Introduction
Toxicology is defined as a branch of medical science, which deals with poison in relation to their sources, properties, action, the symptoms which they produce, fatal dose, toxicity, diagnosis, treatment and autopsy features.
Classification: Toxicology is divided into four main categories:
- Forensic toxicology
- Clinical toxicology
- Industrial toxicology
- Environmental toxicology
Poison
Any substance if, taken in any account, by any route, produces harmful effect (i.e. disease, deformity or death, the 3 D’s) over the body then it will be called as poison.
Drug
Drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient (WHO).
Routes of administration and elimination
Oral
- Dermal
- Ocular
- Nasal
- Vaginal
- Rectal
- Urethral
Systemic
- Oral
- Sublingual
- Rectal
- Cutaneous
- Inhalation
- Nasal
- Parenteral
Routes of Elimination
- Urine
- Feces
- Exhaled air
- Saliva
- Sweat
- Milk
- Bile
Action of poison
1. Local action: A poison may act at the site of application, for example, application of concentrated sulphuric acid to face produces chemical burns.
2. Systemic action: A poison may act over a given system when taken, for example, ingestion of aconite causes cardiac toxicity and death.
3. Combined action: Some poison have local action and similarly they act as a systemic poison, for example, carbolic acid when applied to skin it act locally as corrosive and when ingested acts as systemic poison.
Factors Affecting the Action of Poison
- Route of administration
- Age
- Idiosyncrasy
- Dose
- Concentration of poison
- Chemical state of poison
- Physical state of poison
- Area of application
- Tolerance
Classification
- Based on Nature of Poison
- Corrosive
- Strong acids:
Mineral or inorganic acids, e.g. H2SO4, HCL;
Organic acids, e.g. carbolic, acetic, oxalic acid
- Strong alkalis, e.g. sodium hydroxide
- Metals, e.g. mercuric chloride, ferric chloride
- Strong acids:
Irritants
Inorganic:
Non-metal, e.g. phosphorus, iodine; Metal, e.g. arsenic, lead etc.
- Organic:
Animal, e.g. snake, scorpion; Plant or vegetable, e.g. castor, calotropis etc.
- Mechanical: e.g. chopped hair, metal pieces etc.
Systemic
Cerebral poisons
Somniferous
Inebriants
Stimulants
Deliriant
Depressant
Psychotropics
- Spinal poisons, e.g. strychnine
- Peripheral nerve poison, e.g. curare
- Cardiac poison or cardio-toxic, e.g. aconite
- Asphyxiants, e.g. carbon monoxide
- Nephrotoxic, e.g. mercury
- Hepatotoxic, e.g. phosphorus
- Miscellaneous, e.g. food poisoning
- Corrosive
Based on Manner of Use
- Homicidal poisons
- Suicidal poisons
- Accidental poisons
- Abortifacient poisons
- Stupefying poisons
- Cattle poisons
- Arrow poisons
- Use to fabricate injury or malingering
- Use to cause injury
- Use for torture
Based on Source of Poison
- Domestic or house hold poisons
- Agricultural poisons
- Environmental poisons
- Industrial poisons
- Food and drinks poisons
- Drugs and medicines
Diagnosis of poisoning
A patient with consumption of poison may present as:
- Fulminant poisoning
- Acute poisoning
- Subacute poisoning
- Chronic poisoning
Diagnosis in Living
- History
- Symptoms
- Signs
- Laboratory examination
History and symptoms
- Sudden onset of vomiting/diarrhoea/pain in abdomen
- Onset of symptoms to many persons who had taken food Together.
