Hyperuricemia & Gout

台中榮民總醫院
臨床藥學科
鄭鴻基主任
 前言 -1
 痛風為現代人常見的文明病之一，根據估
計約有 5﹪ 的國人（約 100 萬人）血中的
尿酸值偏高，但絕大多數沒有任何徵狀，
只是抽血時偶然發現血中的尿酸濃度偏高
。
 一般而言，尿酸值越高或持續越久越容易
得到痛風，尤其是每 100 ㏄血中尿酸超過
9 毫克者，約有 70-90﹪ 機會得到痛風。
 前言 -2
 早期痛風被視為一種富貴人家才會得到的帝
王病，因為歷史上許多名人，君王如牛頓、
亞歷山大大帝、英王喬治亞四世、路易十四
、富蘭克林、達爾文等均罹患過此病
 近年來患者年齡層也有逐漸下降的趨勢，原
本好發於 30-50 歲以上的痛風疾病，近年來
20 多歲的患者也大有人在。
 尿酸的 形成 和排泄
 尿酸是由嘌呤 (Purine) 代謝所產生的最終產物，而
嘌呤則存在於食物中或體內的細胞。一般而言，體
內尿酸約 20﹪ 來自飲食， 80﹪ 來自身體的新陳代
謝。正常人約有三分之二的尿酸由腎臟經尿液排出
，約三分之一由腸內細菌分解代謝，另約有小於百
分之一由汗腺排泄。
 但腎臟功能異常的病人則由腎臟排泄的量減少，相對地由腸
道排泄的量會增加。
 正常人血中尿酸濃度受性別、年齡影響，女性在停經前尿酸
值較男性低，但停經後則尿酸會慢慢增高。
 青春期前血中尿酸濃度較低，但青春期後則會逐漸增加接近
成年人。因此，若尿酸產生過多或排泄減少，均會造成血中
尿酸過高。
They add color to your life
Uric acid
QUESTIONS
 人體內正常貯存量尿酸約多少 mg?
 人體正常每天應排除多少尿酸 ?
 XANTHINE 分解成尿酸是藉何物完成 ?
 尿酸需要何物可以分解為 ALLANTION
 在酸性溶液中 :URIC ACID &
ALLANTOIN 何者溶解度大 ?
Uric acid
 Excretion by
kidney
 GFR(95%)

Proximal tube:
1.reabsoption(98%)
2.resecretion(50%)
Distal
tube,colleting
tube:reabsorption(4
0%)
They wipe your tears
 何謂高 尿酸 血症
 是指血中尿酸濃度約大於 7 mg/dl 以上，但一般
在實驗室中常用的化學自動分析儀，則以超過
8mg/dl 為高，實際上尿酸在體液中之飽和溶解度
是 6.4mg/dl ，因此如果血清尿酸值超過
6.4mg/dl 以上即為過飽和狀態，就開始有尿酸鹽
結晶會析出。
 流行病學的定義中，所謂的「正常人」事實上包
含一些無症狀的高尿酸血症的病人。 但高尿酸血
症並不ㄧ定等於痛風， 它
需要經過一段很長的時
間才會有第一次痛風關節炎的發作，這時候才開
始稱為「痛風」，在從未有過關節炎發作者，只
能稱為無症狀的高尿酸血症。
Asymptomatic hyperuricemia
 High level of serum uric acid
concentration
 No clinical syndrome
Serum uric acid level (mg/dl) Incidence of gout

>9.0 7.0-8.9%

7.0–8.9 0.37-0.5%

<7.0 0.1%
 高尿酸 血症 的原因 -1
A. 尿酸生成過多：
1. 原發性生成過多：
i. 遺傳：家族中若有痛風或尿酸過高者，其子女發生
痛風的機率為一般人的 10 倍 。
ii. 肥胖：肥胖的人較易流汗，也因此經腎臟、膀胱
排出之尿量會減少，如此經腎臟排出之尿酸量也相
對的減少而造成高尿酸血症，此外肥胖的人如果減
肥或飢餓時，體內脂肪會燃燒而產生酮體，此酮體
由尿中排泄，排泄時會阻礙尿酸之排泄，因此會使
血中尿酸值增高而造成高尿酸血症。
 高尿酸 血症 的原因 -2
A. 尿酸生成過多：
1. 原發性生成過多：
iii. 年齡
iv. 性別：一般男性較女性容易罹患痛風，但女性
停經後痛風之發生率增加。
v. 飲食：飲酒、高嘌呤飲食
vi. 運動過度：劇烈運動會使出汗量增加，尿酸由
尿液中排出減少，運動後所產生的過多的乳酸，亦
會阻礙其排泄，運動時肌肉收縮的關係，使肌肉中
ATP 下降，造成 AMP 上升，結果 adenosin
degradation 增加，而引起血液中尿酸值增加。
 高尿酸 血症 的原因 -3
A. 尿酸生成過多：
2. 續發性高尿酸血症
 i.  核蛋白產生過多：如白血病、 Hodge king 病，

紅血球增多症等血液疾病，主要是因細胞破壞太快，
而使細胞內之主要成份核蛋白新陳代謝加速，而產生
太多尿酸存積在體內來不及排出所引起之高尿酸血症
。
 ii. 酵素缺損或增加：如 HGPRT 的先天性欠損所引起

之一種病叫 Lesch-Nyhan syndrome ， PRPP Synthetase

的活性過高，糖尿病 type I 等，這類疾病的主要特
徵是家族性遺傳因素。
 高尿酸 血症 的原因 -3
A. 尿酸生成過多：
2. 續發性高尿酸血症
iii. 腎障礙：主要是因腎障礙，或某些藥物會
抑制尿酸經腎臟之排泄，例如抗結核病藥
(PZA) ，降壓利尿劑，少量之
Aspirin(<2g/day) 等。此外副甲狀腺機能亢進
症及 Sarcoidosis 等也會使血中鈣增加而影響
尿酸在腎之代謝，結果造成尿酸之上升。
 高尿酸 血症 的原因 -4

B. 尿酸排 泄量減少
1. 尿酸排泄機能降 低
2. 腎臟功能障礙： 如慢性腎炎 等
3. 服用藥物影響尿 酸排泄：如 利尿劑
等
4. 酸中毒如：糖尿 病、乳酸血 症、飲
酒過多
 會造成 高尿 酸血症 的疾病
1. 酒精成 隱症
2.  糖尿病 酮酸 中毒
3.  高血脂 症
4.  副甲狀 腺機 能亢進
5.  肥胖
6. 急慢 性腎衰 竭
7. 牛皮 癬
8. glucose-6-phosphatase 缺陷
會造成 高尿 酸血症 的藥物
1. 酒精
2.  抗癌藥，如： cytotoxic drug
3.  利尿劑，但 Spironolactone 不會引 起高尿 酸血
症
4. 抗結核病藥物，如： PZA
5. Levodopa
6. Nicotinic acid
7. Salicylates (<2g/day)
 容易與 痛風 混淆的 疾病
1. Pseudogut ：乃 CCPD(calcium
pyrophosphate dihydrate) 沉積於關節形成。
2. Palindromic Rheumastism ：急性發生時常伴隨
紅血球沉降速率 (ESR) 的升高。
3. Trauma/Haemarthrosis ：
4. Infected joint/cellulitis ：
5. Secondary gout/unreclated hyperuricemia ：
如高血壓、三酸甘油脂過高、乾癬、肥胖、甲狀腺
機能低下、腎衰竭等造成尿酸過高而引發續發性痛
風。
痛風的 臨床 症狀
 無症狀症高尿酸血症
 急性痛風

 中間緩解期 (INTERCRITICAL

GOUT)
 慢性痛風
痛風所 引起 的相關 疾病
 痛風性 腎病變
 尿路結 石
 其它相 關疾病 ：痛風病人常合併有高血
壓、糖尿病、血管硬化和高脂血症。目前
痛風已被美國心臟病協會列為缺血性心臟
病的危險因素之一，即痛風是動脈硬化的
促進因子，因為痛風如未好好治療的話，
則由長期間持續的高尿酸血症會使過多的
尿酸鹽結晶沈積在冠狀動脈內，加上高尿
酸血症也會使血小板的凝集亢進，這些原
因加速了動脈硬化的進展。
Gout complications(1)

