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Toxicology

gmch.gov.in/e-studyMathieu Orfila

Dr .Shabbir2nd year PG

MD Emergency Medicine

• Toxicology is "the science of poisons.“

• "the study of the adverse effects of chemicals or physical agents on living organisms".

• Mathieu Orfila is considered the modern father of toxicology.

• Ecotoxicology: It is concerned with the toxic effects of chemical and physical agents on living organisms, especially in population and communities within defined population.

• Environment toxicology• Forensic toxicology• Medical toxicology• Aquatic toxicology• Entomotoxicology: is the analysis of toxins in

arthropods (mainly flies and beetles) that feed on carrion.

Poison

• A Poison is defined as any substance ( solid, liquid or gaseous) which when administered in living body through any route (Inhalation, Ingestion, surface absorption etc) will produce ill health or death by its action which is due to ‐its physical, chemical or physiological properties

• A toxic substance is simply a material which has toxic properties.

• A toxic agent is anything that can produce an adverse biological effect.

Classification of poisons

1. According to the site and mode of action (A) LOCAL ACTION

Corrosive :

Strong Acid: mineral acid: eg H2SO4, HCl: organic acid: Carbolic,oxalic,acetic,

salicylicStrong alkali: Hydrates and

carbonates of Na, K, & ammonia

Metallic salts: Mercuric Chloride, KCN

Irritant

1) Agricultural2) InorganicNonmetallic: P, Iodine, Cl, bromineMetallic: Arsenic, Antimony, Pb, Cu,

ZincMechanical: Glass, Diamond dust, Hair3) OrganicAnimal: Snakes, insects CantharidesVegetable: Abrus, Castor,

Croton,Calotropis

(A) LOCAL ACTION

• 1) Cerebral i. Somniferous: opium and its alkaloids, Barbiturates. ii. Inebriant (Intoxicant): Alcohol, ether, Chloroform.iii. Psychotropic: AD: TCAD, Amphetamines, Caffeine, MAOI Neuroleptics: Phenothiazenes, thioxanthenes Hallucinogens: LSD, Phencyclidine, psilocybe iv. Deliriant: Dhatura, Belladona, cannabia Indica. vi. Hallucinogens

2) Spinal i . Strychnos Nux Vomica

3) Peripheral Nerves i. Local Anaesthetics: Cocaine, Procaine.ii. Relaxants (curare)

2. Classification of Poison according to motive or nature of use:

1. Homicidal: Arsenic, Aconite, Digitalis, Abrus Precatorius, Strychnos nux vomica.

2. Suicidal: Opium, Barbiturate, Organophosphorus, carbolic acid, copper sulphate.

3. Accidental: Aspirin, organophosphorus, copper sulphate, snakes bite, Ergot, CO, CO2, H2S.

4. Abortifacient: Ergot, Quinine, Calotropis,.

5. Stupefying agent: Dhatura, cannabis, chloral hybrate.

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MANAGEMENT OF POISON

Journal of Indian Academy of Clinical Medicine Vol. 5, No. 2

1. Resuscitation and initial stabilization2. Diagnosis of type of poison3. Nonspecific therapy4. Specific therapy5. Supportive care

1. Resuscitation and initial stabilization

• Airway • Breathing • Circulation (consider stabilizing the C-spine) • D1 Drugs• ACLS as necessary to resuscitate the patient • universal antidotes • D2 Draw bloods• D3 Decontaminate• Expose (look for specific toxidromes)/Examine the Patient • Full vitals, ECG monitor, Foley, x-rays, etc... • Give specific antidotes

2. Diagnosis of type of poison

• History : • Examination :-head-to-toe• Laboratory Investigations :

Examination– signs of trauma – signs of seizures– signs of infection

(meningitis) – signs of chronic alcohol

abuse – signs of drug abuse– mental status

• Specific toxidromes

Toxidrome

• A toxidrome is a constellation of findings, either from the physical examination or from ancillary testing, which may result from any poison.

• The term was coined in 1970 by Mofenson and Greensher.

