COMMON DRUG AND PLANT POISONING

DR.ZAHEEN ZEHRA 1ST YEAR MD PAEDIATRICS.

Topics of Discussion

• Drugs commonly used.• Drugs of Abuse.• Plant Poisoning.

PRE TEST• What is the toxic substance which

Acetaminophen is metabolized into?• What is the Antidote for Iron Poisoning?• Name some plant poisons• Antidote for yellow Oleander Poisoning.• Toxic dose of Paracetamol.• What is the nomogram use to identify hepatic

toxicity in paracetamol poisoning?

Common Drug Poisoning

• Poisoning due to drug Ingestion has become very common.

• One of the most common emergencies in children presenting in the Emergency Room.

• Most of the drug poisoning is accidental and trivial but it can be life threatening sometimes.

Commonly Available Drugs

1. Acetaminophen.2. Iron3. Anticonvulsants.4. AntiHistamines.5. Miscellaneous

ACETAMINOPHEN• Acetaminophen, N-acetyl-para-aminopheno

is the most common Antipyretic and Analgesic.

• Therapeutic dose: 10-15mg/kg every 4 hours. Max-60mg/kg/day.• Toxic dose- 150mg/kg• 150micrograms/mL at 4 hours after ingestion

is Hepatotoxic in 25% (therapeutic levels-10-30micrograms/ml)

ACETAMINOPHEN-Pathophysiology

• 95% of acetaminophen gets metabolised in Liver.

• PCM Liver Non Toxic Glucoronide and Sulphate Conjugates.

• PCM Cytochrome P450 system NAPQI• NAPQI+Glutathione Non Toxic Mercapturates• In overdose situations, glutathione is depleted,

and the excess NAPQI is toxic to hepatocytes, causing centrilobular necrosis.

• N-acetylcysteine (NAC) acts as a substitute for glutathione, and binds with NAPQI, therefore

blocking hepatocellular toxicity if initiated within 8–12 hours of ingestion.

CLINICAL FEATURES

INVESTIGATIONS• Elevated Aspartate Aminotransferase, Alanine

Aminotranferase(AST & ALT), Bilirubin, PT

• Baseline Electrolytes and Glucose

• Blood Levels: The Rumack-Matthew nomogram.

Only intended for use in patients who present within 24 hours of single acute acetaminophen ingestion with known time of ingestion.

MANAGEMENTPotentially toxic ingestions are defined as:1) a level above the “possible toxicity”

nomogram line2) the ingestion that is complicated by multiple

doses.3) the time course is not defined if reliable.

Management• Decontamination:1. GI decontamination is indicated in the first 1-2

hours after potentially toxic ingestions. 2. Activated charcoal (AC)- High affinity A single dose of AC 1g/kg orally or throughnasogastric tube is administered. 3. Gastric Lavage is indicated for multiple drug

ingestions- can be eliminated with early decontamination.

Management• Antidote Therapy:1. N-Acetyl Cysteine-indicated in any potentially toxic ingestion

or with evidence of hepatic injury (elevated AST/ALT,PT)2. NAC is most effective in the first 24 hours post-ingestion,

even if activated charcoal has been given. 3. NAC is administered orally or through nasogastric tube in

140 mg/kg initial loading dose, then 70 mg/kg q 4 hours for 18 total doses.

iv dose – dilute 20% NAC solution to a 3% solution with 5% dextrose

150 mg/kg over 60 minutes 50 mg/kg over next 4 hours 100 mg/kg over 16 hours

Management• Liver Transplantation:• Increasing PT on day 4, pH <7.30, PT >100

seconds, creatinine >3.4 mg/dl or hepatic encephalopathy at any time.

• Supportive Treatment:1. Intergral Part of Management.2.Rehydration and maintenance fluids are

indicated for the severely vomiting and/or anorectic patient.

3. Mental health evaluation- Suicidal Attempt

IRON

• Leading causes of non-intentional ingestion deaths in children.

• Readily available and bright coloured sugar coating.

