Organophosphorus Insecticides Toxicity - PowerPoint Presentation

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Organophosphorus Insecticides Toxicity

4th stage Assistant lecturer: Shahad S.aldeen Department of pharmacology and toxicology May-2021

Introduction

Pesticide is a common term that comprise several classes of insecticides, herbicides, fungicides, rodenticides, wood preservatives, garden chemicals and household disinfectants that are used to kill or protect from pests.

The pest can be insects, plant pathogens, weeds, nematodes (roundworms) and microbes that compete with humans for food, or spread diseases.

Cont…

There are 3 methods of pesticides classification :Classification based on the mode of entry

Classification based on pesticide function and the pest organism they kill

Classification based on the chemical composition of the pesticide

Cont.…

The most common and useful method of classifying pesticide is based on their chemical composition and nature of

active ingredients,

because it gives the clue about the

efficacy

,

physical

and

chemical properties

of the respective pesticides.

Cont..

Based on chemical composition, pesticides are classified into four main groups namely:organochlorines

organophosphorus carbamates

pyrethrin and pyrethroids.

Organophosphate pesticides

Organophosphate (OP) pesticides are considered to be one of the broad spectrum pesticides

which control wide range of pests due to their multiple functions. These pesticides are also biodegradable, cause minimum environmental pollution and are slow pest resistance.

Cont..

Some of the widely used organophosphorus insecticides include parathion, malathion,

diaznon and glyphosate

Mechanism of OP toxicity

Organophosphorus insecticides are more toxic to vertebrates and invertebrates as cholinesterase inhibitors

OP cause phosphorylation to the active site of choline esterase enzyme cause inactivation of the enzyme with accumulation of acetylcholine neurotransmitter on its receptors

The results are

rapid twitching of voluntary muscles leading to paralysis and death

Mechanism of OP toxicity

Routes of Exposure to OP Insecticides

More common routs Ingesting of contaminated food

Hand -to-mouth contact with surfaces containing organophosphorus insecticides.

Less common routs

Inhalation

Dermal contact.

In general, the organophosphorus insecticides have

better gastrointestinal than dermal absorption.

Signs and Symptoms of OP Toxicity

Clinical features in acute OP poisoning has centered on receptor specific effects on muscarinic, nicotinic ,central nervous system (CNS) receptors and adrenal medulla that result in diverse symptoms and signs.

Overstimulation of nicotinic receptors found at neuromuscular junctions can lead to fasciculations and myoclonic jerks

. This eventually leads to

flaccid paralysis

because of the depolarizing block. Nicotinic receptors also are found in the adrenal glands which may cause

hypertension, sweating, and tachycardia

.

Cont..

Cont..

The most common term that captures the muscarinic effects of organophosphate poisonings is DUMBELS:D =

Defecation/d

iaphoresis

U =

U

rination

M =

M

iosis

B =

B

ronchospasm/

b

ronchorrhea

E =

E

mesis

L =

L

acrimation

S =

S

alivation.

Treatment Strategies of OP Poisoning

Termination of exposure

Decontaminate the patient by removing all clothing because it may be contaminated even after washing. The patient’s skin needs to be flushed with water.

Activated charcoal can be given if the patient presents within 1 hour of ingestion. Emesis should not be induced.

The definitive treatment for organophosphate poisoning:

1- atropine as antidote, which competes with acetylcholine at the muscarinic receptors. 

If the patient does not respond to the treatment, double the dose every 3 to 5 minutes until respiratory secretions have cleared and there is no bronchoconstriction.

In

patients with severe poisoning

, the victims may need repeated doses of atropine given in bolus or continuous infusion over several days before the patient improves together

with oxygen

Cont..

2-Pralidoxime (2-PAM) also should be given to affect the nicotinic receptors as antidote since atropine only act on muscarinic receptors.

Note: Atropine must be given before 2-PAM to avoid worsening of muscarinic-mediated symptoms.

Mechanism of Action of Pralidoxime (2-PAM): Called ‘’Acetylcholine Esterase Reactivator or Regenerator’’

Organophosphates bind to (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 poison / antidote then unbinds from the site, and thus regenerates the fully functional enzyme.