年底，又到了很多藥師要整理管制藥的日子(明年一月底前要完成申報)，而藥局常見的管制藥品大概90%是安眠藥。台灣人對安眠藥的感覺非常複雜，非常恐懼他的副作用；不過全台每年卻要吃掉13億顆安眠藥!這邊 就來整理各種安眠藥。
要講安眠藥一定要了解GABA受體，當細胞上的GABA受體活化時，使Cl-通道(Cl-channel)打開，Cl-流入突觸後(postsynaptic)細胞內，導致細胞膜過極化(hyperpolarization)不反應狀態，達到抑制神經及肌肉細胞的興奮性(firing)之作用。這種過極化對人體的影響由輕到重可以有抑制焦慮、預防癲癇、安眠到最後甚至會造成昏迷甚至在也醒不來，這就是很多安眠藥被拿來自殺的原因(目前台灣可以取得的安眠藥已經沒有這種效果)而不同的安眠藥就是活化GABA受體的不同部位。例如: Barbiturates是直接活化GABAA受體；benzodiazepine 是作用在GABA受體的阿法跟家馬次單元上(也有人說是benzodiazepine receptor)；zolpidem是作用在加碼次單元上。
這次我將藥物分為Barbiturates、benzodiazepine、zolpidem跟其他不是安眠藥卻可以幫助睡眠的藥物四個大類。
Barbiturates
Barbiturates的作用機轉是直接活化GABAA受體，而且可以一直活化到之前提到得造成死亡。再加上成癮性的問題所以現在台灣已經非常少用。目前大家最長聽到的反而是毒品secobarbital (Seconal)，因其藥品膠囊外觀為紅色，故俗稱紅中；amobarbital (Amytal)因其藥品膠囊為青色，所以俗稱青發。
benzodiazepine
benzodiazepine是安眠藥最常見的種類，一樣是在GABA受體上開起氯離子通道導致細胞膜過極化(hyperpolarization)不反應狀態，不一樣的地方是benzodiazepine不是直接作用在GABA受體上而是作用在在GABA受體的阿法跟家馬次單元上(也有人說是benzodiazepine receptor)。所以一樣能穩定神經有安眠的效果，卻不會進一步造成昏迷跟死亡。所以目前可以取得的安眠藥基本上不能用來自殺。
benzodiazepine依作用時間還分為短效(<8小時)、中效(10-20小時)跟長效(>24小時)
短效的benzodiazepine為 Brotizolam(戀多眠)，主要針對年以入睡的患者。也比較能預防患者醒後精神不濟、跌倒之類的副作用。
中效的benzodiazepine，強度由弱到強是(圖片也是由弱到強排列)oxazolem(益可寧)，bromazepam(立舒定)，lorzepam(安定文)，alprazolam(讚安諾)，escazolem(悠樂丁)跟最強的大名鼎鼎的flumtrazepam(FM2)。
這類的特色是抗焦慮，可用以搭配用於同時有焦慮症和失眠的病患，一般建議從弱效開始使用，療效不好再逐漸使用到強效。這類藥品大家最耳熟的可能是(FM2)其英文名字叫作Flunitrazepam, 為羅氏藥廠所製造，為歐州所流行的濫用藥物之一。由於其安眠作用快速(20分鐘)，作用強(為一般安眠藥的十倍)，安眠效果久(8-12小時)，因此被一些有心人士加以利用, 以在飲料中迷昏特定人物以達到犯罪目的。還有這張圖沒包括道的Clonazepam為癲癇治療用。起始作用時間約半小時。
benzodiazepine皆由肝臟代謝，其中 Lorazepam較特別，只直接藉由 glucuronide conjugation代謝，並由腎臟排除，不透過 cytochrome P450，因此較適用於肝功能較差 (ex.酒精性肝炎，因此相較於其他 BZD，較適合用於酒精戒斷症候群病患的治療)、有 P450藥物交互作用的病患。
長效的benzodiazepine為 diazepam(丹祈屏) 作用時間長，可用於睡眠時間不夠長、清晨容易清醒的病患來維持睡眠，diazepam同時也有抗焦慮、抗癲癇的作用
zolpidem
除了benzodiazepine外安眠藥最常見的可能就是zolpidem，就是大名鼎鼎的史蒂諾斯。其主要作用機轉，是在中樞神經系統，選擇性地與 GABA-A 受體群組中之ω1 次型的調節性連結點結合後，發揮正向的促進劑 (agonist) 作用，局部增加 GABA 系統的傳遞作用。對ω1 次型的高度選擇性連結，形成高度選擇性的助眠作用。由於受體連結選擇性高，而較少出現副作用。標準釋放型式的 zolpidem，半衰期短 (一般成人 2.4 小時，老年人 2.9 小時，平均 1.5~3.2 小時)，因此少有隔夜宿醉作用，也由於沒有活性的代謝物，重複使用之後，不會在體內有堆積的問題。
