Toxicology
Toxicolog
y
⚫ The traditional definition of toxicology is "the science of
poisons.“
⚫ "the study of the adverse effects of chemicals or
physical agents on living organisms".
⚫ is the science dealing with properties, action, toxicity,
fatal dose, detection, estimation of, interpretation of the
result of toxicological analysis and management of Poisons
⚫ Forensic Toxicology is a branch of Forensic Medicine
dealing with Medical and Legal aspects of the harmful
effects of chemicals on human beings.
⚫ 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. Eg: alphos,
sulphuric acid, arsenic etc.
The definition of poison is vague and unsatisfactory for
1)A substance which is harmless in small quantities may act as
poison, and cause death when taken in large amounts, and
2)bacterial toxins are not regarded as poisons in ordinary sense
of terms
⚫ Drug (WHO 1996): “Drug is any substance or product that
is used or intended to be used to modify or explore
physiological systems or pathological states for the benefit
of the recipient.” Eg: paracetamol, ciprofloxacin, salbutamol,
oestrogen, insulin etc.
⚫ Toxicant, toxin, and poison are often used interchangeably in
the literature; however, there are subtle differences as
indicated below:
TOXICANTS Subs that produce adverse
biological effects of any nature
May be physical or chemical
TOXIN Specific proteins produced by living
organisms
POISON
⚫ A toxic agent is anything that can produce an adverse
biological effect. It may be chemical, physical, or
biological in form. For example, toxic agents may be
chemical (such as cyanide), physical (such as radiation) and
biological (such as snake venom).
⚫ If the invading organisms excrete chemicals which is the
basis for toxicity, the excreted substances are known as
biological toxins. The organisms in this case are referred
to as toxic [Link] example is tetanus toxin
⚫ A toxic substance is simply a material which has
toxic properties.
⚫ It may be a discrete toxic chemical or a mixture of
toxic chemicals. For example, lead chromate,
asbestos, and gasoline are all toxic substances.
⚫ Lead chromate is a discrete toxic chemical.
⚫ Asbestos is a toxic material that does not consist of an
exact chemical composition but a variety of fibers and
minerals.
⚫ Gasoline is also a toxic substance rather than a toxic
chemical in that it contains a mixture of many
chemicals.
⚫ Toxic substances may be systemic toxins or organ toxins.
⚫ A systemic toxin is one that affects the entire body or many
organs rather than a specific site. For example, potassium
cyanide is a systemic toxicant in that it affects virtually every
cell and organ in the body by interfering with the cell's
ability to utilize oxygen.
⚫ Toxicants may also affect only specific tissues or organs
while not producing damage to the body as a whole. These
specific sites are known as the target organs or target
tissues.
Subdisciplines of toxicology
⚫ Toxicogenomics involves applying molecular profiling
approaches to the study 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, and
⚫ Medical toxicology.
⚫ Aquatic toxicology
⚫ Entomotoxicology: is the analysis of toxins in arthropods
(mainly fl ies and beetles) that feed on carrion.
⚫ Chemical toxicology: study of structure and mechanism
related to the toxic effects of chemical agents, and
encompasses technological advances in research related to
chemical aspects of toxicology.
⚫ Clinical Toxicology: Deals with human diseases caused by, or
associated with abnormal exposure to chemical substances.
⚫ Toxinology: refers to toxins produced by living organism
which are dangerous to man, eg: poisonous plants,
snake venom, fungal and bacterial toxins etc.
HISTOR
Y Egyptian Papyri, Sumerian, Babylonian, Hebrew
⚫ Indian Shastras,
and Greek records.
⚫ Atharv Veda (1500 B.C) describes many poisons
⚫ Kalpasthana, Chikitsasthana, and Uttarasthana of the Shastras,
symptoms and antidotes of poisons are given in detail.
⚫ Sushruta (350 B. C)described poisons
⚫ Kautilya in is Arthshastra ( 2nd century B.C)
⚫ Theophrastus Phillipus Auroleus Bombastus von
Hohenheim (1493–1541) (also referred to as Paracelsus
included numerous references to plant poisons in De Historia
Plantarum (is also considered "the father" of toxicology)
⚫ Mathieu Orfila is considered to be the modern father of
toxicology, having given the subject its first formal treatment in
1813 in his Traité des poisons, also called Toxicologie générale.
History
2700 B.C. - Chinese journals: plant and
fish poisons
1900-1200 B.C. - Egyptian documents
that had directions for collection,
preparation, and administration of more
than 800 medicinal and poisonous recipes.
800 B.C. - India - Hindu medicine includes
notes on poisons and antidotes.
50-100 A.D. - Greek physicians classified over
600 plant, animal, and mineral poisons.
History
50- 400 A.D. - Romans used poisons for
executions and assassinations.
The philosopher, Socrates, was executed
using hemlock for teaching radical
ideas to youths.
Avicenna (A.D. 980-1036) Islamic authority on
poisons and antidotes.
1200 A.D. - Spanish rabbi Maimonides writes
first-aid book for poisonings,
Poisons and Their Antidotes
History
Swiss physician Paracelsus (1493-1541)
credited with being
“the father of modern toxicology.”
“All substances are poisons: there is none
which is not a poison. The right dose
differentiates a poison from a remedy.”
LAW ON POISONS
⚫ 1) The Drugs and Cosmetics Act 1940.
Object of the Act : to regulate the import,
manufacture, distribution and sale of all kind of drugs.
One of the main features is the control of quality, purity
and strength of the drug.
Central Government appoints the Drugs Technical Advisory
Board to advise the Central Government and the State
Governments on technical matters arising out of the
administration of this Act.
This act was amended in 1964
⚫ 2) 2. The Pharmacy Act 1948
The Pharmacy Act was passed in 1948 and was amended in 1959,
1976 and 1984.
Aim:To regulate the profession of Pharmacy in India.
Central Government constitutes a Central Pharmacy Council.
