PHARMACOLOGICAL AND FORENSIC ASPECT OF ORGANOPHOSPHORUS POISONING

1. ORGANOPHOSPHORUS &
ORGANOCHLORINE COMPOUNDS
JOSLIN PRATHEEJA J
2ND YEAR MBBS
KIMS & RC

2. OBJECTIVES OF THIS SESSION…
 INTRODUCTION
 CLASSIFICATION
 AVAILABILITY
 TOXICOKINETICS
 MECHANISM OF ACTION
 USUAL FATAL DOSE
 SIGNS AND SYMPTOMS
 TREATMENT
 POSTMORTEM APPEARANCE
 MEDICOLEGAL IMPORTANCE

3. INTRODUCTION
 Organophosphorus compounds are usually esters, amides, or thiol derivatives of
phosphoric acid and are most commonly used as pesticides in agriculture, field
sprays and as household chemicals
 Organophosphorus poisoning is the most common poisoning in India following
aluminium phosphide
 Availability:
Dust powders
Liquids
ORGANOPHOSPHORUS COMPOUNDS

4. CLASSIFICATION
ORGANOPHOSPHORUS COMPOUNDS
ALKYL COMPOUNDS:
TETRAETHYL PYROPHOSPHATE(TEPP),
HEXAETHYL TETRAPHOSPHATE(HETP)
OCTAMETHYL
PYROPHOSPHATE(OMPA),
MALATHION,
DIMEFOX,
ISOPESTOX,
SULFOTEPP,
DEMETON,
TRICHLORFON.
ARYL COMPOUNDS:
PARATHION(NITROSTIGMINE),
METHYLPARATHION(METACIDE),
CHLOROTHION,
DIAZINON(TIK-20),
PARAOXON.

5. TOXICOKINETICS
ABSORPTION
 These compounds are highly lipid soluble and are well absorped by
inhalation, through the skin, mucous membranes and the gastrointestinal
tract.
 They are rapidly distributed to all body tissues.
 The highest concentrations are found in liver and kidneys.
METABOLISM
 Occurs in liver
 Detoxification occurs with the help of cytochrome P450
monooxygenase(oxidation)
 Oxidative metabolites of malathiona nd parathion(malaoxon and
paraoxon) are active forms. These are then hydrolyzed into inactive
metabolites.
EXCRETION
 The metabolized products are then excreted in urine,bile and faecus.

6. MECHANISM OF ACTION
 Powerful inhibitors of acetylcholinesterase
 Establishment of covalent bond with acetylcholinesterase
 Acetylcholinesterase is necessary for the conversion of acetylcholine to choline and
acetic acid
 Acetylcholine is found in PNS, CNS, Neuromuscular junctions, and RBCs.
 Inhibition results in accumulation of acetylcholine
with continued stimulation of local receptors causing
paralysis of nerves and muscles.

7. USUAL FATAL DOSE and FATAL PERIOD
 TEPP 50mg IM or 100mg orally
 OMPA 80mg IM or 175mg orally
 Parathion 80mg IM or 175mg orally
 HETP 60mg IM or 350mg orally
 Malathion and diazinon 1g orally
FATAL PERIOD: 24 HOURS.

8. CLINICAL FEATURES
Acute Poisoning
A. Muscarinic effects
Due to muscarinic like action, following clinical features are observed
D - Diarhoea
U - Urination
M - Miosis
B - Bradycardia, bronchorrhea, bronchospasm
E - Emesis
L - Lacrimation
S - Salivation, sweating

9. B. Nicotinic effects
M - Muscle weakness and paralysis
A - Adrenal medullary activity increases
T - Tachycardia
C - Cramps of skeletal muscles
H - Hypertension

10. C. CNS effects
1. Irritability
2. Apprehension
3. Restlessness
4. Fine fibrillary tremors of hands, eyelids, face or tongue
5. Muscular weakness
6. Convulsions- the convulsions may be tonic or may be clonic. Clonic convulsions
are more common
7. Mental confusion progressing to stupor to coma
8. Depression of respiratory and circulatory centers

11. D. Other features
Toxic myocarditis had been reported
Pancreatitis may be noted. The parasympathetic stimulation of the pancreas with
Ach, pilocarpine or vagal stimulation causes augmentation of the secretory flow and
increased intraductal pressure.
Organophosphorus compound produce metabolic acidosis by respiratory
depression, bronchoconstriction, pulmonary edema, CNS depression and lactacidosis
CAUSES OF DEATH
Respiratory failure
Cerebral hypoxia
Hyperthermia
Hepatic failure
Renal failure.