Narcotics, Sedatives/Hypnotics, Alcohol Overdose

• signs and symptoms – hypothermia – bradycardia – hypotension – respiratory depression – dilated/constricted pupils – CNS depression

Sympathomimetics

❏ signs and symptoms• increased temperature• CNS excitation (including seizures)• tachycardia• nausea and vomiting• hypertension• diaphoresis• dilated pupils

Drug / Substance Withdrawal

• withdrawal state generally opposite to the physiological effect of the drug signs and symptoms of sedative withdrawal

• increased temperature ,agitation• tachycardia• tremor• hypertension•hallucinations• dilated pupils•seizures• diaphoresis

Cholinergic

• signs and symptoms (DUMBELS) – Diaphoresis, diarrhea, decreased blood pressure – Urination – Miosis – Bronchorrhea, bronchospasm, bradycardia – Emesis, excitation of skeletal muscle – Lacrimation – Salivation, seizures

Anticholinergics

❏ signs and symptoms

• hyperthermia

• dilated pupils• decreased sweating

• vasodilatation

• agitation– tachycardia – hypo/hypertension – Pralytic ileus – urinary retention

Extra pyramidal

❏ signs and symptoms• dysphonia• rigidity and tremor•dysphagia• torticollis•laryngospasm• trismus ,oculogyric crisis drugs – major tranquilizers

Use of the Clinical Laboratory in the Initial Diagnosis of Poisoning

Test Finding Selected Causes

ABGs hypoventilation (elevated Pco2) CNS depressants (opioids, sedative-hypnotic agents phenothiazines, and EtOH)

hyperventilation Salicylates, CO, other asphyxiantselectrolytes anion-gap metabolic acidosis “A MUDPILE CAT”

hyperkalemia digitalis glycosides, fluoride, potassiumhypokalemia theophylline, caffeine, beta-adrenergic agents,

soluble barium salts, diureticsglucose hypoglycemia oral hypoglycemic agents, insulin, EtOHosmolality elevated osmolar gap EtOH, methanol, ethylene glycol, isopropyland osmolar gap alcohol, acetone

ECG wide QRS complex TCAs, quinidine, other class Ia and Icantiarrhythmic agents

prolongation of QT interval quinidine and related antiarrhythmics,terfenadine,astemizole

atrioventricular block calcium antagonists, digitalis glycosides,phenylpropanolamine

Abdominal x-rayradiopaque pills or objects Calcium, Chloral hydrate, CCl4, Heavy metals,

Iron, Potassium, Enteric coated, Salicylates,serum elevated level (>140 mg/lacetaminophen 4 hours after ingestion) Acetaminophen (may be the only clue to a recent

ingestion)

3. Nonspecific therapy

• Gastric Decontamination- emesis, gastric lavage, and use of activated

charcoal and cathartics• Whole bowel irrigation• Enhancing Excretion- Forced alkaline diuresis- Dialysis : Peritoneal and haemodialysis

4.Specific therapy

5. Supportive care

• most cases of poisoning is largely supportive.• It is important not to waste time in locating an

antidote.• preserve the vital organ functions till poison is

eliminated.• proper care for coma, seizures, hypotension,

arrhythmias, hypoxia, and acute renal failure.

CLINAL TOXICOLOGY

Emergency Medicine

Type of poison consumed

Al-Ameen Medical College, Bijapur, KARNATAKA, JAN1015-DEC2016

Type of poison consumed

SDM MEDICAL COLLEGE, DHARWAD, KARNATAKA, AUG2011-JULY2012

Number of drugs Frequency Percentage

Benzodiazepine 9 22.5%

Antiepileptic 6 15.0%

NSAIDS 5 12.5%

Antihypertensive 5 12.5%

Unknown 5 12.5%

Oral hypoglycaemic agent 4 10.0%

Tricyclic antidepressant 3 7.5%

H2blocker/PPI 1 2.5%

Anticholinergic 1 2.5%

Oral iron 1 2.5%

Antihistamine 1 2.5%

Thyroid drugs 1 2.5%

Antipsychotic 1 2.5%

DRUG OVERDOSE

KIMS MEDICAL COLLEGE , BANGALORE

PESTICIDES POISON

http://www.insecticidesindia.com/Insecticides.htm

ORGANOPHOSPHATE POISONING

• Organophosphates (pesticides and nerve agents) irreversibly bind and deactivate cholinesterases, including acetylcholinesterase.