The President and Vice‐President of the Central Council of Pharmacy
are elected by the members of the Council among themselves, hold
office for five years and are eligible for re‐election.
The conducting of courses of study for pharmacists, and the
examinations in Pharmacy in the states are subject to the approval of
the Central Council.
Besides the Council has the responsibility to supervise the Education
of Pharmacy in the States. Where it is found that the course of study is
not in conformity with the Education Regulations, the Council may
withdraw approval accorded to the course or the examination. The
Central Council can approve qualifications granted by an outside
authority for qualifying for registration under this Act.
⚫ THE DRUGS (CONTROL) ACT, 1950
⚫ An Act to provide for the control of the sale, supply and distribution of drugs.
⚫ 1. Short title and extent. ? (1)This Act may be called the Drugs(Control) Act, 1950.
⚫ 2. Interpretation. ? (1) In this Act, unless the context otherwise requires, ?
⚫ (a) ?dealer? (b) ?drug (c) ?offer for sale? (d) ?producer?
⚫ (2) A drug shall be deemed to be in the possession of a person ?
⚫ 3. Drugs to which this Act applies. ? The Central Government may by notification in
official Gazette, declare any drug to be a drug to which this Act applies.
⚫ 4. Fixing of maximum prices and maximum quantities which may be held
or sold.
⚫ 5. Restrictions on sale, etc., where maximum is fixed under Section. ?
⚫ 6. General limitation on quantity which may be possessed at any one time.
⚫ 7. Duty to declare possession of excess stocks. 8. Refusal to sell. ? 9. Cash
memorandum to be given of certain sales. ? 10. Marking of prices and
exhibiting list of prices and stocks. ?
⚫ 11. Obligation to state price separately on composite offer
⚫ 12. Prohibition or regulation of the disposal of drugs.
⚫ 13. Penalties. ? (1) Whoever contravenes any of the provisions of this Act or fails to
comply with any direction made under authority conferred by this Act shall be
punishable with imprisonment for a term which may extend to three years, or
with fine, or with both.
⚫ 14. Offences by corporations..15. Procedure. ? 16. Powers of search and seizure.
17. Power to make rules. ?
⚫ 18. Protection of action in good faith..19. Saving of other laws. ? 20.? [* * *
Repealed].
⚫ 5) Narcotic Drugs and Psychotropic Substances Act, 1985
The cultivation, production, manufacture, possession, sale,
purchase, transportation, warehousing, consumption, inter‐State
movement, trans shipment and import and export of narcotic
drugs and psychotropic substances is prohibited, except for
medical or scientific purposes and in accordance with the terms
and conditions of any license, permit or authorization given by
the Government.
⚫ The Central Government is empowered to declare any substance,
based on an assessment of its likely use in the manufacture of
narcotics drugs and psychotropic substances as a controlled
substance
⚫ Assets derived from drugs trafficking are liable to forfeiture.
⚫ The NDPS Act is in effect a comprehensive code not only for
the control and regulation of Narcotics Drugs and Psychotropic
Substances; but also for the control of selected chemicals ‐
commonly known as precursors ‐ which can be used in the
illicit manufacture of narcotic drugs and psychotropic
substances, as well as for the investigation and forfeiture of
drug related assets.
⚫Laws in relation to poison and drugs:
⚫ Sec. 272 I.P.C. ‐ Punishment for adulterating food or drink
intended for sale, so as to make the same noxious, may
extend upto 6 months imprisonment of either term
and/or fine upto one thousand rupees.
⚫ Sec. 273 I.P.C. ‐ Punishment for selling noxious food or drink
may be imprisonment of either description for a period of 6.
months and or fine upto one thousand rupees.
⚫ Sec. 274 I.P.C. ‐ Punishment for adulteration of drugs in any
form with any change in its effect knowing that it Will be
sold and used as un‐adulterated drug, may be imprisonment
of either description for a period‐of 6 months and or fine.
⚫ Sec. 275 l.P.C. ‐ Punishment for knowingly selling
adulterated drugs with less efficacy or altered action
serving it for use as unadulterated may be imprisonment of
either description for 6 months and or fine.
⚫ Sec. 276 I.P.C. ‐ Punishment for selling a drug as a
different drug or preparation, may be imprisonment of
either description which may extend upto 6months and or
fine. .
⚫ Note ‐ In the State of West Bengal, the punishment for
these offences described under sections 272 to 276 may be
upto imprisonment for life with or without fine.
⚫ Sec. 277 I.P.C. – Punishment for fouling water of public
spring or reservoir may be imprisonment of either
description which may extend up to a period of 3 months
and or fine.
⚫ Sec. 278 I.P.C. ‐ Punishment for voluntarily making
atmosphere noxious to health is fine which may extend
upto five hundred rupees.
⚫ Sec. 284 I.P.C. Punishment for negligent conduct with
respect to poisonous substance may be imprisonment of
either description which may extend upto 6 months and
or fine which may extend upto one thousand rupees.
⚫ Sec. 328 I.P.C. :Punishment' for causing hurt by means of
poison or any stupefying, intoxicating or unwhlolesome
drug or any other thing with the intent to commit an
offence shall be imprisonment of either description for a
term which may extend to ten years with or without fine.
⚫ Culpable Homicide: Sec 299 IPC; Causing death of a
person by an act, with the intention of causing such bodily
injury and is likely to cause death, or with the knowledge
that he is likely, by such an act to cause death.
Sources of Poison:
⚫ 1. Domestic or household sources ‐ In domestic
environment poisoning may more commonly occur from
detergents, disinfectants, cleaning agents, antiseptics,
insecticides, rodenticides etc.
⚫ 2. Agricultural and horticultural sources‐ different
insecticides, pesticides, fungicides and weed killers.
⚫ 3. Industrial sources‐ In factories, where poisons are
manufactured or poisons are produced as by
products.
⚫ 4. Commercial sources‐ From store‐houses, distribution
centers and selling shops.
⚫ 5. From uses as drugs and medicines – Due to
wrong medication,
⚫ overmedication and abuse of drugs.
