Chapter 20

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Chapter 20 Chapter 20 Antipyretic- Antipyretic- analgesic and anti- analgesic and anti- inflammatory drugs inflammatory drugs

description

Chapter 20. Antipyretic-analgesic and anti-inflammatory drugs. T. 稽留热. 40 0 c. 弛张热. 低热. 37 0c. day. 0. 1 2 3 4 5. 解热镇痛抗炎药. objecter. 掌握 解热镇痛抗炎药的一般药理. 阿司匹林、对乙酰氨基酚、吲哚美辛 的药理作用、临床应用、不良反应和药物的相互作用。 - PowerPoint PPT Presentation

Transcript of Chapter 20

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Chapter 20Chapter 20

Antipyretic-analgesic and Antipyretic-analgesic and anti-inflammatory drugsanti-inflammatory drugs

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0

40 0c

37 0c

1 2 3 4 5

day

低热

稽留热

弛张热

T

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objecterobjecter

• 掌握掌握 解热镇痛抗炎药的一般药理解热镇痛抗炎药的一般药理 .. 阿司匹阿司匹林、对乙酰氨基酚、吲哚美辛林、对乙酰氨基酚、吲哚美辛的药理作用、的药理作用、临床应用、不良反应和药物的相互作用。临床应用、不良反应和药物的相互作用。

• 熟悉 熟悉 布洛芬、双氯芬酸、选择性布洛芬、双氯芬酸、选择性 COX-2COX-2抑制药的药理作用特点。抑制药的药理作用特点。

• 了解了解 其他解热镇痛抗炎药的作用特点。其他解热镇痛抗炎药的作用特点。

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IntroductionIntroduction• [ [ definition]definition] p.185 p.185

11 ) ) have strong antipyretic have strong antipyretic (( 解热解热 )) 、、 22 )) analgesic analgesic 、、 33 )) anti-inflammatory anti-inflammatory (( 抗炎抗炎 )) 44 )) antirheumatic antirheumatic (( 抗风湿抗风湿 ) ) effects.effects. non-steroidal anti-inflammatory non-steroidal anti-inflammatory

drugs drugs

(NSAIDs (NSAIDs 非甾体抗炎药非甾体抗炎药 ))

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a wide variety of drugs, a wide variety of drugs, chemical structure are various.chemical structure are various.

Anti-inflammatory drugs

NSAIDs aspirin ( 阿司匹林)

SAIDs hydrocortisone ( 氢化可的松)

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[ [ mechanism ]mechanism ]

Membrane phospholipids

PLA2

Arachidonic acid

COX

LTs( 白三烯 )

PGG2, PGH2

vess

el

PGI2 PGF, PGE

platelet

TXA2

SAIDs (–)

NSAIDs(–)

甾体激素

非甾体抗炎药

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【【 commonnesscommonness 】】一、一、 antipyretic actionantipyretic action11 ) ) pyreticpyretic

细菌毒素病毒等

粒细胞吞噬、处理

产生、释放内热原

CNSPG 合成与释放

体温调定点>370C

发热

aspirin ㈠

2 ) antipyretic mechanism

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33 )) characterscharacters 11 、 、 temperature temperature normal normal

( patients with ( patients with fever );fever );

2 2 、、 the actionthe action independent independent of environment temperature; of environment temperature;

3 3 、、 mainly influence dispel mainly influence dispel fever .fever . (散热)

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Meaning of pyreticpyretic

advantagesadvantages :: recovery recovery ,, diagnose diagnose ;;

disadvantagesdisadvantages :: high fever or high fever or durative fever durative fever consume physical consume physical force force ,,

CNS function disorders . CNS function disorders .

T > 39ºc (especially weanT > 39ºc (especially wean !)!)

NoticeNotice

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二、二、 analgesic actionanalgesic action

Characteristics Characteristics ::

11 )) moderate analgesicsmoderate analgesics ,,

Inflammatory pain well, Inflammatory pain well,

but severe or colic pain but severe or colic pain useless.useless.

22 ) ) no addictionno addiction ,,

no respiratory depressionno respiratory depression . .

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Mechanism of analgesicMechanism of analgesic

局部释放 致痛物质

BK 、 PG等

( + ) 痛 觉

感受器

痛觉增敏疼痛

NSAIDs ㈠

NSAIDs ㈠ COX PG analgesic

组织损伤局部炎症

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22 )) (-) COX(-) COX PG PGS S

synthesize synthesize ;; 3) 3) sensitize to sensitize to inflammatory mediators.inflammatory mediators.