Oh my
God!!
Mommy..
Help!!
Gout complications(2)
 Renal function impairment
1.urate nephropathy
2.uric acid calculi
3.acute uric acid obstructive nephropathy
 Cardiovascular disease

-Ischemic heart disease

-arteriosclerosis risk factor
 Hyperlipemia,diabetes,hypertension

—obesity,(UA,CH,TG)
 腦血管病變
尿酸腎結石 (Uric acid
nephrolithiasis)
 尿酸是尿路結石常見的成份。
 在美國尿酸結石的盛行率約為

5~10% ，而在原發性痛風的患者
，尿酸結石的發生率高達
10~20% 。
 部份病人其尿酸結石的發生早於痛

風性關節炎的發作。
 尿酸腎結石之致病機轉
 尿酸屬於一種弱酸，且具有
兩個解離係數 (dissociation
Constants) 。
 尿酸的溶解度決定於兩個主
要因素 :1) 尿酸的濃度 ,
2) 尿液的酸鹼值(pH) 。
 當尿液 pH 值 小於 5.5 時，
其尿酸呈現過度飽和而易形
成尿酸結石。
 但在 pH 大於 6.5 時，大部
份的尿酸皆會以離子型尿酸
鹽存在。
尿酸結石的形成三因素
 酸性尿 (pH 值小於 5.5)

 尿液之尿酸濃度過高
(hyperuricuria) ( 亦即 24 小時尿
液尿酸量大於 600mg)

 每日尿液量過少。
 尿酸結石診斷評估
 詳細的病史 ( 高尿酸血症之原因及其相關疾病 )
 尿液的 pH 值
 24 小時尿液尿酸含量
 腹部平面 X- 光 : 由於尿酸結石不含鈣或含鈣量
較少，不易顯示
 超音波或逆流性腎盂攝影
 無顯影劑的電腦斷層 : 最佳的顯影方法，它可用
來偵測與定位尿酸結石、與其他結石做區分、且
可排除腫瘤或其他病因 ( 如乳突狀壞死 ) 。
無顯影劑的電腦斷層攝影
 痛風的診斷
美國風濕病協會 (1977) 診斷標準
 以下三大項出現一大項 ( 含 ) 以上即可診斷為痛
風:
 一、關節液 : 特徵性的尿酸鹽晶體
 二、痛風石 : 含有尿酸鹽晶體
 三、以下 12 小項中包括臨床生化及 X 光檢查中
出現六項以上 :
1. 一天即可達最嚴重的發炎， 2. 發作一次以上
， 3. 單一關節的關節炎， 4. 發作處有紅腫熱
痛， 5. 第一蹠趾關節痛腫， 6. 單側大腳
趾侵犯， 7. 單一跗骨侵犯， 8. 痛風
石， 9. 高尿酸血症， 10. 不對稱性腫脹，
11.X 光 - 皮質下囊腫沒有糜爛， 12. 關節液培養
 病人呈現急性關節腫痛
臨床懷疑痛風性關節炎

鑑別診斷
1. 假痛風 2. 反覆性風
濕症
3. 血清陰性關節病變 4. 感染性關節
炎
5. 外傷性 / 關節血腫 6. 第 II 型血
高脂症 確立診斷
1. 詢問高尿酸血症 / 痛風病史
2. 儘可能抽取關節液及分析結晶體且
排除感染及其他關節炎之可能性
3. 關節超音波及 X 光之特徵
They spread fragrance
Hyperuricemia is a risk factor
for gout, but some patients with
normal serum uric acid levels
develop acute gouty arthritis.
 Overproduction of urate
• Primary idiopathic hyperuricemia
• Hypoxanthine-guanine phosphoribosyl-transferase
deficiency
• Phosphoribosylpyrophosphate synthetase overactivity
• Hemolytic processes
• Lymphoproliferative disease
• Myeloproliferative disease
• Polycythemia vera
• Psoriasis (severe)
• Paget's disease
• Rhabdomyolysis
• Exercise
• Alcohol
• Obesity
• Purine-rich diet
 Decreased excretion of uric acid
• Primary idiopathic hyperuricemia
• Renal insufficiency
• Polycystic kidney disease
• Diabetes insipidus
• Hypertension
• Acidosis
--Lactic acidosis
--Diabetic ketoacidosis
• Down syndrome
• Starvation ketosis
• Berylliosis
• Sarcoidosis
• Lead intoxication
• Hyperparathyroidism
• Hypothyroidism
• Toxemia of pregnancy
• Bartter's syndrome
 Decreased excretion &
Overproduction of uric acid
Combined mechanism
• Glucose-6-phosphate dehydrogenase
deficiency
• Fructose-1-phosphate aldolase deficiency
• Alcohol
• Shock
Decreased excretion of uric acid

• Drug ingestion
--Salicylates (less than 2 g per day)
--Diuretics
--Alcohol
--Levodopa-carbidopa (Sinemet)
--Ethambutol (Myambutol)
--Pyrazinamide
--Nicotinic acid (niacin; Nicolar)
--Cyclosporine (Sandimmune)
痛風的 治療
( 一 ) 飲食控 制
( 二 ) 藥物治 療
無症狀 高尿酸血症
急性痛 風
慢性痛 風
 Most acute gout attacks
occur in a lower extremity
joint, often the first
metatarsophalangeal joint.

 Because an acute gout attack

may be associated with
edema, erythema, warmth and
tenderness, the differential
diagnosis includes septic
arthritis and cellulitis.
 TREATMENT
 Serum uric acid concentrations may be
reduced with nonpharmacologic therapy.
Useful dietary and lifestyle changes include
weight reduction, decreased alcohol
ingestion, decreased consumption of foods
with a high purine content, and control of
hyperlipidemia and hypertension. Used
alone, however, these measures will
probably not reduce serum uric acid levels
to normal, which is the treatment goal for
the prevention of acute gout attacks.
Symptomatic hyperuricemia usually
They make you laugh
Acute Gouty Arthritis

Three treatments currently

available for acute gouty arthritis
attacks are nonsteroidal anti-
inflammatory drugs (NSAIDs),
colchicine and corticosteroids.
 Prevention of Recurrent Attacks

 Hyperuricemic therapy should be initiated in

patients with frequent gout attacks, tophi or
urate nephropathy. A low dosage of an
NSAID or colchicine is effective in
preventing acute gouty attacks.
Hyperuricemic drug therapy should not be
started until an acute attack of gouty
arthritis has ended, because of the risk of
increased mobilization of uric acid stores. A
reasonable goal is to reduce the serum uric
acid concentration to less than 6 mg per dL
(360 µmol per L).
Acute gouty arthritis
 Rapid onset,
swelling,
inflammation
 mildnight ,peak:24-
48hr,3-14 days
spontaneous
recovery
 Monoarticular,MTP
joint
 A number of
condition may
precipitate an
attack
 Signs
Radiographic Findings
Treatment
 Goals: relieve pain and inflammation not
aimed at lower serum UA conc with
hypouricemic agents.
 Rest
 Adequate fluid status assessment
 correct dehydration if no contraindication
3. Evaluation of prediposing factors

DC offending drug
4. Medications
Medication for Acute GA
 NSAID
 Colchicine

 Steroid or ACTH

1.all highly effective

2.selection depend on co-existent
condition:
(renal dysfunction, physician or p’t preference)
NSAIDs
 most important for acute attack

 IV/IM form is not superior to oral

form
 in GI toxicity, in Nephrotoxicity or any
other aspects
 Ketolac injection is the only injected
NSAID proved by FDA
 NSAIDs
 優先選 short-acting, short duration,
potent antiinflammatory effect
 Indomethacin( indocin  ):50mg tid-qid
 Diclofenic acid: Cataflam, Voren
 Naproxen:750mg st→250mg tid
 Special NSIADs:
 Specific COX-2 inhibitors: celecoxib, rofecoxib
 Meloxicam: preferential COX-2 inhibitor, least
GI side effect
 Sulindac: least nephrotoxicity
 Cinopal: least GI toxicity
NSAIDs
Clinical Contraindications
 History of peptic ulcer with active

bleeding or GI intoerance
 Age >65 y/o (relative)

