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Toxicology

Poisons & Envenomation

History & General Concepts

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Introduction

Poison:- L-Potion, potio ( to drink) A substance that causes death or harm when introduced in to or absorbed by a living organism. Something which has a destructive influence.

A substance that through its chemical action usually kills, injures or impairs an organism
Any substance which when taken in to the body in a single dose of 1gm or less is injurious to human body or dangerous to life

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Introduction

Toxicology:- Gk-Toxicon (an arrow poison) + Logia(discourse/ science)
Toxicology- The scientific study of poisons, their effects, and their antidotes
The branch of science concerned with the nature, effects, and detection of poisons
It is the study of the adverse effects of chemicals on living organisms.
Toxicology is the science of the adverse effects of chemicals on living organisms

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INTRODUCTION

Poisoning refers to the development of dose related adverse effects following exposure to chemicals, drugs, or other xenobiotics
“ Dose makes the poison” Paracelsus
A poison in a small dose is a medicine, and a medicine in a large dose is a poison Alfred Swaine Taylor- 19^th century Toxicologist

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History of Toxicology

Earliest humans used animal venoms, and plant extracts, for hunting, warfare, and, assassination
All ancient civilizations knew about poisons and used these for purposes as by modern men

2500 BC, the Sumerians worshipped a goddess named Gula, who was a master of poisons and charms.
Menes (the earliest known Egyptian king) 3000 BC devoted himself to the research of poisonous plants
Ebers papyrus 1500 BC mentions metals (lead copper, antimony) and plants like aconite, opium, and hemlock, as poisons.
Homer in Odyssey(800 BC) mentions arrow poison.

Odyssey An epic poem written by Homer 6-8 Century BC which describes the journey of Odysseus the King of Ithaca’s to home after Trojan war. It provides both an insight in to a long lost civilization and a gripping narrative rich in evocative details, complex character and universal themes.

Iliad- Also an ancient Greek poem describing the siege and capture of Troy, ascribed to Homer and probably composed by oral tradition, over several centuries before 700 BC.

Troy – A city of ancient Greece in present day NW Turkey on the Aegean Sea

Trojan-a person who came from ancient Troy; pertaining to Troy.

Paparus- Writing material resembling paper made from the pith of the stem of an acquatic plant used by ancient Egyptians Greeks, and Romans.

The earliest records of poisoning in Egypt date to 3000 BC, and Menes (the earliest known Egyptian king) devoted himself to the research of poisonous plants. it appears the Egyptians were using antimony, copper, crude arsenic, lead, opium and mandrake, and were also the first to extract poison from the peach kernel.

the roman empire ushered in the era of “dinner table” poisoning and it(as illustrated by Nero) became a wicked way to rid yourself of unwanted family members.

Papyrus, Writing paper in ancient Egypt

Georg Moritz Ebers (Berlin, March 1, 1837 – Tutzing, Bavaria, August 7, 1898), German Egyptologist and novelist, discovered the Egyptian medical papyrus, of ca. 1550 BCE, named for him (see Ebers Papyrus) at Luxor (Thebes) in the winter of 1873–74. Now in the Library of the University of Leipzig, the Ebers Papyrus is among the most important ancient Egyptian medical papyri. It is one of two of the oldest preserved medical documents anywhere—the other being the Edwin Smith Papyrus (ca. 1600 BCE).

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Ebers Papyrus Egypt 1550 B.C.E

Ebers Papyrus treatment for cancer: recounting a "tumor against the god Xenus," it recommends "do thou nothing there against".

it is a collection of diverse medical texts that offers the most complete record of Egyptian medicine

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Gula Master of Poison & Charms- Summerian

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History of Toxicology

Greeks were first to use poison as a form of capital punishment. They were also able to standardize the fatal dose of the‘official poison’ ‘hemlock’ given to Socrates in 399 BC
Hippocrates was aware of effect of overdosing by drugs and that it depended on its absorption.
In China circa 250 BC a ceremonial dance form involving burning of poisons and catching its fumes on feather was developed.
Use of Visakanyas (“poison damsels”) is known during Chandragupta’s period

An insight in to modern toxicology and the roles, points of view, and activities of toxicologists can be obtained by examining the historical evolution of the discipline.

