胆碱受体阻断剂培训课件

胆碱受体阻断胆碱受体阻断剂剂Cholinoceptor blocking drugslCholinoceptor blocking drugs:l Bind to cholinoceptor(affinity),but can not or has little result in cholinomimetic action(intrinsic activity),preventing the binding the receptor site to the cholinergic transmitter or cholinoceptor agonist，therefore result in anticholinic effects.lOn the basis of specific receptor affinities(receptor selectivity of these antagonists),the antagonist fall into two major families.2胆碱受体阻断剂Cholinoceptor blocking drugs classify drugsAntimuscarinic agents M1、M2R antagonistsatropine scopolamine anisodamine M1R antagonistspirenzepine M2R antagonistsgallamineAntinicotinic agents N1R antagonistsmecamylamine N2R antagonistssuccinylcholine tubocurarine3胆碱受体阻断剂4胆碱受体阻断剂Antimuscarinic agents plant alkaloidsAtropa belladonnaHyoscyamine(atropine)Datura stramoniumHyoscyamineDatura sp.Feng qieerscopolamineHyoscyamus niger tianxianziHyoscyamineScopolia tanguticaAT3 anisodamine5胆碱受体阻断剂6胆碱受体阻断剂7胆碱受体阻断剂Antimuscarinic agentslAtropa belladonnal 颠茄颠茄lAtropine 阿托品阿托品 dl-hyoscyaminelScopolamine 东莨菪碱东莨菪碱lAnisodamine 山莨菪碱山莨菪碱 654 654-2lAT3 樟柳碱樟柳碱8胆碱受体阻断剂9胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 1.pharmocokinetics tertiary amine alkaloid esterslAbsorption:well absobed from the gut and across the conjunctival membrane.Oral administration tmax 1h；injection tmax 15-20 min.lDistribution:widely，passing across blood-brain barrier10胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品阿托品阿托品阿托品Metabolism and excretion:ldisappear rapidly from the blood,half-life of 2-2.5 hours,1/3 of the dose is excreted unchanged in the urine,most of the rest(2/3)appears in the urine as hydrolysis and conjugation products.l The effect of the drug on parasympathetic function decline rapidly in all organs except the eye.Effects on the iris and ciliary muscle persist for 72 hours or longer.11胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品2.pharmacodynamics and clinical useslMechanism of action competitively block muscarinic receptors(atropine and Ach or cholinomimetics competition for a common binding site on the receptor protein)highly selective for muscarinic receptor,its potency at nicotinic receptors is much lower than at MR,large dose it has ganglion-blocking action.12胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品阿托品阿托品阿托品lThe effectiveness varies with the tissue and atropine effects are dose dependent,the action appears in order as follow duo to increase of dose：glands secretions decrease,mydriasis,bradycardia,smooth muscle relax,tachycardia,gastric secretion depress,CNS signs.13胆碱受体阻断剂14胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 1 reduction of gland secretion salivary gland,sweat glands:greatly reduced(small dose 0.5mg)dry mouth,dry skin(or red skin)lacrimal glands,bronchial glands:decreased(large dose)dry or sandy eyes,reduction the accumulation of secretions in the trachea.gastric secretion，gastric acid(more large dose)thermoregulatory sweating suppressed and body temperature is elevated(large doses or infants and children):may cause atropine fever15胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品Clinical pharmacology(therapeutic applications)l salivate,l night sweat,(hyperhidrosis)l preanesthetic treatment (used prior to administration of inhalant anesthetics to depress bronchial secretion and to reduce the possibility of laryngospasm,to prevent pronounced bradycardia during abdominal surgical procedures)16胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 2 ophthalmologic disorders mydriasis cycloplegia blocked of the ciliary muscle,loss of the ability to accommodate,cannot focus for near vision increase intraocular pressure narrow anterior chamber angle17胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品application：1)prevent synechia(adhesion)formation in uveitis and iritis 2)ophthalmoscopic examination:because it is a long-acting drug(duration of effects are 7-10 days),so shorter-acting drugs are preferred(homatromine)3)optometry always measurement in young children18胆碱受体阻断剂19胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品20胆碱受体阻断剂21胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 3 cadiovascular systerm 1)heart 0.5mg bradycardia brevity,and not marked,(initial)(central)1-2mg tachycardia(blockade of vagal)toxic concentration intraventricular conduction block22胆碱受体阻断剂23胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 