 Renal insufficiency or CCr <50 ml/min

(relative)
 Poor compensated CHF

 Hepatic dysfunction

 Anticoagulation therapy

 History of allergic or rash to NSAIDs

QUESTIONS
 血中尿酸濃度大於 9mg/dl 時 , 其發生痛
風的機率 ?
 請列舉三種易引起高尿酸血症之葯物 ?
 請列舉三種易引起高尿酸血症之疾病 ?
 易引起尿酸結石形成的三個因素 :?
 急性痛風之首選藥物 ?
 高尿酸血症不是引起痛風的必要條件 ,
why?
 受影響者 影響者 作用 備註

降血糖藥 Sulfonylureas 抑制 sulfonylureas 的代謝 應監測血糖，宜避免併用。

如 henylbutazone ，延長其半衰期，增加發
glyburide 、 tolbutamid 生低血糖的危險性。
e 、 chlorpropamide xyphenbutazone

口服抗凝血劑 所有非類固醇類消炎 損害腸胃道黏膜並抑制血 避免併用，若需併用應監測

藥 小板凝集，增加腸胃道出 prothrombin time 。
  血的可能性。

降壓效果減弱 避免併用，必要時使用
CEI ndomethacin sulindac ，並監測血壓。
Enalapril 及 lisinopril 與
Captopril buprofen indomethacin 間的交互作用
很小。
β- 交感神經阻斷劑 他非類固醇類消炎藥
非類固醇類消炎藥 降壓效果減弱 避免使用非類固醇類消炎
(sulindac 除外 )

利尿劑，包括 Loop 、 Indomethacin 降壓及排鈉效果減弱，可 避免使用非類固醇類消炎藥

保鉀與 thiazides 類 其他非類固醇類消炎 能惡化充血性心衰竭。 ，必要時使用 sulindac ，並
藥 (sulindac 除外 ) 監測體液滯留的徵兆。

Ketoprofen Methotrexate 排出減少，血 不可同時給藥。 完成高劑

ethotrexate 其他非類固醇類消炎 中濃度上升，毒性增加， 量療法後 12 小時再服用
藥 可能致死。 ketoprofen 較安全。
( 高劑量 )
非類固醇類消炎藥 競爭蛋白質結合部位 監測藥品血中濃度
henytoin

Aminoglycosides
ulfonamides 非類固醇類消炎藥 腎功能減弱， amino- 應監測 aminoglycosides 的血
glycosides 廓清率降低，血 中濃度，並適當調整劑量。
中濃度增高。

出血時間 (Bleeding Ketoprofen, ASA 延長出血時間約 3-4 分鐘  

time )
they see only the good in
you
COX II INHIBITORS
COX II INHIBITORS
COX II INHIBITORS
老年人需要服用 NSAIDs 時 , 最佳
的選擇順序是 ?
1. INDOMETACIN
2. CELEBREX(COX II INHIBITERS)
3. SULINDAC
4. PIROXICAM
5. CATAFLAM
老年人需要服用 NSAIDs 時 , 最佳
的選擇順序是 ?
 INDOMETACIN---4
 CELEBREX(COX II INHIBITERS)---1
 SULINDAC---2



PIROXICAM---4
CATAFLAM---3
?
 急性痛風避免使用那些藥物 ?
 ALLOPURINOL
 BENZBROMARONE
 CORTICOSTEROIDS
 NSAIDS
 COLCHICINE
They give you support
老年 人是否 選擇 COX II INHIBITORS ?
Becoz they are your true
friends
Allopurinol
100mg/tab
 Indications
 Oral: Prevention of attack of gouty arthritis
and nephropathy; treatment of secondary
hyperuricemia which may occur during
treatment of tumors or leukemia;
prevention of recurrent calcium oxalate
calculi
 Pregnancy Risk Factor C
 Lactation Enters breast milk/compatible
 Contraindications Hypersensitivity to
allopurinol or any component of the
formulation
 Warnings/Precautions-1
 Do not use to treat asymptomatic
hyperuricemia. Discontinue at first signs of
rash;
 Reduce dosage in renal insufficiency,
reinstate with caution in patients who have
had a previous mild allergic reaction,
 Use with caution in children; monitor liver
function and complete blood counts before
initiating therapy and periodically during
therapy,
 Warnings/Precautions-2

 Use with caution in patients taking

diuretics concurrently.
 Risk of skin rash may be increased
in patients receiving amoxicillin or
ampicillin. The risk of
hypersensitivity may be increased
in patients receiving thiazides, and
possibly ACE inhibitors.
 Adverse Reactions
 The most common adverse reaction to
allopurinol is a skin rash (usually
maculopapular; however, more severe
reactions, including Stevens-Johnson
syndrome, have also been reported). While
some studies cite an incidence of these
reactions as high as >10% of cases (often in
association with ampicillin or amoxicillin), the
product labeling cites a much lower
incidence, reflected below. Allopurinol should
be discontinued at the first appearance of a
rash or other sign of hypersensitivity.
Steven johnson syndrome
 嚴重的過敏反應通常
由藥物引起會出現紅
疹情形於手掌腳底是
一種多型性紅斑疾病
(erythema
multiforma) 會產生
泡狀病兆也有可能經
病毒或黴漿菌
(mycoplasma) 感
染
Steven johnson syndrome
Steven johnson syndrome
Allopurinol 藥害救濟
 藥害救濟是衛生署為使
民眾在正當使用合法藥
物卻發生藥物不良反應
，而導致死亡、障礙或
是嚴重疾病時，能獲得
迅速救濟之服務。
 AHS( 數天 - 數月出
現 ),SJS,TEN
 Discontinute drug,
supportive
therapy
個案詳細資料
They never blame you
 Drug Interactions-1
Hepatic enzyme inhibitor; isoenzyme profile
not defined
Decreased effect:
 Ethanol decreases effectiveness, uricosurics

Increased toxicity:
 Inhibits metabolism of azathioprine and

mercaptopurine (reduce to 1/3 or 1/4 of

usual dose)
 Use with ampicillin or amoxicillin may

increase the incidence of skin rash

 Drug Interactions-2
Increased toxicity:
 Urinary acidification with large amounts of

vitamin C may increase kidney stone

formation
 Thiazide diuretics enhance toxicity, monitor

renal function; thiazide diuretics and

captopril (possibly other ACE inhibitors) may
increase risk of hypersensitivity
 Vidarabine neurotoxicity may be enhanced

 Cyclosporine levels may be increased

Table 1. Standard allopurinol
desensitization protocol

Curr Opin Rheumatol 2002 May;14(3):281-286

Copyright © 2002 Lippincott Williams & Wilkins
All rights reserved
 Drug Interactions-3
Increased toxicity:
 Hepatic iron uptake may be increased

with iron supplements

 Allopurinol prolongs half-life of oral

anticoagulants; allopurinol increases

serum half-life of theophylline; allopurinol
may compete for excretion in renal tubule
with chlorpropamide and increases
chlorpropamide's serum half-life
 Ethanol/Nutrition/Herb Interactions Ethanol:

Avoid ethanol (may decrease

effectiveness).
 Mechanism of Action
 Allopurinol inhibits xanthine oxidase,
the enzyme responsible for the
conversion of hypoxanthine to
xanthine to uric acid. Allopurinol is
metabolized to oxypurinol which is
also an inhibitor of xanthine oxidase;
allopurinol acts on purine catabolism,
reducing the production of uric acid
without disrupting the biosynthesis of
vital purines
 Pharmacodynamics/Kinetics
Onset of action: Peak effect: 1-2 weeks
Absorption: Oral: ~80%; Rectal: Poor and erratic
Distribution: Vd: ~1.6 L/kg; Vss: 0.84-0.87 L/kg;
Protein binding: <1%
Metabolism: ~75% to active metabolites, chiefly
oxypurinol
Bioavailability: 49% to 53%
Half-life T1/2: Parent drug: 1-3 hrs; Oxypurinol: 18-30 hours
End-stage renal disease: Prolonged
Time to peak, Oral: 30-120 minutes
Excretion: Urine (76% as oxypurinol, 12% as unchange
ALLOPURINOL 主要活性代謝物
是?
 OXIPURINOL
 ALLANTOIN
 ALLOPURINE
 QUESTIONS
 ALLOPURINOL T1/2=?
 OXIPURINOL T1/2=?
 ALLOPURINOL INTERACTION:
 CYCLOPHOSPHAMIDE---? BONE MARROW
SUPPRESSION
 VIDRARBINE-------?
 CYCLOSPORINE-----?
 WARFARIN----?
 Usual Dosage(Oral)
 Children 10 years: 10 mg/kg/day in 2-3
divided doses or 200-300 mg/m2/day in 2-4
divided doses, maximum: 800 mg/24 hours
 Alternative: <6 years: 150 mg/day in 3
divided doses; 6-10 years: 300 mg/day in 2-
3 divided doses
 Children >10 years and Adults: Daily doses
>300 mg should be administered in divided
doses uric acid level is obtained
 Usual Dosage(Oral)-2
Myeloproliferative neoplastic disorders:
600-800 mg/day in 2-3 divided doses for
prevention of acute uric acid nephropathy
for 2-3 days starting 1-2 days before
chemotherapy
Gout: Mild: 200-300 mg/day; Severe: 400-600
mg/day
Elderly: Initial: 100 mg/day, increase until
desired uric acid level is obtained
 Dosing adjustment in renal
impairment: Must be adjusted due
to accumulation of allopurinol and
metabolites:
 Oral: Removed by hemodialysis;
adult maintenance doses of
allopurinol* (mg) based on
creatinine clearance (mL/minute):
See table.
 Adult Maintenance Doses of Allopurinol*
Creatinine Clearance (mL/min) Maintenance Dose of Allopurinol (mg)
140 400 qd
120 350 qd
100 300 qd
80 250 qd
60 200 qd
40 150 qd
20 100 qd
10 100 q2d
0 100 q3d
*This table is based on a standard maintenance dose of 300
mg of allopurinol per day for a patient with a creatinine
clearance of 100 mL/min.
Hemodialysis: Administer dose posthemodialysis or administer 50% supplemental
dose
 Monitoring Parameters CBC, serum uric acid
levels, I & O, hepatic and renal function, especially
at start of therapy
 Reference Range Uric acid, serum: An increase
occurs during childhood Adults:
Male: 3.4-7 mg/dL or slightly more
Female: 2.4-6 mg/dL or slightly more
 Values >7 mg/dL are sometimes arbitrarily
regarded as hyperuricemia, but there is no sharp
line between normals on the one hand, and the
serum uric acid of those with clinical gout. Normal
ranges cannot be adjusted for purine ingestion, but
high purine diet increases uric acid. Uric acid may
be increased with body size, exercise, and stress.
 Dietary Considerations Should administer oral
forms after meals with plenty of fluid.
 Patient Information-1
 Maintain adequate hydration (2-3 L/day of
fluids unless instructed to restrict fluid
intake) to avoid possible adverse renal
problems.
 While using this medication, do not use
alcohol, other prescription or OTC
medications, or vitamins without consulting
prescriber.
 You may experience drowsiness (use
caution when driving or engaging in tasks
requiring alertness until response to drug
is known);

 Patient Information-2
 hair loss (reversible). Report skin rash or
lesions; painful urination or blood in urine
or stool; unresolved nausea or vomiting;
numbness of extremities; pain or irritation
of the eyes; swelling of lips, mouth, or
tongue; unusual fatigue; easy bruising or
bleeding; yellowing of skin or eyes; or any
change in color of urine or stool.
 Pregnancy precautions: Inform
prescriber if you are or intend to be
pregnant.
They give you support
 Colchicine 0.5mg/tab

秋水仙素
COLCHICINE
Colchicine mechanism

PMN: Polymorphonuclear neutrophil

 Use
 Treatment of acute gouty
arthritis attacks
 prevention of recurrences of

such attacks;
 management of familial

Mediterranean fever
 Unlabeled/Investigational

Primary biliary cirrhosis

 Precaution
 Pregnancy Risk Factor C (oral); D
(parenteral)
 Lactation Enters breast milk/use
caution (AAP rates "compatible")
 Contraindications Hypersensitivity to
colchicine or any component of the
formulation; serious renal,
gastrointestinal, hepatic, or cardiac
disorders; blood dyscrasias;
pregnancy (parenteral)
 Warnings/Precautions

 Severe local irritation can occur

following S.C. or I.M.
administration;
 Use with caution in debilitated
patients or elderly patients; use
caution in patients with mild to
moderate GI, renal, or liver
disease
 Adverse Reactions
>10%:
 Gastrointestinal: Nausea, vomiting,

diarrhea, abdominal pain

1% to 10%:
 Dermatologic: Alopecia

 Gastrointestinal: Anorexia

 <1%: Rash, azoospermia,

agranulocytosis, aplastic anemia, bone

marrow suppression, hepatotoxicity,
myopathy, peripheral neuritis
 Overdosage/Toxicology
Symptoms of overdose include acute
nausea, vomiting, abdominal pain, shock,
kidney damage, muscle weakness,
burning in throat, watery to bloody
diarrhea, hypotension, anuria,
cardiovascular collapse, delirium,
convulsions, and respiratory paralysis.
Treatment includes gastric lavage and
measures to prevent shock, hemodialysis
or peritoneal dialysis. Atropine and
morphine may relieve abdominal pain.
 Drug Interactions
Decreased effect:
 Vitamin B absorption may be decreased
12

Increased toxicity:
 Sympathomimetic agents

 CNS depressant effects are enhanced

Ethanol: Avoid ethanol.

Food: Cyanocobalamin (vitamin B12):
Malabsorption of the substrate. May result
in macrocytic anemia or neurologic
dysfunction.
They rejoice with joy
Mechanism of Action
Decreases leukocyte motility,
decreases phagocytosis in
joints and lactic acid
production, thereby
reducing the deposition of
urate crystals that
perpetuates the
inflammatory response
長期服用 COLCHICINE 需要補充
?
 VITAMINE A
 VITAMINE E
 VITAMINE B2
 VITAMINE B12
 VITAMINE C
 FOLIC ACID
 VITAMINE K
服用 COLCHICINE 常見的副作用
?
 Nausea,
 vomiting,
 diarrhea,
 abdominal pain
 Alopecia
 Anorexia
 Pharmacodynamics/Kinetics
Onset of action: Oral: Pain relief: ~12 hr if adequately dosed
Distribution: Concentrates in leukocytes, kidney, spleen,
and liver; does not distribute in heart, muscle, and
brain
Protein binding: 10% to 31%
Metabolism: Partially deacetylated hepatically
Half-life elimination: 12-30 minutes; ESRD: 45mins
Time to peak, serum: Oral: 0.5-2 hours,
Excretion: Primarily feces; urine (10% to 20%)
 Usual Dosage
Gouty arthritis, acute attacks: Adults:
 Oral: Initial: 0.5-1.2 mg, then 0.5-0.6 mg

every 1-2 hours or 1-1.2 mg every 2 hours

until relief or GI side effects (nausea,
vomiting, or diarrhea) occur to a maximum
total dose of 8 mg; wait 3 days before
initiating another course of therapy
Gouty arthritis, prophylaxis of recurrent
attacks: Adults: Oral: 0.5-0.6 mg/day or
every other day; patients who are to
undergo surgical procedures may receive
0.5-0.6 mg 3 times/day for 3 days before
 Dosing adjustment in renal
impairment
 Clcr<50 mL/minute: Avoid chronic
use or administration
 Cl <10 mL/minute: Decrease dose
cr
by 75% for treatment of acute
attacks
Hemodialysis: Not dialyzable (0% to
5%); supplemental dose is not
necessary
Peritoneal dialysis: Supplemental dose
 Colchicine
 Most effective drug for prevention of
recurrence
 Ever the drug of choice for acute gout
attacks.
 Advantage: provide
1.symptomatic relief to 95% p’ts in
early course
2.diagnostic confirmation
Colchicine
 Traditional acute gout attack:
1mg st0.5mg q1-2hr to symptom relief or GI
side effects or total dose 6mg
 Current trend: low dose: 1# BID-1# TID
 For prophylasix: 1# po bid

 In renal insufficiency: 1# po qd-qod

GFR< ml/min------50% dose

GFR< ml/min------DC
 Prophylatic dose of colchicine induce GI

adverse effects in 4% p’ts.