Aconite-Chinese arrow poison, hemlock- the state poison of the Greeks. Opium both as a poison and an antidote.

Socrates was given hemlock in 399B.C.E. by the order of the Govt. of the day as ‘capital punishment’ His cup of hemlock being considered adequate for his death.

Theophrastus a student of Aristotle described poisonous plants in his book- De Historia Plantarum . Dioscorides (1^st Century A.D.)a Greek physician in the court of Nero classified poisons in his book on drugs.

Mithridates the great 132-63 B.C.E.made him self immune to poisons by constantly taking taking a bundle of antidotes- 36 (Galen reports 54)- The word mithridatize meaning immune to poison by taking gradually increasing dose of poison has come from his name.

in 246 BC, the Chinese developed a drama form known as the chou ritual, which comprised six ceremonial dances carried out with feathers. The ritual involved the burning of five poisons: cinnabar (mercury), realger (arsenic), green vitriol (copper sulphate), lodestone and an unknown poison — and the catching of the fumes on a bunch of feathers for external use.

To assassinate kings Vishkanyas would saturate their bodies with gradual doses of poison, and then flirt their way into the victims trust.

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History of Toxicology

Lucius Cornelius Sulla the Roman general 138-78 BC enacted a law against poisoning which became a regulatory statute against careless dispensation of drugs in ancient times
Cleopatra the famous queen of Egypt 30 BC committed suicide by using the services of a snake.
Nero AD 37- 68 killed his step brother by giving poison. He had employed food tasters for himself
Dioscorides’s classification of poisons (AD 40) in to plant, animal, & mineral is used even today. He mentions the role of emetics & treatment of snakebite by caustic & cupping.

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History of Toxicology

Middle Ages

Circa the 8th century, an Arabian chemist ‘Geber’ transformed arsenic into an odourless, tasteless powder (As₂O₃, arsenious oxide)that would elude detection for at least ten centuries, thus providing the world with 'inheritance powder'.
During Renaissance professional poisoners like lady Toffana with her Acqua Toffana, ladies Hieronyma Spara & Catherine de medici & others were practicing the art of poisoning in Europe
In Italy around 1455 Lucrezia Borgia with her father pope Alexander VI, and brother Cesare, became notorious poisoner’s trinity.
The most infamous poisoner in France Catherine Deshayes was executed for poisoning cases which included over 2000 infants among her victims

Sandarach or orpiment (arsenic trisulfide)

The snake was called- asp which means a viper or a Greek cobra

Dioscorides’s classification of poisons in to plant, animal, & mineral is used even today. He also valued the role of emetics in poisoning and use of caustics and cupping in snake bite.

Art of poisoning reached alarming proportion during Renaissance when there were professional poisoners like lady Toffana with her Agua Toffana(arsenic containing cosmetics with full instruction for use) ladies Hieronyma Spara (formed the club wealthy married women who wanted to be wealthy widows. Catherine de medici, Borgias and many other families practicing poisoning from generation to generation in Europe . Catherine noted the rapidity of the toxic response(Onset of action), the effectiveness of the compound(potency), degree of response of parts of body(specificity, site of action) and complaints of the victim(clinical sign & symptoms)

Renaissance-Revival of interest in art & literature (14^th-16^th Century). It began in Florence and spread to Venice and Rome and then to rest of Europe

When arsenic compounds are heated under oxidizing conditions (as in air) the oxide As₂O₃, arsenious oxide, is often produced. This is a volatile substance appearing as a dirty white vapour smelling of garlic and condensing as a white powder, or forming small octahedral crystals. Strictly speaking, the name arsenic applies to this compound, not to the metal. In German, the metal is called Arsen, the oxide Arsenik, but in English "arsenic" is used for both. This is by far the most common way that arsenic appears. It is the most common way arsenic is produced and sold at present, and is usually called "white arsenic." White arsenic was described by the Arabic alchemist Geber (Jabir ibn-Hayyan, 760-815) in the 8th century, but he took it for a form of sulphur driven out when metallic arsenic was heated. A little later, the Arab iatrochemist Avicenna (Ibn-Sina, 979-1037) recognized the toxic properties of white arsenic.