- History of consumption of poison or suspicious material
- Persistent vomiting and/or diarrhoea with or without dehydration
- Pain in abdomen
- Altered sensorium/drowsiness/unconsciousness/coma
- Breathlessness, constriction in chest, choking sensation
- Convulsions
- Palpitations, arrhythmias, chest pain
- Hypothermia
- Paralysis
General Examination
- Peculiar odor
- Taste
- Temperature-hypothermia/hyperthermia
- Ocular changes
- Oral manifestations
Smell of different poisons
Poison | Smell |
---|---|
Cyanide | Bitter almond like |
Phosphorus | Garlicky |
Arsenic | Garlicky |
Selenium | Garlicky |
Thallium | Garlicky |
Aluminium Phosphide | Garlicky |
Phenol | Phenolic |
Organophosphorus | Kerosene like/Garlicky |
Conium | Mousy |
Marijuana | Burnt rope like |
Hydrogen Sulphide | Rotten egg like |
Zinc Phosphide | Fishy |
Carbon monoxide | Coal gas |
Nitrobenzene | Shoe polish |
Chloroform | Acetone like |
Camphor | Moth balls |
Acetic acid | Vinegar |
Taste of different poisons
Taste | Poison |
---|---|
Bitter | Strychnine |
Burning | Acids |
Acrid | Calotropis |
Sweet | Aconite |
Sour | Oxalic acid |
Metallic | Copper, iodine |
Sweet burning | Carbolic Acid |
Caustic | Alkali |
Poisons causing hyperthermia and hypothermia
Action | Poison |
---|---|
Producing Hyperthermia | Strychnine, datura, cocaine |
Producing Hypothermia | Opiates, alcohol, barbiturates, Carbon monoxide |
Poisons producing oral changes
Oral changes | Poison |
---|---|
Salivation (Sialorrhrea) | Oraganophosphates Mineral acids Alcohol Aconite Croton Chilli Seeds Tobacco Scorpion Copper |
Dryness of Mouth | Datura Ephedrine Scopolamine Anti-histaminics Anti-depressants |
Xerostomia | Narcotics Tricyclic Antidepressants |
Gingival hyperplasia | Phenytoin Sodium valporate |
Stomatitis | Cyanide Calotropis Iodine |
Parotitis | Iodine |
Glossitits | Cyanide |
Discoloration of teeth | Flouride Tetracycline |
Central Nervous System
- Grading of coma
- Patient may be drowsy, deliriant or in coma
- Convulsions
- Tremors
- Neuropathy
- Movement disorder
- Paralysis
- Headache
- Paraesthesia
- Gait
- Delirium
- Tingling
- Ataxia
Gastrointestinal System
- Vomiting
- Diarrhoea
- Constipation
- Gastroenteritis
- Melena
- Abdominal pain
- Abdominal distension
- Thirst
- Dysphagia
- Pancreatitis
Genitourinary System
- Colour of urine
- Albuminuria
- Hemoglobinuria
- Glycosuria
- Hematuria
- Porphyrinuria
- Oliguria
- Polyuria
- Dysuria
Cardiovascular System
- Pulse-tachycardia/bradycardia
- Blood pressure
- Arrhythmias
- Circulatory collapse
- Vasoconstriction
Respiratory System
- Dyspnoea
- Pulmonary edema
- Respiratory distress
- Cough
- Laryngospasm
- Bronchitis
- Emphysema
Musculoskeletal System
- Myopathy
- Myalgia
- Rhabdomyolysis
- Fasciculation
- Smooth muscle depressant/stimulant
Blood Manifestations
- Anemia
- Blood dyscrasia
- Thrombocytopenia
- Leukocytosis
- Leukopenia
- Polycythemia
- Bone marrow depression
- Hemolysis
- Methemoglobin formation
Ear Manifestations
- Rhinorrhea
- Deafness
- Vertigo
- Tinnitus
Features observed | Score |
---|---|
Eye Opening Spontaneous To Speech To pain Nil | 4 3 2 1 |
Best motor response Obeys Localizes Flexes (withdraw) Flexes abnormally (decorticate rigidity) Extends (decerebrate rigidity) Nil | 6 5 4 3 2 1 |
Best verbal response Oriented Confused conversation Inappropriate words Incomprehensible sounds Nil | 5 4 3 2 1 |
Management of the case of poisoning
Principles of management
- Stabilization and evaluation
- Decontamination
- Eye
- Skin
- Gut
Emesis/emetics
Gastric lavage
Activated charcoal
Bowel irrigation
- Poison elimination
- Antidote administration
- Nursing care
- Psychiatric care
Stabilization and Evaluation
- A: maintenance of airway
- B: maintenance of breathing
- C: maintenance of circulation
- D: disability (neurologic status) management: assess level of consciousness.
