Some Terms

Toxicology is the science dealing with properties, actions, toxicity, fatal dose, detection and estimation of, interpretation of the results of toxicological analysis, and treatment of poisons.

Forensic toxicology deals with the medical and legal aspects of the harmful effects of chemicals on human beings.

Clinical toxicology deals with human diseases caused by or associated with abnormal exposure to chemical substances.

Poison is a substance (solid, liquid, or gaseous), which if introduced into the living body, or brought into contact with any part thereof, will produce ill-health or death, by its constitutional or local effects or both.

Toxinology refers to toxins produced by living organisms which are dangerous to man, e.g. poisonous plants, the venom of snakes, spiders, bees, etc., and bacterial and fungal toxins.

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

Toxin: A toxin is a poisonous substance produced within living cells or organisms.

 

Ideal Homicidal Poison:

The characters of an ideal homicidal poison should be:

Cheap

Easily available

Colorless, odorless, and tasteless,

Capable of being administered, either in food, drink, or medicine, without producing any obvious change to prevent suspicion,

Highly toxic

Signs and symptoms should resemble a natural disease, or the serious ill-effects should be delayed sufficiently long for the accused to escape suspicion,

There should not be any antidote,

There should be no postmortem changes,

Should not be detected by chemical tests, or other methods, and

Must be rapidly destroyed or made undetectable in the body

Organic compounds of fluorine (used as rodenticides), and thallium satisfy several of the above criteria. Arsenic and aconite are commonly used.

 

 

Ideal Suicidal Poison:

The characters of an ideal suicidal poison should be:

Cheap

Easily available

Highly toxic

Tasteless or of pleasant taste

Capable of being easily taken in food or drink, and

Capable of producing painless death.

Opium and barbiturates satisfy several of the above criteria. Organophosphorus compounds and endrin are commonly used as suicidal poisons.

 

 

Medicolegal Classification of Poison

 

According to Mode of Action/symptoms

A) Corrosives:

1) Strong acids: Sulphuric, nitric, hydrochloric, Carbolic acid, oxalic acid, acetic acid, salicylic acid

2) Strong alkalis: Hydrates and carbonates of sodium, potassium, and ammonia

3) Metallic salts: Zinc chloride, ferric chloride, copper sulphate, silver nitrate, potassium cyanide, chromates, and bichromates

B) Irritants:

1) Agricultural: Organophosphorous compound (OPC) Poisoning

2) Inorganic: a) Non-metallic: Phosphorus, iodine, chlorine, bromine b) Metallic: Arsenic, antimony, copper, lead, mercury, silver, zinc. c) Mechanical: Powdered glass, diamond dust, hair, etc.

3) Organic: a) Vegetable: Castor oil, Croton oil, Calotropis, aloes, Abrus precatorius b) Animal: Snake and insect venom, cantharides, ptomaine

C) Systemic:

D) Miscellaneous:

Food poisoning, botulism.

 

Routes of Administration:

In order of rapidity of action:

1. Inhaled in gaseous or vapourous form.
2. Injection into blood vessels.
3. Intramuscular, subcutaneous, and intradermal injection.
4. Application to a wound.
5. Application to a serous surface
6. Application to a bronchotracheal mucous membrane.
7. Introduction into the stomach
8. Introduction into the natural orifices, e.g. rectum, vagina, urethra, etc.
9. Application to unbroken skin.

 

Routes of Elimination:

The absorbed portion of poison is mainly excreted by the kidneys and to some extent by the skin. Other routes are bile, milk, saliva, mucous and serous secretions. The unabsorbed portion is excreted in the vomit and feces.

 

ACTION OF POISONS:

1) LOCAL: The local action by coming in direct contact with the part.

2) Remote: Due to absorption of the poison into the system

3) Combined: Local & remote action

 

FACTOR MODIFYING ACTION OF POISONS

1. Quantity

2. Form: Poisons act most rapidly when gaseous

3. Mode of Administration: The rapidity of the action is in the order described under the route of administration.

4. Condition of the body:

• Age
• IDIOSYNCRASY:
  It may be defined as the inherent personal hypersensitivity to the agent in question. Certain people are sensitive to certain drugs
• Habit
• STATE OF HEALTH
• SLEEP AND INTOXICATION:
  The action of poison is delayed if a person goes to sleep soon after taking it. The action is also delayed if one takes poison in an intoxicated condition.
• CUMULATIVE ACTION:
  Poisons that are eliminated slowly may accumulate in the body when given in repeated doses for a long time and may ultimately produce symptoms of poisoning.

