Chapter 20 Analgesic-Antipyretic and
Antiinflammatory Drugs
(Non-steroidal Anti-inflammatory
Drugs,NSAIDs)
Mechanism of NSAIDs
•The basis of these action of NSAIDs is due
primarily to the inhibition of prostaglandin(PGs)
synthesis.
Cell membrane phospholipids
-
PLA2
NSAIDs
steroidals
—
Arachidonic acid(AA)
COX-1
COX-2
PAF
5-Lipoxygenase
PGG2
PGH2
Leukotriene
血管舒张剂
PGI2
PGE2 PGD2
PGF2
血管舒张
血小板解
聚
体温、炎症
疼痛传递、
胃粘膜保护
TXA2
血栓形成
血管收缩
参与过敏反应
诱发炎症
支气管收缩
白细胞趋化
血管通透性增加
支气管收缩
趋化性增强
Pharmacological effects of NSAIDs
• Analgestic action mild or moderate pain following
injury,disease,or minor surgery,as well as chronic pain
states including arthritis and cancer.
• Antipyretic action NSAIDs reset the set-point to the
normal level and lower the elevated body temperature in
patients with fever by inhibiting the endogenous synthesis of
PGs in hypothalamus.
• Anti-inflammatory action NSAIDs may provide
symptomatic relief from fever,pain,and other signs of
rheumatic or rheumatoid arthritis,but do not arrest the
progression of pathological injury to tissue.
• Some nonselective NSAIDS also have anti-thrombotic
actions.
Classification of NSAIDs
aspirin （sodium salicylate）阿司匹林
Acetaminophen 醋氨酚（扑热息痛）
Indomethacin 吲哚美辛（消炎痛）
Ibuprofen 布洛芬（芬必得）
Nonselective COX inhibitors
Selective COX-2 inhibitors
Phenylbutazone 保泰松
Rofecoxib罗非昔布
Celecoxib塞来昔布
Etodolac依托度酸
Nimesulide尼美舒利
Salicylates---Aspirin
[Pharmacological Effects and clinical
Uses]
• 1. Analgesic Effects:
☆ Aspirin is most effective in reducing pain of mild
to moderate intensity (headache,
toothache,dysmenorrhea<痛经>，arthralgia,etc).
☆ It is not effective for severe visceral pain, e.g.
myocardial infarction or renal or biliary colic.
☆ It acts peripherally through its effects on
inflammation but probably also inhibits pain
stimuli at a subcortical site.
Aspirin
• 2. Antipyretic Effects:
☆ Aspirin reduces elevated temperature, whereas
normal body temperature is not affected.
☆Aspirin’s antipyretic effect is mediated by
cyclooxygenase-2 (COX-2) inhibition in the
central nervous system.
☆ The fall in temperature is related to increased
dissipation of heat caused by vasodilation of
superficial blood vessels and may be
accompanied by profuse sweating.
Aspirin
• 3. Anti-inflammatory Effects:
☆ The anti-inflammatory property of aspirin in
high dosage (3-6 g/d) is responsible for
treatment various kinds of inflammation
including acute rheumatic fever, rheumatoid and
other types of arthritis.
☆ It has been advocated as a diagnostic test when
acute rheumatic fever(风湿热) is suspected.
Aspirin
• 4. Effect on platelets
☆Low doses of aspirin can inhibit platelet aggregation and
produce a slightly prolonged bleeding time by
irreversible inhibition of platelet COX.
☆Low doses of aspirin can irreversibly inhibit the
production of TXA2 in platelets without markedly
interfering with PGI2 production in endothelial cells.
☆ In general, Aspirin should be stopped 1 week prior to
surgery to avoid bleeding complication.
☆ Aspirin has been shown to decrease the incidence of
transient isochemic attacks (短暂局部缺血性休克）,
unstable angina,coronary artery thrombosis（血栓形成）
with myocardial infarction,and thrombosis after
coronary artery bypass grafting.
Aspirin
Adverse Effects
• 1. Gastrointestinal tract
• This effect can be decreased with suitable
buffering(taking Aspirin with meals ). The
gastritis that occurs with Aspirin may be due to
irritation of gastric mucosa by the undissolved
tablet, or to inhibition of production of
protective prostaglandins.
☆ Therefore, aspirin should be avoided by
individuals with peptic ulcer disease.
Aspirin
Adverse Effects
• 2.Blood Aspirin increases bleeding
time,decreases platelet adhesiveness,,and ,at
large doses,may cause
hypoprothrombinaemia.
• 3.hepatotoxicity
• 4.Hypersensitivity aspirin asthma
• 5.Salicylate intoxication
• 6. Reye’s syndrome
Antipyretic-analgesic and antiinflammatory drugs--苯胺类
Acetaminophen and Phenacetin
Acetaminophen is the active metabolite of
phenacetin responsible for its analgesics effect.
▽ It is a weak prostaglandin inhibitor in peripheral
tissues and possesses no significant antiinflammatory effects.
▽ Acetaminophen is one of the most important drugs
used for the treatment of mild to moderate pain
when an anti-inflammatory effect is not necessary.
▽
▽
Phenacetin is more toxic and has no rational indications
Antipyretic-analgesic and antiinflammatory drugs
Indomethacin （吲哚美辛）
Indomethacin is an indole derivative.
▽ It enjoys the usual indications for use in
rheumatic conditions and is particularly
popular for gout and ankylosing spondylitis
（强直性脊柱炎）. In addition,it has been used to
treat patient ductus arteriosus（动脉导管闭锁不
全）.
▽ It is one of the most potent COX inhibitors,
and has more adverse effects.
▽
Antipyretic-analgesic and antiinflammatory drugs--其他有机酸类
Ibuprofen (布洛芬）其缓释胶囊称“芬必得”.
Ibuprofen is a simple derivative of Arylpropionic
acid（芳基丙酸）.
☆ In doses of about 2400 mg daily,ibuprofen is
equivalent to 4 g of aspirin in anti-inflammatory
effect.Oral ibuprofen is often prescribed in lower
doses(<2400mg/d),at which it has analagesic but not
anti-inflammatory efficacy.
☆ It is used for treatment of rheumatoid(类风湿的)
arthritis and other inflammatory joint conditions
☆ It is available over the counter in lower dosage under
several trade names.
☆
Antipyretic-analgesic and antiinflammatory drugs--吡唑酮类
Phenylbutazone (保泰松）
• Phenylbutazone,a pyrazolone derivative
rapidly gained favor after its introduction
in 1949 for the treatment of rheumatic
syndromes, but its toxicities,particularly
the hematologic effects (including aplastic
anemia),have resulted in its withdrawal
from many markets.It is rarely used today.
Antipyretic-analgesic and antiinflammatory drugs—
selective COX-2 inhibitors
Celecoxib(塞来昔布)
• Celecoxib is a selective COX-2 inhibitor,
having slight action on COX-1 in therapeutic
dosage.
• The incidence of gastric toxicity is much
lower with it than with non-selective COX
inhibitors.
• It is used for treatment of osteoarthritis and
rheumatoid(类风湿的) arthritis.