• >60mg/kg of elemental Iron is toxic.• Persistent vomiting >4 times indicates serious

ingestion.

Pathophysiology

Two Mechanisms:

1. Direct caustic effects on the gastrointestinal mucosa.

2. Iron also has a direct cytotoxic effect on several tissues and organs, principally the liver, heart and lungs.

• Toxicity of iron depends on the elemental iron ingested.

Eg: Ingestion of 20 tabs of 325 mg ferrous sulfate in a 15 kg child = 20 X [325 X 0.2 mg] = 1300 mg elemental Fe which is equal to 87 mg/kg.

• Ferrous sulphate -20% Ferrous gluconate -12% Ferrous fumarate -33% Ferric phosphate -37% Ferric pyrophosphate-

12% Ferroglycine sulfate -16%

• Toxicity of Iron by blood level:

Serum Iron (mcg/dL)

Level of Toxicity

50 – 150 mcg/dL Normal serum iron concentration

<300 Non-toxic300 – 500 Mild500 – 1000 Moderate: Highly associated with Toxicity

>1000 Severe: Death if Untreated

CLINICAL FEATURES

INVESTIGATIONS• CBC: Total leucocyte count more than 15,000• CBG, Serial ABG.• Serum iron levels.

•Radio opaque material found in an x ray within 2 hours of ingestion.

MANAGEMENT

• Any symptomatic patient requires treatment.• Decontamination:1. Gastric Lavage.2. Activated charcoal: does not bind iron.3. Whole bowel irrigation is contraindicated with

severe GI haemorrhage or perforation.4. Hemodialysis is not effective for free iron.

Antidote/Specific Therapy1. Desferoxamine is an iron chelating agent• Serum iron levels less than 300 mcg/dL usually

do not warrant therapy.• A symptomatic patient with serum iron 300 –

500 μg/dL, needs chelation therapy.• A level more than 500 mcg/dL should be

chelated even if asymptomatic. IV dose is 15 mg/kg/hour for 4 – 6 hour or

until the patient stabilizes, then 6 mg/kg/hour.

• Vin Rose Urine: Desferoxamine causes urine to change to

vin rose colour in presence of iron toxicity.

ANTICONVULSANTS

• Phenytoin. • Phenobarbital. • Valproic acid.• Carbamazepine.

CLINICAL FEATURES

• Phenobarbital- Respiratory Depression,

Hypothermia, Vesicular rash.

• Phenytoin- Ataxia, Nystagmus.

• Carbamazepin- Anticholinergic effects.

• Valproate- Hepatotoxicity and encephalopathy

INVESTIGATIONS• ABG, CBC, electrolytes, urinalysis, hepatic

enzymes and CPK.• Phenytoin sodium:o Therapeutic levels: 10 – 20 μg/mL. o Ataxia and nystagmus occur at >30μg/mL. o Easily available OTC drug.o Most Notorious Anticonvulsant.

INVESTIGATIONS

• Valproic acid: Therapeutic levels: 50–100 μg/mL.

• Phenobarbital: Therapeutic levels range from 15 to 40 μg/mL.

Sedation to coma is common above 70 μg/mL level. Reversible “flat line” EEG may be seen over 120 μg/mL.

MANAGEMENT• Decontamination: 1. Gastric lavage is indicated for recent

ingestions.2. Single dose charcoal is indicated for all.

Multidose charcoal is effective in phenobarbital, phenytoin and carbamazepine

The first dose should be given in the dose 1g/kg NG or P.O. Repeat charcoal doses of 0. 5g/kg once in every 2-4 hours

ANTIHISTAMINES

• Neurotoxicity.• Anticholinergic effects.• Arrhythmias- QT prolongation and Ventricular

arrhythmias.

MANAGEMENT• Decontamination: Gastric lavage is indicated

for recent ingestions with potential for altered mental status. Activated charcoal is used as single dose for non-sustained release preparations and multi-dose charcoal for slowed gastric motility or sustained release ingestions.

