神经系统药理—吴希美解热镇痛药复习课程.ppt

神经系统药理吴希美解热镇痛药2.Antipyretic effectsInhibition of PGE2 production in the hypothalamus induced by endogenous pyregens after pathological stimuli temperature notes:symptomatic symptomatic control control only,only,not not be be indicated indicated in all patients with fever.in all patients with fever.The effect on body temperature is different from The effect on body temperature is different from that of chlorpromazine.that of chlorpromazine.A.General Pharmacological propertiesComparison of properties of two types of drugs3.Analgesic effectsAnalgesic Analgesic effect effect is is resulted resulted from from inhibition inhibition of of PGEPGE2 2 production.production.Effective on the pain of low to moderate intensity Effective on the pain of low to moderate intensity related to inflammatory responses.related to inflammatory responses.PGEPGE2 2:a pain stimulant and hyperalgesic agent a pain stimulant and hyperalgesic agentThe analgesic effect is different from opioid The analgesic effect is different from opioid analgesics.analgesics.A.General Pharmacological propertiesComparison of properties of two types of drugs4.Anti-inflammatory effects PGs induce inflammatory responses.PGs induce inflammatory responses.Inhibition of PG production can relieve Inhibition of PG production can relieve inflammatory responses,such as congestion,inflammatory responses,such as congestion,exudation,pain.exudation,pain.The effect is different from that of The effect is different from that of glucocorticosteroids.glucocorticosteroids.A.General Pharmacological propertiesComparison of properties of two types of drugs5.COX-1/COX-2 and selectivity of the drugsCOX-1:constructive;constructive;involved involved in in physiologic physiologic regulatory functions in GI tract,kidney,regulatory functions in GI tract,kidney,etc.etc.;inhibition of COX-1 is related to the adverse inhibition of COX-1 is related to the adverse effects.effects.COX-2:inducible;inducible;involved in pathological involved in pathological responses such as inflammation,and pregnancy;responses such as inflammation,and pregnancy;inhibition of COX-2 is related to the therapeutic inhibition of COX-2 is related to the therapeutic effects.effects.A.General Pharmacological properties（）（）（）（）（）（）（）（）B.SalicylatesAspirin 阿司匹林阿司匹林Acetylsalicylic acid 乙酰水杨酸乙酰水杨酸Aspirin Aspirin 阿司匹林阿司匹林阿司匹林阿司匹林Salicylic acidSalicylic acid水杨酸水杨酸水杨酸水杨酸Salicylic sodiumSalicylic sodium水杨酸钠水杨酸钠水杨酸钠水杨酸钠Aspirin 阿司匹林阿司匹林1.ADMEtransformed to salicylic acid form in the bodytransformed to salicylic acid form in the bodyhepatic metabolism is primarily conjugation.hepatic metabolism is primarily conjugation.excretion excretion from from urine,urine,the the excretion excretion of of unchanged unchanged forms of aspirin is increased in the alkalinized urine.forms of aspirin is increased in the alkalinized urine.larger larger doses doses(1g/d):1g/d):non-linear non-linear eliminationelimination,zero zero order order kinetic kinetic process,process,easier easier to to accumulation accumulation and and intoxication.intoxication.B.Salicylates2.Pharmacological effects and clinical uses(1)Antipyretic,analgesic and anti-inflammatory effects moderate doses(0.3moderate doses(0.30.6 g):0.6 g):antipyretic and analgesic antipyretic and analgesic effectseffects larger doses(3larger doses(35 g/d):5 g/d):anti-inflammatory and anti-anti-inflammatory and anti-rheumatic effects;only relieves symptoms.rheumatic effects;only relieves symptoms.to treat acute rheumatic fever(to treat acute rheumatic fever(急性风湿热急性风湿热急性风湿热急性风湿热),),to abate pain and symptoms of rheumatic&rheumatoid to abate pain and symptoms of rheumatic&rheumatoid arthritis (arthritis (风湿性和类风湿性关节炎风湿性和类风湿性关节炎风湿性和类风湿性关节炎风湿性和类风湿性关节炎).).B.Salicylates(2)Inhibition of platelet aggregation small doses(30small doses(30100 mg/d):100 mg/d):inhibiting TXA inhibiting TXA2 2 synthesis,preventing thrombosis.synthesis,preventing thrombosis.used to treat ischemic heart disease,reduce the used to treat ischemic heart disease,reduce the mortality of myocardiac infarction,and prevent mortality of myocardiac infarction,and prevent cerebral thrombosis.cerebral thrombosis.larger doses:larger doses:inhibiting PGI inhibiting PGI2 2 synthesis,synthesis,promoting thrombosis.promoting thrombosis.PGIPGI2 2:vasodilation and platelet depolymerization