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CHAPTER # 06 CLINICAL TOXICOLOGY
Definition
Simply it can be defined as the study of poison. However more precisely, it can be defined as
It is the branch of medical science which deals with the poison with reference to the source,
characteristics and properties, the symptoms which they produce, lethal dose, the nature of fatal
treatment, treatment actions that are to be taken to combat their actions, diagnosis, quantitative
estimation of the poison. It is concerned with the last responsible for the manufacture, sale and
distribution.
Poison
Any substance which when administered, swallowed or inhaled, act on the body deleteriously is
called poison.
The two important factors which decide the fate of the substance to be labeled poison are:
i. Quantity
ii. Intention
i. Quantity
A poison may be used as medicine in low quantity, and a medicine may be used as poison
in high dose. E.g paracetamol up to 4 gm/day can be used as medicine, however
exceeding its dose further will make it poison.
ii. Intention
It also decides about the nature of a substance. If the intention is to save ones life, it is
medicine. But if the intention is to kill someone or to produce bodily harms, it is poison.
Types of poisoning
There are two types of poisoning:
1. Endogenous poisoning
2. Exogenous poisoning
1. Endogenous poisoning
It is the poisoning due to accumulation of waste products in the body e.g. uremia.
2. Exogenous poisoning
It occurs due to the substance taken from outside of the body.
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Types Of Poisons
Major types involve two groups:
1. Human poison
2. Cattle poison
1. Human poison
It has following sub types:
i. Suicidal poison
ii. Homicidal poison
iii. Stupefying poison
iv. Accidental poison
i. Suicidal poisons
These are used to kill oneself and they act as virulently.
Examples are potassium cyanide, hydrocyanic acid, powdered glass, organophosphorus,
copper sulphate etc.
ii. Homicidal poisons
These are used to kill someone intentionally. They produce disease like symptoms so that
there is time to escape. Examples are arsenic, aconite, organophosphorus compound,
insulin injection etc.
iii. Stupefying poisons
These are used to stupefy other in order for robbery. These produce clouding of mind and
facilitate the act of robbery. Examples includeDatura hyocyamus, Canabis indica.
iv. Accidental poison
This occur due to faulty storage condition, use of quakes remedies or medicines in large
doses.
2. Cattle poisons
It includes:i. Accidental poisons
ii. Intentional poisons
i. Accidental poison
Sometimes cattle poisoning may occur due to eating of food contaminated with poisons
e.g. linseed.
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ii. Intentional poison
Intentional poison may be given to cattle to take revenge of someone out of enemity,
sometimes intentionally done by the farmer for the sake of hide, sometimes farmer
practice it when the animal becomes weak, aged or sick e.g. arsenic, arblus etc.
Effects/ Actions of poisons
The actions of poison can be divide into four groups.
1. Local action
2. Remote action
3. Combined action
4. General action
1. Local action
As the name indicates the effects of poisons are limited to the area of body which is in
contact with the poison. For example;
Corrosives produce inflammation and ulceration at the site of contact.
Atropine produces pupil dilatation and exhibits naked eye appearance at post
martum examination.
2. Remote actions
These are also known as systemic effects. In this case, the poison is absorbed from the
site of contact into the blood and produce systemic effects. Two types of systemic effects
may be observed:
i. Specific effects
The effets produced are specific to specific organ or tissue e.g.
Opium acts on cerebrl cortex.
Strychnine acts on spinal cord.
Curare acts on motor nerve endings.
ii. Non-specific actions
In this case, the poison act non specifically after absorption e.g. oxalic acid
produces kidney problems.
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3. Combine actions
It is the combination of local actions as well as systemic actions. It means they produce
inflammation at the site of contact locally and then produce systemic effects e.g. oxalic
acid and carbolic acid locally produce inflammation and then systemic effects in the form
of renal failure and CNS disturbances.
4. General actions
They are almost used to affect all parts of body e.g. arsenic, sulphuric acid, DDT etc.
Classification Of Poisons
Poisons can be classified in different manners. One of the simple classifications classifies poison
into following groups:
1. Corrosives
2. Irritants
3. Neurotic poisons
4. Asphyxiants
5. Cardiac poisons
6. Miscellaneous
1. Corrosives
These are the poisons which causes inflammation and ulceration.