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History of Toxicology

The Book of Venoms/ (1424) by Magister Santes de Ardoynis, which told of known poisons at the time, how they worked, and how they could be treated.
A poisoner-assassins' guild called the ‘Council of Ten’ was established in Italy during the 16^th Century by a group of alchemists, to provide 'elimination' services for a fee
A publication called ‘Neopoliani Magioe Naturalis’ (1589) by Giovanni Battista Porta served as a textbook for poisoners.
By 1572, at least 30,000 self- proclaimed poisoners 'sorcerers' were running rampant in the streets of Paris.

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History of Toxicology

By the 17th Century, schools of poisoning had been established in both Venice and Rome
Several attempts were made on the life of Queen Elizabeth I, Henry VIII, and Marie Louise wife of Carlos II of Spain was successfully poisoned by arsenic
In 1662 Louis XIV passed a decree forbidding apothecaries to sell poisonous substances to persons not known to them, and requiring purchasers to register their purposes for the substance

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Golden Age of Poisoning

The Victorian era is generally regarded as the heyday of poisoners.
World's some of most notorious poisoners belong to this period.
Arsenic Act of 1851 was passed to control rampant poisoning by arsenic used as fly paper, rat poison etc.
New poison societies were also being established, including the notorious Philadelphia Poison Ring, disguised as a matrimonial agency.

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19^th& 20^th century

Marsh 1836 and Riensch 1841 found methods for detecting arsenic independently of each other.
At the same time, new and obscure poisons were beginning to emerge in the market, many of them legal medical drugs such as fentanyl, insulin, and various muscle relaxants including Pavulon, and succinylcholine.
Resourceful use of common household chemicals such as antifreeze was also employed.
New methods of poisoning were also introduced,

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19^th& 20^th century

Governments apart from terrorists were also carrying out research into the possibility of using poisons as weapons.

By 1825 phosgene(COCl₂) and mustard gas (bis[B-chloroethyl]sulphide) synthesized and by 1880 more than 10,000 chemical compound were synthesized and studied for their toxicological properties (Magendie [1783-1885]; Orfila [1787-1853]; Bernard [1813-1878]) and others; their research made its impact with enacting of worker’s insurance laws in early 20^th century

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Pallets of 155 mm artillery shells containing "HD" (distilled sulfur mustard agent) at Pueblo Depot Activity (PUDA) chemical weapons storage facility, Colorado USA

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Syria Military 'Moves Chemical Weapons (Sarin nerve gas)To Homs‘ Sky News 14-07-2012

The agents, which may not yet have been weaponised, were moved from previously known stockpile locations

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Bhopal gas disaster- methyl isocyanate (MIC) gas�Dec 2-3of 1984�

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Photographer Pablo Bartholomew came across a man who was burying a child. This scene was photographed by both Pablo Bartholomew as well as Raghu Rai, another renowned Indian photojournalist.

�

Bhopal Gas Tragedy India’s worst industrial disaster. Safety standards and maintenance procedures had been overlooked that triggered a massive environmental and human disaster.

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Died-15,342 Injured-558,125

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Killed By Polonium 210

Nov. 2006 in London

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History of Toxicology

R.N.Chopra 1933 published a book ‘Indigenous drugs of India’ about poisons and antidotes
The race between the quest for the 'perfect poison' and advances in toxicology keeping pace with new poisons continues.
You too can be a toxicologist in two easy lessons, each of ten years.
Orfila (1787-1853) professor of medical jurisprudence, chemistry, & dean in Paris Father of Modern Toxicology

One of Magendie’s student Claude Bernard worked on arrow poisons, mechanism of action of CO poisoning and published a book on toxicology’ An Introduction to the study of Experimental Medicine’(Translated by Greene1949)

You too can be a toxicologist in two easy lessons, each of ten years( Arnold Lehman-circa 1955)

Mathieu Joseph Bonaventure Orfila (1787-1853) is generally regarded as father of modern toxicology. He advocated chemical analysis of viscera from autopsy to detect poisons His book ‘ Traite des Poisons’ published in 1814 laid the foundation of Forensic Toxicology. He was a Spanish. Worked in Paris and took French Citizenship.