12. Intermediate Syndrome
 This syndrome sometimes occurs 1 to 4 days after poisoning due to long lasting
cholinesterase inhibition and muscle necrosis.
 Main features include motor cranial nerve palsies, weakness of muscle flexors and
proximal limb muscles, and acute respiratory paresis.
 It may be due to inadequate treatment of the acute episode, or inadequate assisted
ventilation.
 It doesnot respond to atropine or oximes, hence supportive measures have to be
given
Delayed Sequelae
It occurs after 2 to 3 weeks after poisoning, characterized mainly by
polyneuropathy.

13. DIAGNOSIS
 History of exposure
 Estimation of Plasma or RBC cholinesterase level. Depressed levels are diagnostic
 P-Nitrophenol is a metabolite of many organophosphates which is excreted in the
urine, and can be used as qualitative test
 ECG shows right axis deviation, ST segment depression and T wave inversion

14. MANAGEMENT
Principles of treatment consist of;
 Stabilization of patient
 Decontamination
 Antidote administration
 Supportive measures
 Nursing care
DECONTAMINATION
 Skin – the affected part should be washes thoroughly with copious water
 Ocular – copious eye irrigation with normal saline or tap water
 Ingestion– gastric lavage and administration of activated charcoal.

15. ANTIDOTE ADMINISTRATION
 ATROPINE is competitive antagonist of acetylcholine
 It blocks muscarinic manifestations of organophosphates
 It doesnot reverse peripheral muscular paralysis(nicotinic action)
 Dose 2mg IV , every 10mins till pupil dilates. Continued treatment with
maintenance doses for 1 to 2 weeks
 OXIMES are used as they helps to regenerate acetylcholinesterase at muscuranic,
nicotinic and CNS sites
 It relieves muscle fasciculations and weakness.
 PRALIDOXIME (2 PAM) is given intravenously as 500mg/20ml infusion in a
dose of 1 to 2 gm
 OBIDOXINE

16. SUPPORTIVE MEASURES
 Oxygen administration, ventilator assistance
 Maintain vital parameters, hydration, urine output
 Convulsions should be controlled with judicious use of diazepam
CONTRAINDICATIONS
 Acetylcholinesterase inhibitors like Physostigmine,
endorphonium
 Succinylcholine for rapid intubation

17. POSTMORTEM APPERANCE
 Insecticide like smell (garlicky or kerosine like)
 Froathing at mouth and nostrils
 Cyanosis
 Constricted pupils
 Pulmonary and cerebral edema
 Congestion of organs
 Features of toxic myocarditis
 Microscopic examination reveals dilatation of pericardial
blood vesses with hemorrhages in the surrounding tissues,
intestitial edema of myocardium, inflammatory cells,
hemosiderin-laden macrophages and fatty infiltration of the
myocardium

18. ORGANOCHLORINE COMPOUNDS
 Chlorinated hydrocabons
 Introduced in 1940s after the discovery of
insecticidal properties of DDT and enjoyed widespread popularity till
1960s
 Mainly used as pesticides, mosquito control, scabies treatment(Lindane).
 Known for their high toxicity, slow degradation and bioaccumulation.
 Cause neurological damage, endocrine disorders, and have acute and
chronic health effects.
 These compounds are available as dusting powder, emulsions, granules,
solutions.

