上海交通大学：《药理学 Pharmacology》课程教学资源（讲义课件）Chapter 5 Cholinergic Drugs

Chapter 5 Cholinergic Drugs

Chapter 5 Cholinergic Drugs

Cholinergic Drugs ●Definition -Drugs that stimulate the parasympathetic nervous system (PSNS) -Producing actions similar to that of acetylcholine (ACh) The PSNS is the opposing system to the SNS -Parasympathomimetics/cholinomimetics -Mimic the effects of the PSNS neurotransmitter:acetylcholine (ACh)

Cholinergic Drugs • Definition – Drugs that stimulate the parasympathetic nervous system (PSNS) – Producing actions similar to that of acetylcholine (ACh) – The PSNS is the opposing system to the SNS – Parasympathomimetics/ cholinomimetics – Mimic the effects of the PSNS neurotransmitter: acetylcholine (ACh)

Drug Effects ·The PSNS is the“rest and digest”system ·“SLUDGE -Salivation -Lacrimation -Urinary incontinence -Diarrhea -Gastrointestinal cramps -Emesis

Drug Effects • The PSNS is the “rest and digest” system • “SLUDGE” – Salivation – Lacrimation – Urinary incontinence – Diarrhea – Gastrointestinal cramps – Emesis

Cholinergic Drugs Direct-acting Indirect-acting Receptor agonists Cholinesterase inhibitors Choline ester: Alkaliod: Irreversible: Reversible: Carbachol; Pilocarpine Isoflurophate Neostigmine bethanechol

Cholinergic Drugs Direct-acting Receptor agonists Choline ester: Carbachol; bethanechol Alkaliod: Pilocarpine Indirect-acting Cholinesterase inhibitors Irreversible: Isoflurophate Reversible: Neostigmine

Choline Ester Choline Ester AChE Susceptibility Muscarinic Effect Nicotinic Effect 0 CH3 HgC-C-O-CH2-CH2-N+-CH3 Highest (++++ High (+++ High(+++) CHg Acetylcholine 0 a Hc-c-0Cc-w≤8 Low (+ Highest (++++ None H3 CHa Methacholine (acetyl-B-methylcholine) 0 HN-C-O-CH2-CH-N CHa Negligible Medium (++ High (+++ CHa CH3 Carbachol (carbamoylcholine) 0 CHa Negligible Medium (++ None H2N-C-O-CH-CH2-N+-CH3 CH3 CHa Bethanechol (carbamoyl-B-methylcholine)

AChE Susceptibility Muscarinic Effect Highest (++++) High (+++) Low (+) Highest (++++) Negligible Medium (++) Negligible Medium (++) Choline Ester Choline Ester Nicotinic Effect High(+++) None High (+++) None

Alkaloids:Pilocarpine Action chiefly muscarinic HO CHa HC CH2-+N-CH3 CHa Muscarine H3C-CH2、 CH2 N一CH3 0 Pilocarpine Alkaloid isolated in 1875,and its actions on the eye and salivary gland were described although these actions were long before known by natives of South America. Acting on the M receptor in postganglionic parasympathetic nervous system

Alkaloids: Pilocarpine Alkaloid isolated in 1875, and its actions on the eye and salivary gland were described although these actions were long before known by natives of South America. Acting on the M receptor in postganglionic parasympathetic nervous system

Organ Effects of Pilocarpine(毛果芸香碱) Pilocarpine is applied to the cornea Eye and produces a rapid miosis and (constrict pupil) Lungs (constrict bronchioles contraction of the ciliary muscle and increase secretions) Heart PARASYMPATHETIC (decreased heart rate) Blood vessel (dilate) Ganglion Spinal cord Gastrointestinal (increase peristalsis and secretions) Bladder Pilocarpine is one of the most Salivary gland (contracts) potent stimulators of secretions. (increased salivation) Such as sweat,tears,and saliva

Organ Effects of Pilocarpine (毛果芸香碱） Pilocarpine is applied to the cornea and produces a rapid miosis and contraction of the ciliary muscle Pilocarpine is one of the most potent stimulators of secretions, Such as sweat, tears, and saliva

Therapeutic Use Pilocarpine Hydrochloride eye drops (Pilocar) -s0l.1%,2%,4% 湿 做扣厚 in open angle glaucoma Pilocarpine Hydrochloride Ophthalmic Applied to the eye,it Solution USP 1% penetrates cornea and promptly causes 非进 miosis,ciliary muscle contra- Bxanly 15 mL ction,and fall in intraoccular tension(<22 mm)lasting 4-8 h. Side effect:painful spasm of accommodation for near vision. Sjgoren's syndrome(干燥综合症)：which is characterized by dry mouth and lack of tears,.is treated with oral pilocarpine tablets and cevimeline(西维美林)， a cholinergic drug that also has the drawback of being nonspecific

Pilocarpine Hydrochloride eye drops (Pilocar®) - sol. 1%, 2%, 4% - in open angle glаucoma Applied to the eye, it penetrates cornea and promptly causes miosis, ciliary muscle contra￾ction, and fall in intraoccular tension (< 22 mm) lasting 4-8 h. Side effect: painful spasm of accommodation for near vision. Therapeutic Use Sjgoren’s syndrome(干燥综合症）: which is characterized by dry mouth and lack of tears, is treated with oral pilocarpine tablets and cevimeline (西维美林）， a cholinergic drug that also has the drawback of being nonspecific

Glaucoma Glaucoma is a major cause of blindness and of great pharmacologic interest because the chronic form often responds to drug therapy. The primary manifestation is increased intraocular pressure not initially associated with symptoms.Without treatment,increased intraocular pressure results in damage to the retina and optic nerve,with restriction of visual fields and,eventually blindness

Glaucoma • Glaucoma is a major cause of blindness and of great pharmacologic interest because the chronic form often responds to drug therapy. The primary manifestation is increased intraocular pressure not initially associated with symptoms. Without treatment, increased intraocular pressure results in damage to the retina and optic nerve, with restriction of visual fields and, eventually blindness

Cholinergic Drugs Indirect-acting Cholinesterase inhibitors Reversible Irreversible -Increase acetylcholine concentration and lifetime by inhibiting degradation -Cholinomimetic -Act by binding to AChE active site causing reversible (non covalent)or long lasting (covalent modification)

Cholinergic Drugs Indirect-acting Cholinesterase inhibitors Reversible Irreversible -Increase acetylcholine concentration and lifetime by inhibiting degradation -Cholinomimetic -Act by binding to AChE active site causing reversible (non covalent) or long lasting (covalent modification)