 

TYPES OF POISONING:

1) Acute poisoning is caused by an excessive single dose or several smaller doses of a poison taken over a short interval of time.

2) Chronic poisoning is caused by smaller doses over a period of time, resulting in gradual worsening. The poisons which are commonly used for the purpose of chronic poisoning are arsenic, antimony, phosphorus, and opium.

3) Subacute poisoning shows features of both acute and chronic poisoning.

4) Fulminant poisoning is produced by a massive dose. In this death occurs rapidly, sometimes without preceding symptoms.

 

Nice To Know

Parasuicide (attempted suicide, or pseudocide) is a conscious, often impulsive, manipulative act, undertaken to get rid of an intolerable situation. Most persons are psychologically disturbed. Therapeutic index, or the ratio of the toxic to the effective dose of a drug, indicates the relative toxicity of drugs. Lethal dose is the dose that kills. YOUNG'S RULE: The dose of a drug for a child is obtained by multiplying the adult dose by the age in years and dividing the result by the sum of the child's age plus 12

 

Failure to Detect Poison: 

1) Eliminated by vomiting and diarrhea, e.g, in irritant poisons.

2) From the lungs by evaporation or oxidation.

3) After absorption may be detoxified, conjugated, and eliminated from the system.

4) Some vegetable alkaloidal poisons cannot be definitely detected by chemical methods.

5) Some drugs are rapidly metabolized, making extraction difficult.

6) Some organic poisons especially alkaloids and glucosides may by oxidation during life or due to faulty preservation, or a long interval of time, or from the decomposition of the body, may deteriorate and cannot be detected chemically.

7) Biological toxins and venoms which may be protein in nature cannot be separated from body tissues.

8) If the poison acts slowly and death is delayed following the production of irreversible organic changes

9) Sometimes, decomposition products make the detection difficult or impossible.

10) Treatment may alter the poisonous substance.

11) Many drugs may be present in very small amounts and these may require a considerable amount of viscera for their identification.

12) The wrong or insufficient material may have been sent for analysis.

 

Common poisoning in Bangladesh (Ref Endeavour)

1. Common accidental poisoning

1. OPC poisoning
2. Snake venom poisoning
3. Kerosene poisoning

2. Common suicidal poisoning

1. Organophosphorus Compound (OPC)
2. Opium
3. Endrin
4. Barbiturate

In Rural areas - OPC Poisoning In Urban areas - Barbiturate Poisoning

 

Principle of Treatment of poisoning

1. Removal of the patient from the source of exposure

2. Initial ABCD resuscitation

• A - Airway
• B - Breathing
• C - Circulation (IV fluid administration)
• D - Depression of CNS should be corrected. An unconscious patient should be turned to lie on one side to stop the tongue from blocking the throat and to allow fluid to come out of the mouth (recovery position).

3. Removal of Unabsorbed Poison from the Body

Inhaled Poisons:

If the poison is inhaled as a gas, the patient must be removed into the fresh air, artificial respiration and oxygen should be given. The air passages should be kept free from mucus by postural drainage or by aspiration.

Injected Poisons:

If the poison has been injected subcutaneously from a bite or an injection, a tight ligature should be applied immediately above the wound, which must be loosened for one minute after every ten minutes, to prevent gangrene.

Contact Poisons:

The patient's contaminated clothes, contact lenses, and jewelry should be removed immediately. If poison is applied to the skin or wound or is inserted into the vagina, rectum, or urinary bladder, it should be removed by washing with water for 30 minutes or should be neutralized by a specific chemical.

Ingested Poisons:

Removed from the stomach by emesis or by use of stomach tube

 

4. Diluting the poison & delaying its absorption

The poison in the stomach is to be diluted by giving water to drink. Bulky bland food also helps. Fat delays the process of absorption and also protects the stomach wall from the corrosive action of the poison.

