1. Organophosphate poisoning

2. Organophosphorus compounds are organic compounds containing phosphorus
Organophosphorus compounds are organic compounds containing phosphorus.  They are used primarily in pest control.
Some organophosphorus compounds are highly effective insecticides, although some are extremely toxic to man, including sarin and VX nerve agents.

4. Drugs with acetylcholine-like effects (cholinomimetics) consist of 2 major subgroups on the basis of their mode of action (ie, whether they act directly at the acetylcholine receptor or indirectly through inhibition of cholinesterase).
1/Acetylcholine may be considered the prototype that acts directly at both muscarinic and nicotinic receptors. 
2/Neostigmine is a prototype for the indirect-acting cholinesterase inhibitors.

5. Pathophysiology
The primary mechanism of action of organophosphate pesticides is inhibition acetylcholinesterase (AChE).
AChE is an enzyme that degrades the neurotransmitter acetylcholine (ACh) into choline and acetic acid.
Over a period of time, phosphorylation is followed by loss of an organophosphate leaving group and the bond with AChE becomes irreversible, a process known as aging.
Once AChE has been inactivated, ACh accumulates throughout the nervous system, resulting in overstimulation of muscarinic and nicotinic receptors.

6. Once an organophosphate binds to AChE, the enzyme can undergo one of the two following pathways:
1/Reactivation by a strong nucleophile such as pralidoxime (2-PAM)
2/Irreversible binding and permanent enzyme inactivation (aging)

9. Exposure can be from drinking, breathing in the vapors, or skin exposure. 

10. Signs and symptoms
Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma.
The effects of organophosphate poisoning on muscarinic receptors are recalled using the mnemonic SLUDGEM (salivation, lacrimation, urination, defecatio n, gastrointestinal motility, emesis, miosis) .

11. Treatments
The mainstays of medical therapy in organophosphate (OP) poisoning include atropine, pralidoxime (2- PAM), and benzodiazepines (eg, diazepam). Initial management must focus on adequate use of atropine. Optimizing oxygenation prior to the use of atropine is recommended to minimize the potential for dysrhythmias.
If atropine is unavailable or in limited supply, intravenous glycopyrrolate or diphenhydramine may provide an alternative anticholinergic agent for treating muscarinic toxicity; however, glycopyrrolate does not cross the blood-brain barrier and cannot treat central effects of OP poisoning.
Nebulized ipratropium bromide can also be used to treat muscarinic effects in the lungs.

12. Treatments
2-PAM (2-pyridine aldoxime methyl chloride) --- also called pralidoxime --- is one of a class of chemicals, called oximes that reverse the binding of cholinesterase inhibitors with acetylcholinesterase.
2-PAM attaches to the site where the cholinesterase inhibitor has attached to and blocked cholinesterase. 2-PAM then attaches to the cholinesterase inhibitor and removes it from cholinesterase, allowing the enzyme to work normally again. This is sometimes referred to as “regeneration” of cholinesterase.

13. Treatments
Some phosphate-acetylcholinesterase conjugate continue to react after the phosphate docks to the esteric site, evolving into a more recalcitrant state. This process is known as aging.
Aged phosphate-acetylcholinesterase conjugate are resistant to antidotes such as pralidoxime. Pralidoxime is often used with atropine (a muscarinic antagonist) to help reduce the parasympathetic effects of organophosphate poisoning.
Pralidoxime has an important role in reversing paralysis of the respiratory muscles but due to its poor blood–brain barrier penetration, it has little effect on centrally-mediated respiratory depression. Atropine, which is choice of drug to antagonise the muscarinic effects of organophosphates, is administered even before pralidoxime during the treatment of organophosphate poisoning.
Dosage
Adults: 30 mg/kg (typically 1-2 g), administered by intravenous therapy over 15–30 minutes, repeated 60 minutes later. It can also be given as a 500 mg/h continuous IV infusion.
Children: 20–50 mg/kg followed by a maintenance infusion at 5–10 mg/kg/h.
Intravenous infusions can lead to respiratory or cardiac arrest if given too quickly.