Thread by @RashidLui, A #tweetorial on proton pump inhibitors (PPIs) Just for fun, which drug [...]

A #tweetorial on proton pump inhibitors (PPIs)

Just for fun, which drug class is archetypal of a gastroenterologist?

https://abs.twimg.com/emoji/v2/... draggable="false" alt="😉" title="Zwinkerndes Gesicht" aria-label="Emoji: Zwinkerndes Gesicht">

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PPIs would be my pick!

The advent of these potent and effective acid suppression medications led to a paradigm shift in the mx of many GI conditions

The market for PPIs is MASSIVE! Just the projected 5 year growth from 2018 - 2023 estimated to be $3.24 billion!

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So how do #PPIs work?

A reminder on physiology: this class of drug acts on the gastric parietal cells by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, aka the gastric proton pump), hence the elegant name

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Do they work? YES THEY DO!

They are great meds and essential for:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="1⃣" title="Tastenkappe Ziffer 1" aria-label="Emoji: Tastenkappe Ziffer 1"> Erosive esophagitis / Barrett& #39;s

https://abs.twimg.com/emoji/v2/... draggable="false" alt="2⃣" title="Tastenkappe Ziffer 2" aria-label="Emoji: Tastenkappe Ziffer 2"> Peptic ulcer / prophylaxis for pts taking NSAIDs/aspirin / ZE

https://abs.twimg.com/emoji/v2/... draggable="false" alt="3⃣" title="Tastenkappe Ziffer 3" aria-label="Emoji: Tastenkappe Ziffer 3"> H. pylori eradication

They are also prescribed for symptoms such as non-erosive reflux +/- dyspepsia

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The AspECT trial in @TheLancet showed that a chemoprevention strategy of aspirin + high dose #PPI offered the best event-free survival in patients with Barrett& #39;s

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)31388-6/fulltext">https://www.thelancet.com/journals/...

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Acute treatment of peptic ulcers has been covered in a previous thread on #UGIB https://twitter.com/RashidLui/status/1383817746010435592?s=20">https://twitter.com/RashidLui...

https://twitter.com/RashidLui/status/1383817746010435592?s=20

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As for prophylaxis, our Dean Prof @FrancisKLChan @CUHKMedicine led a RCT in @NEJM of pts with Hx of #UGIB + H pylori infection + low dose aspirin or NSAIDs, showing that prophylaxis with PPI is better than eradication alone in preventing recurrent bleeding for NSAIDs

8/
How about H pylori infection?
From the latest Maastricht V/Florence, Toronto & AP consensus, most if not all eradication regimens contain PPIs

https://gut.bmj.com/content/66/1/6

https://gut.bmj.com/content/6... href=" https://www.sciencedirect.com/science/article/abs/pii/S0016508516301081

https://www.sciencedirect.com/science/a... href=" https://onlinelibrary.wiley.com/doi/full/10.1111/j.1440-1746.2009.05982.x">https://onlinelibrary.wiley.com/doi/full/...

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PPIs also work for certain conditions to relief symptoms such as reflux in the absence of esophagitis +/- dyspepsia

This great tweet on the NNT for esophageal symptoms highlights that the stronger the indication, the more effective PPIs are https://twitter.com/EsophagusDoc/status/1388141322632974342?s=20">https://twitter.com/Esophagus...

https://twitter.com/EsophagusDoc/status/1388141322632974342?s=20

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So PPIs are great, but are they safe?

Being one of the most frequently prescribed

https://abs.twimg.com/emoji/v2/... draggable="false" alt="💊" title="Tablette" aria-label="Emoji: Tablette">around the

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🌏" title="Asien-Australien auf dem Globus" aria-label="Emoji: Asien-Australien auf dem Globus">, my take is that PPIs are largely safe

The problem actually stems from its relative safety. Many a time they are prescribed far too carefree and liberally

A discussion below:

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These are some of the reported adverse events associated with long term PPI use with their proposed mechanisms from a great review by Vaezi et al. @AGA_Gastro @AmerGastroAssn

https://pubmed.ncbi.nlm.nih.gov/28528705/ ">https://pubmed.ncbi.nlm.nih.gov/28528705/...

