Toxicology Clinical Pharmacy

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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).