19. CLASSIFICATION
ORGANOCHLORINE
DDT &
ANALOGUES:
DDT
(dichlorodiphenyltr
ichloroethane),
METHOXYCHLOR
BENZENE
HEXACHLORIDE GROUP:
BENZENE
HEXACHLORIDE(BHC),
GAMMAHEXACHLOROC
YCLOHEXANE
(LINDANE)
CYCLODIENES & RELATED
COMPOUNDS:
ALDRIN,CHLORDANE,
CHLORDECONE(KEPONE)
ENDRIN,DIELDRIN,
ENDOSULFAN(THIODAN),
HEPATACHLOR,
ISOBENAN,
MIREX(DECHLORANE).
TOXAPHENE &
RELATED
COMPOUNDS:
TOXAPHENE

20. TOXICOKINETICS
ABSORPTION:
 Absorped transdermally, orally, and by inhalation.
 Higly lipid soluble,
 Fats and fat solvents enhance absorption
 DDT is the least absorbed,
 DIELDRIN is very well absorbed.

21. METABOLISM
 Metabolized slowly in liver,
 Gets concentrated in body tissues(adipose tissue) for a long period.
EXCRETION
 Excreted in urine, faecus, milk.
 ELDRIN is rapidly metabolised and eliminated and does not persist in
body tissues.

22. MECHANISM OF ACTION
Interfere with nerve impulse transmission by altering membrane Na+ and K+ flux
causing CNS Hyperexcitability
 Behavioural changes(first stimulate and then depress the CNS)
 Involuntary muscle activity(repetitive body tremors)
 Myocardial irritability predisposing to cardiac arrhythmias
 Depression of the respiratory center
 DDT acts on sodium channels and affect sodium conductance across the
neuronal membrane
 Lindane inhibits the GABA mediated chloride channels

23. USUAL FATAL DOSE
 DDT - 15 to 30 gm
 LINDANE - 15 to 30 gm moderately toxic
 Aldrin, Endrin, Dieldrin – 2 to 6 gm highly toxic.

24. CLINICAL FEATURES
 CNS:
Excitability, vertigo, headache, myoclonus,
confusion, convulsions and coma.
Pupils are dilated
 GI TRACT:
Nausea, vomiting, abdominal pain, diarrhoea
ACUTE POISIONING

25.  RESPIRATORY SYSTEM:
Cough, wheezing, if aspiration or inhalation occurs.
OTHER CAUSES:
 Renal Failure
 Hepatitis
 Dermatitis
 Hyperaesthesia or paresthesia of mouth and face .

26. CHRONIC POISONING
 Leads to cumulative toxicity characterized by
Anorexia, weakness, weight loss, tremors,
opsoclonus, ataxia, pseudotumor cerebri,
abnormal mental changes, oligospermia,
thrombocytopenic purpura
 Agranulocytosis and aplastic anemia
(Lindane and BHC)

27. TREATMENT
 ABC
 Decontamination
 removal of contaminated clothing
 washing of affected skin with soap and water,
 gastric lavage and administration of activated charcoal and cathartics
 Use CHOLESTYRAMINE to accelerate the biliary-fecal excretion of the
some organochlorines
Dosage of Cholestryamine
Adults: 4 g doses, 4 times a day, before meals and at bedtime
Children: 240mg/kg/24 hours, divided, every 8 hours

28.  No specific antidote
 Arrhythmias can be managed with Lidocaine
 Manage convulsions using antiepileptic drug
 Calcium gluconate may also help
Dosage of Diazepam
Adults:5 -10 mg IV and repeat every 5 -10 minutes to maximum of
30mg
Children:0.2 to 0.5mg/kg every 5 minutes to maximum of 10mg in
children over 5 years, and a maximum of 5 mg in children under 5 years

29.  CONTRAINDICATIONS
 Atropine (no effect in organochlorine poisoning),
 Epinephrine( may exacerbate ventricular arrhythmias),
 Animal or vegetable oils or fats (enhance absorption).

30. POSTMORTEM APPEARANCE
 EXTERNAL
 Characteristic odour(kerosine like odour)
 Froathing at mouth and nose
 Cyanosis of extremites
 INTERNAL
 Pulmonary and cerebral oedema
 Congestion of GI tract and other viscera

31. MEDICOLEGAL IMPORTANCE
 Occupational And Accidental Exposures
 Suicidal is very common
 Homicidal is rare.

32. REFERENCE
 “The Essentials of Forensic Medicine and toxicology” by Narayan Reddy ; 33rd
edition; pg:520 -526
 “Modern Medical Toxicology” by V V Pillay; 3rd edition; pg:202 to 205