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Pathway Description
Atropine M1/3/5 Muscarinic Poisoning Action Pathway
Homo sapiens
Category:
Metabolite Pathway
Sub-Category:
Drug Action
Created: 2022-06-01
Last Updated: 2023-10-25
Atropine is a muscarinic agents used to treat poisoning by muscarinic agents such as organophosphates and other muscarinic drugs. Organophosphates are insecticides used on many crops, and are also poisonous to mammals.
Organophosphate inhibits acetylcholinesterase which prevents the breakdown of acetylcholine. This leads to a high concentration of acetylcholine which continuously activates muscarinic acetylcholine receptors, causing muscle contractions.The high concentration of acetylecholine from organophosphate poison causes contraction of skeletal, smooth, and cardiac muscles throughout the body which causes defecation/diaphoresis, urination, miosis, bronchospasms/bronchorrhea, emesis, lacrimation, and salivation, remembered by the mnemonic DUMBELS.The poison can also cause anxiety, confusion, drowsiness, emotional lability, seizures, hallucinations, headaches, insomnia, memory loss, and circulatory or respiratory depression. Atropine antagonizes muscarinic acetylcholine receptors M1-M5 in order to counteract the high concentration of acetylcholine causes by muscarinic poisons.
These receptors are coupled to the Gq cascade which is being prevented by Ipratropium. The inhibition of the Gq cascade prevents the acitvation of phospholipase C, which would convert Phosphatidylinositol (3,4,5)-trisphosphate to inositol (3,4,5)-trisphosphate (IP3) and diacylglycerol (DAG). IP3 would then activate IP3 receptors on the sarcoplasmic reticulum leading to the release of stored calcium into the cytosol. the muscarinic acetylcholine receptors being inhibited prevents calcium from entering the cell which means calcium does not readily bind to calmodulin, and calmodulin isn't present to activate myosin light chain kinase. Since myosine light chain kinase is not activated, Serine/threonine-protein phosphatase continues to dephosphorylate myosin LC-P, and more cannot be synthesized so myosin remains unbound from actin causing muscle relaxation. This relaxation prevents the muscles from seizing due to organophosphates or another muscarinic drug. Atropine can be administered in a variety of ways, including intravenous injection, oral tablet, opthamalic solution, and intramuscular injections.
References
Atropine M1/3/5 Muscarinic Poisoning Pathway References
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