 

5. Elimination of absorbed poison:

Purging: Elimination of poison from GIT by excretion

Diuresis: For increased urination

Diaphoresis: Increased perspiration can be tried with the help of neostigmine/pilocarpine

Dialysis: Hemodialysis, urinary dialysis, peritoneal dialysis

Use of chelating agents

 

6. ADMINISTRATION OF SPECIFIC ANTIDOTES:

For OPC: Atropine

For Dautra: Physostigmine

For morphine/Opium: Naloxone

Barbiturate: For strychnine

Atropine: Physostigmine

7. SYMPTOMATIC TREATMENT

Control of convulsion: Diazepam

Control of vomiting: Ondansetron

8. Follow-up

 

 

Overview of Antidotes 

 

 

Contraindications of Stomach Wash:

Absolute Contraindication

The only absolute contraindication is corrosive poisoning (except carbolic acid), owing to the danger of perforation.

Relative Contraindication

1) Convulsant poisons, as it may lead to convulsions. Lavage should be done after controlling the convulsions.

2) Comatose patients, because of the risk of aspiration of fluid into the air passages.

3) Volatile poisons, which may be inhaled.

4) Upper alimentary disease, e.g. oesophageal varices.

5) In patients with marked hypothermia and hemorrhagic diathesis.

 

Complications of Gastric lavage:

• Laryngeal spasm
• Aspiration pneumonitis
• Perforation of the stomach
• Sinus bradycardia

 

EMETICS:

Syrup of ipecac contains cephaeline and emetine. It induces vomiting by local activation of peripheral sensory receptors in the GIT, and stimulation of the vomiting center. This is the only and best method of producing vomiting.

Ingestion of an excessive amount of saltwater may cause fatal hypernatremia.

Household emetics, i.e. mustard powder (one teaspoon) and common salt are not effective and can lead to complications.

Tickling throat:

Make the patient lie face down or sit well forward with the head lower than the chest, and ask the patient to touch the back of the throat with his fingers or with your own finger or a blunt object, such as a spoon handle or a wooden tongue depressor. This is usually ineffective.

 

ANTIDOTES:

Antidotes are substances that counteract or neutralize the effects of poisons.

 

Common modes of action of antidotes are:

• Inert complex formation e.g. chelating agents for heavy metals,
• Receptor site blockade, e.g. naloxone for opiates; atropine for organophosphates at muscarinic receptor sites.

 

Types of Antidotes

A) Mechanical or Physical Antidotes:

They neutralize poisons by mechanical action or prevent their absorption.

1) Activated charcoal

Activated charcoal is a fine, black, odorless, and tasteless powder. It acts mechanically by adsorbing and retaining within its pores organic, and also to a less degree mineral poisons, and thus delays the absorption from the stomach.

Barbiturates, atropine, benzodiazepines, opiates, quinine, strychnine, phenothiazines, digitalis, amphetamines, antidepressants, antiepileptics, antihistamines, chloroquine, cimetidine, tetracycline, theophylline, pyrethrins, aluminum phosphide are well adsorbed.

It is not useful in poisoning with corrosives, heavy metals, cyanide, hydrocarbons, and alcohol.

 

2) Demulcents

Demulcents are substances that form a protective coating on the gastric mucous membrane and thus do not permit the poisons to cause any damage, e.g. milk, starch, egg-white, mineral oil, milk of magnesia, aluminum hydroxide gel, etc.

Fats and oils should not be used for oil-soluble poisons, such as kerosene, phosphorus, organophosphorus compounds, DDT, phenol, turpentine, aniline, acetone, carbon tetrachloride, etc.

 

3) Bulky food

Bulky food acts as a mechanical antidote to glass powder by imprisoning its particles within its meshes, and thus prevent damage from being affected by the sharp glass particles.

 

B) CHEMICAL ANTIDOTES:

They counteract the action of poison by forming harmless or insoluble compounds or by oxidizing poison when brought into contact with them.

1) Alkalis neutralize acids by direct chemical action. It is safer to give the little weak solution of an alkaline hydroxide, magnesia, or ammonia. Bicarbonate should not be given, because of the possible risk of rupturing the stomach due to liberated CO2.

2) Acids neutralize alkalis by direct chemical action. Only those substances which are by themselves harmless should be given, e.g. vinegar, lemon juice, canned fruit juice.

3) Potassium permanganate has oxidizing properties. 1:5000 solution is used in poisoning for opium and its derivatives, strychnine, phosphorus, hydrocyanic acid, cyanides, barbituric acid and its derivatives, atropine, and other alkalis.

