Chapter 6 Muscarinic [,mʌskə‘rinik]毒蕈碱的 receptor agonists

Subtypes and effects of cholinergic receptors Nicotine receptor N1 receptor: excitation of nerve ganglion N2 receptor promoting the contracting of skeletal muscle M1 receptor M3 receptor M2 receptor: inhibition of heart promoting the contracting of smooth muscle  [‘gæŋglɪən] 神经节  Muscarine receptor promoting the secretion of glands

Pilocarpine /,pailə'kɑ:pi:n; ,pi-/ M receptor agonist Pilocarpine /,pailə'kɑ:pi:n; ,pi-/ （毛果芸香碱,匹鲁卡品） Pharmacological effects: 1 Eye 1.1 Miosis /mai'əusis/缩瞳: Constriction of the sphincter /'sfiŋktə/括约肌 muscle of iris /'aiəris/虹膜 Pilocarpus

1.2 Reduce the intraocular [,intrə'ɔkjulə] 眼内的 pressure

1.3 Spasm /'spæzəm/痉挛 of accommodation 调节痉挛

Clinical application: 2 Increasing glandular /'ɡlændjulə/腺体的 secretion; 3 Promoting the contracting of smooth muscle. Clinical application: 1 Glaucoma[glɔ:‘kəumə] 青光眼 ( to decrease intraocular pressure) angle-closure glaucoma open-angle glaucoma 2 Iritis [ai'raitis]虹膜炎 3 Dry mouth 口干

Anti-cholinesterase agents /,kəuli'nestəreis/ 胆碱酯酶

Neostigmine /,ni:əu'stiɡmi:n; -min/ 新斯的明 Effects and mechanisms Stimulate skeletal muscle strongly, by: 1) Inhibiting Ach E→ Ach concentration↑ 2) Stimulating N2 receptors directly 3) Promoting the release of Ach at the motor nerve ending.

Clinical uses 1 Myasthenia /,maiəs'θi:niə/肌无力gravis 重症肌无力 2 Postoperative urinary /'juərinəri/retention and abdominal distention (/dis'tenʃən/膨胀/扩张) resulting from general anesthesia 3 Paroxysmal supraventricular tachycardia阵发性室上性心动过速 /,pærək‘sizməl/阵发性的 /,tæki'kɑ:diə/心动过速 4 Reverse the effects of non-depolarizing muscle relaxants 非去极化型肌松药

Adverse reactions： “Cholinergic crisis” A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine. The muscles stop responding to ACh, leading to flaccid [‘flæsɪd] 无力的paralysis, respiratory failure, other symptoms include increased sweating, salivation /,sæli'veiʃən/ 流涎, bronchial secretions along with miosis.

Contraindication 禁忌症 ileus['iliəs] , urinary obstruction, bronchial asthma 肠梗阻、泌尿道阻塞、支气管哮喘

Supplementary reading Myasthenia gravis is either an autoimmune or congenital [kən‘dʒenɪt(ə)l] 先天的neuromuscular disease that leads to fluctuating muscle weakness and fatigue. In the most common cases, muscle weakness is caused by circulating antibodies that block acetylcholine receptors at the postsynaptic neuromuscular junction, inhibiting the excitatory effects of the neurotransmitter acetylcholine on nicotinic receptors at neuromuscular junctions. Alternatively, in a much rarer form, muscle weakness is caused by a genetic defect in some portion of the neuromuscular junction, that is inherited at birth as opposed to developing it through autoimmunity later in life or through passive transmission by the mother's immune system at birth. Myasthenia is treated medically with acetylcholinesterase inhibitors or immunosuppressants, and, in selected cases, thymectomy [θaɪ'mɛktəmi]胸腺切除术. The hallmark of myasthenia gravis is fatigability[,fætigə'biləti]易疲劳性. Muscles become progressively weaker during periods of activity, and improve after periods of rest. Muscles that control eye and eyelid movement, facial expressions, chewing, talking, and swallowing are especially susceptible. The muscles that control breathing and neck and limb movements can also be affected.

大纲要求 Objective and requirements Understand the concepts and classification of choline receptor agonists; Master the pharmacological actions, clinical applications, and adverse reactions of pilocarpine and neostigmine; Be familiar with the N-like and M-like functions of acetylcholine. Teaching contents (1) Conception and classification of choline receptor agonists; (2) N-like and M-like functions of acetylcholine; (3) M-like function (ocular function) induced by pilocarpine; the clinical applications and adverse reactions of pilocarpine (4) Pharmacological actions, in vivo process, characteristics, clinical applications, and adverse reactions of neostigmine.

Essential vocabulary Pharmacological effects Clinical application/ clinical use Adverse reaction Contraindication Miosis/Spasm of accommodation/Glandular secretion Glaucoma/Iritis/Myasthenia gravis Dry mouth/Abdominal distention/Urinary retention/Tachycardia/bradycardia Cholinergic crisis Anti-cholinesterase agents