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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第三頁(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第四頁(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥（）（）（）（）第十二頁(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十三頁(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十四頁(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十五頁(yè)，共四十

8、頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第十八頁(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。神經(jīng)系統(tǒng)藥理吳希美(解熱鎮(zhèn)痛藥第三十四頁(yè)，共四十頁(yè)。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(yè)，共四十頁(yè)。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