神經(jīng)系統(tǒng)藥理-吳希美解熱鎮(zhèn)痛藥課件

1、Chapter 27Antipyretic-Analgesic and Antiinflammatory Drugs第一頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥A. General Pharmacological properties1. Inhibition of prostaglandin synthesisinhibiting cyclooxygenase (COX，環(huán)氧酶), decreasing the synthesis of PGs and TXA2, resulting antipyretic, analgesic, and anti-inflammatory effect

2、snon-steroidal anti-inflammatory drugs (NSAIDs, 非甾體抗炎藥）。第二頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第三頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第四頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥2. Antipyretic effectsInhibition of PGE2 production in the hypothalamus induced by endogenous pyregens after pathological stimuli temperature notes: symptomatic control onl

3、y, not be indicated in all patients with fever. The effect on body temperature is different from that of chlorpromazine.A. General Pharmacological properties第五頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Comparison of properties of two types of drugs第六頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥3. Analgesic effectsAnalgesic effect is resulted

4、from inhibition of PGE2 production. Effective on the pain of low to moderate intensity related to inflammatory responses.PGE2: a pain stimulant and hyperalgesic agentThe analgesic effect is different from opioid analgesics.A. General Pharmacological properties第七頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Comparison of pr

5、operties of two types of drugs第八頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥4. Anti-inflammatory effects PGs induce inflammatory responses.Inhibition of PG production can relieve inflammatory responses, such as congestion, exudation, pain.The effect is different from that of glucocorticosteroids.A. General Pharmacologica

6、l properties第九頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Comparison of properties of two types of drugs第十頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥5. COX-1 / COX-2 and selectivity of the drugsCOX-1: constructive; involved in physiologic regulatory functions in GI tract, kidney, etc.; inhibition of COX-1 is related to the adverse effects.CO

7、X-2: inducible; involved in pathological responses such as inflammation, and pregnancy; inhibition of COX-2 is related to the therapeutic effects. A. General Pharmacological properties第十一頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥（）（）（）（）第十二頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十三頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十四頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十五頁，共四十

8、頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥B. SalicylatesAspirin 阿司匹林( s p ln)Acetylsalicylic acid 乙酰水楊酸Aspirin 阿司匹林( s p ln)Salicylic acid水楊酸Salicylic sodium水楊酸鈉第十六頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Aspirin 阿司匹林( s p ln)1. ADMEtransformed to salicylic acid form in the bodyhepatic metabolism is primarily conjugation.excretion from urine,

9、 the excretion of unchanged forms of aspirin is increased in the alkalinized urine.larger doses ( 1g/d): non-linear elimination, zero order kinetic process, easier to accumulation and intoxication.B. Salicylates第十七頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十八頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥2. Pharmacological effects and clinical

10、 uses(1) Antipyretic, analgesic and anti-inflammatory effects moderate doses (0.30.6 g): antipyretic and analgesic effects larger doses (35 g/d): anti-inflammatory and anti-rheumatic effects; only relieves symptoms. to treat acute rheumatic fever(急性(jxng)風(fēng)濕熱), to abate pain and symptoms of rheumatic

11、 & rheumatoid arthritis (風(fēng)濕性和類風(fēng)濕性關(guān)節(jié)炎).B. Salicylates第十九頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥(2) Inhibition of platelet aggregation small doses (30100 mg/d): inhibiting TXA2 synthesis, preventing thrombosis. used to treat ischemic heart disease, reduce the mortality of myocardiac infarction, and prevent cerebral th

12、rombosis. larger doses: inhibiting PGI2 synthesis, promoting thrombosis. PGI2: vasodilation and platelet depolymerization (血小板解聚). B. Salicylates第二十頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥The mechanism of aspirin:Target enzymes acetylated第二十一頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥3. Adverse effects(1) GI reactions stimulating gastric

13、 mucosa and CTZ (larger doses);inhibiting PG synthesis in GI tractirritant symptoms; gastric bleeding; ulcerous disorders Contraindications: ulcerous disordersB. Salicylates第二十二頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥(2) Prolongation of bleeding timesmall doses: inhibiting platelet aggregationlarger doses: inhibiting

14、 synthesis of thrombogen Contraindications: one week prior to surgery; severe hepatic damage; vitamin K deficiency,; prothrombinopenia (凝血酶原減少(jinsho)癥).B. Salicylates第二十三頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥(3) Allergic reactions urticaria(蕁麻疹), angioneurotic edema, aspirin-induced asthma, occasionally anaphylact

15、ic shock. Contraindications: bronchial asthmaB. Salicylates第二十四頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Aspirin-induced asthma: Phospholipids of cell menbrane Aspirin Phospholipase A2 (PLA2) (-) Arachidonic acid Cyclooxygenase Lipoxygenenase (環(huán)氧酶) PGH2 5-HPETE (脂氧酶) Prostaglandins (PGs) Leukotrienes (LTs) (前列腺素) (白三烯)

16、第二十五頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥(4) Salicylism dose 5g/d: CNS symptoms, including mental confusion; hyperventilation. i.v. NaHCO3 can promote the excretion of aspirin. (5) Hepatic damage Overdose: hepatic damage Reyes syndrome(瑞夷綜合征): in children, severe hepatic damage (嚴(yán)重(ynzhng)的肝損害) and encephalopathy

17、(腦病)B. Salicylates第二十六頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Dose-response relationship of aspirin:therapeutic effects; adverse effects第二十七頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥4. Drug interactionsB. Salicylates第二十八頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥C. Para-aminophenol derivativesAcetaminophen 對(duì)乙酰氨基酚Paracetamol 撲熱息痛第二十九頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Ace

18、taminophen （對(duì)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 derivatives第三十頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美

19、(解熱鎮(zhèn)痛藥Differences between NSAIDs and Acetaminophen第三十一頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥Toxic metabolites of acetaminophen第三十二頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥D. Other anti-inflammatory drugsSalicylates: aspirinPara-aminophenol derivatives: acetaminophenIndole and indene acetic acid derivatives: indomethacin, sulindacProp

20、ionic acid derivatives: ibuprofen, naproxen, fenopofen, ketoprofenCOX-2 selective inhibitors: meloxicam, celecoxide, rofenxidOthers: phenylbutazone, diclofenac第三十三頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第三十四頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥indomethacin吲哚(yn du)美辛piloxicam吡羅昔康ibuprofen布 洛 芬第三十五頁，共四十頁。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥D. Other anti-inflammatory drugsindomethacin 吲哚(yn du)美辛：stronger efficacy, controlling special types of fever; severe adverse effectsibuprofen 布洛芬