Most anti-reflux medications work by either neutralizing stomach acid or by preventing its production altogether. Below you will find descriptions as well as links to animations for each category of drug, explaining how each one works and what the advantages and disadvantages of these various medications are in terms of their efficacy and side effects.

 

Sodium bicarbonate
Calcium carbonate
Magnesium Hydroxide
Aluminum Hydroxide

What are antacids?

Antacids are chemical compounds that are able to raise the stomach pH above 3.5 in 10 minutes (see Acid and pH in the gastrointestinal tract )

How do antacids work?

Antacids neutralize gastric acid.
Gastric acid (hydrochloric acid or HCl) consists of hydrogen and chloride ions. It is the hydrogen ions that give acid its caustic, damaging properties. Antacids are able to attract and hold onto the hydrogen ions. Grabbing up the hydrogen makes the pH of the stomach less acidic.
Because antacids reduce excess acid, they alleviate symptoms of heartburn, help allow the natural healing process to take place in any damaged areas, and may serve as a protective coating against further damage. However, they are a short term solution because they do not maintain a reduced level of acidity in the stomach.

Administering antacids

• Antacids come in multiple forms including tablets, liquids, capsules, and lozenges.
  
• They are available without a prescription, but your doctor may give you specific instructions for giving them to your child.
  
• Antacids should be used only occasionally and short-term (less than 2 weeks).
  
• Three doses per day are all that should be given.
  
• They are best if used between doses of other treatments, 1 and 3 hours after a meal, to provide quick relief of symptoms such as heartburn.

Some antacid recommendations:

Maalox Quick Dissolve Chewable Extra Strength tablets:

• Wild berry has a good flavor
  
• Contains calcium carbonate (1000mg/tablet), effective for temporary relief of reflux symptoms
  
• for children under 12 months, dissolve ¼ tablet into water or milk
  
• for children 1-3 years, dissolve into water or milk or have child suck on ½ tablet
  
• children 4 and older can suck on ½ - ¾ tablet

Maalox Quick Dissolve Extra Strength with anti-gas:

• for the child who is having a lot of gas
  
• Contains calcium carbonate (1000mg/tablet), effective for temporary relief of reflux symptoms
  
• contains simethicone (60mg/tablet), to break up gas bubbles making them easier to pass
  
• dose as above

Mylanta Cherry Supreme flavored liquid

• a liquid form with good flavor
• one 5mL teaspoon contains calcium carbonate (400mg) and magnesium hydroxide (135mg), effective for temporary relief of reflux symptoms.
  
• recommended if your baby is having constipation or hard and compact stools
  
• for children under 12 months, ½ tsp in a bottle of milk
  
• for children 1-3 years, ¾ - 1 tsp in a bottle of milk or alone
  
• for children 4 and older, give 1 tsp in medicine cup/spoon

Interactions with other anti-reflux medications

Antacids should not be taken with:

• Delayed-release PPIs
  Antacids dissolve the protective enteric-coating that surrounds delayed-release PPIs, exposing the drug to the stomach acid, which will then destroy the drug.
• Sucralfate
  Sucralfate requires acid in order to be converted to its active form; by neutralizing the acid in the stomach, antacids inhibit this conversion.

A final word on antacids

• Some antacids have rapid onset, while others have more sustained action. Your doctor may combine antacids to take full advantage of the properties of the different types of antacid, as well as minimize adverse effects or antagonize side effects (like diarrhea and constipation)
• May delay absorption rate of other drugs
• May damage protective enteric-coating on some drugs
• Those with magnesium may have a laxative effect
• Those with aluminum may cause constipation
• Patients on a low-sodium diet must be cautious using antacids containing sodium bicarbonate
• Patients with lactose intolerance should be aware of antacids containing milk products

 

 

 

Ranitidine (Zantac®)
Famotidine (Pepcid®)
Cimetidine (Tagamet®)
Nizatidine (Axid®)

What are H₂ blockers?

H₂ blockers are histamine2-receptor antagonists that prevent stomach acid production from taking place.

How do H₂ blockers work?

H₂ blockers block the message that tells stomach acid production to begin. Acid is produced by parietal cells located in the stomach lining. These cells don’t secrete acid until they receive a signal to begin. That signal is delivered by a messenger hormone called histamine. Histamine communicates with the cell by attaching to contact points located on the cell surface called receptors. The H₂ blocker works by occupying the receptors so that histamine cannot bind and communicate to the parietal cell to start producing acid.

Administering H₂ blockers

• H₂ blockers come in different dosage forms, including tablets, capsules, liquids, and effervescent tablets.
  
• They are available over-the-counter (OTC) and by prescription.
  