• Acetylcholine accumulates at neural synapses, causing central and peripheral cholinergic overdrive.

• Mortality is secondary to respiratory failure: Weakness of respiratory muscles

Bronchorrhea and bronchoconstriction Central depression of respiratory drive

Pediatric Considerations

• Symptoms are difficult to differentiate in toddlers

• Common symptoms: Miosis, salivation, and muscle weakness

• Seizure activity in 25% of pediatric cases:• Only 3% in adults

Classic presentation: Cholinergic toxidrome:

DUMBELS:• Diarrhea/diaphoresis• Urination• Miosis/muscle fasciculations• Bradycardia, bronchorrhea, bronchospasm• Emesis• Lacrimation• SalivationMay have garlic odor

• CNS: Muscle fasciculation then flaccid paralysis, Respiratory muscle weakness ,In coordination and ataxia, Agitation,Tremors, Confusion

• Visual: Pinpoint nonreactive pupils• Respiratory: Respiratory muscle weakness.

Bronchorrhea• Cardiovascular: Bradycardia• GI: Nausea/vomiting,Abdominal cramps

ESSENTIAL WORKUP

• Obtain original container if suicide attempt.• Look for parasympathetic and CNS signs with

muscle weakness or paralysis.

DIAGNOSIS TESTS

• RBC and plasma cholinesterase levels to confirm diagnosis:

• RBC (true) cholinesterase level is best for synaptic inhibition .

• Plasma (pseudo)cholinesterase level not as reliable but more timely:

• These are markers for poisoning• Depending on the agent and the patient, these

levels may vary

• CBC, electrolytes, glucose, BUN, creatinine• ABG when respiratory symptoms are present.• CXR if respiratory difficulty is present.• ECG• CT scan of head for altered mental status

when diagnosis is uncertain,

TREATMENTPRE HOSPITAL • Decontamination is initial priority:• Remove all clothes and store as toxic waste• Decontaminate skin with soap and water:• INITIAL STABILIZATION/THERAPY• Maintain airway and oxygenate.• For unstable airway, intubate, and ventilate.• IV access with D5W 0.9% NS• Altered mental status: Administer thiamine, glucose,

and naloxone

ED TREATMENT

• Atropine: Administer test dose 1–2 mg IV/IM:• No clinical response: Double dose q5min until

muscarinic findings subside• Dose: 1–4 mg IV q5min (peds: 0.05–0.2 mg/kg)• Pralidoxime: 1–2 g (peds: 25–50 mg/kg)

dissolved in 0.9% NS over 30 min IV; , then q6h as needed:

FOLLOW-UPAdmission Criteria• ICU admission for any exposure confirmed with atropine

response.• Any symptomatic patient should be admitted for monitoring.• Avoid opioids, phenothiazines, and antihistamines; these

may potentiate toxicity of organophosphates.

Discharge Criteria• Asymptomatic for 6–12 hr after exposure• Ensure close reliable follow-up and specific instructions when

to return for evaluation.

Aluminum phosphide poisoning

Indian Journal of Critical Care Medicine February 2015 Vol 19 Issue 2

• Aluminum phosphide poisoning is known worldwide, especially in developing countries like India and Iran,

• Lethal dose of ALP is 1–1.5 g. Deaths are reported even with a dose of 150–500 mg.

• ALP, when ingested, liberates a lot of phosphine gas. Phosphine leads to noncompetitive inhibition of the cytochrome oxidase of mitochondria, blocking the electron transfer chain and oxidative phosphorylation, producing an energy crisis in the cells

• .

• severe toxicity of ALP particularly affects the cardiac and vascular tissues, which manifests as profound and refractory hypotension, congestive heart failure, ECG abnormalities, myocarditis, pericarditis and subendocardial infarction.

• The frequency of hypotension varied from 76% to 100%, which is a cardinal feature in ALP toxicity.

• Cardiac arrhythmias,[7] respiratory failure and requirement of mechanical ventilation[7,8] are poor prognostic markers with ALP poisoning.

