Concept about organophosphorus poisoining...

1. Acute Organophosphorus And Carbamates
Posioning
Presented By: Pooja Rimal
M.Pharm, 1st Sem
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2. Introduction
 A compound containing phosphorus bound to organic
molecule is known as organophosphorus compound.
 Carbamates are derived from a carbamic acid and cause
carbamylation of acetylcholinesterase at neuronal synapses
and neuromuscular junctions.
 Carbamates are a class of insecticides structurally and
mechanistically similar to organophosphate (OP) insecticides.
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3. Introduction
 Oraganophosphorus and
carbamates are wide spread use
throughout the world, mainly in
agriculture.
 Exposure to organophosphorus and
carbamates commit to suicide is a
key problem, particularly in
developing countries.
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4. Classification of Organophosphates
 Highly Toxic : (Parathion, Tetra-ethyl Pyrophosphate),
These are mainly used agriculture insecticides.
 Intermediately Toxic : (Trichlorfon, these are used as animal
insecticides.
 Low toxicity: (Malathion, Dichlorovos), these are used for
household application.
 Fatal dose: Parathion- 80 mg IM or 175 mg orally
 Aldicarb, carbaryl, oxamyl and terbucarb are carbamates.
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5. Mechanism of Action
 They possess a similar MOA to the irreversible phosphorylation
of acetylcholinesterase by organophosphates, carbamates bind
to acetylcholinesterase reversibly.
 Acetylcholine is the neurohumoral mediator at the cholinergic
junctions.
 Since acetylcholinesterase is the enzyme that degrades
acetylcholine by stimulation of a nerve, by inhibiting
acetylcholinesterase, organophosphates allows acetylcholine
to accumulate and result in initial excessive stimulation
followed by depression
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Figure: MOA of acetylcholineesterase

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EXAMPLES

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Muscarinic receptors Nicotinic receptors Central receptors
Cardiovascular Cardiovascular General effects
Bradycardia, Hypotension Tachycardia, Hypertension Anxiety, Ataxia
Respiratory Musculoskeletal Insomnia
Rhinorrhoea, Cough Weakness/ cramps Convulsions
Bronchospasm Paralysis Coma
Gastrointestinal Fasiculations Tremors
Nausea/ vomiting/diarrhoea Respiratory depression
Abdominal cramps Circulatory collapse
Increased salivation
Sign and symptoms

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Muscarinic receptors
Genitourinary
Urinary continence
Eyes
Increased lacrimation
Blurred vision/ miosis
Glands
Excessive salivation
Sign and symptoms continue…

10. Management :
Initial stabilization
 Removal of the patient from the source of exposure and
contamination.
 Maintain an open airway and assist ventilation if necessary . Pay
careful attention to respiratory muscle weakness because sudden
respiratory arrest may occur.
 Treat hydrocarbon pneumonitis , seizures , and coma if they
occur. Seizures should be treated with benzodiazepines such as
diazepam.
 If cyanosis is present, maximal oxygenation should be achieved.
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11. Decontamination
 Remove all contaminated clothing and wash exposed areas with
soap and water, including the hair and under the nails. Irrigate
exposed eyes with saline.
 Gastric lavage with KMnO4 solution.
 Activated charcoal should be administered if large amount is
ingested
Enhanced elimination.
 Dialysis and hemo-perfusion generally are not indicated because
of the large volume of distribution of organophosphates.
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12. Specific drugs and antidote:
 Give atropine, 0.5–2 mg IV initially , then double the dose
every 5 minutes until signs of atropinization are present
(decreased secretions and wheezing, increased heart rate)
 Pralidoxime is a specific antidote that acts to regenerate the
enzyme activity at all affected sites prior to aging (before 24
hrs).
 Pralidoxime should be given immediately to reverse muscular
weakness: 1–2 g initial bolus dose (20–40 mg/kg in children)
IV over 5–10 minutes, followed by a continuous infusion.
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13. How does Pralidoxime works:
 Organophosphates bind to the the
esteric site of the active site of
the acetylcholinesterase enzyme,
thereby blocking its activity.
Pralidoxime binds to the other half
(the unblocked, anionic site) of the
active site and then displaces the
phosphate from the serine residue.
The conjoined antidote then
unbinds from the site, and thus
regenerates the fully functional
enzyme. 13

14. Organochlorines Posioning
Presented By: Pooja Rimal
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15. Introduction
 Organochlorine
pesticides are chlorinated
hydrocarbons used
extensively in agriculture and
mosquito control.
 Organochlorines insectides,
solvents and fumigants are
widely used around the world.
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16. Classification
 Dichlorodiphenylethanes
DDT, Methoxychlor
 Hexachlorocyclohexane
Lindane
 Cyclodienes
Aldrin, endrin, chlordane, dieldrin, endosulphan
 Chlordecone
Mirex
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17. Mechanism of Action
 The major toxic action of this group of chemicals is on the
nervous system, both central and peripheral. They act by
altering the electrophysiological properties of the cell
membranes (particularly nerve axons) disturbing sodium and
potassium ion exchange through the membrane causing
hyperexcitability of the nervous system.
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18. Toxic dose
 Ingestion of 1 gm of lindane can produce seizures in a child,
and 10–30 gm is considered lethal in an adult. The estimated
adult lethal oral doses of aldrin and chlordane are 3–7 gm
each; that of dieldrin, 2–5 gm.
 Skin absorption is a significant route of exposure, especially
with aldrin, dieldrin, and endrin. Whole body application of
lindane to infants has resulted in seizures and death.
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19. Why dangerous???
Action of sunlight on chlorinated hydrocarbons forms
chlorine monoxide which contributes to breaking-down of
the ozone-layer, causing wide 'holes' through which
cancer-causing ultraviolet (UV) rays can reach the earth’s
surface.
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Signs and symptoms:
 Nausea, vomiting,
 Diarrhea,
 Fever,
 Headache,
 Malaise,
 Fatigue, tremor,
 Convulsion and coma.
 Inhalation causes pulmonary edema, palpitation
 Irritation to eyes, nose, throat.
 Dermatitis.

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Antidote
 No specific antidotes
 Treat seizures, coma and respiratory depression (Ventilatory
failure) if they occur.
 Ventricular arrhythmias may respond to beta-adrenergic
blockers such as propranolol (Propanolol) and esmolol.
 Seziures can be treated by diazepam.
 Diazepam 5-10 mg IV slowly (Paediatric dose 0.2 mg/kg).
 10ml of 10% calcium gluconate can be given.

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Management:
(Initial stabilization and decontamination same as OP,
 Remove contaminated clothing.
 Wash skin with soap and water and do not rub the skin.
 Induce vomiting, stomach wash or saline cathartic.
 Administer sedative for convulsion.
 Administer cardio-respiratory stimulants.
 Initial therapy with benzodiazepines should be instituted.

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