• The recommended way to take H₂ blockers is about 1 hour before eating. That gives the drug time to be absorbed into the bloodstream and reach the parietal cells before histamine can (which would trigger acid production).

Interaction with other anti-reflux medications

H₂ blockers should not be taken with:

• PPIs
  H₂ blockers prevent PPIs from working if they are taken too closely. For this reason, H₂ blockers should not be given within 4 hours of giving a PPI.
  In-depth look: PPIs work by directly inactivating the acid-producing pumps in the parietal cells, but they can only have this effect if the pumps are actively secreting acid. Because H₂ blockers prevent the activation of pumps, they can actually inhibit the ability of a PPI medication to have its effect when they are given at the same time (together).  However, giving a PPI in the morning and at midday and then an H2 blocker at bedtime can allow these two classes of medicines to work together (since they are not in the bloodstream/body at the same time).
• Sucralfate
  Sucralfate requires acid to be converted to its active form. By neutralizing acid in the stomach, H₂ blockers inhibit this conversion. If sulcrafate is not converted to its active state, it will not adhere to and protect damaged areas.

A final word on H₂ blockers

• Tolerance to H₂ blockers can occur with prolonged administration; that is, the medication will no longer inhibit acid production, even if the dose is increased. Although your child may feel better at first, the symptoms will often return within one or two weeks, even after increasing the dosage.
• H₂ blockers inhibit only one stimulus of acid production. For example, H₂ won't block production stimulated by the nervous system (stress-induced acid production).

 

 

 

Lansoprazole (Prevacid®)
Esomeprazole (Nexium®)
Pantoprazole (Protonix®)
Rabeprazole (Aciphex®)
Omeprazole + buffer (Zegerid®)

What are PPIs?

Proton pump inhibitors (PPIs) are chemical compounds that irreversibly inactivate the pumps that produce stomach acid.

How do PPIs work?

PPIs work within the parietal cells of the stomach, the site of acid secretion by way of proton pumps on the cell surface. PPIs reach the parietal cells via the bloodstream and react with the pumps. This reaction completely inactivates the pumps, stopping acid secretion.
Unlike H₂ blockers, PPIs can stop acid production regardless of the source of the stimulus because they work against the pump itself rather than on the receptors involved in triggering acid production. The only way for more acid to be produced is for the body to make more acid pumps.

PPI protection

The chemical structure of PPIs makes them susceptible to degradation by acid, so when taken orally, they must be administered in dosage forms that will protect them from gastric acid.

Oral PPI medications are available in two forms to provide acid protection:

Delayed-release

in which the PPI is contained within enteric-coated granules that are resistant to stomach acid. This coating does not dissolve until the granules reach the more alkaline environment of the small intestine. Only then is the PPI released and absorbed into the bloodstream for delivery to the parietal cells. Note: if the enteric-coating is broken from chewing or crushing the granules, the PPI will be degraded by stomach acid and the medication will not be effective in shutting down acid production.

Immediate-release

in which the PPI is suspended in an alkaline buffer solution that can neutralize stomach acid, replacing the use of enteric-coating.
Zegerid is currently the only commercially available, FDA-approved, immediate-release PPI. Zegerid is a powder, which, when water is added, delivers omeprazole suspended in a solution of sodium bicarbonate. The sodium bicarbonate acts to neutralize stomach acid to protect the omeprazole as it passes through the stomach. Zegerid is an immediate release medication because without an enteric coating that must dissolve, the PPI can be absorbed into the bloodstream more rapidly.

 

The importance of an alkaline buffer in immediate-release PPI suspensions:

• protects the PPI from degradation while the drug is in suspension prior to administration.
• protects the PPI from degradation from the stomach acid after administration.
• acts as an antacid to neutralize the acid present in the stomach. This provides immediate relief and also allows the PPI to be absorbed earlier on (rather than waiting for the enteric-coating to dissolve in the small intestine)
• “turns on” the proton pumps, which must be in an active state in order for the PPI to work.

Administering PPIs

PPIs come in multiple forms, including tablets, capsules, and suspensions. Most PPIs require a prescription.
Zegerid powder for oral suspension is the only commercially available immediate-release suspension that is FDA-approved. It is helpful for pediatric use because it is a true suspension that contains no enteric-coated granules that are difficult for young children to ingest. Parents therefore don’t have to worry about their child chewing the granules, which would expose the PPI to stomach acid and reduce the effectiveness of the drug.

See Zegerid Preparation for instructions on preparing a 2mg/mL suspension from a 40mg packet of Zegerid.

The PPI Dosing Information page provides specific dosing information for your child. One thing to realize is that children metabolize PPI drugs faster than adults, and as such, they may require the drug to be given 2-3 times per day to make up for the rapid elimination.