不過zolpidem有一個最匪夷所思的副作用，就是夢遊。夢遊症或稱為睡眠遊走症，一般發生在慢波睡眠之第三至第四期。在夢遊時期，正常的覺醒機轉被改變，造成部分覺醒的半意識狀態。一般而言，藥物會造成夢遊或夢魘，通常是會干擾慢波睡眠的生理狀態或增長慢波睡眠的時間。在腦波檢查上，使用 zolpidem 後，會造成快速動眼期 (rapid eye movement, REM) 睡眠的抑制現象，而且也有報告指出在年輕成人群的研究當中，zolpidem 會增加 delta 波，因此都會增加夢遊的可能性。無論如何，要確定夢遊症的診斷，都必須進行整夜的睡眠腦波紀錄。
雖然介紹了這麼多安眠藥，不過因為台灣人對安眠藥的恐懼的結果有些醫生開立會比較謹慎。所以這些謹慎的醫師的第一線用藥可能就不是使用安眠藥，而是同時有安眠效果的其他藥品。如果這樣病患還是睡不著再使用安眠藥，這樣不止病患一直有藥可用，也比較不會有副作用。
mirtazapine是一種抗憂鬱劑，可以在憂鬱症狀發作時作為治療之用。為tetracyclic piperazinoazepine類抗憂鬱劑，化學結構與三環抗憂鬱劑，單胺氧化酶抑制劑，SSRIs都不同。 mirtazapine 是作用在中樞突觸前拮抗α2-adrenergic receptors，增加正腎上腺素及血清素（serotonin）的活性。 mirtazapine 的抗組織胺H1作用會導致其鎮靜效果。
Trazodone(Mesyrel，美舒鬱)，近十年來經常被當成慢性失眠的輔助劑，在美國的用量僅次於安眠藥使蒂諾斯(Stilnox)，甚至近來有超越之傾向。
除了mirtazapine外，另一種更嘗用再失眠的抗憂鬱藥是Trazodone。藥理上Trazodone是一種SSRI(Selective serotonin reuptake inhibitors ，血青素再回收抑制劑)在動物上，Mesyrel選擇性的抑制Brain synaptosomes對於serotonin的吸收，同於對於serotonin的前驅物，5-hydroxytryptophan所誘發的行為改變有所加強作用。
目前這麼長使用Trazodone治療失眠的原因有三，第一是可以增加睡眠中非動眼期(Non-REM)第三期及第四期的熟睡期，且可以延長整體睡眠時間。很多病人並不知道傳統安眠藥不管吃幾顆都只能增加非動眼期第二期之淺睡期而無法增加熟睡期，因此患者服用安眠藥雖然可以睡著，但會經常抱怨睡眠品質不佳，而低劑量的美舒鬱則可以改變此現象；第二個好處是長期服用抗憂鬱劑並不會產生耐受性及成癮性，很多慢性失眠的患者不想長期吃安眠藥，但不吃藥又會睡不著，對此情況常常感到無可奈何！因為安眠藥一般而言只要服用超過三至四個月，即使規則服用醫生開立之劑量，也可能逐漸產生耐受性而需增加劑量來達到助眠的效果。很多人常突然停用安眠藥想嘗試可否自然入眠，卻因出現反彈性失眠或戒斷症狀，而從此對失眠感到害怕而不敢隨意亂停藥。新一代的安眠藥(例如使蒂諾斯)起初被認為不太容易成癮且較不影響記憶及白天精神，但臨床觀察發現對於有藥物濫用病史或人格障礙的病人一樣會成癮！有些女性或長年患者服用使蒂諾斯後，會出現半夜起來亂吃食物、亂打電話、遊走或開車出去的行為，但隔天卻完全記不起來！抗憂鬱劑治療失眠第三個好處是美舒鬱並沒有傳統三環類抗憂鬱劑的抗膽鹼副作用及對心臟之毒性。
除了可以充當安眠藥外，這個藥品另一個神奇的副作用就是...... 會導致異常勃起
http://forums.chinatimes.com/report/viagra/87051601.htm
最後，如果只是輕微失眠，也可以吃這種指是用藥。我們家賣得這款是抗組織胺，安全少副作用。
http://www.tma.tw/magazine/ShowRepID.asp?rep_id=1359
http://www.tma.tw/magazine/ShowRepID.asp?rep_id=2152
請問美舒鬱買的到嗎?還是得去給精神科才能拿到
美舒鬱是處方藥，還是需要醫師處方簽
*****
*****
非常實用的文章，謝謝提供，已點廣告表示支持 https://www.abodisc.com
可以自費買使蒂諾斯嗎?