vasodilation and platelet depolymerization(血小板解聚血小板解聚血小板解聚血小板解聚).).B.SalicylatesThe mechanism of The mechanism of aspirin:aspirin:Target enzymes Target enzymes acetylatedacetylated3.Adverse effects(1)GI reactions stimulating stimulating gastric gastric mucosa mucosa and and CTZ CTZ(larger(larger doses);doses);inhibiting PG synthesis in GI tractinhibiting PG synthesis in GI tractirritant irritant symptoms;symptoms;gastric gastric bleeding;bleeding;ulcerous ulcerous disordersdisorders Contraindications:Contraindications:ulcerous disordersulcerous disordersB.Salicylates(2)Prolongation of bleeding time(2)Prolongation of bleeding timesmall doses:small doses:inhibiting platelet aggregation inhibiting platelet aggregationlarger doses:larger doses:inhibiting synthesis of thrombogen inhibiting synthesis of thrombogen Contraindications:Contraindications:one week prior to surgery;one week prior to surgery;severe hepatic damage;severe hepatic damage;vitamin K deficiency,;vitamin K deficiency,;prothrombinopenia(prothrombinopenia(凝血酶原减少症凝血酶原减少症凝血酶原减少症凝血酶原减少症).).B.Salicylates(3)Allergic reactions urticaria(urticaria(荨麻疹荨麻疹荨麻疹荨麻疹),),angioneurotic edema,angioneurotic edema,aspirin-induced asthma,aspirin-induced asthma,occasionally anaphylactic shock.occasionally anaphylactic shock.Contraindications:bronchial asthmaB.SalicylatesAspirin-induced asthma:Phospholipids of cell menbrane Aspirin Phospholipase A2(PLAPLA2)(-)Arachidonic acid Cyclooxygenase Cyclooxygenase LipoxygenenaseLipoxygenenase (环氧酶环氧酶环氧酶环氧酶)PGH PGH2 2 5-HPETE 5-HPETE (脂氧酶脂氧酶脂氧酶脂氧酶)Prostaglandins(PGs)Leukotrienes(LTs)(前列腺素前列腺素前列腺素前列腺素)(白三烯白三烯白三烯白三烯)(4)Salicylism dose 5g/d:dose 5g/d:CNS symptoms,including mental CNS symptoms,including mental confusion;hyperventilation.confusion;hyperventilation.i.v.i.v.NaHCO NaHCO3 3 can promote the excretion of can promote the excretion of aspirin.aspirin.(5)Hepatic damage(5)Hepatic damage Overdose:Overdose:hepatic damage hepatic damage Reyes syndrome(Reyes syndrome(瑞夷综合征瑞夷综合征瑞夷综合征瑞夷综合征):):in children,in children,severe hepatic damage(severe hepatic damage(严重的肝损害严重的肝损害严重的肝损害严重的肝损害)and)and encephalopathy(encephalopathy(脑病脑病脑病脑病)B.SalicylatesDose-response Dose-response relationship of aspirin:relationship of aspirin:therapeutic effects;therapeutic effects;adverse effectsadverse effects4.Drug interactionsB.SalicylatesC.Para-aminophenol derivativesAcetaminophen 对乙酰氨基酚对乙酰氨基酚Paracetamol 扑热息痛扑热息痛Acetaminophen（对乙酰氨基酚）：（对乙酰氨基酚）：antipyretic and analgesic effects are mild and lasting,but almost no anti-inflammatory effects,-not a NSAID higher selectivity to COX in CNS.mainly used in cold,fever,and headache,etc.overdose can damage liver and kidney.C.Para-aminophenol derivativesDifferences between Differences between NSAIDs and NSAIDs and AcetaminophenAcetaminophenToxic metabolites of Toxic metabolites of acetaminophenacetaminophenD.Other anti-inflammatory drugsSalicylates:Salicylates:aspirin aspirinPara-aminophenol derivatives:Para-aminophenol derivatives:acetaminophen acetaminophenIndole and indene acetic acid derivatives:Indole and indene acetic acid derivatives:indomethacin,sulindac indomethacin,sulindacPropionic acid derivatives:Propionic acid derivatives:ibuprofen,naproxen,fenopofen,ketoprofen ibuprofen,naproxen,fenopofen,ketoprofenCOX-2 selective inhibitors:COX-2 selective inhibitors:meloxicam,celecoxide,rofenxid meloxicam,celecoxide,rofenxidOthers:Others:phenylbutazone,diclofenac phenylbutazone,diclofenacindomethacin吲哚美辛吲哚美辛piloxicam吡罗昔康吡罗昔康ibuprofen布布 洛洛 芬芬D.Other anti-inflammatory drugsindomethacin 吲哚美辛：吲哚美辛：stronger efficacy,stronger efficacy,controlling special types of fever;severe adverse controlling special types of fever;severe adverse effectseffectsibuprofen 布洛芬布洛芬（芬必得）（芬必得）：stronger stronger antipyretic,analgesic and anti-inflammatoryantipyretic,analgesic and anti-inflammatory effects;effects;weaker GI reactions;vision damageweaker GI reactions;vision damagepiloxicam 吡罗昔康吡罗昔康:long-acting anti-long-acting anti-inflammatory and analgesic agent;long-term use inflammatory and analgesic agent;long-term use induces hemorrhage and ulcers in GI tractinduces hemorrhage and ulcers in GI tractCOX-2 selective anti-inflammatory drugsMeloxicam 美洛昔康美洛昔康stronger effect on COX-2 than COX-1long-acting(t1/2 20 h)weaker GI reactions 此课件下载可自行编辑修改，仅供参考！此课件下载可自行编辑修改，仅供参考！感谢您的支持，我们努力做得更好！谢谢感谢您的支持，我们努力做得更好！谢谢