 藥品 作用

Cyclosporine 升高 cyclosporine 血中濃度及腎毒性，包括胃腸、肝

、腎、及肌神經毒性。應監測血中濃度，適時調整劑量

Erythromycin 使 colchicine 代謝受抑制，升高血中濃度，加強作用

Vitamin B12 可能改變迴腸黏膜功能而引起可逆性 vitamin B12 吸

收不良。

中樞神經抑制劑 中樞神經抑制劑敏感性增加

擬交感神經作用 加強擬交感神經作用劑的反應
劑
檢驗值 使 alkaline phosphatase 及 AST 值升高，血小板數
目減少。尿中紅血球或血紅素試驗可能呈偽陽性。
 Patient Information-1
 Do not exceed recommended dosage. Consult prescriber
about a low-purine diet. Maintain adequate hydration
(2-3 L/day of fluids unless instructed to restrict fluid
intake). Do not use alcohol or aspirin-containing
medication without consulting prescriber. You may
experience nausea, vomiting, or anorexia ; hair loss
(reversible).
 Stop medication and report to prescriber if severe
vomiting, watery or bloody diarrhea, or abdominal pain
occurs. Report muscle tremors or weakness; fatigue;
easy bruising or bleeding; yellowing of eyes or skin; or
pale stool or dark urine.
 Patient Information-2
 Pregnancy/breast-feeding precautions: Inform
prescriber if you are or intend to be pregnant.
Consult prescriber if breast-feeding.
 Dietary Considerations May need to
supplement with vitamin B12.
Becoz they are your true
friends
BENZBROMARONE
100MG/TAB
•A.Benzbromarone is a benzofuran derivative
used as a uricosuric for the treatment of hyperuricemia and
gout.

•B. DOSING INFORMATION: Oral doses of 50 to

200 mg once a day have been effective for hyperuricemia.

•C. PHARMACOKINETICS: Benzbromarone is

variably absorbed; oral bioavailability is dependent on particle
size, and has been estimated as 50 to 55%. Peak serum
levels occur 2 to 3 hours after oral administration; peak
effects occur in 8 to 12 hours. BENZBROMARONE is greater
than 99% protein bound. Its half-life is approximately 3
hours; it is mainly eliminated via the bile, with small
amounts appearing in the urine.
 .

•D. CAUTIONS: The main adverse reactions

associated with benzbromarone are gastrointestinal
(ie, diarrhea). Hypersensitivity reactions with
dermatologic manifestations have occurred.
Benzbromarone should be used with caution in the
presence of renal failure. Benzbromarone may
precipitate an acute attack of gout and/or uric acid
nephropathy.
•E. CLINICAL APPLICATIONS:
Benzbromarone is effective for reducing serum uric acid
levels in the treatment of asymptomatic and
symptomatic hyperuricemia and gout.
 IMPORTANT NOTE
 Benzbromarone should not be used to treat
acute gouty attacks since it may cause an
exacerbation if given during an attack.
Benzbromarone should be initiated only
after an acute attack has subsided.
 During treatment initiation with
benzbromarone for gout, a NSAIDS or
colchicine should be administered to reduce
the risk of precipitating an acute gouty
attack. In general, an adequate fluid intake
should be maintained and the pH of the
urine should be adjusted to neutral or
slightly alkaline to reduce the risk of renal
 DOSAGE IN RENAL FAILURE
 The efficacy of BENZBROMARONE is
decreased in the presence of renal
dysfunction, and the drug is not
recommended if glomerular filtration rate
is less than 20 mL/minute (Heel et al,
1977).
 One study reported a marked decrease in
efficacy of BENZBROMARONE in patients
with renal insufficiency, and the drug was
ineffective in patients undergoing
hemodialysis (Masbernard & Giudicelli;
1981).
BENZBROMARONE
使用時 注意病人腎 功能 ?

 The efficacy of BENZBROMARONE

is decreased in the presence of
renal dysfunction, and the drug is
not recommended if glomerular
filtration rate is less than 20
mL/minute (Heel et al, 1977).
 CONTRAINDICATIONS
A. Acute gout attack
PRECAUTIONS
A. BENZBROMARONE may precipitate
an acute gout attack and/or uric
acid nephropathy
B. Hepatic disease
C. Maintain adequate fluid intake
and maintenance of a relatively
high urine pH to reduce the risk of
nephrolithiasis
D. Renal failure
 PLACE IN THERAPY
 BENZBROMARONE is a useful uricosuric
with potent serum urate lowering
properties. Like SULFINPYRAZONE and
PROBENECID, BENZBROMARONE
increases urinary excretion of uric acid.
However, BENZBROMARONE is more
potent than either of these 2 agents, and
may have a more favorable side effect
profile than existing drugs. It also has a
more favorable pharmacokinetic profile
than existing uricosurics, and is suitable
for once-daily dosing.
 MECHANISM OF ACTION
 BENZBROMARONE lowers serum uric acid
concentrations and increases urinary urate
excretion, probably by inhibition of
proximal renal tubular urate reabsorption
with no effect on uric acid synthesis
(Sinclair & Fox, 1975; Gilman et al, 1990).
 It increases urinary uric acid excretion
shortly after an oral dose, and reduces
serum urate levels by 33% to 59% in a
dose-dependent manner after single or
repeated dosing.
?
And let you up
 病患衛教
1.  從未有過痛風關節炎發作的高尿酸血症患者通常不
需要藥物治療，但如果尿酸持續過高，就要找出原因
及開始注意飲食，如有相關疾病如：肥胖、高血壓、
高血脂症等也應加以一起治療。
2. 約一半的痛風患者在急性痛風發作前有誘因存在，
其中以啤酒為最重要原因（佔 60﹪ ），其次為海產
( 佔 18﹪) ，內臟食物（佔 14﹪ ）而豆類製品則幾
乎很少引起發作，根據台灣、日本、及美國學者測量
，各種嘌呤含量也不太高，因此可以推翻民間誤傳痛
風不可以吃豆類的說法。另一個間接證據就是常吃豆
類食品的出家人也很少得到痛風。
 病患衛教 - 飲食調整建議
1. 維持標準的體重：若體重過重應慢慢減胖，不宜快速減肥或斷食，
以免因細胞大量崩解產生尿酸而導致痛風發作。減重應以每月減輕一公
斤為宜。
2. 在醣類方面：所有五穀根莖類皆可食用，蔬菜類除 乾的香菇、紫菜
不宜大量食用外，如豆芽、豆苗皆可食用。水果則無禁忌。
3. 在蛋白質方面：含有高 的食物如內臟、魚類（海參、海哲皮例
外）宜減少攝取。
4. 在油脂方面：由於高脂肪食物會抑制尿酸排泄，在急性痛風期應避
免大量食用。
5. 酒精：酒精在體內會代謝成乳酸影響尿酸排泄，並且本身會加速尿酸
形成，故患者須禁酒，尤其是啤酒最容易導致痛風發作，應絕對禁止。
6.  水分：每天至少 3000 ㏄的水，多喝水份可以促進尿酸排泄及預防尿
路結石。
Even if you dont
When you need them and
doesnt
 高尿酸血症
( 血中尿酸 >8mg/dl)

