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蜥蜴拯救人类
作者:USMedEdu
发表时间:2010-12-03
更新时间:2010-12-03
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蜥蜴拯救人类
http://www.mitbbs.com/clubarticle_t/Pre_Resident_Club/26315.html



发信人: againstwind (逆风而行), 信区: ResidentsWhisper
标 题: 深更半夜写医学八卦:一只拯救人类的蜥蜴
发信站: BBS 未名空间站 (Fri Dec 3 03:51:58 2010, 美东)

http://www.mitbbs.com/clubarticle_t/Pre_Resident_Club/26315.html


在美国西南部的沙漠地带,生活着一种濒临灭绝的蜥蜴,名字叫做Gila Monster。和他
们的名字一样,这些家伙们长得凶神恶煞,而且带着毒液。虽然如此,因为他们行动缓
慢,所以对人类没有什么威胁,但是因为他们的吓人外表,仍然不断地被游客猎人杀害
。所以现在受到亚利桑那州的严格保护。

他们有一种特别的本领,就是耐饿,在环境艰苦的沙漠中,他们可以一年只吃三到四次
,但是每次一吃,就可以吃掉同等于他们体积的小动物。

如果没有一个来自纽约Bronx的内分泌医生多年不懈的研究,这些Gila Monster们就还
在沙漠里默默无闻地生活着。John Eng医生,默默地在纽约布朗区老兵医院工作了二十
多年,和其他内分泌医生一样,他看了无数的糖尿病患者,憧憬有一天有一个药物能够
和人体自身的激素一样精确地调整胰岛素和血糖的平衡,既能治疗高血糖,又能避免药
物引起的低血糖。

90年代初期,研究者发现,同样的试验人群,如果给口服葡萄糖,或者给静脉葡萄糖,
同样的血糖控制,但是口服葡萄糖的人群胰岛素分泌量有一个高峰,明显区别于静脉葡
萄糖,这就是著名的incretin effect。

Incretin是我们回肠分泌的一种肠道肽,进食以后,incretin分泌增加,引起胰岛素分
泌增加,同时抑制高血糖素,并且延缓胃的吸收,并且还反射性地引起食欲满足的感觉
,从多方面起到调控血糖的作用。最美好的是,这些作用都是根据血糖情况自动反馈,
只有血糖升高时候才会作用,血糖正常的话就没有作用,从而不引起低血糖。

GLP-1是incretin的一种,糖尿病人的GLP-1分泌缺陷,从而导致进食后高血糖素分泌反
常升高,导致血糖失去控制。所以大家就开始想,对哦,那我们可不可以多给病人一点
GLP-1,这样就可以纠正糖尿病啦。有一个问题是我们人体分泌的GLP-1的生命力非常短
,只有一到两分钟,所以从药学作用来说就没有意义了。原因是因为有一个叫做DDP-4
的酶,在孜孜不倦地切掉GLP-1的N端结构,使得他们失效。

这时候,这个布朗区的Eng医生,在自己的实验室里,被那些一年只吃三次饭的蜥蜴们
给迷住了,他从它们的唾液中提取出一种蛋白和人类GLP-1的结构一半相似,他给这个
蛋白取名叫作exendin-4。这个蛋白因为结构相似,在人体里也能起到GLP-1的作用,但
是孜孜不倦的DDP-4却傻呼呼地认不出这个蛋白,所以exedin-4在DDP-4的眼皮底下刺激
胰岛素,抑制高血糖素,却不会被迅速分解掉。

聪明的研究者们很快就开始人工合成exedin,名字叫做 Exenatide,商品名就是现在的
Byetta。从2005年到现在,Byetta因为相似的调整血糖作用却没有低血糖而受到青睐,
最重要的是有独特的减轻体重的效果。副作用是恶心,不过现在有warning引起胰腺炎
和肾脏副作用。



--

※ 修改:·againstwind 於 Dec 3 03:58:38 2010 修改本文·[FROM: 65.24.]
※ 来源:·WWW 未名空间站 海外: mitbbs.com 中国: mitbbs.cn·[FROM: 65.24.]

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共有1条评论
1   [USMedEdu 于 2010-12-04 17:02:59 提到] [FROM: 24.]
发信人: chipmunk (花栗鼠), 信区: Pre_Resident_Club
标 题: Re: 深更半夜写医学八卦:一只拯救人类的蜥蜴
发信站: BBS 未名空间站 (Sat Dec 4 14:29:02 2010, 美东)


Saw one patient a few of weeks ago. A 58 yo M, psychiatrist, with h/o
complicated DM insulin dependent, GERD, presented with recurrent sore throat
, hoarseness, nausea and vomiting. He was initiated with Byetta 5mg SQ Q12h
in July. The dose was increased to 10mg later in September. He never
realized it was his medication's side effect as he responded to the
medication very well. He lost 10+ lbs and his blood sugar was under better
control, bla bla. To me, his symptoms were most likely secondary to his
diabetes associated autonomic neuropathy and gastroparesis caused by Byetta.
Thankfully his diabetes mellitus was still under good control. He did not
develop any glycemia-associated complications.



