胆碱能与胆碱酯酶抑制剂.pptVIP

An improved version of atracurium is the purified form of just one of the ten possible stereoisomers, that has the highest efficacy and least side effects The name of the blocking agent is cisatracurium (NIMBEX) This is the most widely used agent surgically. 80% of the drug is metabolized via Hofmann elimination, thus lowering variability in patients with possible liver or renal disease. The Hofmann degradation is only dependent on the pH and temperature of the plasma. 13.3 Analogues of tubocurarine Mivacurium Faster onset (2 min) Shorter duration (15 min) 13. Cholinergic Antagonists (Nicotinic receptor) The use of mivacurium has declined in recent years, in favor of other agents with better overall profile. Assigned Reading Introduction to Medicinal Chemistry by Graham L. Patrick, Chapter 19, pp 558-590 Bowman, W. C.. Neuromuscular block. British Journal of Pharmacology (2006), 147(Suppl. 1), S277-S286. Homework Questions: Briefly describe the differences between the sympathetic and parasympathetic divisions of the autonomic nervous system, including the neurotransmitter used at the respective neuromuscular junctions. Cholinergic receptors are divided into nicotinic and muscarinic classes. How are these receptors different? Draw the structures of nicotine and muscarine and show how they might resemble the natural agonist, acetylcholine. Methacholine, carbachol, and bethanechol are acetylcholine agonists at the muscarinic receptor. Draw the structure of each and explain the rationale behind the structural modifications. Describe how each agonist is used clinically. Atropine and scopolamine (hyocine) are cholinergic antagonists at the muscarinic receptors. Draw their structures, illustrate the structural resemblance to acetylcholine, and describe their clinical utility. Describe the difference between a nondepolarising blocking drug and a depolarizing blocking drug. Provide an example of each. Describe the ‘safe’ technique of ‘balanced