Organophosphates nicotinic effects

Carbamates effect the reversible carbamylation of acetylcholinesterase, permitting accumulation of acetylcholine at cholinergic neuroeffector junctions (muscarinic effects), at the myoneural junctions of skeletal muscle, and in the autonomic ganglia (nicotinic effects). CNS function is also impaired. However the relatively large dissociation constant of the carbamyl-enzyme complex indicates that it dissociates more readily than does the organophosphate-enzyme complex, mitigating the toxicity of the carbamate pesticides. The reversibility of the carbamyl-enzyme complex affects (limits) the utility of blood enzyme measurements as a diagnostic tool. 

Organophosphate and car- Acute nicotinic effects of cholinesterase inhibition allow Muscle fasciculations and tremors leading to paralysis at... 

Well-known symptoms of sarin toxicity include miosis, hypersecretions, bradycardia, and fasciculations. However, the mechanism of organophosphate toxicity seems to involve conflicting actions. For example, mydriasis or miosis, and bradycardia or tachycardia may occur. Acute respiratory insufficiency is the most important cause of immediate death. Early symptoms include (i) tachypnea due to increased airway secretions and bronchospasm (a muscarinic effect), (ii) peripheral respiratory muscle paralysis (a nicotinic effect), and (iii) inhibition of respiratory centers (a CNS effect), all of which lead to severe respiratory deficiency. If left untreated at this stage, death will result. Cardiovascular symptoms may include hypertension or hypotension. Various arrhythmias can also occur, and caution is required when the QT interval is prolonged. In particular, if hypoxemia is present, fatal arrhythmias may occur with intravenous administration of atropine... 

Nerve agents are organophosphates (OPs). Acute exposure to OPs can cause muscarinic, nicotinic, and CNS signs. Muscarinic effects include salivation, lac-rimation, urination, dyspnea, diarrhea, and emesis (SLUDDE), along with miosis, bradycardia, hypotension, and bronchoconstriction. Nicotinic effects include... 

Van den Beukel I, van Kleef RGDM, Oortgiesen M. Differential effects of physostigmine and organophosphates on nicotinic receptors in neuronal cells of different species. NeuroToxicol. 19(6) 777-788, 1998. 

Receptor interactions were seen at nicotinic and muscarinic receptors. No correlations were found, however, between atropinelike or curare-like actions of these compounds and their protective effects against organophosphate poisoning. 

Diazinon, an anticholinesterase organophosphate, inhibits acetylcholinesterase in the central and peripheral nervous system. Inhibition of acetylcholinesterase results in accumulation of acetylcholine at muscarinic and nicotinic receptors leading to peripheral and central nervous system effects. These effects... 

Another important example is the nicotinic acetylcholine receptor, which is activated by the agonist nicotine causing muscular fibrillation and paralysis. Indirect effects can also occur. For example, organophosphates and other acetylcholinesterase inhibitors increase the amount of acetylcholine and thereby overstimulate the receptor, leading to effects in a number of sites (see chap. 7). Alternatively, botulinum toxin inhibits the release of acetylcholine and causes muscle paralysis because muscular contraction does not take place (see chap. 7). 

Tetraethylpyrophosphate (TEPP) was the first organophosphate compound to be used as an insecticide. This compound was developed in Germany during World War II and was substituted for nicotine as an insecticide. It is a white to amber hygroscopic liquid (bp, 155°C) that readily hydrolyzes in contact with water. Because of its tendency to hydrolyze and its extremely high toxicity to mammals, TEPP was used for only a very short time as an insecticide, although it is a very effective one. It was typically applied as an insecticidal dust formulation containing 1% TEPP. 

Nicotine binds to a type of receptor, now called a nicotinic receptor, and causes the same effects as a release of the neurotransmitter acetylcholine at nerve endings. In this it is similar to organophosphates, which lead to excess acetylcholine at nerve endings (see pp. loo-ioi). Nicotine first excites and then inhibits the central nervous system it first stimulates and then paralyses nerves. It reacts with receptors in muscle and nerves, and is able to enter the brain from the bloodstream and interact with nicotinic receptors. At first there is a stimulation, with the smoker experiencing alertness and decreased irritability, aggression, and anxiety. With higher doses there is depression of the brain as a result of saturation of the receptors. 

Menking, D.E., Thompson, R.G., Wolff, V.L., Valdes, J.J. (1990). Irreversible organophosphate effects on nicotinic acetylcholine receptor/ion channel complex. Def. Techn. Inf. Cent. Rep. 

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