⚫ 6. Food and drink – contamination in way of use of
preservatives of food grains or other food material, additives
like colouring and odouring agents or other ways of
accidental contamination of food and drink.
⚫ 7. Miscellaneous sources‐ snakes bite poisoning, city
smoke, sewer gas poisoning etc.
Classification of poisons
⚫ 1. According to the site and mode of action
⚫ (A). local Action
⚫ a) Corrosive :
Strong Acid: mineral acid: eg H2SO4, HCl
: organic acid:Carbolic, oxalic,acetic,salicylic
Strong alkali: Hydrates and carbonates of Na, K, &
ammonia
Metallic salts: Mercuric Chloride, KCN,
⚫ b) Irritant
1) Agricultural
2) Inorganic
Nonmetallic: P, Iodine, Cl, bromine
Metallic: Arsenic, Antimony, Pb, Cu, Zinc
Mechanical: Glass, Diamond dust, Hair
3) Organic
Animal: Snakes, insects Cantharides
Vegetable: Abrus, Castor,
Croton,Calotropis
⚫ (B) Systemic 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, Hyocyamus, cannabia
Indica.
⚫ vi. Hallucinogens
2) Spinal
⚫ i . Strychnos Nux Vomica
⚫ Ii. Gelsemium
⚫ 3) Peripheral Nerves
⚫ i. Local Anaesthetics: Cocaine, Procaine.
⚫ ii. Relaxants (curare)
⚫ CNS DEPRESSANTS
⚫ 1) Alcohols
⚫ 2) General anaesthetics
⚫ 3) Opioid analgesics
⚫ 4) Sedative hypnotics
Sedatives are those drugs that decrease activity, moderate
excitement and exert a calming effect
Hypnotics produce drowsiness and facilitate a state of
sleep, resembling natural sleep.
1) Barbiturates 2) Benzodiazepines
3) Non barbiturates 4) Alcohols
5) Propanediols 6) Glutethimide
7) quinazolines: methaqualone
⚫ 4) Cardiac Poisons
⚫ • KCN, NaCN, Digital is, Aconite, Nicotine, Quinine,
Oleander
⚫ 5) Asphyxiants: Carbon Dioxide, CO, hydrogen
sulphide
⚫ C) Miscellaneous: Food Poisons.
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, Plumbago.
⚫ 5. Stupefying agent: Dhatura, cannabis, chloral hybrate.
⚫ 6. Agents used to cause bodily injury: Corrosive acids
and alkalies.
⚫ 7. Cattle Poison: Abrus precatorius, Calotropis,
plumbago.
⚫ 8. Used for malingering: semicarpus
anacardium
⚫ 9. Arrow Poison: Abrus precatorius, Calotropis, Aconite,
Strychnos nux vomica.
⚫ 10. Aphrodisiacs : Cantharides, Cannabis, Cocaine,
arsenic, opium
⚫ Ideal Suicidal poison: should be easily available, No bad taste,
cause No pain, cheap, highly toxic, tasteless or pleasant taste,
capable of being taken with food or drink.
⚫ Ideal Homicidal poison: it should be cheap, easily available,
colorless tasteless, odourless, highly toxic, No residual product
left, S/S resembles natural diseases, No antidote, Shows no post‐
mortem changes, capable of being administered with food or
drink.
⚫ Route of Administration/absorption:
⚫ Oral (commonest) eg: alphos, acids,
⚫ Inhalation: gas poison
⚫ Parenteral (IM, IV, Sub‐Cutaneous, Intra‐Dermal)
⚫ Natural Orifices other than mouth (Nasal, Rectal, Vaginal,
Urethral),
⚫ Ulcers, wounds and intact skin.
Fate of poison in body:
⚫ Vomiting and purging, defecation.
⚫ Before absorption the poison may exert its effects in the
G.I. Tract.
⚫ When absorbed, the poison reaches different parts of the
body
⚫ Cumulative poisons get accumulated in some organs or
tissues.
⚫ A part of poison is eliminated as such through different route
of elimination. But major part is detoxified or metabolized in
the body and than excreted
⚫ Liver is the main organ to detoxify or metabolize most of
the poisons.
⚫ Certain poisons like Chloroform, Phosphorus, Nitrates and Acetic
acid disappear by evaporation or oxidized or destroyed in the
body and no trace of them can be detected in the body of post‐
mortem is delayed.
⚫ Excretion of poisons: Unabsorbed poisons are excreted
through faeces and vomitus. Absorbed poisons are excreted
mostly by urine. A part of volatile poison is exhaled out.
Some portion of poison is excreted through bile, saliva,
milk, sweat, tear, hair and nails.
Factors influencing the actions of a poison
in the body
⚫ 1. Quantity:
⚫ Quantity
‐ large = more effect ?
‐ idiosyncracy (individual susceptibility to
a substance)
‐ addiction (tolerance)
‐ different actions of different doses
⚫ A high dose of poison acts quickly and often resulting in fatal
consequences. A moderate dose causes acute poisoning. A low
dose may have sub‐clinical effects and causes chronic
poisoning on repeated exposure. Very large dose of Arsenic may
produce death by shock without dose irritant symptoms, While
smaller dose than lethal dose produces its therapeutic effects.
⚫2. Physical form:
⚫Physical State: ‐ Gas > liquids > powders > solids
Some poisonous vegetable seeds may pass through
the
intestinal canal ineffective when taken intact due to
their impermeable pericarp. But when taken crushed,
they may be rapidly fatal.
⚫Chemical Combination: Ag nitrate and HCL
⚫Mechanical Combination: ‐ relative density of the poison
and the vehicle
⚫ 3. Chemical form: Chemically pure arsenic and mercury
are not poisonous because these are insoluble and are not
absorbed.
⚫ But white arsenic(arsenic oxide) and mercuric chloride
are deadly poisonous. Barium sulphide is deadly toxic but
barium sulphate is non‐toxic.
