ORGANOPHOSPHATE Poisoning

ORGANOPHOSPHATE Poisoning

Introduction 

Organophosphates poisonings common in Malaysian hospitals , hold a very high level of mortality. Because of this, medical personnels must thoroughly understand the pathophysiology and signs and symptoms of organophosphate poisoning , and also its management. 

Organophosphates include insecticides (malathion, parathion, diazinon, fenthion, dichlorvos, chlorpyrifos, ethion), nerve gases (soman, sarin, tabun, VX), ophthalmic agents (echothiophate, isoflurophate), and antihelmintics (trichlorfon). 

Herbicides (tribufos [DEF], merphos) are tricresyl phosphate–containing industrial chemicals

Physiology

Acetylcholine (ACh) is a simple molecule synthesized from choline and acetyl-CoA through the action of choline acetyl-transferase. Neurons that synthesize and release ACh are termed cholinergic neurons. When an action potential reaches the terminal button of a presynaptic neuron a voltage-gated calcium channel is opened. The influx of calcium ions, Ca2+, stimulates the exocytosis of presynaptic vesicles containing ACh, which is thereby released into the synaptic cleft. 

During neurotransmission, Acetylcholine ( ACh ) is released from the nerve into the synaptic cleft and binds to ACh receptors ( muscarinic and nicotinic receptors ) on the post-synaptic membrane, relaying the signal from the nerve. Acetylcholinesterase ( AchE ), which is located on the post-synaptic membrane, terminates the signal transmission by hydrolyzing ACh. The liberated choline is taken up again by the pre-synaptic nerve and ACh is synthetized by combining with acetyl-CoA through the action of choline acetyltransferase.

Patophysiology

Organophosphates acts as an acetylcholinesterase inhibitor (often abbreviated AChEI) or anti-cholinesterase irreversibly bind to acethylcholinesterase, causing the phosphorylation and deactivation of acetycholinesterase (AchE) from breaking down acetylcholine. 

Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of cholinergic junctions (muscarinic effects), in the CNS, at skeletal nerve-muscle junctions, and at autonomic ganglia (nicotinic effects). Acetylcholinesterase inhibitors are classified as reversible, irreversible, or quasi-irreversible (also called pseudo-irreversible)

Signs and symptoms of organophosphate poisoning can be divided into three broad categories: 

(1) muscarinic effects, 

(2) nicotinic effects

(3) central nervous system effects.

1. Muscarinic effects 

Mnemonic devices used to remember the muscarinic effects of organophosphates are SLUDGE (salivation, lacrimation, urination, diarrhea, GI upset, emesis) and DUMBELS (diaphoresis and diarrhea; urination; miosis; bradycardia, bronchospasm, bronchorrhea; emesis; excess lacrimation; and salivation). 

Muscarinic effects by organ system include the following:

• Cardiovascular - Bradycardia, hypotension 
• Respiratory - Rhinorrhea, bronchorrhea, bronchospasm, cough, severe respiratory distress 
• Gastrointestinal - Hypersalivation, nausea and vomiting, abdominal pain, diarrhea, fecal incontinence 
• Genitourinary - Incontinence 
• Ocular - Blurred vision, miosis 
• Glands - Increased lacrimation, diaphoresis

2. Nicotinic effects : 

Nicotinic signs and symptoms include muscle fasciculations, cramping, weakness, and diaphragmatic failure. Autonomic nicotinic effects include hypertension, tachycardia, mydriasis, and pallor.

3. CNS and Neuropsychiatric Effects :

• Anxiety 
• Emotional lability 
• Restlessness 
• Confusion 
• Ataxia 
• Tremors 
• Seizures 
• Coma 
• Impaired memory 
• Confusion 
• Irritability 
• Lethargy 
• Psychosis 
• Chronic organophosphate-induced neuropsychiatric disorders 

General Treatment :

1. Airway control and adequate oxygenation are paramount in organophosphate (OP) poisonings. Intubation may be necessary in cases of respiratory distress due to laryngospasm, bronchospasm, bronchorrhea, or seizures. Immediate aggressive use of atropine may eliminate the need for intubation. Succinylcholine should be avoided because it is degraded by plasma cholinesterase and may result in prolonged paralysis. 

2. Decontamination

3. Central venous access and arterial lines may be needed to treat the patient with organophosphate toxicity who requires multiple medications and blood-gas measurements. 

4. Torsades de pointes should be treated in the standard manner , use of intravenous magnesium sulfate

Spesific Treatment

• Atropine,
• Pralidoxime (2-PAM) 
• Benzodiazepines (eg, diazepam) 

1. Atropine

Initiated in patients with OP toxicity who present with muscarinic symptoms.

Competitive inhibitor at autonomic postganglionic cholinergic receptors, ( competitive muscarinic antagonist ) It works by occupying muscarinic receptor sites, preventing or reducing the mucarinic response to acetylcholine. It is classified as an anticholinergic drug (parasympatholytic). 

The endpoint for atropinization is dried pulmonary secretions and adequate oxygenation. Tachycardia and mydriasis must not be used to limit or to stop subsequent doses of atropine. The main concern with OP toxicity is respiratory failure from excessive airway secretions.

2. Pralidoxime

The acetylcholinesterase enzyme has two parts to it , an acetylcholine molecule, bound at both ends to both sites of the enzyme, is cleaved in two to form acetic acid and choline. In organophosphate poisoning, an organophosphate binds to just one end of the acetylcholinesterase enzyme (the esteric site), blocking its activity. 

Pralidoxime is able to attach to the other half (the unblocked, anionic site) of the acetylcholinesterase enzyme. It then binds to the organophosphate, the organophosphate changes conformation, and loses its binding to the acetylcholinesterase enzyme. The conjoined poison / antidote then unbinds from the site, and thus regenerates the enzyme, which is now able to function again. 

3. Diazepam

For treatment of seizures. Depresses all levels of CNS (eg, limbic and reticular formation) by increasing activity of GABA.

Patient should be refered for psychiatric team assesment and made police report. 

Source : www.emedicine.com

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