1. Part 3 Cholinoceptor Antagonists

2. A Muscarinic receptor antagonists

3. Action sites of cholinoceptor antagonist

4. NM

5. Atropine 阿托品 Scopolamine 东莨菪碱 Anisodamine山莨菪碱 Atropine-like alkaloids

6. A Muscarinic receptor antagonists §1. Pharmacological effects §(1) Inhibition of exocrine gland secretion salivary, sweat glands § salivary, sweat glands § tear, respiratory tract glands § relatively ineffective: GI tract §(2) Eye mydriasis § rise in intraocular pressure § paralysis of accommodation Atropine 阿托品

8. pilocarpine atropine

9. Durations of the action atropine-like drugs on eye

10. §(3) Antispamodic action on smooth muscle §sensitive: GI, urinary bladder (spasmodic state) §relatively insensitive: bile duct, urinary tract, bronchial tract §insensitive: uterus §(4) Heat HR↓: because of M 1 blockade; § HR↑: if vagal tone ↑ § A-V conduction: if vagal tone ↑ A Muscarinic receptor antagonists

11. §(5) Blood vessels and blood pressure § Therapeutic doses: no remarkable effect § Larger doses: vasodilatation in the skin (indirect) § and in septic shock § §(6) Central stimulation Larger doses § Larger doses A Muscarinic receptor antagonists

12. §2. Clinical uses §(1) Spasms of smooth muscles § GI, biliary or renal colic, enuresis §(2) Inhibiting exocrine gland secretion § Preanesthetic medication, over-secretion §(3) Ophthalmology § Acute iritis or iridocyclitis: mydriatics/miotics § Measurement of the refraction: children A Muscarinic receptor antagonists

13. §(4) Bradyarrhythmia sinus or nodal bradycardia, A-V block § sinus or nodal bradycardia, A-V block §(5) Septic shock §(6) Antidote for organophosphate poisoning A Muscarinic receptor antagonists

14. §3. Adverse effects §(1) Side effects §(2) Central toxicity § Lethal dose: 80~130 mg (adults), 10 mg (child) § but not including the case of treating § organophosphate toxication A Muscarinic receptor antagonists

15. §(3) Detoxication § Symptomatic treatment: diazepam, etc. § Physostigmine ( 毒扁豆碱 ) or pilocarpine ( 毛果芸香碱 ) §(4) Contraindications § glaucoma, prostatauxe, fever A Muscarinic receptor antagonists

16. §Actions and clinical uses §Peripheral effects are similar to atropine; but has stronger central effects (depression) §Pre-anesthetic medication, prevention of motion sickness, Parkinson’s disease Scopolamine 东莨菪碱 A Muscarinic receptor antagonists

17. § Actions and clinical uses §Primarily acts on the smooth muscles of peripheral organs; weak in CNS, glands, eye §Septic shock, spasms of smooth muscles of GI and biliary duct Anisodamine 山莨菪碱, 654-2 A Muscarinic receptor antagonists

18. §Synthetic mydriatics §Homatropine 后马托品 §shorter duration (1~2 days) §Examination of eyes generally §Tropicamide 托吡卡胺 （ 1/4 day ） Synthetic Substitutes for atropine A Muscarinic receptor antagonists

19. §Synthetic Antispasmadics §Airway §Ipratropine bromide 异丙托溴铵 ( 溴化异丙托品 ) §poor absorption and BBB penetration; antispasmodic effects in bronchial smooth muscle §treatment of bronchial asthma and chronic bronchitis; injection or aerosol A Muscarinic receptor antagonists

20. §G.I. §Propantheline bromide 溴化丙胺太林 ( 普鲁本辛 ) §poor absorption (po) and BBB penetration §antispasmodic effects in GI, treatment of peptic ulcer disease §Benactyzine 贝那替秦 ( 胃复康 ) §peptic ulcer disease with anxiety, GI and urinary bladder spasms A Muscarinic receptor antagonists

21. §M 1 receptor antagonists §Pirenzepine 哌仑西平 §inhibition of gastric acid and pepsin secretion §weak in salivary glands and eye, poor penetration into CNS §used in treatment of peptic ulcer disease A Muscarinic receptor antagonists

22. B Nicotinic receptor antagonists

23. §Ganglion Blockers (N N receptor antagonists) §Acting on sympathetic and parasympathetic ganglionic cells; reducing blood pressure by inhibiting sympathetic ganglia §Short-acting; tachyphylaxis §Used for controlled hypotension B Nicotinic receptor antagonists

24. B Nicotinic receptor antagonists neuromuscular blockers

25. §1. Depolarizing neuromuscular blockers § ( depolarizing skeletal muscle relaxants ) §Binding to N M receptors, initial excitation action, then persisting depolarization and resistance to ACh § initially transient fasciculations § tachyphylaxis after repeated uses § anti-AChE potentiates their effects § no ganglion-blocking effects at therapeutic doses B Nicotinic receptor antagonists

26. Succinylcholine 琥珀胆碱, Scoline B Nicotinic receptor antagonists

27. §1.1 Pharmacological effects § Transient excitation (fasciculations), and then inhibition (relaxation) § neck, limbs > face, tongue, throat; less effective on breath muscles at therapeutic doses § Short-acting (5 min), degradation by plasma pseudocholinesterases B Nicotinic receptor antagonists

28. §1.2 Clinical uses An adjuvant in anesthesia or operation § An adjuvant in anesthesia or operation § Intubation of trachea, esophagus, etc. § Prevention of trauma during electroshock therapy § Contraindicated in awake patients, should be used under anesthesia B Nicotinic receptor antagonists

29. §1.3 Adverse effects §(1) Apnea (respiratory paralysis) § overdose or hypersensitive patients; § neostigmine potentiates the toxic effects §(2) Muscle spasm § muscular pain after operation B Nicotinic receptor antagonists

30. §(3) Elevation of K + in plasma § contraindicated in patients with a tendency of hyperkalemia §(4) Malignant hyperthermia § genetic abnormality §(5) Others § rise in intraocular pressure (glaucoma) § histamine release B Nicotinic receptor antagonists

31. §1.4 Drug interactions §Thiopental §ChE inhibitors: § AChE inhibitors, cyclophosphamide, procaine, etc. §Some antibiotics: kanamycin, polymyxins, etc. (synergism in neuromuscular blocking) § kanamycin, polymyxins, etc. (synergism in neuromuscular blocking) B Nicotinic receptor antagonists

32. §2. Nondepolarizing neuromuscular blockers §(nondepolarizing skeletal muscle relaxants) §2.1 Effects: competitive blockade of N M receptors §2.2 Uses: adjuvant treatment of anesthesia or operations Tubocurarine 筒箭毒碱 B Nicotinic receptor antagonists

33. §2.3 Adverse effects §Respiratory paralysis: can be reversed by neostigmine §Enhancing histamine release: BP , bronchoconstriction, salivery secretion §Blocking ganglion: BP  §Contraindications: myasthenia gravis, bronchial asthma, shock, child (< 10 y) B Nicotinic receptor antagonists

34. §Benzylisoquinolines （ 苄基异喹啉类 ） § atracurium 阿曲库铵 doxacurium 多库铵 § mivacurium 米库铵 §Ammonio steroids （ 类固醇铵类 ） § pancuronium 泮库铵 vecuronium 维库铵 § pipecuronium 哌库铵 rocuronium 罗库铵 Other nondepolarizing neuromuscular blockers B Nicotinic receptor antagonists