Sean Mackey, M.D., Ph.D.
speaker
373 appearances
1 recordings
1 series
first heard Apr 2025
last heard Apr 2025
Sean Mackey, M.D., Ph.D.’s voice in public audio — every appearance, attributed to the second.
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The beauty of Neurontin or Gabapentin and its cousin Pregabalin, which was introduced immediately after Gabapentin's patent ran out. Conveniently. Very conveniently. Both have the same mechanism of action. They work on the alpha-2-delta subunit of a calcium channel in the spinal cord, in the brain.
That's a little too jargon-y and technical, but think of them as agents that turn down the signals that are in the spinal cord being processed and in the brain. So they're really not impacting your nerve out here or in your leg. They can be very effective. The beauty of these two drugs is there's no lethal dose.
The only way they could kill the rats when they were studying it was to drown them in it. I used to say, or hit them over the head with the tablets. And I would tell a patient somewhat jokingly, the only way you can be hurt taking this drug is if you're struck by a truck that's carrying it. It's a little bit more nuanced than that because there are side effects.
You can fall asleep driving. I tell people, don't operate heavy machinery. Don't go dune buggy riding. Don't blah, blah, blah. There is, in elderly patients in particular, I warn them about falls because you can get a little unstable.
Well, it's more I see water retention. I see a little peripheral edema in both.
I don't know the data on the sleep architecture, and that would be something I'd be putting out to you or some of the sleep experts. I have taken it after surgery. I find that it makes me sedated. I don't find the quality of the sleep. Okay.
That's it. That's it. It could just simply be my experience. The truth is, I do tend to, when I dose it, I'll dose lower in the day. and then I'll wallop a little harder at night for the very reason. So let's imagine gabapentin maybe in the day 300, 300, 600 at night. And I'm trying to titrate that so that, one, it helps them sleep.
Because you brought up an incredibly important point, which is during the day, we've got all these modulatory things we can do around our pain. Distraction, for instance. Other coping strategies at night, you're just trying to get into this relaxed state. And that is the worst time for somebody with chronic pain. And so the gabapentin and sometimes other agents can help with that.
So yeah, I do use it to help people sleep. No lethal dose. Maxes out at around 900 to 1,000 milligrams at a dose because it's taken up by an active transport system in the small intestine. Once you take more than about 1,000 milligrams, the rest of it's just passed out your backside. Pre-gabalin is different.
It has what's called a linear kinetic profile, simply meaning the more you take, the more that gets in your system. So the only times I will typically switch somebody from a gabapentin if they're getting benefit is when they've maxed out the dose. They're getting benefit, but there's no point in giving them more. I'll switch to pre-gabalin where I can drive more into their system.
I'm using these for the most recalcitrant pain in general. So that's an important point. While I can speak to perioperative pain, acute pain, subacute pain, and chronic pain, Stanford, we tend to see, we're a tertiary referral center. I tend to see, we see people after they've seen everybody else.
There's various definitions. Some like to put a time frame on it, which I think many of us believe is a little artificial. It's not three months or six months. It is pain that persists beyond the expected time of tissue healing. So, it is nuanced. It's context-specific, meaning...
If you have an inguinal hernia repair or a prostatectomy, which should heal up pretty quickly and your pain should go away pretty quickly, but if you've got pain after a couple, few months, that's starting to get to that point where I'm a little worried something's going on from a chronic pain. But if you had a total knee replacement...
that is a massive, massive surgery and you're going to have pain for quite some time. So I wouldn't call chronicity for a total knee. Totally makes sense. Context specific. This gets into also some of the whole issue around opioid prescribing and these rigid timeframes for surgery and what have you, but persistence beyond the time of expected tissue healing.
These are credibly effective agents, not necessarily for their antidepressive properties. They frequently work through modulating a couple neurotransmitters, serotonin and norepinephrine, and to varying extent.
We find that the classic, what we refer to as SSRIs, the selective serotonin reuptake inhibitors, haven't been as effective for pain as the older dirty drugs of the tricyclic antidepressants. We call them dirty, which simply means they act at multiple receptors. They hit multiple systems.
So these tricyclics hit the serotonin and norepinephrine systems, and then they also happen to be pretty potent sodium channel blockers. Why the sodium channel blocking property is important is when we talked earlier about the peripheral nerves, one of the main drivers of an action potential is activity around the sodium channels. You block the sodium channels, the action potential stops.
Do you remember how much you gave me? Of? How much sodium?
Yeah, that's the thing. We all get comfortable with our top two or three of any class. My go-to is desipramine, nortriptyline, and amitriptyline. They're broken up into different categories based on mainly side effect profiles. After nortriptyline, what was it? Amitriptyline or alevin.
So Elavil's an older tricyclic that has a lot of histamine release, a lot of sedating properties. I would never give that to an older guy with a big prostate because he couldn't pee and he'll be very angry with me. I will never give that to a young woman who's looking to watch her weight because she's going to get the munchies and she's going to put on 10 or 20 pounds and she's going to hate me.
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