• Metabolic acidosis is again common probably due to the accumulation of lactic acid caused by blockage of oxidative phosphorylation and poor tissue perfusion.

Zinc phoshide

Introduction

• Zinc phosphide is a highly effective rodenticide.

• It is a crystalline, dark grey powder mixed into food as rodent bait. Also

• Available as pellet.• It is also used widely to protect grain in stores

and during transportation

Mechanism of action

• Zinc phosphide ingested orally reacts with water and acid in the stomach and produces phosphine gas.

• Phosphine acts by disrupting mitochondrial function through blocking cytochrome C oxidase.

• Phosphides produce toxicity rapidly, generally within 30 min of ingestion; and death may follow in less than 6 h.

• Phosphide ingestions over 500 mg are often fatal .

c/f:• profuse vomiting and abdominal pain are

often the first symptoms . Respiratory signs and symptoms include tachypnea, hyperpnea, dyspnea, cough and chest tightness .

• Hepatomegaly, raised transaminases, hepatic failure, severe hypoglycemia or severe metabolic acidosis with acute distal renal tubular acidosis.

• Complete blood count (CBC) , Glucose,ECG Electrolytes, Pregnancy tests - In women of childbearing age, LFT

• PT, Aptt, INR with blood grouping and Rh typing

• repeat PT- INR measurements 24 and 48 hours post ingestion to ensure that no effects on the coagulation pathway are present.

• If a coagulopathy is documented -vitamin K, fresh-frozen plasma may be needed to rapidly reverse anticoagulation

• ASPTAMATIC CASE– SUPPORTIVE CARE.

Pyrethroid toxicitY

• Pyrethroids are insecticides that are synthetic modifications of natural pyrethrins.

• Pyrethroids have a very high “selective toxicity” for insects compared to mammals, which is due to higher insect nerve sensitivity.

• Pyrethroids ,relatively low toxicity, compared to organophosphate .

• Pyrethroids are ion channel toxins,• neuronal voltage-sensitive sodium channels ,• delay their closure and thereby prolonging

neuronal excitation

Clinical features

Treatment• There is no antidote for pyrethroid poisoning.

• Treatment consists in preventing further exposure together with supportive and symptomatic measures.

• In case of dermal exposure rinse the skin with abundant water and soft detergents.

• After accidental ingestion administer activated charcoal (2g/kg), • Spasms can be treated with anticonvulsants (e.g. diazepam). If ineffective,

fenobarbital or pentobarbital can be tried.

• Hypersalivation can be treated with atropine.

CORROSIVE POISONING

• Corrosives are a group of chemicals that have the capacity to cause tissue injury on contact by a chemical reaction.

• They most commonly affect the GI tract , respiratory system and eyes.

• The estimated prevalence of corrosive poisoning is 2.5-5% while the morbidity is above 50% and the mortality is 13%.

Indian Journal of Clinical Practice, Vol. 23, No. 3, August 2012

• Acids• Car battery fluid (sulfuric acid)• Descalers (hydrochloric acid)• Metal cleaners (nitric acid)• Rust removers (hydrogen fluoride)• Alkalis• Bleach (hypochlorite)• Sodium hydroxide (liquid lye)

Uses of Common Caustic Agents

• Hydrochloric acid-metal/toilet bowl cleaner• Sulfuric acid-automobile batteries• Sodium hydroxide-paint remover/drain

cleaner• Phenol-antiseptic

Factors Determining Corrosiveness

• Physical form: Solid/liquid• Duration of contact with tissue• Concentration of agent• Quantity of agent• pH of agent: pH <2 and >11 are more corrosive• Food: Presence or absence of food in stomach

Mechanism of Action of Corrosive Agents

• Alkali ingestion: Causes liquéfaction necrosis. • Acid ingestion: Causes coagulation necrosis.

• Both acids and alkalis cause fibrosis and cicatrisation (stricture formation).

Consequences of Ca ustic Injury

• Necrosis: Occurs within seconds of exposure to caustic agent

• Ulceration and perforation: Occurs within 24-72 hours of exposure

• Fibrosis: Occurs within 14-21 days of exposure• Stricture: Occurs after weeks to years of

exposure• Carcinoma formation: Occurs after decades of

alkali exposure.