INDIGENOUS DRUGS OF INDIA Academic Publishers�Sir R. N. Chopra, I. C. Chopra, K. L. Handa and L. D. Kapur�This is the monumental and immortal work done under the leadership of Sir R. N. Chopra at the Calcutta School of Tropical Medicine and the Drug Research Laboratory, Jammu and Kashmir. The age-old indigenious drugs of India now treated scientifically for the first time in this book. This book is divided into 5 parts and an addendum.�Part I – Medical and Economic aspects of Indian Indigenous�Drugs.�Part II – Potential Drug Resources of India : Pharmacopoeia and Allied Drugs.�Part III – Drugs used in the Indigenous Medicine.�Part IV –Indian Materia Medica.�Part V – Common Bazaar Medicines of India.�Addendum – Index of common vernacular and popular�names. Index of chemical constituents. Index of scientific�names.�ISBN 81-85086-80-X �First edition reprint 2006 �Rs. 500.00

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Definitions

Toxin-

Toxic substances directly produced by living organisms like plants, animals, fungi, bacteria or virus.

Venom-

Is a toxin secreted by animals like snake, or scorpion that is injected to cause its effect

Toxicant-

Poisonous Chemical derivatives Ex. MIC. Similarly Arsenic both naturally as well as due to industrial activity may contaminate shallow wells. Polyaromatic hydrocarbons toxicants are produced during forest fire and also by burning of coal or smoking cigarettes

The derivative forms "toxic" and "poisonous" are synonymous.

poisons are substances that can cause injury, illness, or death to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism. Paracelsus, the father of toxicology states-- "Everything is poison, there is poison in everything. Only the dose makes a thing not a poison".

a poison is often distinguished from a venom. Venoms are usually defined as biologic toxins that are injected to cause their effect, while poisons are generally defined as substances which are absorbed through epithelial linings such as the skin or gut.

Some poisons are also toxins, usually referring to naturally produced substances, such as the bacterial proteins that cause tetanus and botulism. A distinction between the two terms is not always observed, even among scientists.

Animal toxins that are delivered subcutaneously (e.g. by sting or bite) are also called venom. In normal usage, a poisonous organism is one that is harmful to consume, but a venomous organism uses poison to defend itself while still alive. A single organism can be both venomous and poisonous.

Within chemistry and physics, a poison is a substance that obstructs or inhibits a reaction, for example by binding to a catalyst.

The derivative forms "toxic" and "poisonous" are synonymous.

Toxicant- Dioxin(2.3.7,8-tetrachlorodibenzo-p-dioxin[TCDD]) produced during combustion of some chlorinated organic chemical is a toxicant. Similarly Arsenic both naturally as well as due to industrial activity may contaminate shallow wells. Polyaromatic hydrocarbons toxicants are produced during forest fire and also by burning of coal or smoking cigarettes

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Terms Used

Poisons act usually by chemical reaction on the molecular scale, and are absorbed through epithelial linings such as the skin or gut.
A poisonous organism is one that is harmful to consume, but a venomous organism uses poison to defend itself while still alive. A single organism can be both venomous and poisonous.
Risk (Hazard)

Defined as probability of an adverse outcome

Risk Assessment-

Systematic scientific study of potential adverse health effects resulting from human exposures to hazardous agents or situations

like pesticide residue in food, contaminants in drinking water and environmental pollution

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Agent LD₅₀ mg/kg body Wt.

