1/
HOW does gabapentin work?
DOES gabapentin work?
WHY is gabapentin so shady?

Join me for a #tweetorial?

Keywords: Glutatmate, Asterixis, Alcohol-use disorder
#livertwitter #MedTwitter #meded

2/

Admitting a non- #cirrhosis patient with gabapentin overdose as an intern, I saw asterixis

This https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤯" title="Explodierender Kopf" aria-label="Emoji: Explodierender Kopf">

If it caused asterixis (throwback: https://twitter.com/ebtapper/status/1293647872290938880?s=20),">https://twitter.com/ebtapper/... did that mean it causes HE?

Gabapentin has confused me ever since

3/
Everything about gabapentin ishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🍌" title="Banane" aria-label="Emoji: Banane">
What follows is no different

There once was ahttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Elektrische Glühbirne" aria-label="Emoji: Elektrische Glühbirne">dreamhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="💡" title="Elektrische Glühbirne" aria-label="Emoji: Elektrische Glühbirne"> of using GABA signaling 2 prevent seizures. Yada yada yada, we made GABApentin. It approved in 1993!

Just one prob:
GABApentin doesnt bind GABA-receptors!

Like I said…https://abs.twimg.com/emoji/v2/... draggable="false" alt="🍌" title="Banane" aria-label="Emoji: Banane">

4/

5 Gabapentin facts re: how it https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">https://abs.twimg.com/emoji/v2/... draggable="false" alt="🧠" title="Gehirn" aria-label="Emoji: Gehirn">inhibitory tone

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">lipid soluble (crosseshttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🩸" title="Tropfen Blut" aria-label="Emoji: Tropfen Blut">/https://abs.twimg.com/emoji/v2/... draggable="false" alt="🧠" title="Gehirn" aria-label="Emoji: Gehirn">barrier)
https://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2">Binds voltage-gated Ca Channel
https://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3">https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">GABA & Glutamate release
(nb: Glu is excitatory)
https://abs.twimg.com/emoji/v2/... draggable="false" alt="4⃣" title="Tastenkappe Ziffer 4" aria-label="Emoji: Tastenkappe Ziffer 4">Probhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">GABA concentration inhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🧠" title="Gehirn" aria-label="Emoji: Gehirn">
https://abs.twimg.com/emoji/v2/... draggable="false" alt="5⃣" title="Tastenkappe Ziffer 5" aria-label="Emoji: Tastenkappe Ziffer 5">https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">Noradrenaline release, causing descending inhibition

5/

These gabapentin effects may reduce pain

So people prescribe it for pain... a lot

Problem number two...

The evidence for pain control is far from awesome

6/

Q: Why would people use so much gabapentin for pain when the evidence is lacking?

A: Pfizer systematically promoted off-label use, filling PubMed with biased results, burying negative studies. The FDA fined them $1 billion for this (& other issues)

7/

Suffice it to say, I have been suspicious of gabapentin for a long time. First the asterixis, then the shady marketing

We even found it was associated with incident hepatic encephalopathy! #cirrhosis
https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep4.1425#:~:text=Among%20166%2C192%20Medicare%20enrollees%20with,nonalcoholic%20fatty%20liver%20disease%20cirrhosis.">https://aasldpubs.onlinelibrary.wiley.com/doi/full/... #livertwitter

8/

I was done with gabapentin!

Then we found alcohol-related liver disease was becoming an epidemic, particularly of the young
We wanted 2 do more!

That& #39;s when my friend, Jessica "Dr. ALD" Mellinger said:

"Did you know GabaP can be used for alcohol-use disorder?"

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤯" title="Explodierender Kopf" aria-label="Emoji: Explodierender Kopf">

9/

It turns out that the neurocognitive effects of alcohol may be largely mediated by glutamate signaling

Glutamate also has a huge role in reward pathway signals

What medication reduces glutamate signaling?

You guessed it...

10/

It turns out that if you put an alcoholic drink in front of someone with alcohol-use disorder, gabapentin reduces their cravings

It also turns out that gabapentin treats alcohol withdrawal symptoms

11/

In multiple RCTs, gabapentin has been shown to reduce the rate of risky drinking

12/

To review

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1">Gabapentin https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">glutamate & GABA signaling without binding GABA receptors
https://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2">Glutamate & GABA play a role in alcohol use disorder (AUD) & in etoh-withdrawal physiology
https://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3">Gabapentin may be useful for AUD
https://abs.twimg.com/emoji/v2/... draggable="false" alt="4⃣" title="Tastenkappe Ziffer 4" aria-label="Emoji: Tastenkappe Ziffer 4">That& #39;s cool. But gabapentin is still super shady

/end

This concludes a #tweetorial on gabapentin. I hope you enjoyed!
https://abs.twimg.com/emoji/v2/... draggable="false" alt="🙏" title="Folded hands" aria-label="Emoji: Folded hands">Thank you for reading https://abs.twimg.com/emoji/v2/... draggable="false" alt="🙏" title="Folded hands" aria-label="Emoji: Folded hands">
It has been a rollercoaster of emotion and rapidly changing opinions for me as I have tried to understand thishttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🍌" title="Banane" aria-label="Emoji: Banane">drughttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🍌" title="Banane" aria-label="Emoji: Banane">