有服利尿劑
無症狀者 ASPIRIN 類者 痛風
( 血中 U.A.>10mg/dl) 尿中尿酸 <0.7Gm/day

可停藥者 不可停藥者 血中 痛風石

U.A>10mg/dl 或
痛風反覆發作

促尿酸排泄劑 抑制尿酸生成劑
(probenecid) (Allopurinol)
長期追蹤 (Benzbromarone)
 PATIENT EDUCATIONS
What is gout?
Gout is a kind of arthritis caused by too much uric acid
in the joints. The acid causes joint pain.
Who can get gout?
If you eat a lot of foods that are rich in purines, you
may get gout. Some of these foods are salmon,
sardines, liver and herring.
You may get gout if you're overweight, drink alcohol or
have high cholesterol. Men have gout more often than
women.
Some medicines may cause gout, such as certain
diuretics ("water pills"), niacin (a B-complex vitamin),
aspirin (taken in low doses), cyclosporine and some
 PATIENT EDUCATIONS-2
What is a gout attack like?
It may be sudden. It usually starts at night, often in the
big toe. The joint becomes red, feels hot and hurts.
The joint hurts more when you touch it. Other joints
may also be affected.
What should I do if I have a gout attack?
The sooner you get treatment, the sooner the pain will
go away. Your doctor can prescribe medicine to stop
the joint swelling and pain.
You should rest in bed. Putting a hot pad or an ice pack
on the joint may ease the pain. Keeping the weight of
clothes or bed covers off the joint can also help.
With treatment, your gout attack should go away in a
few days. You may never have another attack.
 PATIENT EDUCATIONS-3

What if I don't get treatment?

If you don't get treatment, a gout attack can last for
days or even weeks. If you keep having more
attacks, more joints will be affected, and the
attacks will last longer.
If you have gout attacks for many years, you may
develop tophi (say: toe-fee). These are soft tissue
swellings caused by uric acid crystals. Tophi usually
form on the toes, fingers, hands and elbows. You
may also get kidney disease or kidney stones. Over
time, the bone around a joint may be destroyed.
 PATIENT EDUCATIONS-3

What can I do to avoid gout attacks?

Your doctor can prescribe medicines to prevent future
gout attacks. These medicines wash the uric acid
from your joints, reduce the swelling or keep uric
acid from forming.
You should lose weight if you need to. If you have high
blood pressure or high cholesterol, get
treatment and follow a low-salt, low-fat diet.
Stay away from alcohol and foods that are high in
purines.
Drinking lots of water can help flush uric acid from
your body.
When they need you
FIGURE 1. Acute gout. Note erythema and swelling
of the first metatarsophalangeal joint.
TABLE
The Purine Content of Foods and Beverages

High
Best to avoid:
Liver, kidney, anchovies, sardines, herring, mussels, bacon, codfish,
scallops, trout, haddock, veal, venison, turkey, alcoholic beverages
Moderate
May eat occasionally:
Asparagus, beef, bouillon, chicken, crab, duck, ham, kidney beans,
lentils, lima beans, mushrooms, lobster, oysters, pork, shrimp, spinach
Low
No limitation:
Carbonated beverages, coffee, fruits, breads, grains,
macaroni, cheese, eggs, milk products, sugar, tomatoes and
green vegetables (including lettuce and excluding vegetables
listed above)
FIGURE 2. Gouty tophi involving the
proximal interphalangeal joint with
erythema of the overlying skin.
Corticosteroids
Oral Prednisone, 0.5 mg per kg Fluid retention;
on day 1, taper by 5.0 mg
impaired wound healing
each day thereafter

Intramuscular Triamcinolone May require repeat

acetonide (Kenalog), injections; risk of soft
60 mg
intramuscularly, tissue atrophy
repeat in 24 hours if
necessary
Intra-articular Large joints: 10 to 40 Preferable route for
mg* monoarticular involvement
Small joints: 5 to 20 mg*

ACTH† 40 to 80 IU Repeat injections are

commonly needed; requires
intramuscularly;
intact pituitary-adrenal axis;
repeat every 8 hours stimulation of
as necessary mineralocorticoid release may
cause volume overload
ACTH=adrenocorticotropic hormone
Guideline of acute gout
Do you act along
 Case presentation 1.
 陳 X 鏗 , 男性 ,60 歲 ,165 公分 .
 入院日期 : 91-10-07
 出院日期 : 91-10-12
 主訴 : nausea, vomiting, diarrhea, general
malaise in recent 3 weeks.
 PI: HTN, DM, & hyperlipidemia for 7 yrs without regular
control. About 3 weeks ago, gout attack of R’t knee & he
took colchicine 1# q2hr x 10’s by himself. Diarrhea
, dry mouth, polydipsia, polyuria, general malaise were
noted. BW loss about 7-8 kg/3wks. Check one touch
sugar: 920mg/dl on 7/10,osmolarity:343. Under the
impression of HHNK he is admitted for further
evaluation.
Case presentation 1.
 Past history:
1.Hx of type II DM for 3-4 yrs with diamicron
2# bid + glucophage 2# bid keep BS:150-
200mg/dl
2.Hypertension:
Rx: amlodipine 2# qd + Lisinopril 10mg bid
3.Hyperlipidemia:Rx simvastatin 1# qn
4.GB stone S/p op at 85-01-24
5.Gouty arthritis without regular control.
Case presentation 1.
Progression note:91-10-07
 S:dry mouth & tongue mucosa, general
weakness,
 O: osmolarity:343, blood sugar: 981mg/dl,
blood keton (-), BUN/Cr:51/2.0,
Clcr: 81ml/min, DUP: 3.6g, Na:127, K: 6.1
WBC:10170
 Impression: HHNK
1 NPO.
2 Hydration.6L N/S –G/S in 24hr
3. Insulin pump(100U in 500ml N/S keep infusion
rate5U/hr adjust by BS ), keep BS:150-200mg/dl
4. KCL supplement: 10meq in 500ml iv fluid.
5.After blood sugar was stable, N7/R3: sc bid was
prescribed.
Case presentation 1.
91-10-08:
S: general malaise, but improved.
O: BUN/Cr: 35/1.3, Bp:130/75, PR:100
BS: 389-293-310-414-260-102-232-
279-high-448
Chol: 257, TG:845mg/dl---156 (12/10),
HDL:48, T.C/HDL-C:5.4, WBC:10170
P:1.P’t education with diet control
2.Shift Insulin to N7/R3 SC, monitor BS
3.Shift Simvastatin----→Gemfibrozil 2# bidac
4.F/U: electrolyte, BS, renal function.
Case presentation 1.
 91-10-10:
S: Acute onset of painful erythematous swelling
change over of R’tlateral mid-tasal area with
local heat since 9/10 night, UA:8.1, consult
IMRH & sono showed: multiple microtophi &
swelling in soft tissue over middle tarsal bones..
 Imp: Acute gouty arthritis & cellulitis

Rx: cortrosyn inj 0.5mg im stat

colchicine1# stat & bid
celecoxib 2# stat & bid
Case presentation 1.
Date Na K Cl Ca BUN Cr TG UA
7/10 133 5.0 95 10.9 8.8
8/22

