Clinical Toxicity

Poisons

• Poisons are substances administered either by mouth, injection, inhalation or through skin/mucous membrane and they produce harmful, dangerous or fatal symptoms in animals and human beings.

• Poisoning could be accidental, occupational, suicidal or criminal.

• Generally self-medication is an important cause of drug poisoning and is particularly seen with OTC drugs. Acute poisoning is generally observed with over use of drugs or insecticides and hence emergency treatment of acute poisoning is symptomatic.

Classification of Poisons

Poisons are classified into three main categories:1. Corrosives:Strong acids (H2SO4, HNO3,HCl)

Strong alkalis (caustic soda, caustic potash)2. Irritants:a) InorganicNon-metallic (P, Cl, Br, I)Metallic (heavy metals – As, Sb, Pb etc.)b) OrganicHerbal - castor seed, croton oil etc.Animal – snake venoms, cantharides c) Mechanical – diamond dust, grass powder.

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3. Neurotics:a) Cerebrali. Sleep causing (narcotics) opiums and its

derivatives.ii. Intoxicants – alcoholsiii. Anesthetics – ether, chloroformiv. Deliriant – datura, belladonnab) Acting on spinal cord – nux vomicac) Acting on cardiac system – digitalis, aconite, tobaccod) Poisons acting peripherally – CO2, CO, coal gas.

Toxins

• Toxin can be defined as an antigenic poison or venom of plant or animal origin, especially one produced by or derived from microorganisms and causing disease when present at low concentration in the body.

Toxins of Animal Origin

• Natural toxin of animal origin may be a product of metabolism or a chemical that is passed along the food chain. While poisoning after eating terrestrial animals is relatively uncommon, poisoning due to marine toxins occurs in many parts of the world.

• Marine toxins are usually produced by toxic microalgae and are accumulated in shellfish, crustacean and finfish following their consumption.

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• Tetrodotoxin, a potent marine neurotoxin, is thought to be produced by certain bacteria. It is found in over 90 species of puffer fish and may cause lethality after ingested even a small amount.

• Seafood poisoning commonly reported in coral reef fish is due to the presence of ciguatoxin that may be found in more than 300 species of fish. Histamine produced by bacterial spoilage of scombroid fish causes another kind of seafood poisoning.

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• There are approximately 1 200 species of poisonous and venomous animals in the world. While most of them are not used as food, care must be taken to avoid the poisonous glands or tissue containing the toxins when these animals are used as food.

• Glands of some animals that are not considered poisonous or venomous when ingested can also cause food poisoning such as gall-bladder of grass carp which contains the cyprinol related chemicals.

Poison Center

Poison centers are established for two reasons:• To provide rapid access to information

valuable in assessing and treating poisonings.

• To assist with poisoning prevention.

Role of Poison Center

Following are the roles performed by the poison centers:• Assess and treatment recommendations during

poisoning via 24-hour emergency telephone services

• Provide public and professional educational programs

• To collect data on poisonings• To perform research• Assist the public and health care providers during

hazardous material spills

General Treatment of Poisoning

The general treatment of poisoning can be described under the following headings_1. Immediate removal from the environment2. Emesis3. Gastric lavage4. Common antidotes5. Acceleration of elimination of poisons6. Treatment of general symptoms

1. Immediate removal from the environment

When poisoning appears to have occurred due to gases like carbon monoxide or from surface absorption, the patient must be immediately removed for fresh air.

2. EmesisEmesis plays very important role in poisoning with oral ingestion of some materials. The methods that are used to induce vomiting are as follows;i) Mechanicallyii) Ipecac syrup or powderiii) Mustard powderiv) 3 teaspoonful of salt in waterv) Apomorphine (6mg) causes prompt vomiting usually

within 3-5 minutes. But the disadvantages are that it should be administered parenterally and should never be used if the poison itself is a CNS depressant.

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Note: Vomiting should never be attempted in the following cases:i) Ingestion of corrosives (acids and gases) -

perforations may occur.ii) Kerosene oil – aspiration pneumonia may

occur.iii) Convulsant drug – vomiting may induce

convulsions.

