February 1, 2023

Ever wondered how a PPI (proton pump inhibitor) works? Well, wonder no more. Here’s the explainer with the what, how, why, side effects and history and pharmacology to boot (two advanced sections in the 2nd half). For reflux, dyspepsia, heartburn, GERD, GORD, curries and everything in between.

A ppi is a proton pump inhibitor you may know  it as omeprazole, lanzoprazole, pantoprazole   and anything else that’s ending in ‘zole’. it’s one  of the most commonly prescribed medications in   the world and it’s used to neutralize your stomach  acid. now if you didn’t know your stomach is full   of some pretty strong acid –

Hydrochloric acid  in fact and it helps to break down any food   that goes into it. you release about one and a  half liters of acid into your stomach every day so   fun fact a few people follow the alkaline diet  but that doesn’t work because your stomach just   that diet probably only works from about   here to here. never

Mind. so anyway ppis – why  do you need it? well you need it if you need   to neutralize stomach acid. now the most common  reasons a doctor might prescribe that drug is   ongoing indigestion, so a feeling of bloatedness   but it’s often tied into number two or three.  stomach and starts burning your throat. you might  

Have heard this is heartburn or gord or gerd, and  sometimes it can go quite high and that can cause   a cough. being overweight, smoking, drinking,  having spicy foods – that can make it worse.    so this is inflammation of your stomach lining.   it can be caused by booze, smoking, painkillers,  bacteria and even stress. now that

Inflammation   gets rid of the protective layer in your stomach  so your acid starts burning your stomach lining,   ulcers (ulcers are like those things when you   bite your lip) but if they get really bad they  can punch through your stomach and that can be   conditions where either the reflux has gotten so   bad

That it’s leading to a change in cell type in  your throat known as barrett’s oesophagus or other   ones where for whatever reason you’re secreting  too much acid. how does it work? well it neutralizes   your stomach acid don’t worry you can still digest  things because there’s still a bit of acid in   there and you also release

Other chemicals that  help you digest. now the way acid is secreted is   complicated but if you’re interested i’ll go into  that a bit later – but basically at a chemical level   hydrochloric acid is hcl – hydrogen and chloride.  these ions are released separately into the   stomach where they join up form the acid and start 

Digesting everything the h of hcl is hydrogen or   by itself a hydrogen ion that’s h-plus. a hydrogen  ion is also called a proton. now this doesn’t just   flow into the stomach it’s pumped into it. so a ppi – proton pump inhibitor – how does that work? well it   blocks the pump stopping the hydrogen getting into  the stomach and so

That stops your acid forming.   becomes activated by the acid and it irreversibly   binds to those pumps. at low doses it probably has  an effect for a couple of days, as the dose goes up   that might last for a bit longer. side effects – well there’s not many this is a pretty safe drug.   some people have nausea headaches,

Occasionally  rashes and you know they can talk to their doctor   about changing medications if that’s the case. very  rarely it’ll cause low sodium, but you’ll probably   know about that if that happens to you. as always  if you don’t feel right when you’re taking a drug   talk to your doctor. now onto the geeky stuff  so

Goodbye most of you but please do subscribe   to stick around here’s the history and the   pharmacology – that’s two sections which i’m putting  in because most people, even a lot of doctors, don’t   know where these drugs came from or what they  do to you. so the history. well in the late 1960s   a pharmaceutical company

Called hassle decided  to start a gi research division with the aim   of finding a drug to block stomach acid. in 1972  they began to strike a little bit of gold because   another company had found a compound which stopped  the secretion, but it was very toxic. this compound   had a thioamide group on it which is nasty stuff 

And was killing all the dogs they were testing on,   so the hassle guys got rid of that by locking it  in a chemical ring system. as with all science bit   of trial and error until they eventually hit a  winner – a compound called a benzimidazole – h123/26  – catchy name. and it stopped secretion. yeah!!  oh hang on a second, turns out

A hungarian company   had already discovered this and were using it to  treat tb, but our cunning team found a metabolite   of h123/26 which the hungarians hadn’t discovered.  hello timoprazole – it worked! yeah!! oh no, not quite.   it did cause some thyroid problems. but about the  same time scientists had discovered that h+,

K+ atpase pump   as the proton pump – remember that? and they   realized that timoprazole was blocking it. so  studying the action at the pump they could almost   compound they called h168/68 – even more catchy   celebrations! and it worked! over time that  chemical has been tweaked and twisted to form   they’re

All very much based on the same thing.   so how does it work in a bit more detail? well to  understand this we kind of need to understand how   acid is produced in your stomach. like all things  in your body it’s not simple it’s a glorious   medley of a lot of processes all coming together  and they come together around two

Main things.  cells of your stomach. so when you eat food, smell  food, taste it and see it it sends nerve signals   to get your digestive juices going. that’s done by  the vagus nerve, which stimulates a few things one   of which is your parietal cells. once food is in  your stomach it stretches it causing a bunch of  

Other receptors to fire and stimulate parietal  cells even more. starting at the beginning the   vagus nerve and a hormone called gastrin whack  into a cell that’s next to the parietal cells this   causes the release of histamine and more gastrin,  and these bind to receptors on the parietal cell.   activates protein kinases,

Which activates the pump!   but what goes through the pump? well an enzyme  called carbonic anhydrase causes carbon dioxide   that breaks down immediately into bicarbonate   and hydrogen ions or protons. now these protons  go to that pump and they’re pushed through   and as they get pushed through potassium comes the 

Other way a bit like a revolving door. that helps   the process a bit but basically this is still a  really energy rich thing that your body has to   do. meanwhile chlorine, which is banging around  anyway slips out through a chlorine channel and   to form glorious hydrochloric acid. voila!   now the ppi directly inhibits

The pump. as i said  before they’re inactive when you swallow them but   as they get close to the parietal cell membrane  they get protonated by the strong acid environment   that’s right next to the cell, so this activates  them and they covalently link irreversibly to   the proton pump and stop it working. and there 

You go ppis – awesome little drugs which stop   better after a curry. lots more drug explainers   you next time, like, subscribe and toodaloo!

Transcribed from video
What is a PPI and how does it WORK? – Omeprazole, Prilosec, Losec for GERD (proton pump inhibitors) By Stealth Health