⚫ 4. Concentration (or dilution): concentrated form of poison are
absorbed more rapidly and are also more fatal but there are
some exceptions too.
⚫ 5. Condition of the stomach: food content presence of food‐
stuff acts as diluent of the poison and hence protects the
stomach wal l. Dilution also delays absorption of poison. Empty
stomach absorbs poison most rapidly. In cases of achlorohydria,
KCN and NaCN is ineffective due to lack of hydrochloric acid,
which is required for the conversion of KCN and NaCN to HCN
before absorption
⚫ 6. Route of administration: absorption rate is different
for different routes.
⚫ 7. Age: some poisons are better tolerated in some age
groups. Opium and its alkaloids are tolerated better by
elderly subjects but badly by children and infants.
Belladonna group of drugs are better tolerated by children
than by adults.
⚫ 8. State of body health: A well built person with good
health can tolerate the action of poison better than a
weak person.
⚫ 9. Presence of disease: In certain diseased conditions
some drugs are tolerated exceptionally wel l e.g.: sedatives
and tranquilizers are tolerated in very high dose by manic
and deliriant patients.
⚫ 10. Intoxication arid poisoning states ‐ In certain
poisoning cases some drugs are well tolerated, like, in case
of strychnine poisoning, barbiturates and sedatives are
better tolerated. Whereas in case of barbiturate poisoning
any sedative or tranquilizer will accentuate the process of
⚫ 11. Sleep ‐ Due to slow metabolic process and depression
of other body functions during sleep, usual ly the
absorption and action of the poison is also slow. But
depressant drugs may cause, more harm during the state
of sleep.
⚫ 12. Exercise ‐ Action of alcohol on C.N.S. is slowed during
exercise because more blood is drawn to the muscles
during exercise.
⚫ 13. Cumulative action of poisons: Preparations of
cumulative poisons (poisons which are not readily excreted
from the body and are retained in different organs of the
body for a long time) like lead may not cause any toxic
effect when enters the body in low dose. But when such
poisons enter over a long period of time, may cause harm
when their concentration in different tissue reaches high
level due to their cumulative property.
⚫ 14. Tolerance may develop by individuals on long term
exposue to a particular poison.
⚫ 15. Idiosyncracy: some persons may react adversely to a
particular drug though the general population tolerates the
drug well.
⚫ DEFINITIONS
⚫ Acute poisoning: is caused by an excessive single dose, or
several dose of a poison taken over a short interval of time.
⚫ Chronic Poisoning: is caused by smaller doses over a period
of time, resulting in gradual worsening. eg: arsenic,
Phosphorus, antimony and opium.
⚫ Subacute poisoning shows features of both acute and
chronic poisoning.
⚫ Fulminant poisoning is produced by a massive dose. In this
death occur rapidly, sometimes without preceding symptoms.
⚫ Parasuicide (attempted suicide or pseudicide) is a conscious
often impulsive, manipulative act, undertaken to get rid of
an intolerable situation.
⚫ Antidote: Antidotes are substances which counteract the effect of
poison. They are divided into Mechanical, Chemical,
Physiological and specific receptor antagonists.
Signs and symptoms:
⚫ The signs and symptoms may be different for different
poisons and is responsible on the nature and action of
the poison.
⚫ They can be local, remote or combined.
Diagnosis of
poisoning In the
Living
1. History of the case
2. Signs and symptoms.
3. Details of examination.
4. Preservation and laboratory investigation
Diagnosis of poisoning ( contd.)
⚫In the Dead:
⚫ 1. History
⚫ 2. Post‐mortem Examination
⚫ 3. Chemical Analysis
⚫ 4. Preservation of viscera
PM Findings
External Examination
⚫ 1. Postmortem staining:
Deep blue ‐ In case of asphyxiant poisons and aniline.
Bright red – In case of CO poisoning
Cherry red ‐ In case of HCN
poisoning. Dark brown or yellow ‐
Phosphorus
⚫ 2. Deep cyanosis ‐ With opium and
cardiac poisons.
⚫ 3. Early rigor mortis ‐ With strychnine.
⚫ 4. Early appearance of the sign of decomposition ‐
With H2S gas.
⚫ External Examination (contd.)
⚫ 5. Detectable smell ‐ In case of volatile
poisons, opium and HCN, KCN or NaCN.
⚫ 6. Haemorrhagic spots under the skin and
mucus membrane: Phosphorus.
⚫ 7. Ulceration on lips, angles of mouth ‐ Corrosive
poisons.
⚫ 8. Stain near mouth ,on hands – HNO3 and
CuSO4.
⚫ 9. White froth from mouth and nose – Opium
and its alkaloids.
⚫ External Examination (contd.)
⚫ 10. Blood tinged froth from mouth and nose
Organophosphorus compounds.
⚫ 11. Alopecia, hyper pigmentation and hyperkeratosis –
Ch. Arsenic poisoning.
⚫ 12. Staining, erosion and ulceration near the female
external genitalia ‐ Use of abortifacient agents or
torturing agents.
⚫ 13. Injection marks ‐ Injection of poisons (snake bite
or otherwise), sign of treatment.
Internal findings:
⚫ Hyperemia, softening, ulceration and perforation.
⚫ 1. Corrosion, ulceration and desquamation of inner aspects
of lips, mucus membrane of mouth and tongue ‐ Corrosive
agents.
⚫ 2. Soft, swollen, sodden, translucent, bleached tongue and
mucus membrane of mouth‐ Corrosive alkali
⚫ 3. Hardening of mucus membrane ‐ Phenol
⚫ 4. Phenol Yellowish ‐ Nitric acid
⚫ 5. Bluish ‐ Copper sulphate
⚫ 6. Carbonization and charring‐ Conc. Sulphuric acid
PM Internal findings (Contd.)