Ethyl Alcohol
Sodium Chloride
Ferrous sulphate
Morphine
Phenobarbitone
Picrotoxin
Strychnine
Nicotine
D-tubocurarine
Botulinum toxin

10000
4,000
1500
900
150
5
2
1
0.5
0.00001

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Toxicity Rating

Usual Fatal Dose
Less than 5 mg / kg
5 to 50 mg / kg
51 to 500 mg / kg
501 mg / kg to 5 gm/kg
5.1 gm /kg to 15 gm /kg
More than 15 gm / kg

Rating
6 Super Toxic
5 Extremely Toxic
4 Very Toxic
3 Moderately Toxic
2 Slightly Toxic
1 Practically Nontoxic

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Acute Versus Chronic Exposure

Poison delivered in single exposure causing poisoning is called ‘acute poisoning’
A dose inadequate for acute poisoning if given repeatedly may cause subacute or chronic poisoning depending on dose and cumulative toxic effects in body
Effect of acute exposure to a poison often differs significantly from subacute or chronic poisoning

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Study of Poisons

Absorption, Distribution, and Excretion
Biotransformation of Xenobiotics

Metabolites are poisonous- Parathion, acetaminophen
Phototoxic Reactions-Tetracyclines, sulphonamides, Chlorpromazine,& nalidixic acid
Photoallergic- Sulphonamides also

Reactive Oxygen Species (ROS)-

Toxicity of Paraquat a herbicide is not due to the chemical or its compound but due to formation of reactive Oxygen species.

Toxicokinetics

Modelling and mathematical description of time taken in absorption, distribution, biotransformation and Excretion

Reactive oxygen species (ROS) are chemically-reactive molecules containing oxygen. Examples include oxygen ions and peroxides. Reactive oxygen species are highly reactive due to the presence of unpaired valence shell electrons. ROS form as a natural byproduct of the normal metabolism of oxygen and have important roles in cell signaling and homeostasis. However, during times of environmental stress (e.g., UV or heat exposure), ROS levels can increase dramatically. This may result in significant damage to cell structures. This cumulates into a situation known as oxidative stress. ROS are also generated by exogenous sources such as ionizing radiation.

Toxic effect in a biological system are not produced by a chemical agent unless that agent or its metabolic breakdown (Biotransformation) products reach appropriate sites in the body at a concentration and for a length of time sufficient to produce a toxic manifestation . Many chemicals are relatively of low toxicity in the native form but when acted on by the enzymes in the body are coverted to intermediate forms that interfere with normal cellular biochemistry and physiology. To appreciate fully the potential hazard one must know about the agent, the exposure and its disposition ( Absorption,distribution and excretion) by the recepient over and above what type of effect it produces and the dose required to produce that effect Major factors that influence toxicity are the route of administration and duration and frequency of exposure.

Phototoxic reactions occur because of the damaging effects of light-activated compounds on cell membranes and, in some instances, DNA. By contrast, photoallergic reactions are cell-mediated immune responses to a light-activated compound. Phototoxic reactions develop in most individuals if they are exposed to sufficient amounts of light and drug. Drug-induced photosensitivity refers to the development of cutaneous disease as a result of the combined effects of a chemical and light. Exposure to either the chemical or the light alone is not sufficient to induce the disease; however, when photoactivation of the chemical occurs, one or more cutaneous manifestations may arise. These include phototoxic and photoallergic reactions. Photosensitivity reactions may result from systemic medications and topically applied compounds. In patients who present with photosensitivity, it is often difficult to differentiate phototoxic from photoallergic reactions. However, they have a number of distinguishing characteristics.

ROS/RNS includes the oxygen-derived free radicals and oxidants, superoxide (O₂^-), hydrogen peroxide, hypochlorite, nitric oxide (NO), hydroxyl radical, nitrogen dioxide, peroxynitrite (ONOO^-), and other amino acid- and lipid-derived radicals. Although ROS/RNS plays an important role in immune-mediated defense against invading microorganisms and serve as cell-signaling molecules, at high concentrations, ROS/RNS are capable of damaging host tissues, i.e., ROS/RNS can modify or damage DNA, lipids, and proteins (4). ROS/RNS levels are controlled through an intricate network of enzymes and antioxidant molecules that are responsible for both production and consumption of specific reactive species. In this regard, intake of dietary antioxidants has received much attention, with the concept being that these molecules can affect disease by modulating the biological reactivity of ROS and RNS (8). In certain pathological conditions, including those that are risk factors for CVD, alterations in the control of ROS/RNS formation and metabolism result in activation of signaling pathways that lead to altered cell function or cell death (9). Such processes are believed to underlie the initiation and development of atherosclerosis and other inflammatory diseases. At lower nontoxic concentrations, however, ROS/RNS modulates redox-dependent pathways that lead to adaptive increases in antioxidant enzymes and co-factors (10). An interesting example is the intracellular antioxidant glutathione, which is induced in endothelial cells by exposure to low concentrations of oxidized low-density lipoproteins (LDL)