3. Gastric Lavage

It is necessary if the poison is ingested. The poison is washed out by inserting catheter into alimentary canal upto stomach.Washings are usually done with:i) NaHCO3, 2gm in 300ml water

ii) 30gm MgSO4 or Na2 SO4 in ¼ liter water

iii) 100 ml liquid paraffin in 150ml water.iv) 8gm of activated charcoal in water.v) Use of emetics, e.g., common salt, ipecac powder, mustard

powder.

Note: It should never be attempted in drowsy or in coma patients because of risk of inhalation of stomach contents.

4. Common Antidotes

Following is a chart of common antidotes for various types of poisoning:

Drug Antidote Mechanism1. Acids (Corrosive)

Antacid or weak alkali (Milk of magnesia) [Avoid inducing emesis or gastric lavage]

Antagonism

2. Alkalis (Caustic)

Weak acid (Lemon juice or diluted vinegar)

Antagonism

3. Acetaminophen

Acetyl cysteine Restores depleted glutathione stores, protects against renal and hepatic failure

Drug Antidote Mechanism

4. Alkaloids (Nicotine, quinine, strychnine)

Potassium permanganate Antagonism

5. Aspirin Activated charcoal Adsorption

6. Hydrocarbons (Gasoline, kerosene etc.)

Mineral oil cathartics followed by lavage with sodium bicarbonate 1 to 2%

Antagonism

7. Iron salts Desferoxamine, sodium bicarbonate 1% lavage

Chelation of ferrous ions

Drug Antidote Mechanism

8. Arsenic, copper, lead, mercury

Penicillamine, dimercaprol Chelation

9. Methanol Sodium bicarbonate 3% lavage

Antagonism

10. Narcotics (opoid) Naloxone Competitive inhibitor at opoid receptor site

11. Lead Sodium-calcium edetate or Ca-EDTA

Chelation of lead ion

12. Phenol Vegetable oil (olive oil or castor oil) and lavage later on

Mechanical antidote

13. Unknown Activated charcoal Adsorption

5. Acceleration of elimination of Poison

Following methods are used to accelerate the elimination of poisoning; 1. Purgation2. Diuresis3. Dialysis4. Peritoneal dialysis5. Haemodialysis

Peritoneal Dialysis

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• Intravenous fluids are administered to excrete poisons. It should be kept in mind not to overhydrate the patient as it may lead to circulatory impairment or even pulmonary edema.

• Forced diuresis is done in amphetamine poisoning. • Peritonial dialysis involves instilling dialysis fluid into

peritonial cavity. Poison in the blood enters the dialysis fluid which is then drained and replaced.

• In Haemodialysis, a semipermeable membrane separates blood from dialysis fluid and poison passes passively from the blood, where it is present in high concentration into the fluid. It is useful for many poisons like barbiturates, bromides, boric acid, salicylates, digitalis and methyl alcohol.

6. Treatment for general symptoms

1. For increase in body temperature sponge with water.2. Morphine sulphate or pethidine relieves pain.

Abdominal pain can be relieved by atropine.3. Convulsions and restlessness can be controlled with

barbiturates.4. To overcome dehydration blood transfusion is

advised.5. In anaphylaxis, antihiatamine and corticosteroids with

adrenaline are used.6. For anaphylaxis, i.e., suffocation, cessation of

breathing, artificial respiration and oxygen through nasal catheter is useful.

Symptoms and Management of Poisoning case with Pesticide

Pesticides or insecticides are generally discussed as _1. Organo-phosphorus compounds- Hexaethyl tetraphosphate (HETP)- Tetraethyl pyrophosphate (TEPP)- Octamethyl pyrophosphamide (OMPA)

2. DDT3. Endrin

Cont…Organo-phosphorus compounds

Symptoms:

-Headache-Diarrhea-Malaise-Giddiness-Profuse sweating-Nausea-Vomiting-Abdominal cramp-Excessive bronchial secretion- Bradycardia

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Antidote: Anticholinergic, i.e., atropine to block the cholinergic reactions.Treatment: Treatment consists of,1. Decontamination: The patients must be

removed from the source of poison by washing the external surface and by inducing vomiting to remove ingested poison.

2. Respiration therapy: Artificial respiration is necessary in some cases. Sometimes suction is applied to cause hyperventilations.

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3. Antidote therapy:i) Atropine can antagonize the peripheral action of

organophosphoric compounds and is administered in dose of 2mg for every 15-30 minutes. IM or IV route is followed, sometimes the dose may be higher as per need of the patient.

ii) Another antidote pyridine-2-aldoxime methiodide is given in dose of 1 gm/IV or by infusion in saline. It is then repeated after half an hour if necessary. This is useful to prevent nicotinic symptoms.