For more information on the medical literature pertaining to pediatric dosing of PPIs, see Research.

Interaction with other anti-reflux medications

PPIs should not be taken with:

• H₂ blockers
  H₂ blockers will prevent PPIs from working if they are taken too close together. For this reason, H₂ blockers should not be given within 4 hours of giving a PPI.
  In-depth look: PPIs work by directly inactivating the acid- producing pumps in the parietal cells, but they can only have this effect if the pumps are actively secreting acid. Because
  H₂ blockers prevent the activation of pumps, they can actually inhibit the ability of a PPI medication to have its effect when they are given at the same time (together).  However, giving a PPI in the morning and at midday and then an H2 blocker at bedtime can allow these two classes of medicines to work together (since they are not in the bloodstream/body at the same time).
• Antacids
  Antacids dissolve the protective coating that surrounds delayed-release PPIs, making them susceptible to destruction by acid as they pass through the stomach.
• Sucralfate
  PPIs will prevent sucralfate from working because acid is required to convert sucralfate to its active form.

A final word on PPIs

• PPIs are highly effective in controlling acid production.
  
• They have a wide safety margin. Although a PPI must travel through the bloodstream to have its effect on the parietal cell, the medication has few side effects due to its high specificity for acting only on the proton pump (located on the parietal cell).
• Delayed-release PPIs should be taken on an empty stomach 30 minutes to 1 hour before a full meal.
  
• Omeprazole and lansoprazole are approved for pediatric use.
• PPIs are often under-dosed in children (see PPI Dosing Information). Because it has been found that children metabolize PPIs more quickly than adults, we recommended administering them 3 times a day for children under 2 years old.
  
• It is important to not chew or crush the enteric-coated granules, although this makes administration to young children difficult.

 

 

 

Metoclopramide (Reglan®)
Cisapride (Propulsid®) no longer available

What are pro-motility drugs?

Metoclopramide and cisapride are dopamine-receptor antagonists, so they work on the nerves that control peristalsis, the wavelike contractions that push food and fluids through the gastrointestinal tract, much like squeezing a tube of toothpaste from the bottom up.

How do pro-motility drugs work?

Pro-motility, or pro-kinetic, drugs increase the pace at which food passes through the stomach into the small intestine. More efficient movement of food out of the stomach reduces the pressure build-up that may lead to reflux of stomach contents back into the esophagus.

Administering pro-motility drugs

Cisapride is no longer available due to side effects (heart arrhythmia)
Metoclopramide comes as a tablet or syrup by prescription only.

A final word on pro-motility drugs

• The best available medical studies and reviews reveal that the currently available pro-motility medications produce low efficacy for resolving reflux. They generally get prescribed in children who have not obtained relief from a PPI. These so-called PPI “failures” are often simply because the PPI is not being dosed properly. Once the dose of the PPI drug is correctly adjusted for the age and weight of the child and the frequency of dose increased to accommodate the higher rate at which children appear to metabolize these medications (i.e., PPI given 2 to 3 times per day depending upon the age), there is generally significant benefit obtained, and the use of pro-motility drugs becomes unnecessary.
  
• Potentially serious side effects:
  Cisapride has caused fatal heart arrhythmia in children as noted in an FDA warning in 2000, and is therefore no longer available.
  Metoclopramide has been known to cause irritability and tiredness and also induce a seizure-like incidents called acute dystonic reactions (see also blood/brain barrier);

 

 

 

Carafate®

What is sucralfate?

An aluminum-containing sticky sugar that acts as an ulcer-adherent paste, binding to open sores in the lining of the esophagus, stomach, and small intestine. Think of it as a Band-Aid specifically for ulcers.

How does sucralfate work?

Sucralfate offers local protection specifically for ulcers. It requires the presence of stomach acid to turn it into a paste that will bind to the ulcer. The paste helps promote healing by preventing more acid from seeping into the ulcer.

Administering sucralfate

Sucralfate comes as a tablet or suspension by prescription only.

Interaction with other anti-reflux medications

Sucralfate should not be taken with antacids, H₂ blockers, or PPIs. These drugs eliminate the acid that sucralfate needs in order to be converted to an active state.

A final word on sucralfate

• Sucralfate is effective in treating ulcers resulting from reflux, but cannot control or inhibit reflux itself.
  
• It may lower the absorption rate of other drugs
  
• Patients generally experience few side effects because sucralfate acts topically and is minimally absorbed into the bloodstream.
  
• The small amount of aluminum that is absorbed into the body may be a problem for patients with impaired renal function, especially if also taking aluminum-containing antacids.