Chapter 18 Cholinoceptor Antagonists

Part A Muscarinic receptor antagonists

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

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

pilocarpine atropine

§(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

§(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 § Larger doses 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 A Muscarinic receptor antagonists

§(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

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

§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

§ 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, A Muscarinic receptor antagonists

§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

§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 Synthetic Antispasmadics A Muscarinic 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 M 1 receptor antagonists A Muscarinic receptor antagonists

Part 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 B Nicotinic receptor antagonists

§1. Depolarizing neuromuscular blockers § (depolarizing skeletal muscle relaxants) §Binding to N N 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

Succinylcholine 琥珀胆碱, Scoline 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 B Nicotinic receptor antagonists

§1.2 Clinical uses An adjuvant in anesthesia or operation § 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 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 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; 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) § kanamycin, polimyxins, etc. (synergism in neuromuscular blocking) B Nicotinic receptor antagonists

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

§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