⚫ 7. Chalky appearance and consistency of teeth ‐:Sulphuric
acid
⚫ 8. Blue lining in the gum ‐ Chronic lead poisoning
⚫ 9. Swollen gum, loose teeth, foetid smell ‐ Acute mercuric
chloride poisoning; Chronic phosphorus poisoning
⚫ 10. Corrosion, irritation, desquamation and hemorrhage in
the inner wall of the esophagus ‐ Corrosive and irritant
poisons
PM Internal findings (Contd.)
⚫11. Hardening and whitish discolouration – In case
of Carbolic acid poisoning
⚫12. Discoloration and staining of inner aspects
of mouth ‐ With coloured poisons
⚫13. Oesophageal stricture ‐ A complication
of sulphuric acid ingestion
PM Internal findings (Contd.)
⚫ 14. Stomach
⚫ (a) Thickening and softening of the wall ‐Corrosive and
irritant poisons
⚫ (b) Hard wall‐ Carbolic acid
⚫ (c) ‐ Hard and leathery wall‐ Formaldehyde
⚫ (d) Hyperemia haemorrhage and desquamation of mucus
membrane ‐ Irritant poison
⚫ (e) Laceration and sloughing – Corrosive poison
⚫ (f ) Perforation ‐ H2SO4 and HNO3
⚫ (g) Yellowish discolouration of mucus membrane ‐
HNO3;
Bluish ‐ CuSO4; Slaty grey ‐ HgCl3 .
PM Internal findings (Contd.)
⚫ (h) Stomach content ‐ Blood ‐ Corrosive and irritant;
Yellowish – HNO3 Bluish ‐CuSO4
⚫ Luminous in dark ‐ Phosphorus;
⚫ Detectable tablet – soneryl; Powder; oxalic acid, white
arsenic;
⚫ Detectable smell ‐ kerosene, alcohol, chloroform,
organophosphorus compounds, chlorinated hydrocarbons,
opium, cyanogen, formaldehyde, phosphorus;
⚫ Detectable liquid ‐ kerosene.
PM Internal findings (Contd.)
⚫ 15. Small intestine ‐ May show ulceration, perforation
sometimes may show presence of poisonous remains.
⚫ 16. Large intestine ‐ May show ulcerations, as in case of
HgCI3 similar in appearance of ulcers of bacillary dysentery.
It particularly involves the ascending and transverse
colons.
PM Internal findings (Contd.)
⚫ 17. Liver ‐ Different degenerative changes.
⚫ 18. Kidneys ‐ Swollen, reddish, soft, sometime greasy in
touch with haemorrhage in calyces and other degenerative
changes ‐ mercury, oxalic acid carbolic acid, phosphorus,
cantherides, viper snake venom etc. In case oxalic acid
poisoning, white powder of oxalate crystals are present in the
tubules and the calyces .
⚫ 19. Urinary bladder ‐ Haemorrhage in cases of
abrus precatorius, viper snake bite, cantherides
poisoning.
PM Internal findings (Contd.)
⚫ 20. Larynx and trachea ‐ Hyperemic, inflamed ‐In cases of
inhalation of irritating gases leaking of corrosive agents while
ingestion vomiting; froth in the lumen of trachea and larynx
in case of opium and organophosphorus poisoning.
⚫ 21. Chest cavity ‐Smell of volatile poisons, cyanogens, opium
etc. can be detected.
⚫ 22. Lungs ‐ Voluminous, congested, presence of Tardieu's
spots ‐ In case of asphyxiants and inhaled poisons. Cut
section gives blood stained frothy‐fluid in case of opium
and other asphyxiants.
PM Internal findings (Contd.)
⚫ 23. Heart‐ Subendocardial haemorrhagic spots in cases
of arsenic, phosphorus, mercuric chloride etc.
⚫ 24. Brain and spinal cord ‐ Congestion and edema.
Brain – may be congested, oedematous with occasional
haemorrhagic points at places ‐ asphyxiant poisons.
⚫ 25. Uterus and vagina ‐ Staining, congestion haemorthage,
ulceration in cases of attempted abortion by use of local
abortifacient agents.
Preservation of viscera and
other materials
⚫ In all cases of poisoning
⚫ 1. Stomach with its full contents.
⚫ 2. A loop of small intestine with its contents.
⚫ 3. Half of Liver or 500 gms whichever is
more.
⚫ 4. Half of each kidney.
⚫ 5. Some portion of spleen
⚫ 6. Blood 100ml
In some particular poisons
1. Blood 100ml : in cases of absorbed poisons.
2. Urine 100ml in all cases where blood is
preserved.
3. Part of both lungs in cases of Volatile poisons.
4. Heart in case of cardiac poisons.
5. Brain in cerebral poisons.
6. Spinal in spinal poisons.
In some particular poisons
(contd.)
7. Bones in arsenic and lead.
8. Hair in arsenic and copper.
9. Nails in arsenic.
10. Skin‐scrap from areas stained with a suspected poison.
[Link] areas of dress, suspected packet of poison, strips of
tablets recovered from pocket.
Preservative used
⚫ For Viscera: Saturated sol. Of common salt,
⚫ absolute alcohol or rectified spirit. Exception: alcohol,
chloroform, chloral hydrate, formaldehyde, ether,
phosphorus (alcohol prevents the luminosity of phosphorus
in dark) etc.
⚫ Blood should be preserved in fluoride, oxalate, E.D.T.A., gold
chloride or citrate
⚫ Urine : 1 ml of conc. HCl, 10 mg of thymol, 100 mg of NaF for
10 ml urine
⚫ clothes: without any preservative.
DUTIES OF A DOCTOR IN CASES OF
POISONING
⚫Save life
⚫Protect from further exposure
⚫Collect samples for chemical analysis
(vomit, urine, faeces, stomach wash
fl uid,
remnants of food, medicine, suspect containers,
clothes soiled with vomit, urine, faeces)
⚫Detailed History
⚫Admit – preferably to a Government Hospital
DUTIES OF A DOCTOR IN CASES OF
POISONING ( contd.)