(1) (1) Functionary Functionary site---- site---- mainly mainly peripheralperipheral ;;

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三、三、 AntiinflammationAntiinflammation

• In the inflammatory reactionIn the inflammatory reaction

PGsPGs produce : produce :

vasodilation;vasodilation;

vascular permeability vascular permeability ;; tissue oedema ……tissue oedema ……

NSAIDs(–) COX

Cellular adhesion molecule ( 细胞粘附分子 )

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Cyclooxygenase , COXCyclooxygenase , COX

• COX-1COX-1 structural type structural type 结构型结构型 参与血管舒张、血小板聚集、胃粘膜血参与血管舒张、血小板聚集、胃粘膜血

流、胃粘液分泌及肾功能的调节;流、胃粘液分泌及肾功能的调节;• COX-2COX-2 derivational type derivational type 诱导型诱导型 一般在正常组织较少表达,而在炎症部一般在正常组织较少表达,而在炎症部

位呈诱导性表达,是产生位呈诱导性表达,是产生 PGEPGE22 等炎症介等炎症介质的关键酶。质的关键酶。

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NSAIDs 对 COX-1 和 COX-2 作用的比较( IC50 : mol/

L )

药 物 COX-1 COX-2 COX-2/COX-1

吡罗昔康 0.0015 0.906 600 阿司匹林 1.6 277.0 173 吲哚美辛 0.028 1.680 68 布洛芬 4.8 72.8 15.16 美洛昔康 0.214 0.171 0.08 萘普生 9.5 5.0 0.58 萘丁美酮 7.0 1.0 0.143 尼美舒利 > 10 0. 07 < 0.007 塞来昔布 15 0.04 0.0027 罗非昔布 0.018 0.0015 < 0.0833

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Classification according Classification according to selectivity of COXto selectivity of COX

NSAIDsNSAIDs

Non-selectivity COX inhibitors

aspirin, …….

selective COX-2 inhibitors

celecoxib, nimesulide…塞来昔布 尼美舒利

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§1 §1 non-selective COX non-selective COX inhibitorsinhibitors

•ClassificationClassification

水杨酸类 水杨酸类 aspirinaspirin ,, sodium sodium salicylatesalicylate ;;

苯胺类 苯胺类 acetaminophenacetaminophen ;;

有机酸类 有机酸类 indomethacinindomethacin ,, ibuprofenibuprofen ;;

吡唑酮类 吡唑酮类 phenylbutazonephenylbutazone ;;

…… ……

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Usual drugsUsual drugs

aspirinaspirin阿司匹林 阿司匹林

acetylsalicylic acid acetylsalicylic acid

乙酰水杨酸乙酰水杨酸

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【【 pharmacokineticspharmacokinetics 】】

11 、、 absorb rapidlyabsorb rapidly ,, distribution wide ;distribution wide ;

22 、 、 metabolism ---liver;metabolism ---liver;

33 、、 non-linearity eliminationnon-linearity elimination, ,

dosage dosage t t1/2 1/2 ( ( >1g>1g, , tt1/2 1/2

15~30h15~30h ) ) ;;

44 、、 excretion---kidneyexcretion---kidney,,

urine pH influence its excreteurine pH influence its excrete..

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【 【 actions and uses actions and uses 】】 1. 1. antipyretic antipyretic 、、 analgesicanalgesic andand

anti-rheumatic effectsanti-rheumatic effects

usually used for:usually used for: various inflammatory pain;various inflammatory pain;

rheumatic rheumatic arthritis arthritis first first choice;choice;

3-53-5g / d, qid. g / d, qid.

风湿性关节炎

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2. treatment of thrombosis ( 2. treatment of thrombosis ( 血栓病血栓病 ))

aspirinLow

dose(-)

Platelet TXA2 synthesize

PLT congregate

therapeutic effect

Large dose(-)

Vessel COX PGI2 -----effect

血栓素 A2

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•high high selectivityselectivity

• 75~10075~100mg/ d mg/ d

prevent prevent thrombosisthrombosis.. (( 血栓形成血栓形成 ))

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【 【 adverse adverse reactions reactions 】】

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11 、、 gastrointestinal gastrointestinal symptomssymptoms

the most common reactionthe most common reaction,,

induce or aggravate (induce or aggravate ( 加重加重 ) ) ulcerulcer ;;

direct stimulation,direct stimulation,

(-) (-) parietal cell COX-1parietal cell COX-1 PGEPGE22

used with misoprostol (used with misoprostol ( 米索前列醇米索前列醇 ) ) peptic ulcer occurpeptic ulcer occur

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22 、、 cruor drawbackcruor drawback ((凝血障碍)凝血障碍) prolonged bleeding timeprolonged bleeding time

prevention and cure prevention and cure ::vitamine Kvitamine K

33 、、 anaphylaxisanaphylaxis ((过敏反应)过敏反应) asthma of aspirinasthma of aspirin ,, AdrAdr — — inefficacy !inefficacy !