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4. Administration of choline esterase reactivation: The oxime compounds like paralidoxime chloride and pyridine aldoxy methiodate are given. The dose of 1 to 2 gm/IV is for adults and 25-50 mg/kg for children. It is given as 5% solution in isotonic saline and repeated after every 12 hours of the day.

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DDT (Dichlorodiphenyltrichloroethane)Symptoms:- Excess of saliva- Paresthesias of tongue, lips face- Vomiting, irritability, tremors- Abdominal pain- Irritation od eyes- Blurring of vision- Cough- Pulmonary edema- Clonic and tonic convulsion- Hyper irritability- Paralysis of limb muscle are sometimes observed DDT in the dose of 150-1000 mg/kg body weight is a fatal dose.

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Treatment:1. Ingested material can be removed by gastric lavage and by

using saline cathartics.2. Adrenaline and its related compounds should never be used.3. Artificial respiration is required in some cases.4. Phenobarbitone in the dose of 100 mg recommended for

tremors along with some antibiotic.5. Wash the skin with soap and water.6. In chronic poisoning removing the patient from site.7. In case of liver/kidney damage a low fat, high carbohydrate

and protein diet is recommended.

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EndrinSymptoms:- Abdominal pain- Vomiting- Tremors- Convulsions- Occasionally blood stained from mouth and nostrilsConvulsion become severe if continued for a long time and followed by coma which may terminate in respiratory failure and ultimately death.The fatal dose is 6 gm.

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Treatment:1. It is always symptomatic (treatment of

general symptoms).2. Decontamination must be carried out.3. For convulsion barbiturates can be used.4. Calcium decrease toxicity of endrin.

Symptoms and Management of Poisoning case with Heavy Metals

Heavy metals block the body enzyme system as they from chelates with body enzymes.ArsenicSymptoms of acute toxicity:- Nausea- Cramps in legs- Dilated pupil- Vomiting- Diarrhea- Faintness- Pale anxious face- Malaria- Tachycardia- Burning pain in stomach- Dyspnea

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• Vomiting initially consists of stomach contents but later it becomes greenish or black in color due to the presence of bile. Diarrhea is complained and stool contain mucous tinged with blood.

• When arsenic dust is inhaled it may cause pulmonary edema, restlessness, cyanosis.

• The fatal dose of arsenic is 130mg – 300mg.

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Treatment:1. Stomach wash with sodium and magnesium

sulphate is recommended.2. Morphine and atropine is given to relieve

colic pain.3. EDTA acts as chelating agent.

Cont…Symptoms of chronic toxicity:- Redness of skin- Loss of weight- Horney growth of cornea- Inflammation of mucous membrane - Coughing- Patchy brown pigmentation of skin- White strips of fingernails- Tenderness of muscles

Cont…Treatment:1. Dimercaprol 3 mg/kg is administered

intramuscularly at 4 hourly intervals.2. Fluid replacement and use of pressor agents

like dopamine is used to control.

Cont…LeadSymptoms of acute poisoning:- Abdominal pain- Cramps in legs, irritability- Headache- Drowsiness, lethergy- Paralysis of limbs- Tremor of eyes, mouth and fingers- Loss of vision, loss of appetite- Hallucination- Delirium- Slurred speech

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Treatment of acute poisoning:1. Gastric lavage with zinc sulphate followed by

large draughts of milk and egg with sodium and magnesium sulphate.

2. Morphine and atropine are used to relieve colic pain.

3. EDTA is used as chelating agent.

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Symptoms of chronic poisoning:- Convulsion- Anaemia- Colic pain and constipation- Bluish black line on the gums- Coma and even death

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Treatment of chronic poisoning:1. Removal patient from source of further

exposure.2. Chelation therapy with edate calcium disodium

is used.3. Dimercaprol (also called British anti lewsite) is

used as complexing agent.4. Penicillamine is also included in the dosage

regimen.

Summery

• Poisons• Classification of Poisons• Toxins• Toxins of Animal Origin• Poison Center• Role of poison center• General Treatment of Poisoning• Symptoms and Management of Poisoning case

with Pesticides and Heavy Metals