⚫Inform police
⚫Arrange for dying declaration
⚫Notify public health authorities
⚫Ask for autopsy in case of death
(DO NOT ISSUE DEATH CERTIFICATE)
⚫Maintain detailed and proper records
PRINCIPLES OF MANAGEMENT
OF A CASE OF POISONING
⚫Stabilization & Evaluation
⚫Decontamination
⚫Poison elimination
⚫Antidote administration
⚫Nursing and Psychiatric
Care
[Link] & Evaluation
‐ Assessment and correction of life‐threatening
problems
1. Hypoxia – Assisted ventilation
2. Coma – Coma cocktail
(Dextrose + Thiamine +
Naloxone)
3. Metabolic acidosis
1. Stabilization & Evaluation
‐ ABCD of resuscitation
‐ Complete, thorough and systematic
examination of the patient (after
stabilization)
Glasgow scoring
Category Response Points
E
Spontaneous, open with blinking at baseline 4
ye opening Opens to verbal command, speech, or shout 3
Opens to pain, not applied to face 2
No response 1
V
Oriented conversation 5
erbal response Disoriented, confused conversation, able to answer questions 4
Inappropriate responses, words discernible 3
Incomprehensible speech 2
No response 1
Intubated 1T
M
Obeys commands for movement 6
otor response Purposeful movement to painful stimulus 5
Withdraws from pain 4
Abnormal (spastic) flexion, decorticate posture 3
Extensor (rigid) response, decerebrate posture 2
No response 1
2. Decontamination
1. Inhaled poisons
2. Injected poisons
3. Contact poisons
4. Ingested poisons
Emesis
Gastric lavage
Catharsis
Activated charcoal
Whole bowel
irrigation
Decontamination (contd.)
1 – Emesis
‐ Substances used‐ ipecacuanha
‐ Contraindications – Relative
1. Very young/very old
2. Pregnancy
[Link] disease/ingestion of cardiotoxic
poison
4. Bleeding disorders
5. Time lapse of more than 6 – 8 hours
Decontamination (contd.)
1 – Emesis
‐ Contraindications – Absolute
1. Convulsions
2. Corrosives
3. Coma
4. Petroleum distillates
5. Foreign body ingestion
6. Emetic poisons
Decontamination (contd.)
1. Emesis
‐ Complications
[Link] toxicity – bradycardia, AF,
myocarditis
2. Aspiration pneumonitis
3. Mallory Weiss tears
Decontamination (contd.)
2. Gastric lavage
‐ Indications
[Link] of life‐threatening dose of
poison and presenting to the casualty
with in 1 – 2 hours of ingestion
2. Presence of gastric concretions
3. Delayed gastric emptying
4. Sustained release preparations
Decontamination (contd.)
2. Gastric lavage ‐Lavage fl uids
a) Warm water
‐ b) Saline
‐ c) Oxidizing solutions:
‐ KMnO4, tannic acid, Iodinated
water d)Na thiosulphate sol. For CN
e) Desferrioxamine‐ for iron
f) Castor oil in warm water‐ carbolic
acid
g) Ca gluconate‐ oxalic acid
Decontamination (contd.)
2. Gastric lavage
Contraindications – Absolute
1. Corrosive substance
ingestion (except
Carbolic acid)
2. Marked hypotherm1ia
3. Prior significant vomiting
4. Petroleum distillate
ingestion
5. Convulsions
6. Ingestion of sharp
substances
Decontamination (contd.)
2. Gastric lavage
‐ Contraindications – Relative
1. Convulsions
2. Hemorrhagic diathesis
3. Coma
4. Esophageal varices
5. Recent surgery
6. Advanced pregnancy
Decontamination (contd.)
2. Gastric lavage
‐ Complications
1. Aspiration pneumonia
2. Laryngospasm
3. Sinus bradycardia and ST elevation on ECG
4. Perforation of stomach or esophagus
Decontamination (contd.)
3. Catharsis
‐ Ionic or Saline cathartics:
1. Magnesium citrate – 4ml/kg
2. Magnesium sulfate – 30 g
3. Sodium sulfate – 30 g
Can lead to serious hypermagnesemia
Decontamination (contd.)
3. Catharsis
‐ Saccharides – Sorbitol
Cathartic of choice in adult
Dose – 50 ml of 70% solution
Efficacy – doubtful
Contraindicated in children due to risk
of fl uid and electrolyte imbalance
Decontamination (contd.)
[Link] Charcoal
Universal adsorbent
Produced by the controlled burning of various
organic products at >600C, washed with
inorganic acids and dried
Small particle with highly developed
internal pore system
Surface area of 50 gm AC = 10 football fields
1 g = 1000 m2
Dose – 1g/kg in 4‐8 times the quantity
of water
Decontamination (contd.)
[Link] Charcoal
‐ Indications: In Salicylates, paracetamol,
barbiturates, TCA, theophylline and manyother
organic and inorganic substances, carbamezepine,
Dapsone, Digoxin, Phenytoin Quinine Theophyline
Barbiturates.
‐ Disadvantages: unpleasant taste, emesis,
constipation/diarrhoea, pulmonary aspiration,
intestinal obstruction, black stools
Decontamination (contd.)
[Link] Charcoal
Contraindications:
1. Absent bowel
sounds/intestinal
obstruction
[Link], heavy metals‐ lithium,
iron, alcohol, ethylene glycol, petroleum
distillates, etc.
Charcoal has no toxicity, may be given before
inducing vomiting or gastric lavage
It is with a universal antidote (activated
charcoal: magnesium oxide: tannic acid [Link])
Decontamination (contd.)
4. Activated Charcoal
Binds most compounds; easier to remember what
it doesn’
t
Decontamination (contd.)
5. Whole bowel irrigation
‐ NS instilled into the GI tract through a
nasogastric tube at a rate of 1.2 to 1.8
l/hr
till rectal effl uent is clear or until 4 – 6 l
have been used up.
‐ Complications: Vomiting, cramps, bloating and
abdominal distension.
