药物研发神经系统药理陈忠2016.pptVIP

* * * Cholinesterase Inhibitors Although cholinesterase inhibitors reverse nondepolarizing paralysis, they markedly prolong a depolarizing phase I block by two mechanisms: - By inhibiting acetylcholinesterase, they lead to a higher ACh concentration at the nerve terminal, which intensifies depolarization. - They also reduce the hydrolysis of succinylcholine by inhibiting pseudocholinesterase. * Therapeutic Applications: - to obtain better muscle relaxation in surgical anesthesia. sensation is unaffected and full anesthesia must be maintained. - skeletal muscle relaxation facilitating tracheal intubation 注射死刑：硫喷妥钠+肌松药+氯化钾 * Succinylcholine (Scoline司可林) Succinylcholine is the only depolarizing agent used clinically (t1/2= 2-4 min). Properties of actions: initially transient fasciculations （肌束震颤） anti-AChE potentiates their effects tachyphylaxis after repeated uses no ganglion-blocking effects at therapeutic doses the drugs are highly polar, poor bioavailability; i.v. as quaternary compounds, do not enter CNS acetylcholine succinylcholine Main pharmacological effects Transient excitation (fasciculations), and then inhibition (relaxation) Succinylcholine, Scoline Relax Skeletal Muscles in neck, limbs face, tongue, throat; less effective on breath muscles at therapeutic doses Clinical uses An adjuvant in anesthesia or operation Intubation of trachea（气管插管术）, esophagus（食管）, etc. Prevention of trauma during electroshock therapy （无抽搐电休克疗法） Contraindicated in awake patients, should be used under anesthesia Succinylcholine (Scoline) Adverse effects (1) Apnea (呼吸暂停respiratory paralysis) overdose or hypersensitive patients; neostigmine potentiates the toxic effects (2) Muscle spasm muscular pain after operation Succinylcholine (Scoline) (3) Elevation of K+ in plasma contraindicated in patients with a tendency of hyperkalemia (4) Malignant hyperthermia（恶性体温过高） genetic abnormality, treated by dantrolene (丹曲林Ca2