ORGANO-PSHOPHOROUS COMPOUND POISONING

7/29/2019 ORGANO-PSHOPHOROUS COMPOUND POISONING

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ORGANO PHOSPOROUS

COMPOUND POISONING


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INTRODUCTION

Organo phosphorous compounds are a large group ofcompounds having the potential to irreversibly inhibitcholinesterase enzymes like Acetyl Cholinesterase &Neuropathy Target Esterase (NTE).

They are not only used as insecticides & pesticides butalso as Chemical Warfare Agents, Petroleum Additives& Industrial Plasticizers.

Serious human exposure leads to muscarinic(cholinergic) hyper stimulation as well as nicotinicreceptor stimulation.


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ORGANO - PHOSPHOROUS

COMPOUNDSNERVE AGENTS

G Agents: Sarin, Tabun, Soman V Agents: VX, VE

INSECTICIDES

Dimethyl Compounds: Diethyl Compounds:

Dichlorvos Chlorpyrifos

Fenthion Diazinon

Malathion Parathion - ethyl

Methamidophos Quinalphos

OTHERS

Acephate Phenthoate

Dimethoate Phorate

Ethion Phosphamidon

Fentrothion Profenofos

Moncrotofos


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HISTORY

First synthesized in the early 1800s when Lassaigne reacted alcohol withphosphoric acid.

1854 Philip de Clermont described the synthesis of Tetra Ethyl Pyro Phosphate at

a meeting of the French Academy of Sciences.

Eighty years later, Lange in Berlin & Schrader, a chemist at Bayer AG, Germany,

investigated the use of Organophosphates as insecticides.

However the German Military prevented the use of OPs as insecticides & instead

developed an arsenal of chemical warfare agents (tabun, sarin, soman).

A fourth agent VX was developed a decade later in England.

During World War II, in 1941, OPs were reintroduced worldwide as pesticides as

were originally intended.


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HISTORY

Jamaican Ginger Palsy incident (1930) - to circumvent prohibition laws

led to massive OP intoxication.

In 1995 - Aum Shinrikyo - a religious sect - used Sarin to poison people on

a Tokyo subway.

Worldwide mortality rates currently range from 3 25%

The compounds most commonly involved are Malathion, Dichlorvos,

Trichlorfon.

Agricultural pesticides accounted for 12.8% of all cases of poisoning in

India.


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Risk Factors for Poisoning

Young age

Low Socio economic strata

Unemployment

Unstable emotional relationships

Psychiatric disorders

Alcohol abuse


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PATHOLOGY

Organophosphate are absorbed through the skin lungs& GI tract and distributed widely in tissues and areslowly eliminated in hepatic metabolism.

The principal effect is inhibition of cholinesteraseenzymes, particularly acetyl cholinesterase (AChE). Thisleads to accumulation of acetylcholine at:

1. Muscarinic receptors- in cholinergic receptor cells2. Nicotinic receptors in skeletal neuromuscular

junctions and autonomic ganglia

3. CNS


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MOA of OP Compounds


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CLINICAL FEATURES

Acute Cholinergic Crisis

Intermediate Syndrome

(IMS)

OPIDN

EPS, CNS

DIPPERS FLU


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ACUTE CHOLINERGIC CRISISMuscarinic Nicotinic Central receptors

CardiovascularBradycardia

Hypotension

RespiratoryRhinorrhea

Bronchorrhea/spasm

Cough

GastrointestinalIncreased salivation

Nausea/vomiting

Abdominal pain

Diarrhoea

Fecal incontinence

GenitourinaryUrinary incontinence

OcularBlurred vision/miosis

Increased lacrimation

CardiovascularTachycardia

Hypertension

MusculoskeletalWeakness

Fasciculations

CrampsParalysis

AnxietyRestlessness

Ataxia

Convulsions

Insomnia

Dysarthria

TremorsComa

Absent reflexes

CS respiration

Resp. depression

Circulatory collapse


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COPIND & EPS

Chronic OP Induced Neuropsychiatric Disorder (COPIND):

Behavioural changes

Impaired vigilance, information processing & memory

Depression, anxiety, irritability

EPS:

Resting tremor

Rigidity

Hypokinesia Dystonia

Chorea

NOTE:

Dose dependent effects: Muscarinic < Nicotinic < CNS

Tachycardia / Hypertension s/o severe poisoning


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PARALYSIS

Type I: Acute Paralysis

due to continued depolarization atthe NMJ

Type II: IMS develops 24 - 96 hrs after resolution of acuteOPP symptoms. Paralysis & resp. distress; weakness of

proximal muscle groups, neck & trunk with sparing of distalmuscles; cranial nerve palsies. Persists for 4 18 days , mayrequire mech. Ventilation & may be complicated byinfections or cardiac arrhythmias.

Type III: OPIDN occurs 2-3 weeks after exposure to largedoses & is due to inhibition of NTE. Distal muscle weaknesswith relative sparing of proximal muscle groups, neckmuscles & cranial nerves. Recovery may take upto 12months.


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OTHERS

Neuro-ophthalmic manifestations:

o Optic neuropathy

o Retinal degeneration

Rarer manifestations:

o GBS

o Ototoxicity

o Sphincter involvement


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MANAGEMENT DIAGNOSIS: Mainly based on the characteristic clinical features

and historyof exposure to a known OP compound. INVESTIGATIONS: Estimation of serum or RBC cholinesterase

levels & electro diagnostic tests (not routinely used)

Clinical features of OP poisoning appear when RBC

cholinesterase activity is < 75% of normal & in clinically overtpoisoning it is usually < 10%

No definite relationship between plasma levels ofcholinesterase & severity of symptoms and prognosis

OTHERS:

CXR - EVALUATE PULMONARY OEDEMA

ECG - CARDIAC ARRHYTHMIAS

ELECTROLYTES

UREA


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TREATMENT - PRINCIPLES

Airway

Breathing

Circulation Decontamination

Gastric lavage

Activated charcoal through ryles tube 4thhourly

Atropine & Oxime therapy


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TREATMENT

MILD CASES:

No specific treatment

Clearing the Airway

Adequate ventilation - consider oxygenation

Remove soiled clothes

Wash contaminated skin, with soap & running

water, to prevent further absorption.


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PATIENTS WITH SYSTEMIC FEATURES

i) ATROPINE:

Initiate as soon as the diagnosis is suspected ADULTS: 2 mg IV bolus - repeat dose very 5-15

minutes till atropinised

CHILDREN: 0.05 mg/kg initially then 0.02-0.05mg/kg

S/O Atropinisation: Heart rate about 100/min

Pupils mid position / dilated Bowel sounds just heard

Clear lung fields

- Reduces - Bronchorrhoea & Rhinorrhoea & wheezing

- It is an anti - muscarinic agent.


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ii) Add an OXIME: e.g. Pralidoxime Dose Slow IV injection 30mg/kg every 4-6 hours i.e. 1-2gms IV

- or infusion 8-10mg/kg/h i.e. 200-400mgs/h

MOA- Reactivates phosphorylated acetyl cholinesterase.

- Prevents permanent binding of the organophosphate tocholinesterase.

iii) Gastric lavage within an hour followed by activatedCharcoal administered via nasogastric tube

iv) Remove soiled clothes

v) Wash the exposed areas of skin with soap & running water - to preventdermal absorption

vi) Monitor patient 2 hourly in left lateral position.

vii) Consider ICU care if in coma or unconscious.


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ORGANO-PSHOPHOROUS COMPOUND POISONING