When it reacts with the poison in the stomach, it loses its pink color.  The wash must be continued till the solution coming out of the stomach is of the same pink color as the solution put in.

4) Tannic acid 4%, or tannin in the form of a strong tea or one teaspoonful of tannic acid in water tends to precipitate apomorphine, cinchona, strychnine, nicotine, cocaine, aconite, pilocarpine, lead, silver, aluminum, cobalt, copper, mercury, nickel, and zinc.

5) Common salt decomposes silver nitrate by direct chemical action, forming the insoluble silver chloride.

6) Dialyzed iron is used to neutralize arsenic.

7) A solution of tincture iodine or Lugol's iodine 15 drops to half a glass of warm water precipitates most alkaloids, lead, mercury, silver, quinine and strychnine.

 

Universal Antidote consists of: Activated Charcoal - 2 parts Magnesium Oxide - 1 part Tannic acid - 1 part So-called universal antidote consisting of activated charcoal, or burnt toast 2 part, magnesium oxide one part, and tannic acid or strong tea one part is not recommended.

 

PHYSIOLOGICAL OR PHARMACOLOGICAL ANTIDOTES:

They act on the tissues of the body and produce symptoms exactly opposite to those caused by the poison. They are used after some of the poison is absorbed into the circulation. These agents act on the principle of antagonism by interfering with another's action upon the enzymes, tissue cells, or opposing nerve systems.

Atropine and physostigmine are two real physiological antidotes, as both of them affect nerve endings and produce opposite effects on the heart rate, state of the pupils, and glandular secretory activity.

Other examples are cyanides and amyl nitrite; barbiturates and picrotoxin or amphetamine; strychnine and barbiturates.

 

Chelating Agents:

Chelating agents (metal complexing agents) are used in the treatment of poisoning by heavy metals. They have a greater affinity for the metals as compared to the endogenous enzymes. The complex of the agent and metal is more water-soluble than the metal itself, resulting in higher renal excretion of the complex. They can form stable, soluble complexes with calcium and certain heavy metals.

1) B.A.L. (British Anti-Lewisite/ Dimercaprol):

It is used as a physiological antidote for arsenic, lead, bismuth, copper, mercury, gold, thallium, and antimony. Many heavy metals have a great affinity for sulphydryl (SH) radicles and combine with them in tissues and deprive the body of the use of respiratory enzymes of tissue cells.

Dimercaprol has two unsaturated sulphydryl groups which combine with the metal and thus prevent the union of arsenic with the SH group of the respiratory enzyme system. The compound formed by the heavy metal and dimercaprol is relatively stable, which is carried into the tissue fluids, particularly plasma, and is excreted in the urine.

2) E.D.T.A. (Ethylene diamine tetraacetic acid/ Calcium disodium versenate):

It is a chelating agent and is effective in lead, mercury, copper, cobalt, cadmium, iron, and nickel poisoning.

It forms chelates with lead which are water-soluble, non-toxic, non-ionized, non-metabolized, and excreted intact in the urine.

It is superior to B.A.L. for the treatment of poisoning by arsenic and mercury.

It is the treatment of choice in lead poisoning.

 

3) Penicillamine:

It is a hydrolysis product of penicillin. It is the chelating agent of maximum efficiency for copper, lead, and mercury.

4) DMSA/Succimer (Meso-2,3-dimercapto-succinic acid):

It is used for lead, mercury, and arsenic poisoning. It is superior to EDTA in the treatment of lead poisoning, as it does not lead to the redistribution of lead to the brain. It is less toxic to the kidneys.

5) DMPS: (2,3-Dimercaptopropane 1-sulfonate) is effective in the treatment of mercury, lead, and arsenic poisoning.

6) Desferrioxamine: It contains trivalent iron as a chelate and is very useful in acute iron poisoning.

 

Purging: 

It is the process of elimination of poison from GIT by excretion.

30 gm sodium sulphate with large amounts of water, hastens the elimination of poison in the stool.

Magnesium sulphate should be avoided, since sufficient may be absorbed to produce central nervous system depression in cases of renal failure.

To remove unabsorbed material from the intestinal tract, poorly absorbable material, such as liquid petroleum which is a solvent for fat-soluble agents is effective.

Sorbitol 50 ml of 70% solution is a better purgative, but in young children, it may cause fluid and electrolyte imbalance.