NSAID - Drugs that Affect the Endocrine System
Nonsteroidal Anti-inflammatory Drugs
消炎作用，exert their clinical effects by inhibiting prostaglandin
synthesis.
不無小補 － Eicosanoid Metabolism
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PGHS/Cyclooxygenase/COX: Single heme-containing
polypeptide chain.
Arachidonate -two O2 inroducing→ PGG2(hydropyroxide
group) -two-electron reduction→ PGE2
Only COX-2 were involved in inflammatory responses;
COX-1 were constitutive form one existing in tissues.
PGE: Stimulates adenylate cyclase in target cells.
PGF: Elevate levels of cyclic GMP in target cells.
TxA2: Platelet aggragation.
PGI: Inhibition of platelet aggregation and relaxation of coronary arteries,
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Steroids: Inhibitors of PLA2, high efficient but also high toxicity.
筆記：NSAID不比類固醇藥物為治療藥物，而是處理症狀／消炎止痛的藥物。
Example: Acetaminophen／鎮痛退燒藥
Aspirin
Irreversible inactivation(acetylation) of COX
考古題：What is NSAID? Describe the action mechanism
of aspirin for its anti-inflammation. 5%
筆記：Irreversible → zero-order kinetics﹔濃度不和藥性成正比，有時Aspirin自體內移除後其實藥性還在，COX尚未恢復活性。
Salicylism: Symptoms of overdose of aspirin - tinnitus(ringing in ears), dizziness,
headache, fever and mental status changes.
pH changes → Respiratory alkanosis(pCO2 decrease) and
increase in plasma CO2, thus stimulates the respiratory
center.
Less specificity to COX-2, and inhibiting COX-1 can cause like ulceration,
side effects on the gastrointestinal system.
筆記：Prostaglandin有增加腸胃黏膜的功能﹔故Aspirin有胃出血的副作用。
Celebrex (late 1998)
Ibuprofen: Acts more specifically to COX-2, less effective than aspirin.
→ Molecular pharmacology: Drug design from structural data → aspirin analogs
that have more specificy to COX-2