Astral Codex Ten Podcast feed 2024年07月17日
Know Your Gabapentinoids
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加巴喷丁类药物,包括加巴喷丁和普瑞巴林,虽然最初设计为模拟神经递质GABA的作用,但后续研究发现它们作用于不同的靶点——钙通道的A2D亚单位。这两种药物被FDA批准使用,加巴喷丁自2004年以来已有仿制药,普瑞巴林虽然上月专利到期,但仿制药尚未上市。尽管普瑞巴林被视为延长专利的策略,但部分患者对其疗效赞不绝口。

🧪 加巴喷丁类药物结构与GABA相似,但作用于不同的靶点,即钙通道的A2D亚单位,这一发现改变了对其作用机制的理解。

🩺 加巴喷丁广泛用于治疗癫痫、神经性疼痛、酒精依赖、药物成瘾、瘙痒、不安腿综合征、睡眠障碍和焦虑等疾病,但其疗效与剂量范围宽泛,使用时需谨慎平衡效果与副作用。

💊 普瑞巴林被视为加巴喷丁的改良版,虽然其上市策略受到质疑,但部分患者称其为奇迹药物,对其疗效给予高度评价。

💰 普瑞巴林高昂的价格限制了其使用频率,但其仿制药的即将上市让医生和患者对其未来应用抱有期待。

The gabapentinoids are a class of drugs vaguely resembling the neurotransmitter GABA. Although they were developed to imitate GABA’s action, later research discovered they acted on a different target, the A2D subunit of calcium channels. Two gabapentinoids are approved by the FDA: gabapentin (Neurontin®) and pregabalin (Lyrica®).

Gabapentin has been generic since 2004. It’s commonly used for seizures, nerve pain, alcoholism, drug addiction, itching, restless legs, sleep disorders, and anxiety. It has an unusually wide dose range: guidelines suggest using anywhere between 100 mg and 3600 mg daily. Most doctors (including me) use it at the low end, where it’s pretty subtle (read: doesn’t usually work). At the high end, it can cause sedation, confusion, dependence, and addiction. I haven’t had much luck finding patients a dose that works well but doesn’t have these side effects, which is why I don’t use gabapentin much.

Pregabalin officially went generic last month, but isn’t available yet in generic form, so you’ll have to pay Pfizer $500 a month. On the face of things, pregabalin seems like another Big Pharma ploy to extend patents. The gabapentin patent was running out, so Pfizer synthesized a related molecule that did the same thing, hyped it up as the hot new thing, and charged 50x what gabapentin cost. This kind of thing is endemic in health care and should always be the default hypothesis. And a lot of scientists have analyzed pregabalin and said it’s definitely just doing the same thing gabapentin is.

But some of my anxiety patients swear by pregabalin. They call it a miracle drug. They can’t stop talking about how great it is. I can’t use it too often, because of the price, but I’m really excited about the upcoming generic version coming out so I can use it more often.

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加巴喷丁 普瑞巴林 药物专利 神经性疼痛治疗
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