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This is all very scary, but what are the effect sizes?

Another excellent review by @UofT_GI_Head in @AmJGastro @AmCollegeGastro summarizes some of the recent estimates
- Enteric infections OR 2.55
- Other reported associations effect size < 2

https://pubmed.ncbi.nlm.nih.gov/29557943/ ">https://pubmed.ncbi.nlm.nih.gov/29557943/...

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@UofT_GI_Head also did a robust study that refuted the causal association between PPI use and fractures with no differences shown using BMD, markers of bone metabolism or measures of bone strength for PPI users

https://pubmed.ncbi.nlm.nih.gov/27845341/ ">https://pubmed.ncbi.nlm.nih.gov/27845341/...

$13/ @UofT_GI_Head also did a robust study that refuted the causal association between PPI use and fractures with no differences shown using BMD, markers of bone metabolism or measures of bone strength for PPI users https://pubmed.ncbi.nlm.nih.gov/27845341/...$

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Recently, several observational studies have reported a

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">risk of stomach cancer in long term PPI users, summarized expertly here:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">likely limited to pts with current or past Hx of HP

https://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">probably already had underlying precancerous lesions

https://pubmed.ncbi.nlm.nih.gov/30886648/ ">https://pubmed.ncbi.nlm.nih.gov/30886648/...

14/Recently, several observational studies have reported ahttps://abs.twimg.com/emoji/v2/... draggable=

risk of stomach cancer in long term PPI users, summarized expertly here:https://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">likely limited to pts with current or past Hx of HPhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">probably already had underlying precancerous lesions https://pubmed.ncbi.nlm.nih.gov/30886648/..." title="14/Recently, several observational studies have reported ahttps://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">risk of stomach cancer in long term PPI users, summarized expertly here:https://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">likely limited to pts with current or past Hx of HPhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="📌" title="Reißzwecke" aria-label="Emoji: Reißzwecke">probably already had underlying precancerous lesions https://pubmed.ncbi.nlm.nih.gov/30886648/..." class="img-responsive" style="max-width:100%;"/>

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Last but not least, the potential for drug-drug interactions (DDI)

Clopidogrel (prodrug)

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">cytochrome P450 2C19

https://abs.twimg.com/emoji/v2/... draggable="false" alt="➡️" title="Pfeil nach rechts" aria-label="Emoji: Pfeil nach rechts">active metabolite

But PPIs may interfere with this which led to FDA drug label change for clopidogrel

(dex)lansoprazole & pantoprazole have less effect on this

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A brief recap:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="✅" title="Fettes weißes Häkchen" aria-label="Emoji: Fettes weißes Häkchen">PPIs are great, effective and largely safe!

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚠️" title="Warnsignal" aria-label="Emoji: Warnsignal">Though there are some safety signals
- Infections: enteric, C. difficile, pneumonia
- GI: fundic gland polyps,

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬆️" title="Pfeil nach oben" aria-label="Emoji: Pfeil nach oben">CA stomach
- Micronutrient

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">
- Dementia
- Renal failure
- Drug-drug interactions with clopidogrel

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We should stop PPIs if not indicated/helping!

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🦪" title="Auster" aria-label="Emoji: Auster">from @UofT_GI_Head on deprescribing PPIs:

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔭" title="Teleskop" aria-label="Emoji: Teleskop">look out for rebound gastric acid hypersecretion

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🧠" title="Gehirn" aria-label="Emoji: Gehirn">mindful of rebound symptoms

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🗓️" title="Spiralkalenderblatt" aria-label="Emoji: Spiralkalenderblatt">take PPIs every other day for 2 weeks, 2x/week for 2 weeks, then stop https://pubmed.ncbi.nlm.nih.gov/29557943/ ">https://pubmed.ncbi.nlm.nih.gov/29557943/...