These can be subdivided into two major groups:
A. Strong acids
B. Strong alkalies
A. Strong acids
These further include:
i. Mineral acids
- Sulphuric acid- Hydrochloric acid
- Nitric acid
ii. Organic acids
- Oxalic acid
- Carbolic acid
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- Acetic acid
iii. Vegetable acid
- Hydrocyanic acid
B. Strong alkalies
These include;
- KOH
- NaOH
2. Irritants
These are the substances which produce inflammation of mucosa but do not produce
ulceration. They produce vomiting, diarrhea, abdominal pain and when applied on the
skin, they produce skin eruptions.
These include:
i. Acids
ii. Inorganic irritants
a. Metals : arsenic, antimony, copper, lead.
b. Non metals: chlorine, bromine, iodine, phosphorus.
iii. Organic irritants
a. Vegetable organic:- Castor oil
- Proton oil
- Capsicum oil
b. Animal organic:
- Snake bite
- Scorpion bite
- Other animals bites
3. Neurotic poison
They act on the nervous system. They produce intense effects even in dilute form.
Its further subtypes include:
i. Cerebral
- Somniferous (opium): Morphine, heroin.
- Inebriants: Alcohol, insecticides, hypnotics, oleander.
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ii. Spinal
- Nux vomica
iii. Peripheral
- Tubocurarine
4. Asphyxiants
These act on the respiratory system. These include:
- CO
- CO2
- Water
- Severage gases
5. Cardiac poisons
These include:
- Digitalis- Aconite
- Tobacco
6. Miscellaneous
i. Analgesics
- Aspirin
- Paracetamol
ii. Antihistamine
- Diphenhydramine- Terfinadine
iii. Tranquilizer
- Diazepam
- chloral hydrate
iv. Antidepressents
- Tricyclic antidepressents
- MAO inhibitors
v. Hallucinogen
- Lysergic acid
- Cannabinolvi. Stimulants
- Amphetamine
- Caffeine
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Types Of Poisoning
Poisoning can be divided into four types:
i. Acute poisoning
ii. Chronic poisoning
iii. Fulminant poisoning
iv. Sub-acute poisoning
i. Acute poisoning
In this case, the poisoning occurs due to exposure to the poison on a single exposure.
After absorption systemic effects are produced. They are well established and strong, and
if there is no absorption, then local effects are produced i.e only local tissues are
destroyed e.g. poisoning due to corrosives.
ii. Chronic poisoning
It is long term, repeated and continous exposure to the poison. In this case, the patient
gradually becomes ill or becomes ill after long latent period. This usually occurs in small
continuous doses like mercury and lead poisoning.
iii. Fulminant poisoning
It occurs by taking massive doses of the poison. The victim dies rapidly without
preceeding symptoms. It is the worth form of acute poisoning.
iv. Sub-acute poisoning
It lies somewhere between acute and chronic poisoning.
Toxicity Rating Of Poisons
Gosselin and his colleagues proposed toxicity rating for the first time and it was reported that
higher the toxicity, greater would be the potency and worse would be the prognosis.
The toxicity rating ranges from 1-6 and can be tabulated as follow:
Toxic Quantity Toxicity rating Remarks
< 5 mg/kg 6 Super toxic
5mg50mg/kg 5 Extremely toxic
50mg500mg/kg 4 Very toxic
500mg5gm/kg 3 Moderately toxic
5gm15gm/kg 2 Slightly toxic
> 15gm/kg 1 Non- toxic
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Toxidrome
The cluster of sign and symptoms in a patient after poisoning is known as toxidrome.
It is important for physician and pharmacist because it helps in identifying which type of poison
has been taken by the patient, so that specific antidote can be given.
Opioid toxidrome:
- Hypotension
- Pinpoint pupil
- Respiratory depression
- Impaired consciousness
Cholinergics toxidrome:
- Salivation
- Lacrimation
- Urinary and fecal incontinence
- Vomiting
- Abdominal pain
- Diaphoresis
Anticholinergics toxidrome
- Tachycardia- Dilatation of pupil
- Dry and warm skin
- Urinary retention
- Drying of mucosal membrane
Antidotes
These are the substances which are used to counteract the effects of poison.
Criteria/ Condition when to use antidotesi. When the poison may not have been completely removed by emesis or gastric lavage or
when these procedures are contraindicated.
ii. When the poison has been absorbed.
iii. When the poisons are administered by the route other than the oral route.
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Classification Of Antidotes
Different types of antidotes are available which can be classified into following groups.