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Effects of Chemicals

Desirable (Therapeutic)

UNDESIRABLE

Non-Deleterious

(Side effects)

DELETERIOUS (Toxic effects)

Reversible /Irreversible

Local /Systemic

Pharmacological

Pathological

Genotoxic

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Major Areas of Toxicology

Mechanistic Toxicologists

To find out the risk that toxicants pose

Descriptive Toxicologists

Find out tests to evaluate the risk

Regulatory Toxicologists

Whether risks are low enough to allow marketing

Forensic Toxicologists

Classical function to find out role of poison in homicide, suicide & accidents

Clinical Toxicologists

Study of Diseases caused by toxins & toxicants

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Target Areas of Toxicology

Chemical Carcinogenesis
Genetic Toxicology
Developmental Toxicology
Target Organ Toxicology

Blood, Liver, Kidney, Respiratory, Nervous, Visual including Eye, Heart & vascular, Skin, Reproductive & Immune, And Endocrine systems

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Effect of Poisons

Depending on

Chemical & Physical Properties-

Molecular size,
water and lipid solubility,
ionised/unionised status,
its destruction in GIT and metabolism in liver

Mechanism of Action

Corrosive,
Affecting physiological functions
Affecting enzyme systems
Its own action
Combination of above

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Effect of Poisons

Route of Exposure-

Skin, breathing
oral,
vaginal, rectal,
Parenteral

Intra muscular
Intravenous
Subcutaneous

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Effect of Poisoning

Poisoning may be

Local-skin, eyes, or lungs
Remote
Systemic
General

Severity & Reversibility of Poisoning

Functional reserve of the Pt

Age & pre-existing disease

Functional reserve of the target organ

Age & pre-existing disease

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Factors Modifying the Action of Poisons

Quantity

Generally larger the dose more intense the action

Form – Solid or liquid or Gas
Mode of Administration- oral or parenteral
Condition of the Body- Healthy or ill, young or adult or old

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Classification

No single classification covers all poisons.

Their target organ- kidney/ liver /bone marrow
Use- Pesticide,solvent, food additive etc
Source- toxin/ toxicant (animal, plant, mineral element, human activities etc)
Effects- Carcinogenic, teratogenic,
Physical state- solid, liquid, gas, fume dust etc
Chemical reactivity- explosive, inflammable, etc
Chemical structure- aromatic amine, halogenated hydrocarbon, alkaloids
Poisoning potential- extremely toxic, very toxic, slightly toxic
Biochemical mechanism of action- alkylating agent, sulfhydryl inhibitor, methaemoglobin producer
Air pollutants,occupational hazard, suicidal, homicidal
Acute poisons, chronic poisons

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Classification

Corrosives- Strong Acids & Alkalis
Irritants-

Inorganic

Non-metallic: Phosphorus
Metallic: Lead, Arsenic, Mercury, Copper, Zinc, Antimony, Thallium

Organic

Vegetable: Croton, Castor, Madar
Animal: Snake, Scorpion, Cantharides
Mechanical: Powdered glass, Diamond, Hair

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Classification

Systemic

Affecting Nervous System

Affecting Brain

Somniferous:

Barbiturates; Opium, its alkaloids & Derivatives

Inebriant

Ethyl & Methyl Alcohol, Ethylene Glycol, Ether, & Chloroform

Deliriant

Dhatura, Belladona, Hyosyamus, Cannabis

Affecting Spinal Cord: Nux Vomica, Gelsemium
Affecting Peripheral Nerve: Curare, Conium