Decontamination
- Eye: If ocular exposure occurs due to poisons, eye should be irrigated with copious water for 15 to 20 minutes.
- Skin: Absorption of poison is possible by dermal route. In case of dermal exposure, the affected area should be washed thoroughly with plain water. Remove the clothes and irrigate the area copiously with water.
- Gut
- Emesis:
- Agents used
- Syrup of ipecacuanha
- Apomorphine
- Stimulation of posterior pharyngeal wall.
- Indications
- Conscious patient
- Ingestion of poison within 4 to 6 hour.
Contraindications
Coma/convulsion/unconscious patient
Impaired gag reflex
Corrosive/volatile poison ingestion
Pregnancy.
Complications
Aspiration pneumonia
Mallory Weiss tears
Laryngospasm.
- Agents used
- Gastric Lavage:
- Indications
- Conscious patient
- Ingestion of poison within 1 to 2 hour.
- Contraindications
- Coma/convulsion/unconscious patient
- Impaired gag reflex
Corrosive/volatile poison ingestion
Marked hypothermia
Oesophageal varices
Significant electrolyte imbalance.
Complications
Aspiration pneumonia
Mallory Weiss tears
Perforation of esophagus/stomach
Laryngospasm
Hypothermia
Electrolyte imbalance.
Procedure
Protect airway
Place patient on lateral position
Tube should be passed orally
Lubricate the inserting end of tube
Use mouth gag
The position of tube in stomach should be confirmed
Lavage is carried out with saline or water.
- Indications
- Activated charcoal:
- Activated charcoal is tasteless, black, fine powder. It adsorbs the poisons in stomach and hence decreases the systemic absorption of poison.
- Dose is given as 1 gm/kg body weight
- Required quantity of activated charcoal is mixed with water and this mixture is administered to patient.
- Disadvantages
Unpleasant taste
Provokes vomiting
May cause diarrhea/constipation
Contraindications
Paralytic ileus
Intestinal obstruction
Perforation of stomach
- Emesis:
Poison elimination
Poison can be eliminated by
- Hemodialysis
- Hemoperfusion
- Peritoneal dialysis
- Plasma perfusion
Antidote administration
Antidotes
Antidotes are the substances used to counteract or neutralize the effects of poison.
Classification
Antidotes are classified as:
- Physical or Mechanical or Non-Specific Antidotes
- These antidotes retard the absorption of poison by mechanical action.
- Examples – activated charcoal, demulcents such as – milk, starch, egg-white (egg albumin)
- Activated charcoal acts mechanically by adsorbing the poison and retaining it within its pores
- Demulcents are the substances that form a protective coating on the gastric mucosa and thus retard absorption.
- Chemical Antidote
- These compounds counteract the action of poison by neutralizing the poison or forming harmless or insoluble components
- Example – in corrosive alkali poisons weak vegetable acids like citric acid, lemon juice may be used.
- Physiological or Pharmacological Antidote
- These agents act on the tissue of the body. These substances work either in one of the following ways:
Reduces the toxic conversion of poison – for example, ethanol is used as antidote in methyl alcohol poisoning because ethanol inhibits the metabolism of methanol to toxic metabolites by competing for the same enzyme (alcohol dehydrogenase)
Competition at receptor site – some antidotes are capable to compete with the poison and displace the poison from the specific receptor site thereby antagonizing the poisonous effects completely. For example, in opiate poisoning naloxone is used. Naloxone antagonizes the effect of opiate by acting at opioid receptors.
