema,
and neuroglycopenia
Activation of the respiratory center of the medulla results in
tachypnea, hyperventilation, respiratory alkalosis
Uncoupled oxidative phosphorylation in the mitochondria
generates heat and may increase body temperature
Interference with cellular metabolism leads to metabolic acidosis

Clinical features

Early symptoms of aspirin toxicity include

tinnitus, fever, vertigo, nausea,
hyperventilation, vomiting, diarrhoea

More severe intoxication can cause altered

mental status, coma, non-cardiac pulmonary
oedema and death

Metabolic
abnormalities

Stimulate the respiratory center directly, early fall in the PCO2

and respiratory alkalosis

An anion-gap metabolic acidosis then follows, due to the

accumulation of organic acids, including lactic acid and ketoacids

Mixed respiratory alkalosis and metabolic acidosis with anion

gap

Arterial Ph variable depending on severity

Metabolic
abnormalities

Metabolic acidosis increases the

plasma concentration of
protonated salicylate

thus worsening toxicity by

allowing easy diffusion of the
drug across cell membranes

Salicylate overdose treatment

directed toward increasing systemic pH by the

administration of sodium bicarbonate

IV fluids +/- vasopressors

Avoid intubation if at all possible ( acidosis)

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

Alkalinization of plasma and

urine

Alkalemia from a respiratory alkalosis is not a

contraindication to sodium bicarbonate therapy

A urine pH of 7.5 to 8.0 is desirable

Blood gas analysis every two hours

Avoid severe alkalemia (arterial pH >7.60)

Haemodialysis - indications

Altered mental status

Pulmonary or cerebral edema

Renal insufficiency that interferes with salicylate excretion

Fluid overload that prevents the administration of sodium

bicarbonate

A plasma salicylate concentration >100 mg/dL (7.2 mmol/L)

Clinical deterioration despite aggressive and appropriate

supportive care

Paracetamol

Widely available

Potential toxicity underestimated

Toxicity unlikely to result from a single dose of less than

150 mg/kg in child or 7.5 to 10 g for adult

Toxicity is likely with single ingestions greater than 250

mg/kg or those greater than 12 g over a 24-hour period

Virtually all patients who ingest doses in excess of 350

mg/kg develop severe liver toxicity unless appropriately
treated

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

Acute alcohol ingestion is not a risk factor for

hepatotoxicity and may even be protective by
competing with acetaminophen for CYP2E1

Clinical features

Stage I (0.5 to 24 hours)

No symptoms; N&V Malaise

Stage II (24 to 72 hours)

Subclinical elevations of hepatic aminotransferases (AST, ALT)
right upper quadrant pain, with liver enlargement and tenderness.
Elevations of prothrombin time (PT), total bilirubin, and oliguria and
renal function abnormalities may become evident

Stage III (72 to 96 hours)

Jaundice, confusion (hepatic encephalopathy), a marked elevation in
hepatic enzymes, hyperammonemia, and a bleeding diathesis
hypoglycemia, 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

Paracetamol overdose

The risk of toxicity is best predicted by relating the time

of ingestion to the serum paracetamol concentration

The dose history should not be used as studies have

found no correlation

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

Paracetamol overdose
treatment

Activated charcoal within four hours of

ingestion

May reduce absorption by 50 to 90

percent

Single oral dose of one gram per

kilogram

Inhibits absorption of oral methionine

N-acetylcysteine

Antidote MOA: a glutathione precursor

Limits the formation and accumulation of NAPQI

Powerful anti-inflammatory and antioxidant effects

IV infusion or oral tablets (also oral methionine)

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

Paracetamol overdose
treatment

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

Indications for liver

transplantation

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
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

Drowsiness which may progress to coma

Inhalation of vomit which can be fatal & should be prevented

Hypoglycaemia in children and some adults

Check BM stix and give 50% glucose i.v. if required

Coma (alcohol induced)

1.
2.
3.
4.
5.

In cases of alcohol induced coma exclude:

Coincident head injury
Hepatic failure
Meningitis
Wernickes 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
Intravenous naloxone has reversed coma in a proportion of