Pharmacotherapy of Toxicology & Heavy metal poisoning

1. Presented By
Dr. Manoj Kumar
Assistant Professor
Department of Pharmacology
Adesh Medical College & Hospital Ambala Can’t

2. Toxicology
 Science that deals with study of poisons,
their source, properties, actions, detection
& treatment of poisoning
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3. Poison
 Any substance, which if administered or comes in
contact with a living being produces ill health, disease or
death.
 All substances are poisons depended on concentration.
 Poison may be of synthetic, mineral, vegetable or animal
origin.
 WHO estimates over 30 lakh poisoning cases with 2,20,000
death per year worldwide.
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4. How poisons enter the body:
 Inhalation
 Ingestion
 Absorption
 Injection
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5. Poisoning
 Accidental, suicidal, homicidal, industrial, medical
purpose.
 Acute, sub acute, chronic.
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6. Classification of Poison
 Poison can be classified based on type of action
exerted or based on Medicolegal purpose.
 Classification based on action
1. Corrosive
2. Irritants
3. Neurotoxic
4. Cardiac poison
5. Respiratory poison
6. Miscellaneous.
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7. Classification based on
medicolegeal purpose:
1. Suicidal
2. Homicidal
3. Accidental
4. Stupefying (dose related adverse effects)
5. Abortificient ((chiefly of a drug) causing abortion.
6. Cattle poison
7. Arrow poison (poison arrow heads)
8. Food poisoning
9. Drug dependence.
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8. Classification based upon action
 Corrosive:
1. Acids: inorganic, organic and vegetables
Inorganic acid: H2SO4, HCl, Nitric acid
Organic acids: Acetic acid, Salicylic acid, Oxallic acid,
Carbolic acid.
Vegetable: Hydrocyanic acid, Potassium cyanide.
2. Alkali: Hydroxides and carbonates:
a) Hydroxides: of sodium , potassium & ammonium.
b) Carbonates of sodium , potassium and ammonium.
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9. Irritants:
a) Inorganic: Non metals like Phosphorus, Boron,
Fluorine, Chlorine, Bromine etc. AND metals like
Arsenic, Lead, Mercury, Iron, Zinc etc.
b) Organic : Vegetables and animals: - Vegetables: castor
oil, croton oil and seed, ergot, capsicum. Animals:
Snakes, Scorpion, Spiders and poisonous insects.
c) Mechanical: Powdered glass, Diamond rust, Hair pin,
Needles, Nails etc.
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10. Neurotoxins:
A: Cerebral neurotoxins:
1. Narcotic or somniferous: Opium and its alkaloids
like morphine, codeine, thebaine, Noscapine and
Narcine etc.
2. Inebriants: Alcohol, anesthetic agents (ether,
chloroform etc), Fuels ( Kerosene, petrol), Sedative
and hypnotics(Barbiturates, Chloral hydrate),
Insecticides( DDT, organophosphorus compounds
like parathion and malathione.
3. Deliriants: Dhatura, Atropa belladonna, Cocaine,
Camphor etc.
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11. B) Spinal Neurotoxins:
a) Excitants: Nux vomica and its alkaloid strychnine.
b) Depressant: Lathyrus sativus and jasmine.
c) Peripheral neurotoxins: Conium & curare
 Cardiac poison: - Digitalis, Tobacco
 Respiratory Poison: - Carbon monoxide, Carbon
dioxide, Sulphur dioxide, - War gas ( tear gas, Chlorine),
Phosphine etc. 11