不可以，這一定要處方簽
你好 什麼藥物能直接購買 讓自己入眠好睡 ？
老實講 馬上入睡的藥都需要醫師處方
洪凱駖藥師~ Solving a long-standing mystery about the desert’s rock art canvas Petroglyphs are carved in a material called rock varnish, the origins of which have been debated for years. Now, scientists argue it’s the result of bacteria and an adaptation that protects them from the desert sun’s harsh rays. By Nathan Collins 5923141600_1bc3f25867_k.jpg Rock art featuring human and animal forms and handprints Petroglyphs at Mesa Verde National Park, Colorado (Christine Fry & Peter Russo) Wander around a desert most anywhere in the world, and eventually you’ll notice dark-stained rocks, especially where the sun shines most brightly and water trickles down or dew gathers. In some spots, if you’re lucky, you might stumble upon ancient art – petroglyphs – carved into the stain. For years, however, researchers have understood more about the petroglyphs than the mysterious dark stain, called rock varnish, in which they were drawn. In particular, science has yet to come to a conclusion about where rock varnish, which is unusually rich in manganese, comes from. Now, scientists at the California Institute of Technology, the Department of Energy’s SLAC National Accelerator Laboratory and elsewhere think they have an answer. According to a recent paper in Proceedings of the National Academy of Sciences, rock varnish is left behind by microbial communities that use manganese to defend against the punishing desert sun. The mystery of rock varnish is old, said Usha Lingappa, a graduate student at Caltech and the study’s lead author. “Charles Darwin wrote about it, Alexander von Humboldt wrote about it,” she said, and there is a long-standing debate about whether it has a biological or inorganic origin. But, Lingappa said, she and her colleagues didn’t actually set out to understand where rock varnish comes from. Instead, they were interested in how microbial ecosystems in the desert interact with rock varnish. To do so, they deployed as many techniques as they could come up with: DNA sequencing, mineralogical analyses, electron microscopy, and – aided by Stanford Synchroton Radiation Lightsource (SSRL) scientist Samuel Webb – advanced X-ray spectroscopy methods that could map different kinds of manganese and other elements within samples of rock varnish. “By combining these different perspectives, maybe we could draw a picture of this ecosystem and understand it in new ways,” Lingappa said. “That’s where we started, and then we just stumbled into this hypothesis” for rock varnish formation. Among the team’s key observations was that, while manganese in desert dust is usually in particle form, it was deposited in more continuous layers in varnish, a fact revealed by X-ray spectroscopy methods at SSRL that can tell not only what chemical compounds make up a sample but also how they are distributed, on a microscopic scale, throughout the sample. That same analysis showed that the kinds of manganese compounds in varnish were the result of ongoing chemical cycles, rather than being left out in the sun for millennia. That information, combined with the prevalence of bacteria called Chroococcidiopsis that use manganese to combat the oxidative effects of the harsh desert sun, led Lingappa and her team to conclude that rock varnish was left behind by those bacteria. For his part, Webb said that he always enjoys a manganese project – “I’ve been a mangaphile for a while now” – and that this project arrived at the perfect time, given advances in X-ray spectroscopy at SSRL. Improvements in X-ray beam size allowed the researchers to get a finer-grained picture of rock varnish, he said, and other improvements ensured that they could get a good look at their samples without the risk of damaging them. “We’re always tinkering and fine-tuning things, and I think it was the right time for a project that maybe 5 or 10 years ago wouldn’t really have been feasible.” The research was supported by the National Science Foundation, the National Institutes of Health and the National Aeronautics and Space Administration. SSRL is a DOE Office of Science user facility. Citation: Usha F. Lingappa et al., Proceedings of the National Academy of Sciences, 22 June 2021 (10.1073/pnas.2025188118) For questions or comments, contact the SLAC Office of Communications at communications@slac.stanford.edu. SLAC is a vibrant multiprogram laboratory that explores how the universe works at the biggest, smallest and fastest scales and invents powerful tools used by scientists around the globe. With research spanning particle physics, astrophysics and cosmology, materials, chemistry, bio- and energy sciences and scientific computing, we help solve real-world problems and advance the interests of the nation. SLAC is operated by Stanford University for the U.S. Department of Energy’s Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States and is working to address some of the most pressing challenges of our time. X-ray Science X-ray Spectroscopy Stanford Synchrotron Radiation Lightsource (SSRL)
如有需要藥物請加賴vovo5577指名找阿Q我為你服務謝謝
有人想要安眠藥物可詢問我歡迎加我的賴討論brolamen