Spacing Doses of PPIs and H2 Blockers

Questions about spacing doses of PPIs and H2 blockers is one of those questions that gets asked to Dr. P over and over again by the Moms of our Facebook group.

A word from Jeffrey Phillips Pharm D:

One of the Moms wanted to know why not use PPI together with a medicine like Zantac, which is an H2 blocker. After all her Pharmacist and her GI doctor said it was ok to do this so is makes sence that she would say, "Wouldn't they know?".

It bothers me as a PharmD to hear this. So here is my Pharmacology lesson for those who are interested.

The answer is based on how both medicines work and how the acid secreting cells make acid. This is one of those items that most persons prescribing these medicines should know about (but as with many situations the understanding of the Pharmacology is often incomplete).

I am a Doctor of Pharmacy (Pharm.D.) and have spent 25 years working in acid reflux disease as well as being focused on infant and childhood acid reflux disease. I invented Zegerid which is a PPI medicine for treating acid reflux disease. I also invented the formulation that pharmacists compound for omeprazole as well as lansoprazole. I tell you this because sometimes you will get criticized by someone and they may say to you, "What are you thinking listening to somebody on the internet or Facebook". In other words they may try to make you feel like you are not able to determine what is valuable information and what is not.

So let's get back to the pharmacology (I don't want bore you all - but the use of knowledge is power). I will start with how the body makes stomach acid and I'll use infants as an example.

  1. The stomach is typically acidic with a pH of ~1 to 3 most of the time (remember that the lower the pH the more acidic and pH of 7 is neutral). If you give your infant some milk or formula (or most foods) the pH of the stomach will go up to above 4, typically to a pH of 4 to 5. Well the stomach has sensors in it that measure pH and when the pH rises that much towards neutral, the sensors are triggered and send a message to the acid secreting cell. These cells are called parietal cells and this message is sent by Histamine type 2 molecules (not Histamine type 2 blocker as that is the medicine to block the Histamine type 2 receptor). Have I lost you? Reading this page on acid & pH will greatly help understand this whole process discussed here and below.
  2. The Histamine type 2 molecules plug into the acid secreting cell on the outer surface of the cell into the Histamine type 2 receptor and this makes the acid secreting cell change on the inside to prepare to make acid (to return the pH to a lower value, like back down below pH 3, in the stomach). So, if you give an H2 receptor blocker (like Zantac or Axid or Pepcid) there will be a blocking of the ability of the acid-secreting cell to change to the "acid secreting state". This is important as you will see in a moment.
  3. Back to the acid secreting cell, remember that the Histamine-2 molecules had plugged into the outside of the acid-secreting cells and there were changes going on in the acid secreting cell as it was changing into the "acid-secreting state". When this change happens inside the cell there are little acid making pumps (proton pumps) that start to move to an area of the acid-secreting cell where the acid-secreting cell communicates with the stomach lining. These little pumps (proton pumps) actually make acid 
(H+ Cl- or HCl, hydrochloric acid) and then the acid escapes into that communication space between the acid-secreting cell and the stomach where it moves into the stomach. Thus making the pH of the stomach come back down into the more acidic pH range. VERY IMPORTANT: Medicines that block this part of acid secretion are called proton pump inhibitors (PPI). The secret (well it isn't a secret but some don't know this part of the pharmacology) is that PPI medicines can only block those little proton pumps that are trying to make acid (HCl).
  4. As more and more acid is made and released into the stomach the acid pH returns to 3 or less and this shuts off that same sensor in the stomach that had previously sent the signal to make acid. With me so far?
  5. Then why not give the H2 blocker medicine (like Zantac, ranitidine) along with the PPI medicine such as omeprazole, Prilosec? Wouldn't that make even more blocking of the acid from being made? You have already figured this out by now. The answer is NO. Remember that PPI medicines can only block the proton pumps that are in place to make acid (from storage - the whole change inside the cell I mentioned that happened because of the Histamine 2 molecule made it happen). 
So if you block the H2 receptor with an H2 blocker medicine (like Zantac) then the little pumps inside the acid secreting cell (called proton pumps) never have the ability to move into the proper place, and because of that, the PPI medicine (such as omeprazole) can't block the acid pumps because they never moved into the site where the PPI medicine needs them to be so that they can be blocked.

A lot of words but really simple.

So, if you want to use a PPI medicine (such as omeprazole) AND an H2 blocker medicine (such as Zantac) in the same day, then you have to let the H2 blocker medicine get out of the body before you give the PPI medicine or the H2 blocker medicine will prevent the PPI medicine from working. This is known as a drug interaction related to the mechanism of acton. After a dose of an H2 blocker it takes approximately 4 hrs for it to be out of the body of the infant. So, if you want to use them in the same day - you should separate them by 4 hours.

In reality, if you just give the correct amount of PPI medicine in one day then you don't need to add more medicines. When you start adding more medicines without need, this is called polypharmacy (good to read about). Optimize one medicine first then if there is a need you can consider the addition of another medicine.

This is basic pharmacology.

Disclaimer: Please review and discuss all treatment options with your doctor.

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