12. Miscellaneous: -
 Analgesics & Antipyretics
 Antihistaminics
 Tranquilizers Stimulants e.g. Amphetamines
 Antidepressants
 Hallucinogens: LSD
 Food poisoning
 Drug dependence.
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13. Classification based on
Medicolegal purpose
Suicidal:-
 The near ideal suicidal poison are opium and
barbiturates.
 Commonly used suicidal poison in India are:
Arsenic, Cyanide, Phenols etc.
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14. Homicidal:
 Homicide is the act of a human being killing
another human being.
 The near ideal homicidal are Thallium and
Fluoride.
 Commonly used homicidal are: Snake venom,
Corrosive, Opium, Cyanide etc.
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15. Accidental poisons:
 Accidental poisoning occurs due to:
 Keeping insecticide at home and field.
 At place of work or industry.
 Carelessness ion storing poisons.
 Quack remedies: fraud remedies - Snake, scorpion
and insect bite.
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16. Stupefying poisons: -
 These are the poisons which alter the
consciousness of person and are commonly give
for purpose of rape, robbery, dacoit, theft, etc.
 E.g. Dhatura, Cocaine, Alcohol, Arsenic, Cigarette,
charas, ganja & bhang.
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17. Abortificient:
 Used to induce criminal abortion. E.g. Lead,
Arsenic, Ergot, Castor oil, Croton oil Calotropis
etc.
 Cattle poison: used to kill cattle. E.g. Arsenic,
Snake venom, Insecticides etc.
 Arrow Poison: which commonly applied on
arrow head. E.g. Curare, Abrus, Calotropis, Snake
venom, Aconite etc.
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18. Treatment
 Stop the source of poison
 Limit the absorption of poison
 Induce vomiting
 Ipecac syrup, mustard powder
 Activated charcoal, stomach wash, change
clothing, wash with soap & water
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19. Treatment of poisoning
 ABC
 Airway
 Clear airway, suction, endotracheal tubing
 Breathing
 Artificial ventilation, O2 therapy
 Circulation
 Assess pulse rate, BP, urine output
 IV fluids, raise foot end
 Vasopressors: Dopamine, phenylephrine
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20. Treatment of poisoning
 Specific therapy
 Antidote, Ethanol in methanol poisoning
 Other measures
 Forced diuresis
 Hemodialysis, peritoneal dialysis
 Barbiturates, ethanol, methanol, phenytoin, Li,
salicylates, thephylline
 Acidic drugs & basic drugs
 Forces alkaline/acid diuresis
 Furosemide, Na bicarbonate/ ascorbic acid, IV fluids
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21. Treatment of poisoning
 Convulsions
 Diazepam 10 mg slow IV
 Phenytoin 10mg/kg IV
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22. Antidotes
 Antidote is defines as the substance which counteract the
deleterious effect of the poison without itself being
harmful to the body.
 Antidotes are used in case of : - Where emetics and gastric
lavage is contraindicated.
 Types of ANTIDOTES are:
A) Physical antidotes, (B) Chemical Antidotes,
(C) Pharmacological & Physiological antidote,
(D) Chelating agent, (E) Universal antidote,
(F) Household antidote.
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23. Antidotes
 Physical: Activated charcoal.
 Weak alkalies (Calcium oxide and magnesium oxide) for
acid poisoning.
 Weak acids( Acetic acid, Vinegar, Lime juice) for alkali
poisoning.
 Calcium carbonate for oxalic acid poisoning.
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Chemical Antidotes

