Chapter 18 Cholinoceptor Antagonists

1. Chapter 18Cholinoceptor Antagonists

2. Part AMuscarinic receptor antagonists

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

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

5. atropine pilocarpine

6. A Muscarinic receptor antagonists • (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 M1 blockade; • HR↑:if vagal tone ↑ • A-V conduction:if vagal tone ↑

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

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

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

10. A Muscarinic receptor antagonists • 3. Adverse effects • (1) Side effects • (2) Central toxicity • Lethal dose: 80~130 mg (adults), 10 mg (child)

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

12. A Muscarinic receptor antagonists Scopolamine 东莨菪碱 • 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

13. A Muscarinic receptor antagonists Anisodamine 山莨菪碱, 654-2 • 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

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

15. A Muscarinic receptor antagonists Synthetic Antispasmadics • Propantheline bromide 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

16. A Muscarinic receptor antagonists M1 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

17. Part BNicotinic receptor antagonists

18. B Nicotinic receptor antagonists • Acting on sympathetic and parasympathetic ganglionic cells; reducing blood pressure by inhibiting sympathetic ganglia • Short-acting; tachyphylaxis • Used for controlled hypotension

19. B Nicotinic receptor antagonists • 1. Depolarizing neuromuscular blockers • (depolarizing skeletal muscle relaxants) • Binding to NN 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

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

21. B Nicotinic receptor antagonists • 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

22. B Nicotinic receptor antagonists • 1.2 Clinical uses • An adjuvant in anesthesia or operation • Intubation of trachea, esophagus, ect. • Prevention of trauma during electroshock therapy • Contraindicated in awake patients, should use under anesthesia

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

24. B Nicotinic receptor antagonists • (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;

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

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

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

28. B Nicotinic receptor antagonists Other nondepolarizing neuromuscular blockers • 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