Pharmacology
Summary
Acetylcholinesterase inhibitors are indirect-acting cholinomimetics that increase the concentration of acetylcholine at the synapse by either binding to and inhibitng acetylcholinesterase. This action enhances the activation of nicotinic receptors, resulting in stronger muscular contractions. Drugs like pyridostigmine and neostigmine are used in the treamtment of myasthenia gravis, an autoimmune condition where antibodies impair nicotinic acetylcholine receptor function at skeletal muscle neuromuscular junctions.
Physostigmine, a tertiary amine that can penetrate the blood-brain barrier, serves as another type of cholinesterase inhibitor. It's especially valuable in reversing the muscarinic receptor blockade induced by an atropine overdose. Although effective, physostigmine isn't frequently utilized in myasthenia gravis treatment due to potential central nervous system side effects. Besides their application in myasthenia gravis, cholinesterase inhibitors also play a role in reversing neuromuscular blockade, treating organophosphate poisoning (pralidoxime), and help treat cognitive impairments in alzheimer's patients (galantamine, rivastigmine, donepezil)
Lesson Outline
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FAQs
Acetylcholinesterase serves to degrade acetylcholine (ACh), a crucial neurotransmitter for nerve signal transmission. Acetylcholinesterase inhibitors block this enzyme, thereby preventing the breakdown of ACh. This action increases the synaptic concentrations of ACh, enhancing its activity and prolonging its effects.
Acetylcholinesterase inhibitors are used in diverse therapeutic scenarios. Drugs with the "-stigmine" suffix, such as pyridostigmine and neostigmine, play a pivotal role in managing myasthenia gravis, a condition characterized by weak skeletal muscles. These drugs boost the action of ACh at the neuromuscular junction (NMJ). Some, like neostigmine, can counteract nondepolarizing neuromuscular blockades. Additionaly, acetylcholinesterase inhibitors, including galantamine, rivastigmine, and donepezil, are prescribed to treat alzheimer's disease.
Physostigmine, an acetylcholinesterase inhibitor with central activity, can effectively counter muscarinic toxicity from atropine and similar substances. Naturally occurring atropine sources include the belladonna flower and the jimson weed. An overdose can manifest symptoms like hallucinations, elevated body temperature, and impaired vision. Since physostigmine has the capability to penetrate the central nervous system, it reverses both peripheral and central symptoms induced by atropine toxicity.
Organophosphates, prevalent in insecticides like parathion and malathion, belong to the acetylcholinesterase inhibitors family. These substances can induce acute cholinergic toxicity, characterized by symptoms encapsulated in the acronym DUMBBELS: Diarrhea, Urination, Miosis, Bronchospasm, Bradycardia, Excitation, Lacrimation, and Salivation. Physostigmine, capable of reaching the central nervous system, can counteract this toxicity. Additionally, pralidoxime can re-activate acetylcholinesterase at both muscarinic and nicotinic receptors, reversing cholinergic toxicity manifestations, including flaccid paralysis.
In the treatment of alzheimer's disease, acetylcholinesterase inhibitors like galantamine, rivastigmine, and donepezil are pivotal. These drugs aim to enhance cognitive function by preventing the breakdown of acetylcholine, which plays a role in memory and learning. By preserving elevated acetylcholine levels in the brain, they mitigate some cognitive and behavioral symptoms of alzheimer’s disease. These drugs can effectively penetrate the central nervous system, ensuring they reach the brain.
