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Part 13
Antipyretic-Analgesic
Drugs
A. General Pharmacological properties
 1. Inhibition of prostaglandin (PG) synthesis
 inhibiting cyclooxygenase (COX，环氧酶),
 decreasing the synthesis of PGs and TXA2,
 resulting antipyretic, analgesic, and antiinflammatory effects
 non-steroidal anti-inflammatory drugs (NSAIDs, 非
甾体抗炎药）
A. General Pharmacological properties
 2. Antipyretic effects
 Inhibition of PGE2 production in the
hypothalamus induced by endogenous
pyregens after pathological stimulation 
temperature 
 notes:
symptomatic control only, not be indicated
in all patients with fever.

The effect on body temperature is different from
that of chlorpromazine.
Comparison of properties of two types of drugs
作用机制
作用
用途
不良反应
解热镇痛药
氯丙嗪
抑制前列腺素合成，使 抑制下丘脑体温调节中枢，
散热增加而解热
使其调节功能减弱，不能随
外界温度变化而调节体温
只能使升高的体温降到 氯丙嗪配合物理降温，不仅
正常
可使升高的体温降到正常，
也可使正常体温降到正常以
下
用于各种发热
用于低温麻醉、人工冬眠
胃肠道反应等
锥体外系统反应等
A. General Pharmacological properties
 3. Analgesic effects
 Analgesic effect is resulted from inhibition of PGE2
production.
 Effective on the pain of low to moderate intensity
related to inflammatory responses.
 PGE2: a pain stimulant and hyperalgesic agent
 The analgesic effect is different from opioid
analgesics.
Comparison of properties of two types of drugs
作用
用途
不良反应
解热镇痛药
抑制前列腺素合成起效；
对慢性钝痛有效，对剧烈
疼痛或内脏绞痛无效
头痛、牙痛、神经痛、肌
肉或关节痛、痛经等
阿片类镇痛药
兴奋阿片受体起效；
对各种疼痛均有效
用于其他药物无效的急性
锐痛，晚期肿瘤的剧烈疼
痛
胃肠道反应等，但无成瘾 有成瘾性
性
A. General Pharmacological properties
 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.
Comparison of properties of two types of drugs
作用
用途
不良反应
非甾体抗炎药
抑制前列腺素合成起效；
缓解软 组织 、骨骼 、关节
的炎症
风湿性 、类 风湿性 炎症，
外伤损伤
胃肠道反应等
糖皮质激素
抑制炎症细胞、炎症分
子，多环节炎症炎症病变
多环节抑制炎症病
变
可用于多种炎症，作用强
抑制机体防御反应，干扰
代谢，不良反应广泛
A. General Pharmacological properties
 5. COX-1 / COX-2 and selectivity of the drugs
 COX-1: constructive; involved in physiologic
regulatory functions in GI tract, kidney, etc.;

inhibition of COX-1 is related to the adverse
effects.
 COX-2: inducible; involved in pathological
responses such as inflammation, and pregnancy;

inhibition of COX-2 is related to the therapeutic
effects.
（－）
（＋）
（＋）
（－）
B. Salicylates
Aspirin
阿司匹林
Acetylsalicylic acid
乙酰水杨酸
COOH
Salicylic acid
COOH
OH
O
O
C
水杨酸
CH 3
COONa
Salicylic sodium
Aspirin
阿司匹林
OH
水杨酸钠
B. Salicylates
 Aspirin
阿司匹林
 1. ADME
 transformed to salicylic acid form in the body
 hepatic metabolism is primarily conjugation.
 excretion from urine, the excretion of unchanged
forms of aspirin is increased in the alkalinized urine.
 larger doses ( > 1 g/d): non-linear elimination, zero
order kinetic process, easier to accumulation and
intoxication.
B. Salicylates
 2. Pharmacological effects and clinical uses
 (1) Antipyretic, analgesic and antiinflammatory effects
 moderate doses (0.3～0.6 g): antipyretic and analgesic
effects

larger doses (3～5 g/d): anti-inflammatory and antirheumatic effects; only relieves symptoms.

