1. Muscarinic receptor agonists

2. A Muscarinic receptor agonists §1. Choline esters ( 胆碱酯类 ) § Acetylcholine 乙酰胆碱 § Carbachol 卡巴胆碱 § Methacholine 醋甲胆碱 § Bethanechol chloride 氯贝胆碱 §2. Natural alkaloids ( 生物碱类 ) § Pilocarpine 毛果芸香碱（匹罗卡品） § Muscarine 毒蕈碱

3. Pilocarpine 毛果芸香碱（匹罗卡品） Pilocarpine 毛果芸香碱 Muscarinic receptor agonists

4. §1. Pharmacological effects § （ 1 ） Eyes  Miosis （ 缩瞳 ） :  Miosis （ 缩瞳 ） : contraction of sphincter muscle of iris §Lowing intraocular pressure （ 降低眼内压 ） : §Lowing intraocular pressure （ 降低眼内压 ） : enlarging angle of anterior chamber, increasing drainage of aquous humor §Spasm of accommodation （ 调节痉挛 ） : §Spasm of accommodation （ 调节痉挛 ） : contraction of ciliary muscle, contraction for near vision Muscarinic receptor agonists

5. Iris, cilliary muscles, and Schelemm canal

6. Aqueous humor drainage

8. Pilocarpine Atropine

9. § （ 2 ） Promoting secretion of exocrine glands （ 外分泌腺体 ） § especially in sweat, salivary and tear glands § especially in sweat, salivary and tear glands Muscarinic receptor agonists

10. §2. Clinical uses § （ 1 ） Ophthamological uses  Glaucoma: narrow- or wide-angles Iritis: miotics/mydriatics  Iritis: miotics/mydriatics  BOX Glaucoma §Acute congestive glaucoma （ narrow-angle ） §Chronic simple glaucoma （ wide-angle ） Muscarinic receptor agonists

11. § （ 2 ） Systemic use § Dry mouth: radiotherapy § Antidote for atropine poisoning Muscarinic receptor agonists

12. §3. Adverse effects  （ 1 ） Local (eye): pain, tears § （ 2 ） Systemic: secretion of exocrine glands, treated with atropine Muscarinic receptor agonists

13. Cholinoceptor antagonists

14. Muscarinic receptor antagonists

15. Action sites of cholinoceptor antagonist

16. NM

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

18. 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

20. pilocarpine atropine

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

22. §(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 ↑ Muscarinic receptor antagonists

23. §(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 Muscarinic receptor antagonists

24. §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 Muscarinic receptor antagonists

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

26. §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 Muscarinic receptor antagonists

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

28. §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 Muscarinic receptor antagonists

29. § 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 Muscarinic receptor antagonists

30. §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 Muscarinic receptor antagonists

31. §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 Muscarinic receptor antagonists

32. §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 Muscarinic receptor antagonists

33. §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 Muscarinic receptor antagonists

34. Nicotinic receptor antagonists

35. §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 Nicotinic receptor antagonists

36. Nicotinic receptor antagonists neuromuscular blockers

37. §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 Nicotinic receptor antagonists

38. Succinylcholine 琥珀胆碱, Scoline Nicotinic receptor antagonists

39. §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 Nicotinic receptor antagonists

40. §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 Nicotinic receptor antagonists

41. §1.3 Adverse effects §(1) Apnea (respiratory paralysis) § overdose or hypersensitive patients; § neostigmine potentiates the toxic effects §(2) Muscle spasm § muscular pain after operation Nicotinic receptor antagonists

42. §(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 Nicotinic receptor antagonists

43. §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) Nicotinic receptor antagonists

44. §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 Nicotinic receptor antagonists

45. §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) Nicotinic receptor antagonists

46. §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 Nicotinic receptor antagonists