4 smooth muscles:relaxation characteristic 1)selectivity gastrointestinal smooth musclebladder detrusorbile duct and ureteruterus,bronchial muscle;no effect on sphincter 2)atropine abolishes any excessive tone and mobility of the intestinal tract,but it has relatively little effect on normal motility.25胆碱受体阻断剂atropine 阿托品4 smooth muscle:relaxationapplication：gastrointestinal disorder(spasm,bellyache etc),reduce involuntary voiding in patients(urinary incontinence)eg children with meninggomyelocele urinary urgency(inflammatory bladder disorder),gallbladder angina（adding pethidine)26胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品5 CNS:Therapeutic dose:no significant effect Then high dose:minimal stimulant effects on the central nervous system,especially the parasympathetic medullary centers(respiration center,excitement,agitation,hallucinations)severity inhibition(coma)27胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 6 Therapeutic applications：cholinergic poisoningl Treatment of poisoning of organophosphates or some mushroom rapidly combat the muscarinic effects reverse some central nervous system effects large dose blockade N1 receptorlprinciple of application：forepart,large doses(enough dose),repeat(continuance)administration28胆碱受体阻断剂Antimuscarinic agentsatropine 阿托品 atropine change 阿托品化阿托品化lReversal of miosis(mydriasis),dry mouth,face flushed,dry skin,mild restlessness,rapid pulse(100-120/min）,pulmonary rale obviously reduce or disappear29胆碱受体阻断剂atropine 阿托品阿托品 adverse reaction*broad range of antimuscarinic effects,treatment with atropine directed at one organ system almost always induces undesirable effects in the other organ systemsigns:dry mouth,mydriasis,blurred vision,photophobia,face flushed,hot and flushed skin,slight restlessness,tachycardia,agitation,delirium,high temperature,dysuria etc*The antidote of atropine poisoning:pilocarpine,neostigiminecontraindications glaucoma prostate hyperplasia(hypertrophy)30胆碱受体阻断剂Antimuscarinic agents atropine654-2scopolamineAT3Smooth muscle relaxweaksimilarweakglandssecreteweakpotentweakeyemydriasis weakpotentweakCardiovascular StachycardiasimilarweakweakCNSexcitesimilarSedation hypnosisSedation hypnosisLD50mg/kg9811515550631胆碱受体阻断剂Antimuscarinic agentsatropine654-2anisodaminescopolamineAT3applicationgastrointestinal spasmOphthalmologic disordersarrhythmiainfection shockorganophosphates poisoningpreanesthetic treatmentgastrointestinal spasminfection shockorganophosphates poisoningpreanesthetic treatmentMotion sicknessparkinsonismHeadacheacute paralysis induced by brain blood vessels32胆碱受体阻断剂Antimuscarinic agents Substitute of atropinelOphthalmic refraction homatropinel tropicamidelSpasmolytic agents propanthelinel glycopyrrolate oxybutyninlGastric ulcer,duodenum peptic ulcer l pirenzepine,telenzepine33胆碱受体阻断剂Antinicotinic agentslN1R antagonists ganglion-blocking drugslN2R antagonists skeletal muscle relaxants The muscle-relaxant drugs most commonly used act by interrupting transmission at the junction between somatic motor nerves and skeletal muscle fibers(interfere with transmission at the neuromuscular end plate),prevent access of the transmitter to its receptor and prevent muscle contraction.34胆碱受体阻断剂Antinicotinic agentsThe two classes of neuromuscular blocking drugs block this process by different mechanisms：nondepolarizing drugs(competitive antagonists)compete with Ach in binding to the receptor site.depolarizing drugs maintain end plate membrane depolarization and thus prevent transmission of another action potential.35胆碱受体阻断剂Antinicotinic agentsdepolarizing drugs transient muscle fasciculation occur(initial excitatory effect on skeletal muscle,especially over the chest and abdomen)easy to produce resistance（continued exposure to succinylcholine）cholinesterase inhibitor augment not reverseSuxamethonium（succinylcholine,scoline 琥珀胆碱琥珀胆碱）onset of neuromuscular blocked is very rapid(within 1min),short duration of action application:trachea intubatton,celioscope examination,adjuncts to anesthesia37胆碱受体阻断剂Antinicotinic agentsnondepolarizing drugs act predominantly at the nicotinic receptor site to compete with Ach.AchE inhibitors(eg,neostigimine)to antagonize nondepolarizing drugs d-tubocurarine（筒箭毒碱（筒箭毒碱）,atracurium (isoquinoline derivatives and steroids)Quaternary nitrogens(poorly lipid soluble)primaryily as adjuncts to general anesthesia38胆碱受体阻断剂39胆碱受体阻断剂