7/10 127 6.1 91 51 2.0

7/10 141 4.2
7/10 140 4.2 35 1.3
8/10 139 3.7 9.2 1.2 845 8.1
9/10 138 3.71
12/1 147 4.1 1.1 156
0 HbA1
CRP 2.5 15.1 GHb 22.7
c
 HHNK 與 DKA 的診斷
HHNK DKA
Typically people Type II Type I
Plasma >600 >250
glucose(mg/dl)
Arterial pH >7.3 <7.3
Serum >15 <15
bicarbonate(mEq/l)
Serum and urine Small Positive
ketones
Effective serum >320 Variable
osmolality(mOsm/kg)
Alteration in sensoria Stupor, Alert/drow
or mental coma sy/stupor,c
obtundation oma
When you are up
Case presentation 2.
 林 X 夫 , 男性 ,63 歲 , 病歷號 :
588254C
 入院日期 : 91-07-22
 出院日期 : 91-07-26
 主訴 :acute onset of painful sensation ,
erythematous change over bil. medial
aspect of ankle & MCPs of feet, Bil wrists
&MCPs of hands, L’t elbow & shoulder.
Case presentation 2.
 Present illness:
quite well before except arthritis over L’t
medial ankle & L’t 1st MCP initially 4 yrs ago.
Intermittent acute attack of poly arthritis
after that time ( add R’t ankle & 1st MCP of R’t
foot)---MCPs & wrist of bil. Hands. The
duration about 1 week/ time.Take black pills
by himself. LMD: hyperuremia was told &
with irregular treatment . Acute onset of
chief complain symptoms in recent 2 days,
came to Er at 91-07-22: BUN:20, Cr: 2.2, K:
5.3, UA: 10.7mg/dl, CRP: 22.5, WBC: 17200
80.6/9, vial ER for admission to ward for
evaluation.
Case presentation 2.
 Progression note:
After admission, SF of R’t ankle was aspirated,
the result show: MSU: (+++), intracellular.
SF/C: (-), CPPD( - ),
SF: WBC: 49300/cumm, N:95%,
24hrs UA excretion: 673.38mg, Clcr:70
 Treatment:
colchicine 1# bid, meloxicam: 1# bid,
Prednisolone: 5mg bid----qd. Fina: 2# bid.
Think of them
Case presentation 3
 王 X 惠 , 女性 ,35 歲 , 病歷號 :1195949C
 入院日期 : 91-04-17
 出院日期 : 91-04-26
 主訴 :General malaise, poor appetite,
impaired LFT.
 P.I:35 yrs female initial presented
with skin rash,photosensitivity since
1987/7. In 1989/11 she developed
general edema, SLE was Dx at
CGMH.because severe proteinuria,19
courses of Endoxan pulse Tx were
given at VGHTP from 1991-1993.Due to
poor Endoxan response, CsA had ever
 Case presentation 3
 1997/7:Renal Bx: Class IV A/C:2/6.
 1998/4:Cellcept 2# bid was added .
 1999-03-13.renal Bx class III & V A/C: 2/9.
 2001/1: Rhabdomyolysis due to bezalip
 2002/1: GA attack over R’t knee & recurred.
Rx: allopurinol 2# qd + colchicine 1# bid.
 2002/2:Persistent proteinuria & impaired
renal function, repeat renal Bx: class VI
A/C:0/9---add immuran 1# qd
 Poor appetite, general malaise, fatigue for
3-4 wks. Check GPT:741---DC immuran
 From OPD transfer to ward for further
evaluation.
Case presentation 3
 Impression:
1.Acute hepatitis R/O drug induce
2.SLE with lupus nephritis class IV
3.Gouty arthritis , R’t Knee
4.HTN
 Progression note:
HbsAg: (-), anti-HCV (-), Abd sono(-) finding, PCR of
CMV DNA (-).
24hr UA: 4.1mg/dl, total vol: 3350ml/24hr
24hr UA excretion: 137.35<700mg----
undercxcretion.
Case presentation 3
D A AST ALT LDH Bil- Bil- TG UA Cr
LKP
ate T D
90- 17 25 180 0.2 0 423
5/16
90- 251 1
5/30
3.7
90- 339
6/27
90- 32 8.1
9/26
90- 61 201 6.7 2.1
11/2
1
91- 218 1 2.1
03/0
1.2
5
91- 138 741 2.5
4/10
91- 133 271 706 561 2.9
4/17
91- 154 83 430 487 2.4
4/22
When you are down
問題 . 請問其診斷為何 ?
(1) 細菌性關節炎 (2) 痛風關節炎 (3)
假痛風
 一位 60 歲已停經女性
，因胃潰瘍穿孔而接受
緊急手術治療，開刀後
第三天，右側大腳趾之
蹠趾關節突然紅腫疼痛
且有發燒
 隔日測其血清尿酸為
4.2mg/dl ( 正常值)
 血尿酸值正常者併發痛風之臨床分
析 (Ann Rheum Dis 2003;
1. 血尿酸值正常者發生痛風的機率可達
62:90-92) 39-43%
(Ann Rheum Dis 1997; J Rheumatol 1997)
2. 韓國痛風發作的病人 226 位，有 27 位 (12%) 之血尿酸值是
正常
=>21 位追踪 3 年，有 17 位 (81%) 事後會有高尿酸血症
( 中間
值為 3 個月，範圍 1 週 ~2 年 ) ，其餘 4 位之血尿酸值仍為
正常，
也未再痛風發作
3. 若與高尿酸血症併發痛風者比較，血尿酸值正常者發生痛風
者
　 痛風發作年齡較大 (60.6±13.9 歲 )
痛風首次徵狀到確定診斷之間隔較短 (32.2 個月 )
問題 . 請問最佳的治療為何 ?
(1) 靜脈注射秋水仙素 (2) 注射消炎藥 Ketorolac
(3) 關節抽液併關節內類固醇注射 (4) 給予
Allopurinol

 一位 64 歲男性，以前常因痛風發作而服用消
炎止痛藥。這次因多處胃潰瘍併大量出血而住
院治療
 第二天，右側膝關節突然紅腫疼痛而且有發燒
 其血清尿酸為 9.8 mg/dl ( 正常值 < 7.2)
 NPO 中
And let you up
 問題 . 試問該病人如何治療高尿酸血症
?
1) 改用促進尿酸排泄的藥物 , 2) Allopurinol 之減
敏治療

 一位 52 歲體型稍胖的男性，最近三
年來常有急性下肢 1-2 個關節腫痛，
大多一週內完全消退 ( 平均一年至少
發作三次 ) 。理學檢查發現左大腳趾
關節處紅腫熱痛，而且周圍已有痛風
石沈積，血清尿酸值為
12.8mg/dl ， 血清肌酸酐為 4.2
mg/dl, 且有腎結石以前曾用過
Allopurinol ，但因發生皮膚紅疹而
停用。
 分解尿酸的藥物 (Uricase)
Rasburicase
 此類藥物屬於分生合成的尿酸鹽氧化酶
(Urate oxidase) ，可將尿酸分解成具高
溶解度的代謝產物 Allantoin ( 其溶解度為
尿酸之 10~100 倍 ) 。
 可迅速降低尿酸濃度，對於血液腫瘤疾病
與將接受化學藥物治療的患者，其治療及
預防高尿酸血症產生的併發症效益很高
( 實証醫學 B 級 ) 。
RASBURICASE
PROPRIETARY NAME: ELITEKTM (Sanofi-
Synthelabo)