多谢风MM指点。我可能不应该用gastroparesis来解释byetta的副作用, other meds
may also contribute his symptoms。这个病人是DM type I, on insulin pump since
2005, f/u by his endocrinogist, prolonged GERD on Nexium. 他的主诉听起来象
是nausea and vomiting为主,一个多月内有好几次吐得一整天almost no oral intake
,喉咙也痛,这才来找PCP看的。刚好我在clinic with my preceptor。他本人是本院
的医生,很注意,血糖一直控制得很好,看门诊当天fast glucose才104, 中午210,马
上调insulin pump了。所以一直没想到可能是exenatide的原因。We asked him to
lower his Byetta's dose, 过了一个星期他也没来followup。刚才查了一下他的EMR,
已经三个星期没有任何新的records,I thought his symptoms had been resolved therefore he
didn't show up。He didn't have swallow difficulty. The symptoms seemed to be related to his increased dose of byetta. 当然如果his symptoms persist, he shall get a GI consult for at least a barium swallow test.

Here is side effect of Byetta I found:
Nausea -- occurring in up to 44 percent of people
Hypoglycemia -- up to 35.7 percent
Vomiting -- up to 13 percent
Diarrhea -- up to 13 percent
Feeling jittery -- up to 9 percent
Dizziness -- up to 9 percent
Headache -- up to 9 percent
Upset stomach or heartburn -- up to 6 percent.

From Uptodate:
Concerns related to adverse effects:
1.Anti-exenatide antibodies: Use may be associated with the development of
anti-exenatide antibodies; low titers are not associated with a loss of
efficacy, however high titers (observed in 6% of patients in clinical
studies) may result in an attenuation of response.
2.GI symptoms: Most common reactions are gastrointestinal related; these
symptoms may be dose-related and may decrease in frequency/severity with
gradual titration and continued use. 3.Pancreatitis: Cases of acute
pancreatitis (including hemorrhagic and necrotizing with some fatalities)
have been reported; monitor for unexplained severe abdominal pain, and if
pancreatitis is suspected, discontinue use. Do not resume unless an
alternative etiology of pancreatitis is confirmed. Consider alternative
antidiabetic therapy in patients with a history of pancreatitis.
4.Weight loss: Use may be associated with weight loss (due to reduced intake
) independent of the change in hemoglobin A1c

Here is his major problem list:
1.diabetes type 1 with insulin pump
2.GERD
3.hypertension
4.dyslipidemia
5.focal segmental glomerulosclerosis renal disease
6.asthma

CURRENT MEDICATIONS:
1. Neurontin/gabapentin 300 mg 2 tabs oral each am (600 mg total), 3
tablets each evening (900 mg total).
2. Metformin ER 500 mg tabs 2 tablets am, 2 tablets pm (total 2000 mg).
3. NovoLog regular insulin/insulin pump.
4. Advair Diskus 250/50 one puff twice daily (bronchial asthma maintenance).
5. Albuterol 2 puffs q4 hours prn rescue.
6. Plavix 75 mg daily (intolerant to aspirin/NSAIDS).
7. Simvastatin 20 mg each evening.
8. Moexipril 15 mg twice daily.
9. Cozaar 100 mg daily.
10. Nexium as omeprazole 40 mg daily.
11. Clobetasol 0.05% cream twice daily x2 weeks chronic eczema.
12. Triamcinolone acetate cream 0.1% apply twice daily chronic eczema.
13. Cymbalta 120 mg daily.
14. Fluoxetine 40 mg daily.
15. Klonopin 0.5 mg to 1 mg oral at bedtime (chronic stable anxiety).
16. Lumigan eyedrop 1 twice daily both eyes (chronic glaucoma).
17. Cosopt 1 drop both eyes bid.
18. Prednisolone acetate 1 drop both eyes bid.
19. CPAP, obstructive sleep apnea, nightly.
20. Flomax 0.4 mg 2 caplets every evening.
21. Proscar 5 mg daily (Urology 2009).
22. Insulin pump for diabetes.
23. Viagra 100-mg tablet, takes 1/2 tablet to 1 tablet as needed, dispense 6, per Urology.
24. Byetta 5 mcg SQ bid.


【 在 againstwind (逆风而行) 的大作中提到: 】
: 我的一点感觉,当然没看过病人,随便说说。
: byetta的主要副作用是胃不舒服加上腹泻。但是应该不会引起sore throat和
: hoarseness,gastroparesis也不会,这个应该想想是不是GERD反酸引起的。如果糖尿
: 病control很好,病人不太会有严重的gastroparesis。
: 50岁的病人,严重的GERD,weight loss,不知道有没有做胃镜,不能完全assume是
 
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