24. .
 Sodium & magnesium sulphate for lead poisoning.
 Copper sulphate for Phosphorus poisoning.
 Sodium thiosulphate for iodine and cyanide poisoning.
 Potassium ferrocyanide for copper poisoning.
 Hydrated ferric oxide for Arsenic poisoning.
 Sodium formaldehyde sulphoxylate in Mercury poisoning.
 Tannins: forms a complex with Metal, Alkaloid and
Glucosides.
 KMnO4 (1 in 1000) and weak solution of iodine (10-15 drops
per 100 ml) oxidizes the poison
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25. Pharmacological or Physiological antidotes
 Atropine for Pilocarpine poisoning.
 Atropine for organophosphorus poisoning.
 Naloxone for opium and morphine poisoning
 Chloroform for strychnine poisoning.
 Physostigmine for Dhatura poisoning.
 Ethyl alcohol for Methanol poisoning
 N-acetyl cystine for Paracetamol poisoning.
 Immunotherapy: Digoxine antibodies & snake antivenin
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26. Household Antidote
 These are substances which are available usually in the
house and can be used in case of poisoning.
 Milk orally is effective in almost all ingested poison.
 Charcoal from burnt bread and toasts.
 Banana, Potato and Demulcent are physical antidotes.
 Common salt and mustard powder as emetic agent.
 Starch solution for iodine poisoning.
 Milk of magnesia for acid poisoning.
 Vinegar, Lemon Juice, Orange juice for alkali poisoning.
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27. Universal antidote
 Part tannic acid
 1 part milk of magnesia
 2 parts burnt toast
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28. .
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29. Heavy metals
 Not metabolized in body
 Bind to functional group of essential tissue
enzymes & inactivate them
 Interfere with normal cell functions
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30. Mercury
 Elemental mercury
 Not absorbed from GIT: Nontoxic
 Inhaled: chest pain, shortness of breath, gastro-enteritis,
n, v, tremors, renal, CNS damage
 Inorganic Hg (Hg+, Hg+2)
 Acute: Severe h’gic gastroenteritis, ATN
 Chronic: gingivostomaitis, renal toxicity
 Organic Hg (methylHg)
 Fish (Minamata’s disease)
 Birth defects, CNS toxicity ( memory loss, depression,
irritability)
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31. Mercury- PK
 Elemental: absorbed from lungs
 Inorganic Hg- Corrosive
 Organic Hg: both lungs, GIT
 Accumulation in kidney, brain
 Excreted by kidneys, faeces
 Traces found in hair, nails
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32. Lead
 Chronic exposure: diet
 Cooking utensils, storage of food in them, paints
 Organic lead: (tetraethyl, methyl lead)
 Antiknock agents in petrol
 Absorbed through skin, lungs
 Mine workers, smelters, lead acid battery workers
 Acute
 Inhibition of heme biosynthesis, excretion of
porphyrins in urine
 Abd colic, renal tubular damage, neuropathies,
encephalopathy
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33. Lead
 Chronic
 Anemia, lethargy, weakness, peripheral neuropathy,
tremors, anorexia
 CNS toxicity: hallucinations, convulsions, coma
 Wide distribution (bone marrow, brain, kidneys,
liver)
 t1/2: months-decades
 Excretion: renal, fecal, skin, hair, nail, sweat
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34. Arsenic
 Environmental, occupational exposure
 Carcinogen
 Acute: gastroenteritis, laryngitis, dehydration,
shock
 Sweet garlicky odour in breath, stool
 Chronic: skin irritation, color change, hair loss, n,
bone marrow depression, anemia
 Accumulates in hair, nails
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35. Iron
 Chronic: hemosiderin accumulation in liver,
spleen, hemochromatosis
 Acute: vomiting, diarrhea
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36. Chelating agents
 Heavy metal antagonists
 Bind to heavy metals & forms a complex
 Stable, non-toxic, water soluble
 Eliminated by kidneys
 CaNa2EDTA, Dimercaperol, d-penicillamine,
desferrioxamine
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37. Ca disodium edetate
 Chelates Pb, Zn, Cd, Mn, Hg, Fe
 Given slow IV: 50-75mg/kg/d q6h x 3-5d
 Adverse effects
 Nephrotoxicity, fatigue, fever, myalgia, dermatitis
 Uses
 Lead poisoning
 Zn, Mn, iron poisoning
 Copper poisoning
 Severe hypercalcaemia
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38. Dimercaprol
 2,3 dimercapto-1- propanol
 British Anti-Lewisite (BAL)
 Developed in antidote to Lewisite (war gas)
 Chelates As, Hg, Bi, Pb, Cu, Antimony (Sb)
 Given IM (5mg/kg stat fol by 2-3 mg/kg q8h x
2d, then, OD x 10 days
 Urine must be kept alkaline
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39. Dimercaprol
 Adverse effects: Hypertension, tachycardia, vomiting,
sweating, headache
 Uses
 As, Hg, Pb poisoning
 Gold, bismuth poisoning
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40. Analogs of Dimercaprol
 Less toxic, more water soluble
 Succimer: PO, 10mg/kg q8h x 5days fol by
10mg/kg q12h x 14days
 More specific for lead toxicity esp kids
 Also given in Hg poisoning
 Adverse effects: anorexia, vomiting, diarrhea,
rash
 Unithiol: PO, IV; 3-5mg/kg q 4h
 For Hg, As, Pb poisoning 40

41. d-penicillamine
 Chelates Cu, Hg, Zn, Pb
 Given orally: 500mg BD
 Toxicity
 Anaphylaxis, dermatitis, aplastic anemia
 Uses
 Cu, Hg, Zn, Pb poisoning
 Wilson’s disease
 Rheumatoid arthritis
 Cystinuria
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42. Desferrioxamine
 High affinity for Iron, forms stable complexes
 Chelates Fe from haemosiderin, ferritin
 Does not chelate Fe in haemoglobin,
cytochrome
 Given IV: 10-15mg/kg/hr; IM: 50mg/kg
 Adverse effects: Allergic reactions, diarrhea,
muscle camps, blurred vision
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43. Desferrioxamine …
 Uses
 Acute iron poisoning (DOC)
 Chronic iron poisoning (Thalassaemia
patients)
 0.5-1g/d IM; 500mg BD
 Aluminium toxicity in renal failure (along
with hemo-dialysis)
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44. Deferiprone
 Orally effective
 Used as an alternative
 Uses
 Thalassemia major (blood transfusion dependent iron
overload)
 ADRs
 Zn depletion, anorexia, altered taste, joint pain, neutropenia
 Status: Not used
 Antidote for acute Fe poisoning: Desferrioxamine (IM)
 Antidote for chronic Fe overload: Deferiprone (oral)
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45. Deferasirox
 Oral Fe chelator
 Better tolerated
 Major adverse effect
 GI upset
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