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44 、、 salicylate reactionsalicylate reaction ((水杨酸水杨酸反应)反应)

overdosageoverdosage ( ( >5g / d)>5g / d) GI GI symptoms + CNS symptomssymptoms + CNS symptoms 1) withdrawal at once;1) withdrawal at once;

2) iv.gtt. NaHCO2) iv.gtt. NaHCO3 3 excretion excretion..

5 5 、、 renal damagerenal damage PGEPGE2 2 、 、 PGIPGI2 2 mediated effects mediated effects

(-).(-). …… ……

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AcetaminophenAcetaminophen 对乙酰氨基酚对乙酰氨基酚 ( ( paracetamol paracetamol 扑热息痛扑热息痛 ))

【 【 characteristics characteristics 】】 11 、、 antipyretic antipyretic 、、 analgesicanalgesic ≈ ≈

aspirinaspirin without antiinflammationwithout antiinflammation ; ; 22 、、 mostly use formostly use for :: headacheheadache 、、 fever fever can’t take can’t take

aspirinaspirin; ; 33 、、 adverse reaction mild,adverse reaction mild, overdosage ----- hepatic damage.overdosage ----- hepatic damage.

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Indomethacin Indomethacin ((吲哚美辛吲哚美辛 ,, 消炎痛)消炎痛)

【 【 characteristics characteristics 】】1. One of the most potent 1. One of the most potent

COX inhibitorsCOX inhibitors ;;2. 2.

Antiinflammatory Antiinflammatory 、、 antiantipyreticpyretic and and analgesic analgesic effectseffects are remarkable are remarkable ;;

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3. 3. Used inUsed in: rheumatoid arthritis : rheumatoid arthritis , ,

(( 风湿性关节炎风湿性关节炎 ))

stiffness of stiffness of osteoarthritis.osteoarthritis.

(( 强直性骨关节炎强直性骨关节炎 ))

4. Adverse reactions: 4. Adverse reactions: severesevere;; cross-irritabilitycross-irritability(( 交叉过敏性交叉过敏性 ))

with aspirin.with aspirin.

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Others Others p.190-191p.190-191

• Ibuprofen Ibuprofen 布洛芬布洛芬• Diclofenac Diclofenac 双氯芬酸双氯芬酸• Piroxicam Piroxicam 吡罗昔康吡罗昔康• Phenylbutazone Phenylbutazone 保泰松保泰松• Nabumetone Nabumetone 萘丁美酮萘丁美酮 …… ……

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§2 §2 selective COX-2 inhibitors selective COX-2 inhibitors P.192P.192

CelecoxidCelecoxid ((塞来昔布)塞来昔布) RofecoxibRofecoxib ((罗非昔布)罗非昔布) nimesulidenimesulide ((尼美舒利)尼美舒利) new-typenew-type NSAIDs ,NSAIDs ,

selective (-) COX-2,selective (-) COX-2,

adverse reactions adverse reactions < non-< non-selective NSAIDs.selective NSAIDs.

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抗感冒药常用的复方制剂抗感冒药常用的复方制剂

• 快克快克 醋氨酚 醋氨酚 250250mg mg 金刚烷胺 金刚烷胺 100100mgmg

氯苯那敏 氯苯那敏 22mg mg 人工牛黄 人工牛黄 1010mgmg

咖啡因 咖啡因 1515mgmg

白 +黑

白片 黑片醋氨酚 0.325g 0.325g

伪麻黄碱 30mg 30mg

右美沙芬 15mg 15mg

苯海拉明 25mg

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泰诺

扑尔敏 对乙酰

氨基酚咖啡因

非那

西丁

2

常用抗感冒药组方 ( Mg/ 片)

325

右美沙芬

伪麻黄碱

苯丙醇胺

苯海拉明

15 30康泰克 4

50克感敏 2 126 30 100

氨基比林

APC 35 162 乙酰水杨酸 226.8

去痛片 126 50 150感冒灵 3 250 30

药物

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三九感冒灵颗粒

维 C 银翘片……

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11 、试比较解热镇痛药与镇痛药、试比较解热镇痛药与镇痛药在镇在镇痛方面痛方面的作用和应用。的作用和应用。

22 、试比较解热镇痛药与氯丙嗪在影、试比较解热镇痛药与氯丙嗪在影响响体温方面体温方面的作用和应用。的作用和应用。

思 考 题

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