• Supportive Care. • Physostigmine for severe anticholinergic

toxicity

Beta Adrenergic Agonist

• ß-adrenergic agonist toxicity is dose dependent

• Ingestion of <1 mg/kg of salbutamol is non-toxic.

• Up to 20 times the normal daily dose of salbutamol has been ingested without serious medical complications or death.

• Rapidly absorbed, and toxic effects are seen within an hour of ingestion.

EFFECTS

• ß1 Receptors -found on the heart.• ß1 effects-tachycardia, Increased cardiac

contractility, tremor, agitation, vomiting.

• Β2 Receptors - found in blood vessels, lungs and pancreas.

• ß2 effects-peripheral vasodilatation, tachycardia, widened pulse pressure, tremor, hypokalemia and hyperglycemia.

BETA ADRENERGIC AGONIST

• GI decontamination is usually not necessary.• Not needed if patient has already vomited. • Activated charcoal may be used if child arrives

early.• Use of ß-adrenergic blockers has been

suggested as helpful in patients with severe toxicity, but rarely used.

Methemoglobinemia• Hemoglobin with the iron oxidized to ferric state

from normal ferrous state.• Consequences: Decreased oxygen binding and impaired O2

transport to tissues. Agents causing methemoglobinemia can also

cause hemolysis.• Drugs causing methHb: Chloroquine, dapsone, LA, High doses of

methylene blue, metoclopramide, naphthalene, nitrites, toluidine.

METHEMOGLOBIN % CLINICAL FEATURES TREATMENT

<30% No symptoms ,mild acrocyanosis

Observation ,no tretament required

30-55% Poorfeeding , lethargy , irritability . The older child maycomplain of fatigue , dizziness , headaches and weakness

Iv methylene blue 1-2 mg/kg/30-60 minutes for severe cyanosis(max 7mg/kg) or methaemoglobin <30% or clinically better

55-70% Respiratory depression, cardiac arrhythmias, seizures and coma.

Methylene blue as above exchange transfusion, hyperbaric oxygen.

>70% Potentially lethal Methylene blue, exchange transfusion, hyperbaric oxygen.

OTHER COMMON DRUG POISONING• Antipsychotics.• Beta blockers.• Benzodiazepines.• Carbon monoxide.• Calcium channel blockers.• Isoniazid.• Lead,mercury• Lithium.• Drugs causing Methemoglobinemia.• Oral Antidiabetic drugs

Common Antidotes TOXIN ANTIDOTE

Benzodiazepines Flumazenil

Valproate L- Carnitine.

Opiates Naloxone

Beta-Blockers Glucagon

Calcium channel blockers Calcium, glucagon, insulin and glucose

Carbon monoxide Oxygen

Cyanide Amyl nitrate, sodium nitrate, sodium thiosulfate

Lead EDTA (Ethylenediaminetetraacetic acid)

Digitalis F(AB) fragments.

COMMON PLANT POISONS• Cleistanthus• Oleander• Datura• Abrus precatorius.• Jatropha• Cerbera Odollam.• Vasambu.

PLANT PART OF THE

PLANTEFFECTS TREATMENT

Cleistanthus (Oduvanthalei, Nillipillai)

All parts Hypokalemia, Persistent metabolic aciosis,RTA

Supportive, Correction of electrolytes.

Yellow Oleander (Arali)

Seeds Cardiac Toxicity Digoxin speific antibody fragments.

Datura (Vellai Umathai)

Seeds and Fruits Anticholinergic effects

Physostigmine

Abrus precatorius (Gundumani)

All parts.Crushed Seeds

GI Toxicity Decontamination, Supportive care.

Jatropa (Kattamanakku)

Seeds (Sweet taste of seeds)

GI symptoms (OPC) Decontamination, Supportive care.

THANK YOU

• NAPQI• Deferoxamine.• Yellow oleander, Datura, Jatropa.• Digoxin speific antibody fragments• >150mg/kg• Rummack Mathew Nomogram.