to treat acute rheumatic fever(急性风湿热),

to abate pain and symptoms of rheumatic & rheumatoid
arthritis (风湿性和类风湿性关节炎).
B. Salicylates
 (2) Inhibition of platelet aggregation

small doses (30～100 mg/d): inhibiting TXA2
synthesis, preventing thrombosis.

used to treat ischemic heart disease, reduce the
mortality of myocardiac infarction, and prevent
cerebral thrombosis.

larger doses: inhibiting PGI2 synthesis,
promoting thrombosis.
PGI2: vasodilation and platelet depolymerization (血小板解聚).
The mechanism of
aspirin:
Target enzymes
acetylated
The mechanism of aspirin: Target enzymes acetylated
B. Salicylates
 3. Adverse effects
 (1) GI reactions
 stimulating gastric mucosa and CTZ (larger
doses);
 inhibiting PG synthesis in GI tract
 irritant symptoms; gastric bleeding; ulcerous
disorders
Contraindications: ulcerous disorders
B. Salicylates
 (2) Prolongation of bleeding time
 small doses: inhibiting platelet aggregation
 larger doses: inhibiting synthesis of thrombogen
Contraindications:
one week prior to surgery;
severe hepatic damage;
vitamin K deficiency;
prothrombinopenia (凝血酶原减少症).
B. Salicylates
 (3) Allergic reactions




urticaria (荨麻疹),
angioneurotic edema,
aspirin-induced asthma,
occasionally anaphylactic shock.

Contraindications: bronchial asthma
Aspirin-induced asthma:
Phospholipids of cell menbrane
Aspirin
(-)
Phospholipase A2 (PLA2)
Arachidonic acid
Cyclooxygenase
(环氧酶)
PGH2
Lipoxygenase (脂氧酶)
5-HPETE
↓Prostaglandins (PGs) ↑Leukotrienes (LTs)
(前列腺素)
(白三烯)
B. Salicylates
 (4) Salicylism （水杨酸反应）

dose > 5 g/d: CNS symptoms, including
mental confusion; hyperventilation.
i.v. NaHCO3 can promote the excretion of
aspirin.

 (5) Hepatic damage

Overdose: hepatic damage
Reye’s syndrome (瑞夷综合征): in children,
severe hepatic damage (严重肝损害) and
encephalopathy (脑病)
Dose-response
relationship of aspirin:
therapeutic effects;
adverse effects
B. Salicylates
4. Drug interactions
C. Para-aminophenol derivatives
Acetaminophen 对乙酰氨基酚
Paracetamol
扑热息痛
NHCOCH 3
OH
C. Para-aminophenol derivatives
 Acetaminophen （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.
Differences between
NSAIDs and
Acetaminophen
Toxic metabolites of
acetaminophen
D. Other anti-inflammatory drugs
Salicylates: aspirin
Para-aminophenol derivatives: acetaminophen
Indole and indene acetic acid derivatives:
indomethacin, sulindac, etodolac
Propionic acid derivatives:
ibuprofen, naproxen, fenopofen, ketoprofen
COX-2 selective inhibitors: meloxicam, celecoxib, rofenxid
Others: phenylbutazone, diclofenac
O
H3CO
CH 2C
N
OH
CH 3
indomethacin
吲哚美辛
C
Cl
O
CH3
ibuprofen
CH3
CH
CHCOOH
CH2
布 洛 芬
CH 3
O
O
S
N
piloxicam
CH3
吡罗昔康
CONH
OH
N
D. Other anti-inflammatory drugs
 indomethacin
吲哚美辛：stronger
efficacy,
controlling special types of fever; severe adverse
effects
 ibuprofen
布洛芬（芬必得）：stronger
antipyretic,
analgesic and anti-inflammatory effects; weaker GI
reactions; vision damage
 piloxicam 吡罗昔康: long-acting anti-inflammatory
and analgesic agent; long-term use induces
hemorrhage and ulcers in GI tract
COX-2 selective anti-inflammatory drugs
Meloxicam
美洛昔康
stronger effect on COX-2 than COX-1
long-acting (t1/2 20 h)
weaker GI reactions
Celecoxib
塞来昔布
Selective COX-2 inhibitor