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
