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
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 🤯
If it caused asterixis (throwback: did that mean it causes HE?
Gabapentin has confused me ever since
Admitting a non-#cirrhosis patient with gabapentin overdose as an intern, I saw asterixis
This 🤯
If it caused asterixis (throwback: did that mean it causes HE?
Gabapentin has confused me ever since
3/
Everything about gabapentin is🍌
What follows is no different
There once was a💡dream💡 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…🍌
Everything about gabapentin is🍌
What follows is no different
There once was a💡dream💡 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…🍌
4/
5 Gabapentin facts re: how it ⬆️🧠inhibitory tone
1⃣lipid soluble (crosses🩸/🧠barrier)
2⃣Binds voltage-gated Ca Channel
3⃣⬇️GABA & Glutamate release
(nb: Glu is excitatory)
4⃣Prob⬆️GABA concentration in🧠
5⃣⬆️Noradrenaline release, causing descending inhibition
5 Gabapentin facts re: how it ⬆️🧠inhibitory tone
1⃣lipid soluble (crosses🩸/🧠barrier)
2⃣Binds voltage-gated Ca Channel
3⃣⬇️GABA & Glutamate release
(nb: Glu is excitatory)
4⃣Prob⬆️GABA concentration in🧠
5⃣⬆️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
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)
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
aasldpubs.onlinelibrary.wiley.com. #livertwitter
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
aasldpubs.onlinelibrary.wiley.com. #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's when my friend, Jessica "Dr. ALD" Mellinger said:
"Did you know GabaP can be used for alcohol-use disorder?"
🤯
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's when my friend, Jessica "Dr. ALD" Mellinger said:
"Did you know GabaP can be used for alcohol-use disorder?"
🤯
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...
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
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
In multiple RCTs, gabapentin has been shown to reduce the rate of risky drinking
12/
To review
1⃣Gabapentin ⬇️glutamate & GABA signaling without binding GABA receptors
2⃣Glutamate & GABA play a role in alcohol use disorder (AUD) & in etoh-withdrawal physiology
3⃣Gabapentin may be useful for AUD
4⃣That's cool. But gabapentin is still super shady
To review
1⃣Gabapentin ⬇️glutamate & GABA signaling without binding GABA receptors
2⃣Glutamate & GABA play a role in alcohol use disorder (AUD) & in etoh-withdrawal physiology
3⃣Gabapentin may be useful for AUD
4⃣That's cool. But gabapentin is still super shady
/end
This concludes a #tweetorial on gabapentin. I hope you enjoyed!
🙏Thank you for reading 🙏
It has been a rollercoaster of emotion and rapidly changing opinions for me as I have tried to understand this🍌drug🍌
This concludes a #tweetorial on gabapentin. I hope you enjoyed!
🙏Thank you for reading 🙏
It has been a rollercoaster of emotion and rapidly changing opinions for me as I have tried to understand this🍌drug🍌
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