[Link] Administration
(Antidotes are substances that counteract the effects
of poisons)
‐ Mode of action:
[Link] complex formation ‐ chelating agents for
metals
2. Accelerated ‐ thiosulfate for
detoxification cyanide
3. Reduced toxic ‐ ethanol for methanol
conversion ‐ naloxone
5. Receptor site blockade ‐ atropine for OP for opiates
4.
6. Receptor
compounds
Toxic site
effect ‐ 100% O2 in cyanide
competition
bypass ‐ dilution in corrosives
7. Mechanical
Antidote (contd.)
⚫Antidotes are substances which counteract
the effect of poison. They are divided into
⚫[Link]
⚫[Link]
⚫[Link]
⚫[Link] receptor antagonists.
Antidotes (contd.)
⚫ Physical or mechanical antidote prevents the action of
poison mechanically, without destroying or inactivating the
damaging actions of the poisons. Eg: adsorbents like
activated charcoal, Demulcents like egg albumin, starch or
milk, Diluents like water or milk, bulky food like boiled
rice or vegetables.
⚫ Chemical antidotes are substances which disintegrate and
inactivate poisons by undergoing chemical reaction with
them. Eg: Weak acids and alkali, common salt, egg
albumin, KMNO4.
Antidotes (contd.)
⚫ 3. Physiological antidote have their own action
producing signs and symptoms opposite to that
produced by the poison. Eg: Naloxone for morphine,
Neostigmine for datura or hyoscin group, Barbiturate for
strychnine.
⚫ 4. Serological Antidote: Anti‐snake venom serum for
snake bites poisoning.
Antidotes (contd.)
⚫ Universal Antidote: It is a combination of physical and
chemical antidotes. When the exact nature of poison is
not known then universal antidote is used which acts
against a wide range of poisons.
⚫ Constituents
⚫ Activated charcoal 2 parts
⚫ Magnesium oxide 1 part
⚫ Tannic acid 1 part
⚫ Dose 1TSF (15gms) in a glass water (can be repeated)
⚫ Activated charcoal for its adsorbent action, Magnesium oxide
neutralizes acids poisons, tannic acid precipitates alkaloids
Household antidotes:
⚫1. Strong liquid tea (contains tannic acid) precipitate
alkaloid and metallic poisons.
⚫2. Starch for iodine.
⚫3. Milk and raw egg for mercury, arsenic, heavy
metal.
⚫4. Flour suspension and mashed potatoes can be used
in place of activated charcoal.
⚫5. Milk of magnesia or soap solution for acid poisoning.
⚫6. Orange, lemon juice or vinegar for alkali poisoning
4 Poison Elimination
1. Renal excretion
2. Purging
3. Whole bowel irrigation
4. Diaphoretics
5. Forced Diuresis
2. Extracorporeal Techniques
1. Hemodialysis
2. Hemoperfusion
3. Peritoneal dialysis
4. Plasmapheresis
What is a toxidrome?
⚫A collection of symptoms and signs that
consistently occur after ingestion of a
particular toxin or drug class or agent
⚫Often identified with a basic history &
physical examination
⚫Rapid identification of the toxidrome saves
time in evaluating and managing a poisoned
patient
Anticholinergic
• Eg. TCA, antihistamines, atropine, benztropine
• Blind as a bat, hot as a hare, dry as a bone,
red as a beet, mad as a hatter
⚫ Mydriasis ⚫ Ileus
⚫ Blurred vision ⚫ Urinary retention
⚫ Fever ⚫ Hypertension
⚫ Flushed dry ⚫ Tachycardia
skin
⚫ Psycosis, coma
⚫ Seizures
AAnticholinergic Toxidrome –
ManagementBC, supportive care, consider GI decontamination
Benzodiazepines
Physostigmine – specific antidote.
May be used if
Severe agitation or psychosis unresponsive to other therapy
Sever peripheral and central anticholinergic features
NO history of seizures
Normal ECG especially QRS duration
NO co‐ingestion of drugs altering intraventricular
conduction
E.g. TCA’s
Cardio‐respiratory monitoring and resus facilities in place
Cholinergic
⚫Eg. organophosphates, nerve
agents
⚫DUMBELS
⚫ D‐diaphoresis, diarrhea, decreased BP
⚫ U‐urination
⚫ M‐miosis
⚫ B‐bronchorrhea, bronchospasm, brady
⚫ E‐emesis, excitiation of skeletal muscle
⚫ L‐lacrimation
⚫ S‐salivation, seizures
Sympathomimetic
(adrenergic) toxidrome
⚫ Increased temp ⚫ CNS excitiation
⚫ Tachycardia ⚫ Seizures
⚫ Hypertension ⚫ Nausea/vomiting
⚫ Dilated pupils ⚫ Diaphoresis
Cocaine, MDMA (“ecstasy”), Amphetamines, Phencyclidine (PCP), Theophylline,
Decongestants (Ephedrine Pseudoephedrine Phenylpropanolamine), Caffeine
(very large doses)
Sympathomimetic
(adrenergic) toxidrome
⚫ Increased temp ⚫ CNS excitiation
⚫ Tachycardia ⚫ Seizures
⚫ Hypertension ⚫ Nausea/vomiting
⚫ Dilated pupils ⚫ Diaphoresis
Cocaine, MDMA (“ecstasy”), Amphetamines, Phencyclidine (PCP),
Theophylline, Decongestants (Ephedrine Pseudoephedrine
Phenylpropanolamine), Caffeine (very large doses)
Adrenergic Toxidrome ‐ Management
⚫ ABC, supportive care, consider GI decontamination
⚫ Investigations
⚫ Screen for other drugs & treatable toxins (eg, acetaminophen, salicylate)
⚫ Electrolytes (esp. sodium), urea, creatinine, blood sugar, anion gap.