1. Mechanical or physical antidotes
2. Universal antidotes
3. Chemical antidotes
4. Receptor antidotes
5. Functional antidotes
6. Pharmacological antidotes
7. House-hold antidotes
1. Mechanical antidotes
These are used to impede/inhibit the absorption of poison. These include:
i. Demulcent
ii. Bulky food
iii. Activated charcoal
i. Demulcent
These produce coating on the mucosa and thus the absorbance of poison is
inhibited.
Examples: Fats, oils, milk, egg albumin etc.
ii. Bulky food
Bananas are used to inhibit the absorption of poison. It is particularly used for
powdered glass poisoning because bananas tend to adsorb the powdered glass
poisoning.
iii. Activated charcoal
It is the best adsorbent due to pores. 1gm of activated charcoal is equivalent to
1000 m.
Formation of charcoal:
When the wood pulp is heated at 900 C, charcoal is formed which is inactive. It
can be activated by passing it over steam or treating it with acid.
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Mechanism: Since it is adsorbent in nature, so it traps poison particles in the
stomch or intestine and form strong chemical bonds with the poison. This
complex formed is then excreted from the body.
It is especially used for alkaloidal poisoning. However it is not suitable for :
- Acids
- Alkalies
- Cyanides
- Iron
- Poisons which are water solube.
- In case when intestinal sound (motility) is lost.
Dose:
Children: 1 gm/kg
Adults: 50 gm
2. Universal antidotes
These are the antidotes which are used when the nature of poison is unknown or when it
is suspected that two or more poisons are invoved. Here is an example of universal
antidote, with its contents and quantity.
Contents Quantity Used for
Activated charcoal 2-parts Adsorbing alkalies
MgO/CaO 1-part Neutralizing acids
Tannic acid 1-part Adsorbing alkaloids and
metals.
3. Chemical antidotes
These are used to neutralize the poison either by forming insoluble compounds or byundergoing oxidation to produce neutral compounds.
Examples:
Dilute acetic acid neutralizes alkalies.
MgO neutralizes acids.
Magnessium sulphate neutralizes carbolic acid.
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Lime neutralizes oxalic acid.
Potassium per mangnate neutralizes barbiturates and cyanides.
4. Receptor anti dotes
These are used to compete with the poison for the receptor. They have strong affinity for
the receptor as compared to the poison. So they tend to inhibit the effects of poison. This
is called competitive antagonism. For example; Naloxone for morphine and Atropine for
physostigmine.
5. Functional antidotes
These act on the same biological system but on the receptors that are entirely different
from the receptors occupied by poison. They are used to reverse the effects of poison.
For example,
i. In anaphylactic reaction due to drugs, there is bronchoconstriction, so epinephrine
is used to cause normal breathing
ii. Atropine for pilocarpine.
6. Pharmacological antidotes
These are also known as chelating agents and used in metal poisoning. In metal
poisoning, metals form complexes with the body cells. When pharmacological antidotes
are given, they replace the metal ions from metal ions-body cells complex and form
complex with the metal ions called chelating agent-metal ions complex . this complex is
water soluble and so excreted out.
Examples:
i. BAL (British Anti Leuisite)
Nowadays BAL is called Dimercaprol. It is used in lead, mercury and arsenic
poisoning. It is sulphydral group protector.
Dose: 3mg/kg every 4-hrs on ist day; then dose is decreased and interval is
increased after 2 3 days. 10 days treatment is recommended for mercurypoisoning.
Toxicity: tachycardia, vomiting, nausea, mouth burning sensation.
Contraindication: Liver damage
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ii. Penicillamine
It is used in copper, lead and zinc poisoning. It has less toxic effects.
Contraindications are similar to penicillin.
Dose: 3060mg.
iii. Calcium-sodium ededate
It is used in copper, lead, mercury, iron, cobalt and manganese poisoning.
It is generally used for any metal that has more binding affinity/capacity as
compared to calcium. It forms complexes with the calcium, causes it to excrete
and produces hypocalcemia. Similarly it causes lead to move from bones to the
blood to be excreted out.
Contraindications: Renal failure
Toxicity: kidney damage, nasal congestion.
Dose: 12gm
iv. Defroxamine:
It is used in case of iron poisoning. It is combination of ferrous and ferric ions. It
is used to remove iron in case of haemosiderin (iron-storge complex) and spare
the iron of cytochrome and haemoglobin.
7. Household antidotes
These are used in case of emergency at homes. These include:i. Strong tea in case of alkaloidal poisoning.
ii. Starch for iodine.
iii. Lime for oxalic acid.
iv. Meshed potatoes and milky bananas are good adsorbent.
v. Lemon and orange for alkali poisoning.
vi. Milk of magnesia or suspension of soap should be used for acid poisoning.