INDICATIONS: Rasburicase is indicated for the

initial management of plasma uric acid levels in
pediatric patients with leukemia, lymphoma, and solid
tumor malignancies who are receiving anti-cancer
therapy expected to result in tumor lysis and
subsequent elevation of plasma uric acid. Decreasing
the hyperuricemia is done in order to prevent acute
renal failure in these patients.
 CLINICAL
PHARMACOLOGY:
 Rasburicase is a recombinant urate-
oxidase enzyme. It is produced by a
genetically modified Saccharomyces cerevisiae
strain cloned with cDNA from a strain of
Aspergillus flavus. This recombinant enzyme is a
tetrameric protein similar to native A. flavus urate
oxidase. Urate oxidase is an endogenous
enzyme in most mammals, but not in humans.
Rasburicase catalyzes enzymatic oxidation of
uric acid into allantoin, a water soluble product
that is easily excreted by the kidneys.
 PHARMACOKINETICS:
 Steady state is achieved within 2 to 3
days following infusion of rasburicase 0.2
mg/kg/day as a 30-minute infusion daily.
The volume of distribution of rasburicase is 110
to 127 mL/kg. Its elimination half-life is 18
hours. Total body clearance is increased about
35% in children and adolescents compared to
adults.1,5 Rasburicase is expected to undergo
peptide hydrolysis like other proteins. Impaired
hepatic function should not alter the elimination of
rasburicase. The pharmacokinetics of rasburicase
have not been evaluated in patients with impaired
renal function, but renal elimination is expected to
be a minor pathway. Allantoin is eliminated renally,
but appears to be nontoxic.
 ADVERSE REACTIONS:
 The most common adverse effects observed during
rasburicase therapy have included
 vomiting (50%), fever (46%), nausea (27%),
headache (26%), abdominal pain (20%), constipation
(20%), diarrhea (20%), mucositis (15%), and rash
(13%).
 Serious adverse reactions caused by rasburicase have
included anaphylaxis (less than 1%), rash (1%),
hemolysis (less than 1%), and methemoglobinemia (less
than 1%).
 Other serious adverse events commonly observed
during rasburicase therapy included fever (5%),
neutropenia with fever (4%), respiratory distress
(3%), sepsis (3%), neutropenia (2%), and mucositis
(2%).1
 DOSING:
 Rasburicase is administered immediately prior to and
during chemotherapy initiation. Chemotherapy
should be initiated 4 to 24 hours after the
first rasburicase dose.
 The recommended dose of rasburicase is 0.15 or 0.2
mg/kg as a single daily dose for 5 days. Rasburicase
should be administered as a 30-minute intravenous
infusion.
 Dosage adjustments are not necessary in patients
with renal or hepatic impairment. The required
quantity of solution is diluted with 0.9% sodium
chloride solution to make a total volume of 50 mL.
The final solution should be infused over 30 minutes.
No filters should be used for the infusion. Glucose
solutions should not be used for dilution due to
potential incompatibility.
治療高尿酸血症
促進尿酸排泄的藥物 (Uricosuric
drugs)
 這類藥物包括
probenecid(Benemid) 、 Sulfinpyrazone 、 Ben
zbromarone (Narcaricid) 、 抗血脂藥物
(fenofibrate) 、及降血壓藥 (Losartan) 。
 由於 probenecid 及 Sulfanpyrazone 在腎功能不
佳的病人 ( 腎絲球瀘過率≦ 50 毫升 / 分鐘 ) 療效減低
，易致尿酸鹽沈積在腎臟，而且具較高的毒性 ( 如出
血或骨髓抑制 ) ，因此目前很少被使用。
 Benzbromarone 在腎功能不佳的病人，仍可有效促
進尿酸由腎臟排泄 ( 實証醫學 C 級 ) ，但須注意防範
尿酸鹽在腎臟的沈積，以及其少見的肝臟副作用。在
歐洲醫療體系，甚至與 Allopurinol 合併使用，具有
降尿酸加乘的效果。
高尿酸血症患者使用 Allopurinol 或
Benzbromarone
治療之效果比較
(Med Assoc Thai 2002; 85:s40-7)

一交叉臨床試驗 實証醫學等級 C
(Allopurinol 4 週—藥物清除 4 週—
Benzbromarone 100mg/ 日，為期 4 週 )

降低尿酸的效果， Benzbromarone 優於
Allopurinol
 促進尿酸排泄的藥物
降血脂藥物 Fenofibrate (Lipansyl)
 最近的研究發現降血脂藥物 Fenofibrate (Lipansyl)
可有效促進尿酸排泄，而且可合併其他降尿酸
藥物 ( 實証醫學 C 級 ) 。由於高尿酸血症患者
若合併有高血脂症，則可考慮使用此藥物。
促進尿酸排泄的藥物
降血壓藥物 Losartan (Cozaar)

 在降血壓藥物中，有一種血管張力
素轉化酶抑制劑 Losartan (Cozaar) ，
被發現有促進尿酸排泄的功效，因
此也可用來降低血尿酸值。當高尿
酸血症患者，若同時併有高血壓，
則可優先使用此降壓藥。
降尿酸藥與降血脂藥 Fenofibrate 或降血壓藥
Loasrtan 之合 療法對於尿酸的作用

1. 這是隨機但非雙盲的臨床藥物試驗 實証醫學等級 C

2. 結果顯示合併降血脂藥物 (fenofibrate) 或合併

降血壓藥物 (losartan) ，皆能促進尿酸由尿液排泄
而降低血尿酸值

Ann Rheum Dis 2003; 62(6): 497-8

使用促進尿酸排泄藥物的問題
1. 併發症
造成尿酸塩沉積在腎臟組織及腎結石
可能增加痛風的發作 ( 初期使用 )
過敏 (Sulfinpyrazone)
骨膸的抑制 (Probenecid)
肝炎 (Benzbromarone)
2. 預防之道
須足夠
飲水及尿液鹼性化
同時口服秋水仙素
以低劑量開始使用，且緩慢增量
痛風的治療
血尿酸 須控制到多少？
預防痛風復發
≤ 6.0mg/dl
促進痛風石吸收

≤ 5.0mg/dl
器官移植合併高尿酸血症
1. 高尿酸血症的原因
腎功能異常
使用環孢靈 (Ciclosporine)
2. 解決方法
儘量矯正高尿酸血症的原因
使用 Allopurinol 或 尿酸分解酶 (uricase)
若有高血壓 => 優先考慮 Losartan
(Cozarr)
若有高血脂 => 優先考慮 Fenofibrate
 難以控制的高尿酸血症 (5-
10%)
1. 原因
• 高尿酸血症的原因持續存在
( 利尿劑的使用、照常喝酒、肥胖 )
2. 處理方法
矯正及排除高尿酸血症的原因
可考慮使用尿酸分解酶
(uricase)
痛風石合併腎功能不好的高尿酸血症
1. 困難處
無法使用高劑量的 Allopurinol ( 易發生副作
用)
促進尿酸排泄藥效果不佳且易致腎結石
這類病人之血尿酸值須控制在 5.0mg/dl
2. 解決方法
儘量矯正高尿酸血症的原因
使用尿酸分解酶 (uricase)
若有高血壓 => 優先考慮 Losartan
(Cozarr)
若有高血脂 => 優先考慮 Fenofibrate
611942C
UA(mg/dl) Scr(mg/dl)
890622 8.4 1.8

891116 5.3 2.0

They may not tell you
1164830J
UA(mg/dl) Scr(mg/dl)
910319 12.1

910510 10.8
910927 6.7
They are always there
234981H
UA(mg/dl) Scr(mg/dl)
910512 12.3 3.0

910513 2.2

910516 2.1
 90112C
CAD - S/P PTCA
Valvular heart disease - AR
Hyperlipidemia
HCVD
藥　　　名 使用劑量及用法
25mg Dithiazid tab 0.5 TAB PO BID
Tapal tab 1 TAB PO QD
Isordil tab 10mg 1 TAB PO TIDAC
Doxazosin tab 2mg 1 MG PO BID
Herbesser tab 30mg 1 TAB PO TID
Perindopril-4 tab 1 TAB PO QD
Benzbromarone-100 100 MG PO QD
Fenofibrate-200cap 1 CAP PO QDCC
Chol TG HDL UA
213 244 11.7
215 289 5.2
250 124 71
 結論 ( 一 )
 痛風是一臨床常見的醫療問題，若未適當的治療，會
產生痛風石、關節及內臟的傷害
 老年發作之痛風常呈現非典型徵狀
 痛風的關節炎的診斷須在受犯關節的關節液有尿酸鹽
結晶，才可確立
 高尿酸血症是痛風的主因，但非必要條件
 治療主在
1) 終止急性痛風 (NSAIDs 及低劑量秋水仙素為主 )
2) 治療高尿酸血症 ( 去除其原因、口服降尿酸
藥物及調整生活飲食 )
3) 評估且治療痛風相關之疾病
 結論 ( 二 )
臨床藥師對痛風應認識的重點
 痛風與高尿酸血症之病態生理學
 急性期與慢性期痛風葯物治療有何不同
?
 高尿酸血症葯物治療的時機 ?
 痛風與高尿酸血症最新葯物
(Allopurinol;
Benzbromarrone;Rasburicase etc.)
之葯動學 (pk) 及葯理學臨床應用 ?
 痛風治療葯物之副作用與葯物交互作
用
Thanks for
your
attention !