神经系统药理魏尔清（传出药理概论抗胆碱药课件

Part 3 Cholinoceptor Antagonists,A Muscarinic receptor antagonists,Action sites of cholinoceptor antagonist,Action sites of cholinoceptor antagonist,N,M,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 tear, respiratory tract glands relatively ineffective: GI tract (2) Eye mydriasis rise in intraocular pressure paralysis of accommodation,Atropine 阿托品,pilocarpine,atropine,Durations of the action atropine-like drugs on eye,(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 ,A Muscarinic receptor antagonists,(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,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, over-secretion (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 (5) Septic shock (6) Antidote for organophosphate poisoning,A Muscarinic receptor antagonists,3. Adverse effects (1) Side effects (2) Central toxicity Lethal dose: 80130 mg (adults), 10 mg (child) but not including the case of treating organophosphate toxication,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, Parkinsons 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, 654-2,A Muscarinic receptor antagonists,Synthetic mydriatics Homatropine 后马托品 shorter duration (12 days) Examination of eyes generally Tropicamide 托吡卡胺 （1/4 day）,Synthetic Substitutes for atropine,A Muscarinic receptor antagonists,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,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,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,A Muscarinic receptor antagonists,B Nicotinic receptor antagonists,Ganglion Blockers (NN 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,B Nicotinic receptor antagonists neuromuscular blockers,1. Depolarizing neuromuscular blockers (depolarizing skeletal muscle relaxants) Binding to NM 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 Intubation of trachea, esophagus, etc. Prevention of trauma during electroshock therapy Contraindicated in awake patients, should be used 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, polymyxins, etc. (synergism in neuromuscular blocking),B Nicotinic receptor antagonists,2. Nondepolarizing neuromuscular blockers (nondepolarizing skeletal muscle relaxants) 2.1 Effects: competitive blockade of NM receptors 2.2 Uses: adjuvant