Role Of Pharmacist In The Treatment Of Poisoning
The key roles of pharmacist are:
1. Assisting th medical team.
2. Act as an advisor
3. Availability of antidotes
4. Management of stock level
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5. Pharmacist in emergency care unit
6. Prevention of unintentional poisoning
7. Plan of therapy
8. Classification of poisoning agents on the basis of treatment.
1. Assisting the medical team
In clinical toxicology, Pharmacist being expert in drug, through physical examination
plays important role in identifying the poison on the basis of toxidrome i.e pharmacist
evaluate the patient on the basis of symptoms and detect the nature of poison.
Clinical toxicology depends upon three important factors:
i. Correct diagnosis: To identify the poison on toxidrome basis.
ii. Assessment of severity: i.e to check mortality or morbidity on toxidrome basis.
iii. Appropriate initial management: It includes to restore the vitals i.e ABC
A = cleared AIRWAY
B= normal BREATHING
C= CIRCULATORY RESUCITATION
Life threatening consequences like hypertension, hypotension, hyperthermia,
hypothermia, tachycardia, bradycardia, cardiac arrhythmias and respiratory
depression should be treated first.
2. As an advisor
Pharmacist plays a vital role in providing advice on therapy regimen and complications
due to poison. After identifying the poison on the basis of toxidrome, the pharmacist can
advise in the light of toxidrome.
3. Availability of antidotes
Pharmacist has got vital role in poison control center and it is his responsibility to make
available antidotes according to the urgency of clinical needs all the time in sufficient
quantity.
4. Stock level
In managing the stock level pharmacist has got dual responsibilities.
i. In usual routine, poisoning cases appear seldomly, so the stock level is kept also
accordingly, keeping the routine need in mind. However, sometimes due to
certain epidemiology in a particular locality, frequent cases may be reported. In
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this case, the pharmacist has to maintain sufficient stock by considering
epidemiology in that particular area.
ii. The pharmacist should also try to find the root cause beyond that epidemic
poisoning in that particular area.
5. Pharmacist in Emergency Care Unit
The pharmacist busy at Emergency Care Unit must have the basic skills to counteract the
situation due overdose of paracetamol, benzodiazepines, antidepressents etc i.e must be
expert in drugs oriented overdose counteracting.
6. Prevention of unintentional poisoning
Unintentional poisoning can be prevented by by considering the core aspects of safe drug
use as well as case history of the patient.
i. Safe drug use: It is the responsibility of pharmacist to tell and explain each and
every aspect of drug to the patient like dose, frequency of administration, side
effects, toxicities etc.
ii. Case history: If a poisoning case is brought to PCC regarding any drug, the
pharmacist is responsible to take complete history of the case e.g. it might be a
case that a woman suffering from epilepsy is prescribed with cap: dilantin
(phenytoin) 30 mg b.i.d and she takes three capsules at a time, three times a day in
order to improve her health soon. Az a result, she suffers from severe vertigo. In
this case it is the responsibility of the pharmacist to take the history .
Thse are the two pre-requisite factors for preventing unintentional poisoning.
7. Plan of therapy
The pharmacist must know the plan of therapy which consists of four basic plans:
i. Decreasing the absorption of poison.
ii. Increasing the elimination of poison.
iii. Availability of specific antidotes.
iv. Managing the local exposure.
How much time has passed after the poisoning, the plan of therapy would change
accordingly e.g. if 15 minutes has passed, the plan may be decreasing the absorption,
if an hour has passed, the plan may be to increase the elimination etc.
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8. Classification of toxic agents
It is the reponsibilty of clinical pharmacist to classify the toxic agents into two groups on
the basis of treatment:
i. Those agents for which specific antidotes are available.
ii. Those agents for which specific antidotes are not available.
Poison Control Center
Pre-requisite
Different types of pre-requisite responsible for establishment of PCC are :
i. Recognition of problems of poisoning ( either poisoning case is intentional or
unintentional).
ii. Special facilities necessary to deal such cases.
iii. Availability of health professional who are expert in human toxicology.
First PCC was launched in North America in 1950.
Definition
It is a special information center set up dealing with how to respond to potential poisoning .
