Charles Darwin Horace Walpole Alfred Tennyson Charles Scudmore
- Slides: 90
著名的痛風罹患者 (無特定排序!) • • • Charles Darwin • Horace Walpole • Alfred Tennyson • Charles Scudmore David Garrick • Queen Anne • W. S. Gilbert • Caleb Parry • William Harvey • John Hunter • Samuel Johnson • Lord Palmerston • Edward Gibbon Alexander Pope Neville Chamberlain • William Congreve Thomas Graz Lord Chesterfield W. H. Woollaston Agrippa George IV Louis XIV Benjamin Franklin James I
著名的痛風罹患者 (無特定排序!) • • • Horatio Nelson • The Medici Brothers Sir John Falstaff • Casanova Harold the Saxon • Martin Luther Oliver Cromwell • John Calvin John Wesley • Lord Burghley Cardinal Wolsey • Thomas Sydenham Robert Boyle • Francis Bacon Christopher Columbus • Isaac Newton William Pitt • John Milton Henry Fielding • Admiral Lord Howe
人類尿酸生成過程中的重要酵素 • 5 - 磷酸核糖 1 -焦磷酸合成� (5 -phosphoribosyl- pyrophosphate , PRPP synthetase) • 次黃嘌呤─鳥糞嘌呤磷酸核糖轉化� (hypoxanthine- guanine phosphoribosyl transferase, HGPRT) • 磷酸核糖焦磷酸銑胺轉化�(amidophosphoribosyl transferase) • 黃嘌呤氧化�(xanthine oxidase) 等。
造成高尿酸血症的酵素異常 • PRPP excess Ribose-5 -Phosphate+ATP PRPP + glutamine 尿酸前身形成過多 excess formation of uric acid precursors Inosinic acid Uric acid PRPP synthetase
造成高尿酸血症的酵素異常 • HGPRT deficiency Guanylic acid Inosinic acid HGPRT Guanine Hypoxanthine 補救途徑受阻 salvage pathways blocked Uric acid
造成高尿酸血症的酵素異常 • APRT deficiency Inosinic acid Inosine Hypoxanthine 補救途徑受阻 salvage pathways blocked Adenylic acid Adenosine Adenine APRT
藥物與血清尿酸 (一)造成高尿酸血症之藥物: 增進嘌呤生物合成或尿酸鹽製造之藥物 乙醇 (Ethanol) Pancreatic extract Fructose Nicotinic acid Ethylamino-1, 3, 4 -thiadiazole 4 -Amino-5 -imidazole carboxamide riboside Vitamin B 12 (惡性貧血病患) Cytotoxic drugs Warfarin
減少腎臟廓清尿酸鹽之藥物 乙醇 (Ethanol) 利尿劑 低劑量之 salicylates Ethambutol Pyrazinamide 輕瀉劑 (Laxative) 濫用 (鹼血症 [alkalosis]) Levodopa Methoxyflurane Cyclosporine
減少腎臟廓清尿酸鹽之藥物 CAN’T LEAP • • Cyclosporine Alcohol Nicotinic acid Thiazides • Lasix (furosemide) levodopa • Ethambutol • Aspirin (low dose) • Pyrazinamide
具促尿酸排泄活性(uricosuric activity) 之藥物 • Acetohexamide • Glyceryl guaiacolate • Adrenocorticotropic • Glycopyrrolate hormone (ACTH) and • Halofenate glucocorticoids • Meclofenamate • Allopurinol • Merbarone • Ascorbic acid • Phenylbutazone • Azauridine
具促尿酸排泄活性(uricosuric activity) 之藥物 • • • Benzbromarone • Phenolsulfonphathalein Calcitonin • Probenecid Chlorprothixene • Salicylates Citrate • Sulfinpyrazone Dicumarol • Roentgenographic • Diflunisal contrast agents • Estrogen • Zoxazolamine
痛風的臨床期程 (自然病程) (一)無症狀高尿酸血症 (asymptomatic hyperuricemia) (二)急性痛風性關節炎 (acute gouty arthritis) (三)痛風未發作期 (間歇期) (intercritical or interval gout) (四)慢性痛風石痛風 (chronic tophaceous gout)
Three Oft-quoted Aphorisms of Hippocrates • Eunuchs do not take the gout (No. 28) • A woman does not take gout unless her menses be stopped (No. 29) • A young man does not take the gout until he indulges in coitus (No. 30)
痛風石發展階段 A 無結晶之巨嗜細胞腺胞 (crystal-free macrophage acinus) B 腺胞之無晶形中心(amorphous center)助成尿酸鹽結晶的形成 C 於結晶團 (crystalline mass)擴張之 同時,環繞之巨嗜細胞冠(surrounding corona)同時變肥厚 D 進一步之結晶化造成環冠變薄,至纖 維性中隔(fibrous septae)分隔個別 之結晶形成核(nidus of crystal formation)為止 E 完全成熟之痛風石 Edwards NL. Gout: Clinical and Laboratory Features. In: Klippel JH, editor. Primer on the Rheumatic Diseases. 12 th ed. Atlanta: Arthritis Foundation; 2001. p. 313 -9.
Allopurinol 給藥劑量表 肌胺酸酐廓清率 Allopurinol 劑量 (creatinine clearance) (ml/min) 0 10 20 40 60 80 100 120 140 每 每 三日 100 mg 每 二日 100 mg 每 日 150 mg 每 日 200 mg 每 日 250 mg 日 300 mg 每 日 350 mg 每 日 400 mg
Allopurinol 之重要藥物交叉反應 • Allopurinol 延長 azathioprine 與 6 - mercaptopurine 之半衰期 (二者均經由 xanthine oxidase-dehydrogenase 使非活化) 加重彼等之治療及毒性效應。 • Allopurinol 增加 cyclosporine 之毒性。 • Allopurinol 使 ampicillin 及其相關之 皮疹發生率增加三倍。 • Allopurinol 使 5 -fluorouracil 之毒性減少。
平均血清尿酸鹽濃度與痛風石 減小速率之關係 r = - 0. 62 r 2 = 0. 48 P < 0. 05 Perez-Ruiz F, et al. Arthritis Rheum (Arthritis Care Res) 2002; 47: 356 -60.
低嘌呤飲食及Allopurinol對血 清尿酸鹽之影響 Emmerson BT. Aust Ann Med 1969; 16: 205 -14.
Multivariate Relative Risk of a New Case of Gout According to Quintile of Intake of Various Food Groups and Body-Mass Index (Panels A, B, and C) or Alcohol Use or Nonuse (Panels D, E, and F) Choi, H. K. et al. N Engl J Med 2004; 350: 1093 -1103
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