Blocking the receptor site – some antidotes are capable of blocking the receptor site acted by poisonous substance thereby blocking the poisonous effect of substance. For example, in organophosphorus poisoning atropine is used. Organophosphorus acts at muscarinic receptors producing toxic effects. Administration of atropine will block the effects of organophosphate
- These agents act on the tissue of the body. These substances work either in one of the following ways:
- Universal antidote
It is an antidote, which is a combination of physical and chemical antidote. It can be administered, when the exact nature of poison taken is not known or when one or more poison is/are taken. However, recently use of universal antidote has been criticized and condemned.
Composition — It is made up of 2 parts (50%) of powdered animal charcoal or burned toast, 1 part (25%) of magnesium oxide or milk of magnesia and 1 part (25%) of tannic acid or tea.
Dose — 1 tablespoon mixed with one glass of water.
Route — Given orally.
- Chelating agents
These agents interact with poison to form an inert complex, which is then excreted from the body.
- These agents are primarily used in heavy metal poisoning
- These agents with metal ions forms ring structure within their molecule. The name chelating is derived from Greek, chele = crab – the compound holds the metal like a crab’s claw.
- Examples – British Anti-lewisite (BAL), Succimer, Disodium edetate, penicillamine, desferrioxamine, calcium disodium edetate.
- British Anti Lewisite (BAL)
- Synonyms: dimercaprol, dimercaptopropanol
Features: It is an oily, pungent smelling liquid, developed during Second World War by British as an antidote to the arsenic war gas, lewisite.
Mechanism of Action: BAL has two SH (thiol) groups. The two SH group binds to those metals that produce toxicity by interacting with sulfhydryl containing enzymes in the body. BAL will combine with these metals forming BAL-metal complex thus dislodge the metal from acting site.
Indications: BAL is useful against metals that interfere with sulfhydryl enzymes in the body such as arsenic, mercury, bismuth, copper, antimony, and nickel.
Contraindications: BAL is contraindicated in iron and cadmium poisoning because BAL-iron and BAL-cadmium complex are toxic.
Dose: BAL is administered intramuscularly as 5 mg/kg stat followed by 2 to 3 mg/kg every 4 to 8 hours for two days and then once a day for 10 days.
Adverse Effects
- Tachycardia
- Vomiting
- Tingling and burning sensation
- Cramps
- Sweating
- Succimer
- Synonym: dimercaptosuccinic acid.
- The agent is similar to BAL in chelating properties
- It is less toxic than BAL and orally effective
- It is used against arsenic, mercury and lead poisoning
- It is less toxic to kidneys
- Dose: 10 mg/kg orally every 8 hours for 5 days, followed by same dose every 12 hours for 14 days
- Calcium disodium edetate
Features
It is not absorbed from gastrointestinal tract. It should be used as intravenous route because intramuscular injection is painful. It is distributed extracellularly.
Mechanism of Action
It chelates metal extracellularly and removes metals from the body by exchanging with calcium. It is rapidly excreted in urine by glomerular filtration carrying the toxic metal along with it. The compound is not metabolized in the body.
Indications: Useful in lead, zinc, cadmium, copper, manganese.
Contraindications: In cases with raised intracranial pressure where fluids are restricted.
Dose : One gram is diluted in 200 to 300 ml in saline or glucose solution and infused intravenously over one hour twice daily for 3 to 5 days.
Adverse Effects: Renal damage, Acute febrile reaction, Anaphylaxis may occur, Thrombophlebitis.
- Penicillamine (D-Penicillamine)
- Synonyms: Cuprimine/Dimethyl cysteine
Features: It is dimethyl cysteine, obtained as a degradation product of penicillin and available in d-isomer and l-isomer form. The d-isomer is used because l-isomer is more toxic and produces optic neuritis. It is absorbed after oral administration, metabolized in the body and excreted in urine and feces.
Mechanism of Action: Exact mechanism is not known.
- Copper poisoning – drug of choice
- Mercury poisoning – alternative to BAL
- Chronic lead poisoning
- Wilson’s disease
- Cystinuria and cystine stones
- Indications:
- Copper poisoning – drug of choice
- Mercury poisoning – alternative to BAL
- Chronic lead poisoning
- Wilson’s disease
- Cystinuria and cystine stones
Dose
- For copper and mercury poisoning – 1 to 1.5 gm/day in divided doses
- For Wilson’s disease – 0.5 to 1 gm/day in divided doses, one hour before meals or two hour after the meals to avoid the chelation of dietary metals.