⚫ CK levels to check for rhabdomyolysis
⚫ Consider cranial CT
⚫ EKG & Cardiac biomarkers (eg, CPK‐MB, troponin)
⚫ Sedation – treats majority of effects
⚫ Benzodiazepines
⚫ Temperature control
⚫ Treat hypertension unresponsive to benzodiazepines
⚫ Nitroprusside
⚫ Nitroglycerine
⚫ Labetalol (avoid isolated ‐blockade in mixed adrenergic agonist toxicity)
Narcotic
⚫ Hypothermia
⚫ Bradycardia
⚫ Hypotension
⚫ Respiratory
depression
⚫ Constricted pupils
⚫ CNS depression
Opioid‐Narcotic Toxidrome ‐ Management
⚫ABC, supportive care
⚫GI decontamination for oral ingestion
⚫Naloxone
⚫ Specific antagonist
⚫ High doses may be needed for methadone
& pentazocine
⚫ Short half‐life compared to opioids
⚫ Infusion may be required
⚫ Pulmonary edema and seizures have been
reported
Serotoninergic Toxidrome
Eg. SSRI’s, MAOI’s, ecstasy
Vital Signs
Respiratory rate Normal/increased
Heart rate Increased
Temperature Increased
Blood pressure Normal/decreased
Physical examination
Mental status Agitated/irritable
Pupils Normal/unreactive
Mucous membranes Normal
Skin Normal/flushed/sweating
Reflexes Increased
Bowel sounds Increased
Urination Normal/decreased (SIADH possible)
Other Diarrhoea, trismus, myoclonus, tremor, rhabdo
Serotoninergic Toxidrome ‐ Features
Cardiovascular Mental status changes
• Sinus tachycardia (36%) • Confusion (51%)
• Hypertension (35%) • Agitation (34%)
• Hypotension (15%) • Hypomania (21%)
• Anxiety (15%)
Motor Abnormalities • Coma (29%)
• Myoclonus (58%)
Gastrointestinal
• Hyperreflexia (52%) • Nausea (23%)
• Muscle rigidity (51%) • Diarrhea (8%)
• Restlessness (48%) • Abdominal pain (4%)
• Tremor (43%) • Salivation (2%)
• Ataxia/incoordination (40%)
• Shivering (26%) Other
• Nystagmus (15%) • Diaphoresis (45%)
• Seizures (12%) • Unreactive pupils (20%)
• Tachypnea (26%)
• Hyperpyrexia (45%)
Sternbach H. The serotonin syndrome. Am J Psychiatry 1991;148:705-13
Mills KC. Serotonin syndrome. Am Fam Physician 1995;52:1475-82
Serotoninergic Toxidrome ‐ Management
⚫Stop intake of causative agent
⚫ABC, supportive care
⚫Absorption
⚫ Gastric lavagein early acute ingestion (1hr)
⚫ Activated charcoal
⚫Benzodiazepines
⚫Others
⚫ Chlorpromazine
⚫ Diphenhydramine
⚫? Serotonin antagonists e.g. cyproheptadine
Diagnosis ‐ Investigation
⚫ Essential labs
⚫ CBC, lytes, BUN, Cr, BS
⚫ Ptt, INR, LFTs
⚫ ABG (calculate AG)
⚫ Serum osmo (calculate osmo
gap)
⚫ ASA
⚫ Acetaminophen
⚫ Other
⚫ Drug levels
⚫ Urine
General Management
⚫ ABC
⚫ Consider thiamine, dextrose, naloxone if depressed GCS
⚫ Prevent further absorption
⚫ Decontaminate eyes, clothes, skin, hair if appropriate
⚫ Activated charcoal + sorbitol (if < 1 hour from ingestion)
⚫ Gastric lavage (if < 1 hour from ingestion and life‐threatening drug or dose)
⚫ In general not used
⚫ Whole bowel irrigation for “body packing” illicit drugs
⚫ In general not used
⚫ Enhance elimination
⚫ Forced diuresis and urinary alkalinisation (salicylates and barbiturates)
⚫ Multiple dose activated charcoal 0.5 g/kg every 2‐4 hours
⚫ binds toxin and interrupts enterohepatic recirculation
⚫ mainly life‐threatening ingestion of carbamazepine, dapsone, phenobarbital, quinine or theophylline
⚫ Extracorporeal removal (for active metabolites, delayed toxicity or poor organ clearance)
⚫ Haemodialysis ‐ low MW (<500 d), soluble, low Vd (< 1L/kg) e.g. methanol, ethylene glycol, salicylates,
lithium
⚫ Haemoperfusion ‐ e.g theophylline, phenobarbital, phenytoin, carbamazepine, paraquat
⚫ Haemofiltration for large Vd and extensive tissue bound toxins but removes virtually all drugs
⚫ Antidotes
General Treatment
⚫Activated charcoal
⚫ Inert, non‐toxic, non‐specific adsorption
⚫ Risk of aspiration
⚫ Dose 1g/kg patients weight
⚫ Ineffective for alcohols or heavy metals
⚫ ? Multi‐dose charcoal
⚫ may cause GI dialysis for some drugs
⚫ Check with poison control!!!
Activated Charcoal
⚫ Binds most compounds; easier to remember what
it doesn’t
Activated Charcoal
⚫ Big question in the use of AC is when to use it
⚫ Effectiveness is time dependent – the longer the
time from ingestion, the less effective AC is
⚫ Toxin already absorbed or past pyloris
⚫ Effectiveness is lost between 1 and 2 hours
AC: problem
⚫ Patients with toxin ingestions will present to the ED
>3 hours after poisoning
⚫ “should not be administered routinely”
Drugs and Extracorporeal Removal
Haemodialysis Haemoperfusion (Charcoal)
• Methanol • Theophylline
• Ethylene glycol • Carbamazepine
• Salicylates • Amanita toxin (if early)
• Lithium • Aminoglycosides
• Paraquat
• Phenobarbital
Haemofiltration
• Procainamide • Phenytoin
• Methotrexate • Sotalol
Urinary Alkalinisation
⚫ Fluoride
⚫ Isoniazid
⚫ Salicylic acid
⚫ Barbiturates
⚫ Methotrexat
e