Functions/Services/Layout/Frame of PCCFollowing are the basic services rendered by PCC.
i. Provision of toxicological information and advices.
ii. Management of poisoning cases.
iii. Provision of lab analytical facility
iv. Toxicovigilence activities ( i.e identification, investigation and evaluation of potential
hazards in the environment).
v. Patient education program.
vi. Training programs for public as well as health care team members.
vii. Treatment of poisoning cases.
viii. A toll free communication system.
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Role Of PCC In Determining The Factors Influencing The Poisoning:
Under this, PCC covers following factors which influence the poisoning.
i. Route of administration
ii. Idiosyncracy
iii. Age
iv. Addiction
v. Dose
vi. Health state
vii. Concentration of poison
viii. Chemical state of poison
ix. Physical state of poison.
i. Route of administration
Poison are administered usually by either oral route or parentral route such as
epidermically, eddermically, pervesically ( direct into the urinary bladder) , I.M, I.V etc.
For poison, rapid action occurs via injectible route than oral. So the PCC has to
determine the route of administration for poisoning as it will further assist in managing
that very case.
Furthermore PCC should also educate the patient and health care team members about
the route of administration of drugs because any wrong administration of drug may resultin life threatening consequences, even death.
ii. Idiosyncracy
It means allergy or intolerance. Due to idiosyncracy the effects produced may be ill-
health or even death. In this case the patient should be told that if he/she has suffered
from any anaphylactic response after taking any drug, food like eggs, shell fish etc,
he/she should never take that again as these are actually poisonous for him/her.
iii. Age
Age has relationship with the poisoning in the sense that sometimes a dose safe for adult
may be poisonous for children e.g. if for adult, the lethal dose of a certain drug is 1gm,
then in children its lethal effects may be observed at 500 mg (although 500mg is safe for
adult).
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iv. Addiction
Prolong Usage of some drugs may lead to addiction or habit formation. So for such
drugs, the PCC should ist determine that whether the person is addicted or not. The
addicted and non addicted patients should be treated in different ways.
v. Dose
In very small dose, poison is used as medicine but in high doses, a medicine may be used
as poison. So PCC should identify that either poisoning has occurred due to overdose of
certain medicine or poison has been taken.
vi. Health state
It is important to consider the health status of the victim. If the patient health status is
good, he/she can withhold poisoning for long time as compared to the one with week
health status.
vii. Concentration/chemical state of poison
The affects of poisoning are also dependent upon concentration. If concentration is high,
affects produced are strong and if concentration of poison is less, affects produced are
also less severe .e.g. conc. Sulphuric acid produces harsh effects than dil. Sulphuric acid.
viii. Physical state of poison
Poisoning effects also depend upon the physical state of the poison. If the solubility of a
poison is high, the rate of absorption will also be high and, so the effects will be rapidly
produced and vice versa.
Poison may be solid, liquid or gas. The order for onset of effects is as :
Gas > liquid > solid
In case of solids, fine solids produce rapid effects as compared to the coarse solids.
Staff of PCC
The staff of PCC includes:
i. Pharmacologist
ii. Emergency ward specialist
iii. Paediatrician
iv. Any other qualified staff who is able to assume the responsibility of full treatment.
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Role Of Pharmacist In PCC
Pharmacist has got following role in PCC:
i. Primary role: i.e poison and drug abuse prevention.
ii. Secondary role: it includes the treatment thereof.
iii. Tertiary role: tertiary role is to initiate development of special facilities to treat the
poisoning case.
Preventive role of pharmacist
i. To provide adequate directions to the patient for safe use of medications.
ii. To affix precautionary labels before dispensing or handing out of medicines to the
patient.
iii. To provide explanation about precautionary labels because sometimes the patient may
not appreciate to look at the precautionary labels.
iv. To make awareness about poison, pharmacist has to participate in the education program
for patient.
v. To inform the patient about adequate safe storage of the dispensed medicines.
Role of pharmacist in teaching
Pharmacist is also involved in teaching facility to teach the pharmaceutical mathematics and
pharmacology to nurses and other health personnel.
The pharmacist can render teaching services in two types of programs:1. Internal teaching program
2. External teaching program
1. Internal teaching program
It involves:
i. Teaching to the student nurses.
ii. Conducting of therapeutic seminars for graduate nurses, health professionals and
other professionals as well.
iii. Patient education programs
iv. Training of clinical pharmacistv. Training of residence of hospital pharmacy.
2. External teaching program
In external teaching program, pharmacist is the soul instructor in-charge of study or
course in the college (college of pharmacy).
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