- Adverse effects:
- Cutaneous reaction
- Febrile illness
- Nephrotoxicity
- Bone marrow depression
- Anorexia
- Nausea
- Loss of taste
- Desferrioxamine
Features: Ferrioxamine is a long chain iron-containing complex obtained from an actinomycete. Chemical removal of iron from it yields desferrioxamine that has great affinity for iron. If administered orally, little amount is absorbed. It binds with iron present in GIT and prevents its absorption. If administered parenterally, desferrioxamine is partially metabolized and rapidly excreted in urine.
Mechanism of Action: Desferrioxamine molecule turns round the ferric ion and forms a stable non-toxic complex that is excreted in urine. One gram of desferrioxamine is capable of removing 85 mg of elemental iron. It removes loosely bound iron and iron from hemosiderin and ferritin but do not remove iron from hemoglobin or cytochrome.
- Indications
- Acute iron poisoning
- Transfusion siderosis
- Dose
- It is drug of choice in iron poisoning. It should be given intramuscularly – 0.5 to 1 gm repeatedly 4 to 12 hourly.
- In severe life threatening poisoning or patient with shock should receive intravenous desferrioxamine – 15 mg/kg/ hour with a maximum daily dose up to 360 mg/kg or up to 6 gm total.
- Adverse effects:
- Fall in blood pressure
- Itching, urticaria, rashes
- Abdominal pain
- Diarrhea
- Muscle cramps
Toxicological Diagnosis in dead
Diagnosis of poisoning in dead is done by:
- Autopsy findings
- Laboratory examination
1. Autopsy Examination:
External Examination
- Evidence of soiling of clothes
- Presence of bottle/container/label in pocket
- Presence of suicide note
- Vitriolage
- Trickling of poison/stigmata of poison over skin
- Presence of injuries
- Smell from body
- Rigor mortis: in some condition rigor may appear early or in some delayed
- Postmortem lividity: poisons may impart peculiar colour
- Some poisons resist decomposition or some may hasten.
Internal Examination
- Cranial cavity: Presence of odour/cerebral edema/hemorrhages.
- Chest cavity: Note for presence of pleural effusion, pericardial effusion, state of lungs and heart, hemorrhages, pulmonary edema
- Abdominal cavity: Stomach contains gastric contents of various colours. Mucosa may show erosions, ulcers, hemorrhagic gastritis or perforation. Gastric mucosa may be stained with the colour of poison
- Examine the state of intestine, liver, spleen, kidneys, pancreas, bladder, esophagus, lip, and oral cavity
Laboratory Examination
It consists of analysis of viscera, body fluids and blood for poisons. The laboratory method consist of:
- Qualitative assays – type of poison is known.
- Quantitative assays – type of poison as well as quantitation can be known.
Qualitative Assays: Thin layer chromatography is a simple and inexpensive technique for qualitative estimation of poison.
Quantitative Assays
- Gas chromatography
- High performance liquid chromatography
- Mass spectrometry
- Radio-immuno-assay
- Atomic absorption spectrophotometry
- Neutron activation analysis.
Poisons and relevant acts and rules
- The Poison Act 1919
- The Drugs and Cosmetics Act 1940
- The Drugs and Cosmetics Rules 1945
- The Drugs (Control) Act 1950
- The Drugs and Magic Remedies (Objectionable advertisements) Act 1954
- The Prevention of Food Adulteration Act 1954
- The Prevention of Food Adulteration Rules 1955
- The Insecticides Act 1968
- The Insecticides Rules 1971
- The Water (Prevention and control of pollution) Act 1974.
- The Water (Prevention and control of pollution) Rules 1975
- The Narcotic drugs and psychoactive substances Act 1985
- The Narcotic drugs and psychoactive substances Rules 1985
- The Narcotic drugs and psychoactive substances (Amendment) Act 2001.