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Classification

Systemic

Affecting Cardiovascular System

Aconite, Oleander, Hydrocyanic Acid, Digitalis, Tobacco

Affecting respiratory System

Carbon dioxide Gas; Carbon monoxide Gas, Coal Gas

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Miscellaneous Poisons

1. Mycotoxins-

aflatoxins from affected food

2. Poisoning by Hormones

Insulin

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Sex & age difference in poisoning

Attempted Suicide
Commoner in Females than Males(M:F-1:1.4)

2^nd & 3^rd decades

Completed Suicide
Commoner in Males than Females(M:F-4.7:1)
6^th decade and above in west. In India among young population

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Types of Poisoning Admitted

Type
Accidental
True attempted suicide
Parasuicide
Homicide

% of Total Admission
10 %
10 %
80%
Occasional

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Clinical features in Poisoning

Vomiting, Depressed resp. Pinpoint pupils

Widely dilated pupil, Bladder distension, Absent bowel sound, Cardiac arrhythmia, Upper motor neurone sign
Sweating, Tinnitus, Deafness, Hyperventilation

Opiates& related, Cholinesterase inhibitors, Dextropropoxyphene
Tricyclic antidepressants, Dhatura

Salicylates

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Cont.

Buccal corrosive burns

Characteristic smell

Hypothermia

Skin blisters

Strong acids, alkalies, phenols, cresols, paraquat

Alcohols, volatile hydrocarbons, solvents
Chlorpromazine, Barbiturates
Barbiturates,Tricyclic antidepressants Carbon monoxide

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Poisons causing Pupillary Changes

Miosis	Mydriasis	Nystagmus
Barbiturates	Cocaine	Alcohol
Benzodiazepins	Dhatura	Barbiturates
Caffeine	Carbonmonoxide	Carbamazepine
Carbamates	Alcohol	Phencyclidine
Carbolic acid	Amphetamine	Phenytoin
Opiates	Belladona
Organophosphates	Hyosine

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Initial Care

Treatment must be prompt.

To maintain the vital functions
Prevent absorption of poison from the route of entry

Containers allegedly containing poison seized
Referred to adequately equipped hospital
Preserve & Carry vomitus along with patient
Provide ABC for CPR.
Treat Shock, arrhythmias, and convulsions
Antidote can be withheld till patient stabilised except in certain poisons

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Poisons Urgently Needing Antidote

Carbon monoxide

100% O₂ Or hyperbaric oxygen

Pot.Cyanide & hydrocyanic acid gas

Amyl nitrite inhalation
Sodium nitrite 3% maximum 10 ml
Sod.thiosulphate 25% 2 ml / kg Or
Hydroxocobalamin-thiosulphate mixture 4- 10 gm

Methanol & Ethylene glycol

Ethanol

Opiates

Naloxone- 2 mg I.V to be repeated as necessary

UNIIVERSAL ANTIIDOTE FOR POISONS

Activated powdered charcoal 2 parts by weight

Magnesium oxide 1 part by weight

Tannic acid 1 part by weight

The mixture should be stored dry and when required for use, add 15g to half a glass of warm

water

Cyyaaniidee Anttiidootteess

For inhaled cyanides the patient should be allowed to inhale amyl nitrate for 15-30 seconds

every 2-3 minutes for a maximum of 15 minutes

For ingested cyanides, if the patient is conscious allow him to drink the following:

Solution A 158g of ferrous sulphate plus 3g of citric acid made up to

1 litre in cold distilled water

Solution B 60g of anhydrous sodium carbonate made up to 1 litre in

cold distilled water

The solutions are stored separately and equal volumes are mixed when required for use

For intravenous injection by medical aid, ampoules of 20ml, each containing 300mg of Cobalt

EDTA (trade name Kelocyanor) should be available

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Cont.