Discontinuing Long-Term PPI Therapy: Why, With Whom, and How? - PubMed

Proton pump inhibitors (PPIs) are among the most widely used class of drugs prescribed over the long term in all of clinical medicine with 8-10% of ambulatory adults have been prescribed a PPI in the...

https://pubmed.ncbi.nlm.nih.gov/29557943/

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In some circumstances H2RA can perform quite well too

Though pts on low-dose aspirin (LDA) + PPI had a slightly lower proportion of recurrent bleeding or ulcer compared with H2RA this was not statistically significant in this study

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🤔" title="Denkendes Gesicht" aria-label="Emoji: Denkendes Gesicht">Reasonable to switch to LDA + H2RA?

18/In some circumstances H2RA can perform quite well too Though pts on low-dose aspirin (LDA) + PPI had a slightly lower proportion of recurrent bleeding or ulcer compared with H2RA this was not statistically significant in this studyhttps://abs.twimg.com/emoji/v2/... draggable=

Reasonable to switch to LDA + H2RA?" title="18/In some circumstances H2RA can perform quite well too Though pts on low-dose aspirin (LDA) + PPI had a slightly lower proportion of recurrent bleeding or ulcer compared with H2RA this was not statistically significant in this studyhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🤔" title="Denkendes Gesicht" aria-label="Emoji: Denkendes Gesicht">Reasonable to switch to LDA + H2RA?" class="img-responsive" style="max-width:100%;"/>

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To conclude, good practice when prescribing PPIs:
- Discuss on indications and potential SEs
-

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚖️" title="Waage" aria-label="Emoji: Waage">risks and benefits
- Consider

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🔁" title="Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn" aria-label="Emoji: Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn">acid suppressants
-

https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">possible dose to control symptoms
-

https://abs.twimg.com/emoji/v2/... draggable="false" alt="🛑" title="Stoppzeichen" aria-label="Emoji: Stoppzeichen">Deprescribe PPIs, not just abruptly stop them

P.S great algorithm by @grepmeded

19/To conclude, good practice when prescribing PPIs:- Discuss on indications and potential SEs- https://abs.twimg.com/emoji/v2/... draggable=

risks and benefits- Considerhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🔁" title="Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn" aria-label="Emoji: Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn">acid suppressants- https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">possible dose to control symptoms- https://abs.twimg.com/emoji/v2/... draggable="false" alt="🛑" title="Stoppzeichen" aria-label="Emoji: Stoppzeichen">Deprescribe PPIs, not just abruptly stop themP.S great algorithm by @grepmeded" title="19/To conclude, good practice when prescribing PPIs:- Discuss on indications and potential SEs- https://abs.twimg.com/emoji/v2/... draggable="false" alt="⚖️" title="Waage" aria-label="Emoji: Waage">risks and benefits- Considerhttps://abs.twimg.com/emoji/v2/... draggable="false" alt="🔁" title="Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn" aria-label="Emoji: Nach rechts und links zeigende Pfeile in offenem Kreis im Uhrzeigersinn">acid suppressants- https://abs.twimg.com/emoji/v2/... draggable="false" alt="⬇️" title="Pfeil nach unten" aria-label="Emoji: Pfeil nach unten">possible dose to control symptoms- https://abs.twimg.com/emoji/v2/... draggable="false" alt="🛑" title="Stoppzeichen" aria-label="Emoji: Stoppzeichen">Deprescribe PPIs, not just abruptly stop themP.S great algorithm by @grepmeded" class="img-responsive" style="max-width:100%;"/>

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I had a great time preparing this and I hope you enjoyed this thread too! Don& #39;t be shy to share/re-tweet

https://abs.twimg.com/emoji/v2/... draggable="false" alt="😉" title="Zwinkerndes Gesicht" aria-label="Emoji: Zwinkerndes Gesicht">!

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