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Education | Consultancy | Training

18 Apr 2019

ECT4Health - Proton Pump Inhibitors not good long term


One of the commonest drug classes we see patients taking for reflux or Gastroesophageal Reflux Disease (GORD) is the proton pump inhibitor.  You know of these drugs as Esomeprazole and Pantoprazole, Omeprazole.  In fact, so common are these drugs, that they are listed in the top 10 most prescribed PBS medications in Australia.

Are they safe for long term use?  No.

Remember all drugs have costs and benefits; so if costs outweigh benefits, perhaps it’s time to wean.

One would think that being so popular and readily available, that they are safe, but this is sadly not the case for many Australians on this class of drug.  The adverse effects of these drugs (like many), are linked to a perfect storm I call the 4Ds.  Dose, duration, and drug/drug interaction (DDI) and diet.

First let’s look at the options for managing heart burn/reflux by understanding some very basic stomach physiology.

There’s three main players:
* Pepsinogen
* Gastrin
* Hydrochloric acid

Pepsinogen - This is a substance classified as a Zymogen or pro-enzyme (note the “ogen” suffix).  All “ogens” are enzymes that are dormant until they are activated by something. You’ve heard of Fibrinogen, and Plasminogen in the blood?  Well this is an ogen in the stomach.  More in a minute on Pepsinogen.

Gastrin - Secreted directly into your blood by G-Cells in your stomach and duodenum when gut receptors detect protein, calcium or stretch of your stomach.  Yeah!!  I know, who would have thought your stomach was an endocrine gland??!!  Gastrin acts systemically to stimulate your stomach’s parietal cells to make hydrochloric acid.

Hydrochloric Acid (HCl) - Also called gastric acid, this is a strong acid with a low pH of 1.5-2 that inhibits ingested fungus/bacteria— yep, remember that mouldy cheese and craft beer you had for s’mores last week!!  As acidity in your stomach rises (pH falls) this acts as a powerful stimulus to tighten the lower oesophageal sphincter (LOS), preventing any regurgitation/refluxing of gastric acid which, when entering up into your oesophagus, irritates the mucosa - inflames it and can ulcer it.  This causes the classic heart burn or reflux symptoms.  Burn baby burn!!  Yay for stomach acid.

Other than antimicrobial, LOS tightening functions, the other vital role of Hydrochloric acid is to convert that Pepsinogen (pro-enzyme) in to the active protein digesting enzyme called Pepsin.  Now Pepsin is the darling of protein digestion.  That steak, eggs, fish, tofu or beans you ate is getting broken down mechanically and chemically into tiny particles called amino acids.  This symphony of chemicals listed above is like an epic startup sequence for protein digestion and absorption.

So... where does that leave PPIs (those *prazole drugs)?

Ok... if you’re still with me, PPIs are prescribed for short term (3 - 6 weeks) inhibition of gastric acid production in the background of GORD or peptic ulcers.  They are safe short term, to inhibit acid production while the inflamed oesophagus or stomach lining is healing.  They do not fix the ulcer, and actually worsen GORD over time - read back to the bit about gastric acid being a trigger to tighten the LOS sphincter.  Inhibit acid production, and you don’t close that sphincter as well, allowing acid to reflux into the same oesophagus that is irritated and inflamed!!

Short term use.   These PPIs are for short term use while your gut is healing.  But what do we see as nurses?  We see people prescribed these drugs forever.  They fly under the radar and are rarely flagged for pharmacy review.

Imagine I gave you a drug that essentially stopped you digesting protein, calcium, vitamin B12 and magnesium; caused you more reflux and indirectly allows potentially harmful pathogens access to your lower GI to play gene splicing monopoly with your healthy gut flora?  You’d probably not be surprised that there would be some discourse hey?  Well you’d be right.  These drugs are not without the costs to health.  Perhaps the most sinister issue with them is the potential for Drug-Drug interactions (DDIs).

DDIs from PPIs (see what I did there?) are common.  Many drugs your patient takes rely on passage through the stomach with a predictable pH.  When altering gastric pH with PPIs, then the chemical dynamics change and alter absorption of all drugs the patient takes orally.  The effects are varied but generally fall into two categories.  Their drug may not be absorbed effectively, or conversely, it may be more absorbed than anticipated leading to toxicity.  Gastric motility can also be altered which further renders bioavailability of every oral drug as unpredictable.  Constipation or diarrhoea, malabsorption, dehydration, and altered gut flora balance opens a whole can of worms (well not actually-but eeeuuu!).

Look these drugs have their place for short term use.  To get a job done, but unlike antihypertensives, or chronic disease preventatives like COPD or HF meds, these drugs are not for the long term use.  Weaning is hard but well supported, and any GP that is up to date will embrace the discontinuation regimens.  If taking these drugs twice daily, a week to two weeks of step down protocols should be introduced.

BD meds down to daily for a week.
Then daily down to every second day.
Then half the dose second daily.

Using H2 blockers like Ranitadine for break through dyspepsia, and anti acids like Gaviscon or Mylanta for break through rebound pain is also toggled with a month of bland, non spicy, acid reduced food.  The stomach needs 3 weeks to 6 weeks to reset its gastrin signalling mechanism that the patient knocked off with long term PPIs.  The whole process is a painful one but long term gains like reduced risk of MI and Stroke, and electrolyte/protein absorption are undeniably important for longer term healthy gut.

GP or Gastro specialist needs to be on board, and like the Statin debates of the early 20teens, finding a doctor that is progressive and evidence based in their approach can sometimes be a challenge. So remember to tread lightly.

But really - PPIs have a role as a short term drug, not long term.