Methaemoglobinaemia

Nitrites, azocompounds, aniline dyes, nitrobenzene

Methylene blue 1-2 mg / kg in 1 % soln.
Exchange transfusion if 2 doses fail

Cholinergic agents

Organophosphates & Carbamates

Start atropine 2-5 mg
Decontaminate with soap & water
Pralidoxime 25to 50 mg/ kg I.v.in 30 mts every 8 hrly

Acetaminophen

N-acetyl cysteine(NAC)

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Antidote

Antidote is an agent that counteracts the action of a poison.

chemical antidote one that neutralizes the poison by changing its chemical nature.
mechanical antidote one that prevents absorption of the poison.
physiological antidote one that counteracts the effects of the poison by producing opposing effects.

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Universal Antidote

Universal Antidote:- A mechanical mixture of

Powdered animal charcoal (or burnt toast)- 2 parts by weight,
Magnesium oxide-1part by weight,
Tannic acid (strong tea)- 1 part by weight.
The mixture should be stored dry and when required to be administered add 15 gm of mixture to ½ glass of warm water

Used to be given but now not favoured

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Activated Charcoal

Activated charcoal alone- 30-100 gm as water slurry with purgative. Most important intervention in orally taken poisons.

Given in charcoal: poison ratio of 10:1
Repeat every 2-6 hrs till comes in stool
Not very effective in heavy metals, alcohols, volatile hydrocarbons, and corrosives poisoning

Activated charcoal slurry is prepared by mixing 50 gm (10 spoonful) in a glass of water

Activated Charcoal is a highly absorbent gritty black material that is commonly found in air and water filters. Activated Charcoal is created by carbonizing organic matter in a kiln under anaerobic conditions and activating the material with oxidizing gases like steam or air at high temperatures. This oxidative process erodes the charcoal's internal surfaces and increases its adsorption capacity by creating an internal network of very fine pores. Usually bone char, coconut shells, peat, coal, petroleum coke, and sawdust are the starting materials for making Activated Charcoal.

Good grade activated charcoal considered very effective in preventing absorption of most of drugs and chemicals by adsorbing chemicals on the surface of charcoal particles and therefore reducing absorption from the gut. Activated charcoal also enhances diffusion of poisons from body to gastroentestinal tract and to the charcoal particles. During the last two decades charcoal used alone (not universal antidote containing also magnesium oxide and tannic acid) is increasing with corresponding decrease in use of ipecac induced vomiting and gastric lavage in the treatment of poisoning. Studies have failed to show a benefit in using ipecac or lavage plus activated charcoal as compared to using activated charcoal alone.

Activated charcoal slurry is prepared by mixing 50 gm(10 table spoonful) in a glass of water and given orally or through tube. If charcoal is in excess then poison once attached remains attached without the risk of being desorbed. Activated charcoal should not be used simultaneously with ipecac as the active principle of ipecac is also adsorbed and emetic effect is reduced. Similarly charcoal may also adsorb antidotes given orally and reduce their action on the poison.

Activated Charcoal detoxifies the body in several manners.�1. Purifies the 6-8 liters of digestive fluids that are secreted daily which in turn helps remove foreign substances from the blood.�2. Adsorbs the intoxicant substance and its metabolites that are excreted into the small intestine from the biliary (bile) tract, preventing their reabsorption.�3. Adsorbs drugs that diffuse back into the stomach and intestines.�4. Decreases the detoxification work load of the liver.

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Cathartic

Used in association with universal antidote or charcoal slurry
Purgatives

Mag.Sulph-250mg/kg
Sod.Sulphate 250-500mg/kg,
Sodium citrate250mg/kg
Phosphosoda250mg/kg
Sorbitol-1g/kg

Whole bowel irrigation

With colonic lavage soln.

Colyte, GoLYTELY

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Other Measures

Antidote &Treatment of Specific poisons
Symptomatic Treatment

Pulmonary or brain oedema, convulsion, arrhythmia, hypo/hyperthermia, hypo/hypertension,acidosis,ketosis etc.

Treatment of organ damage

Liver, kidneys, heart, & brain

Supportive care

Maintain physiologic homeostasis until detoxification
Prevent and treat secondary complications

Prevention of reexposure

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