文档介绍：Chapter 8 Anticholinesterase Drugs and Cholinesterase Reactivators
Pharmacology
Instructor : Lei Linsheng 雷林生
Part 1. Cholinesterase prise a large group of drugs that mimic acetylcholine.
They can act indirectly by inhibiting the hydrolysis of endogenous acetylcholine.
Hydrolysis of Ach
  acetylcholinesterase (AChE)
Ach choline+acetic acid
process takes place in about 150 ms
when it binds to its receptor, it is split
Acetate
Ac-serine hydrolysed
Acetyl-group transferred
to serine-OH
Acetylcholine binds
Esteratic site
Anionic site
Reversible inhibition of AChE
indirect cholinergic stimulants
allow Ach to accumulate at receptor site
exhibit M and N-cholinergic
effects
-1 The interactions of AChE with acetylcholine(A) , reversible anticholinesterase drugs (B) and irreversible anticholinesterase agents(C) .
裂解
Neostigmine 新斯的明
Pharmacologic effects
inhibition of cholinesterase
2. very strong effect on skeletal muscle
-- Ach accumulation at the motor nerve endings
--direct activating N2 receptors
3. strong stimulating effect on GI tract and gallbladder smooth muscle
B. Clinical Uses
symptomatic treatment of myasthenia gravis
Postoperative paralytic ileus , abdominal distension and uroschesis (retention of urine)
---stimulates GI tract smooth muscle and bladder detrusor (contraction)
3. Paroxysmal supraventricular tachycardia
---Decrease heart rate
4. Overdose of nondepolarizing muscle relaxants
--tubocurarine intoxication