Cl inical Presentation in CorrosivePoisoning

GIT• Severe pain of lips, mouth, throat, chest and• abdomen• Excessive salivation• Dysphagia and odynophagia• Epigastric pain and hematemesis• Symptoms and signs of GI perforation

• Respiratory system• Cough• Dyspnea• Bronchoconstriction• Pulmonary edema• Chemical pneumonitis

• Eyes and skin• Pain at the site of exposure• Burns at the site of exposure• Erythema and vesicle formation

Investigations

• Hemogram• Serum electrolytes: Hypocalcemia can occur with• hydrogen fluoride poisoning.• Blood grouping and cross-matching• Renal function tests• Liver function tests• Coagulation profile• Arterial blood gas analysis

Radiology

• Chest X-ray: The radiographic signs of early mediastinal leaks are usually subtle. However,

chest X-ray helps in detection of pneumothorax, pneumomediastinum and pleural effusion. Air under the diaphragm is suggestive of visceral perforation. A lateral view is more sensitive than PA view for detecting intraperitoneal air.

• Abdominal X-ray: detection of pneumoperitoneum.

• Contrast studies: Barium studies have low sensitivity in detecting perforation and high-risk of aspiration and inflammation.

• CT scan: CT scan of neck/chest/abdomen should be considered if there is a high-risk of suspicion for perforation despite negative plain X-rays.

• Contrastenhanced CT (CECT) is used to assess esophageal wall thickness, which can be used to predict the response to dilatation of stricture and the number of sessions required to achieve adequate dilatation.

• CT studies done with water-soluble contrast will allow localization of leak of air.

Endoscopy -‘sine qua non’

• Indications for upper GI endoscopy -Corrosive ingestion by small children -Symptomatic older children and adults -Patients with altered mental status - Patients with intentional ingestion -Patients with ingestion of large volumes -Patients with ingestion of concentrated

products

Contraindications for upper GI endoscopy

• Hemodynamic compromise• Peritonitis and mediastinitis• Mild ingestion

• The commonest practice is to perform endoscopy on Day 1-2.

Zargar’s modified endoscopic classification

Management

• Early Admission• Within 48-72 hours of corrosive ingestion-

Upper GIendoscopy should be performed on Day 1-2.

• If endoscopy reveals only mild lesions, then the patient can be discharged.

• If severe lesions are found on endoscopy, then surgical gastrostomy is indicated.

• Delayed Admission• Within 72 hours to three weeks of corrosive

ingestion: No endoscopy is indicated. • Gastrostomy should be done if there is severe

dysphagia. • Endoscopy and dilatation of stricture (if

present) should be done three weeks after ingestion.

• Late Admission• More than three weeks of ingestion: Requires

endoscopy and dilatation of stricture. If the procedure is successful, then follow-up endoscopy should be done at one month. If the procedure is unsuccessful, then surgical gastrostomy is performed, which is followed by retrograde dilatation of stricture after 10 days of operation.

Clinical Approach

1. Asymptomatic patient: If there is history of minimal corrosive ingestion and no oropharyngeal burns on examination, then the patient requires only observation in the Emergency Room.

2. Symptomatic patient: If there is history of ingestion of large volume of corrosive along with signs like stridor, hoarseness of voice and respiratory distress, then the patient requires admission in intensive care unit (ICU).

• Protection of airway: presence of respiratory distress and airway edema , urgent endotracheal intubation.

• Supraglottic edema-cricothyrotomy or tracheostomy.

• Hemodynamic status:-done by replacement with crystalloid fluids.

• Decontamination: gastric emptying is contraindicated.

• Corticosteroids-no role of systemic steroids.• Antibiotics:not recommended prophylactically• Proton pump inhibitors (PPIs) and H2-blocker-

Stricture management

• Stricture formation begins weeks to months after injury

• Dilatation therapy: This is done 3-6 weeks after injury, progressively larger bougies are passed.

• Surgery: Esophageal strictures resistant to dilatation therapy may require surgery that includes resection