Anti-cholinesterase Poisoning

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Chapter: Essential pharmacology : Cholinergic System And Drugs

Anticholinesterases are easily available and extensively used as agricultural and household insecticides; accidental as well as suicidal and homicidal poisoning is common.


ANTI-CHOLINESTERASE POISONING

 

Anticholinesterases are easily available and extensively used as agricultural and household insecticides; accidental as well as suicidal and homicidal poisoning is common.

 

Local muscarinic manifestations at the site of exposure (skin, eye, g.i.t.) occur immediately and are followed by complex systemic effects due to muscarinic, nicotinic and central actions. They are—

 

§  Irritation of eye, lacrimation, salivation, sweating, copious tracheobronchial secretions, miosis, blurring of vision, breathlessness, colic, involuntary defecation and urination.

§  Fall in BP, bradycardia or tachycardia, cardiac arrhythmias, vascular collapse.

§  Muscular fasciculations, weakness, respiratory paralysis (central as well as peripheral).

§  Excitement, tremor, ataxia, convulsions, coma and death.

§  Death is generally due to respiratory failure.

 

Treatment

 

§  Termination of further exposure to the poison—fresh air, wash the skin and mucous membranes with soap and water, gastric lavage according to need.

§  Maintain patent airway, positive pressure respiration if it is failing.

§  Supportive measures—maintain BP, hydration, control of convulsions with judicious use of diazepam.

§  Specific antidotes—

 

a)    Atropine

It is highly effective in counteracting the muscarinic symptoms, but higher doses are required to antagonize the central effects. It does not reverse peripheral muscular paralysis which is a nicotinic action. All cases of antiChE (carbamate or organophosphate) poisoning must be promptly given atropine 2 mg i.v. repeated every 10 min till dryness of mouth or other signs of atropinization appear (upto 200 mg has been administered in a day). Continued treatment with maintenance doses may be required for 1–2 weeks.

 

   (b) Cholinesterase reactivators

Oximes are used to restore neuromuscular transmission in case of organophosphate antiChE poisoning. The phosphorylated ChE reacts very slowly or not at all with water. However, if more reactive OH groups in the form of oximes (generic formula R–CH = N–OH) are provided, reactivation occurs more than a million times faster (see Fig. 7.2G and H).

 

Pralidoxime (2PAM) has a quaternary nitrogen: attaches to the anionic site of the enzyme which remains unoccupied in the presence of organophosphate inhibitors. Its oxime end reacts with the phosphorus atom attached to the esteratic site: the oxime-phosphonate so formed diffuses away leaving the reactivated ChE. It is ineffective as an antidote to carbamate antiChEs (physostigmine, neostigmine, carbaryl, propoxur) in which case the anionic site of the enzyme is not free to provide attachment to pralidoxime. It is rather contraindicated in carbamate poisoning, because not only it does not reactivate carbamylated enzyme, it has weak antiChE activity of its own.

 

Pralidoxime (NEOPAM, PAMA INJ. 500 mg/20 ml infusion, LYPHE 1 g/vial for inj.) is injected i.v. slowly in a dose of 1–2 g (children 20–40 mg/kg). It causes more marked reactivation of skeletal muscle ChE than at autonomic sites and not at all in the CNS (does not penetrate). Treatment should be started as early as possible (within 24 hours), before the phosphorylated enzyme has undergone ‘aging’ and become resistant to hydrolysis. Doses may be repeated according to need (max. 12 g in first 24 hrs, lower doses according to symptoms for 1–2 weeks). The use of oximes in organophosphate poisoning is secondary to that of atropine.

 

Other oximes are obidoxime (more potent than pralidoxime) and diacetylmonoxime (DAM), which is lipophilic.

 

Chronic Organophosphate Poisoning Repeated exposure to certain fluorine containing and triaryl organophosphates results in polyneuritis and demyelination after a latent period of days and weeks. Sensory disturbances occur first followed by muscle weakness, tenderness and depressed tendon reflexes— lower motor neurone paralysis. In the second phase, spasticity and upper motor neurone paralysis gradually supervenes. Recovery may take years. The mechanism of this toxicity is not known, but it is not due to inhibition of ChE; there is no specific treatment.


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