Acid reducing medications

Definitions & Key takeaways

Acid-reducing medications are a type of drugs that work to reduce the amount of acid in a person's stomach. There are three main groups of acid-reducing medications. The most common type is called a proton pump inhibitor (PPI). This type of medication inhibits the enzyme called H, K-ATPase, which blocks gastric acid secretion by parietal cells of the stomach. PPIs include drugs like omeprazole, esomeprazole, and pantoprazole.

The second group consists of H2 receptor blockers. H2 receptor blockers work by blocking histamine H2 receptors located on parietal cells of the stomach. This in turn inhibits the release of gastric acid. Examples of H2 receptor blockers include cimetidine, famotidine, and nizatidine. The last group consists of antacids, which work by neutralizing stomach acid that's already been produced. Examples of antacids include magnesium trisilicate and aluminum hydroxide.

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Introduction0:00–0:25

Acid reducing medications include antacids that directly lower the acidity of stomach contents, and antisecretory medications that act on parietal cells in the stomach to decrease acid secretion.
They are used to treat conditions like gastroesophageal reflux disorder and peptic ulcer disease by decreasing the acidity of the stomach and allowing the epithelial linings to heal.

Physiology0:25–2:27

Now, the stomach is composed of four regions: the cardia, the fundus, the body, and the pyloric antrum. There’s also a pyloric sphincter, or valve, at the end of the stomach, which closes while eating, keeping food inside for the stomach to digest.
The epithelial layer of the stomach contains different gastric glands which secrete a variety of substances. Starting with the cardia, it contains mostly foveolar cells that secrete a protective mucus, which is mostly made up of water and glycoproteins.
The fundus and the body contain both the parietal cells and enterochromaffin-like cells, and the antrum and pyloric areas contain G-cells.
Now gastric acid is mainly composed of HCl, or hydrochloric acid, which is mainly secreted by the parietal cells. Parietal cells have M3, CCK2, and H2 membrane receptors, which modulate their secretory behavior.
When food enters the stomach, it causes the stomach walls to expand, which leads to the activation of these receptors. First, stomach expansion causes the branches of the vagus nerve that innervates the stomach to release acetylcholine, which activates M3 receptors.
Next, the G cells in the antrum of the stomach release gastrin, which activate the CCK2 receptors. Gastrin and acetylcholine activate the enterochromaffin-like cells, which release histamine, that then activates H2 receptors.
Activation of M3, CCK2, and H2 receptors increases the conversion of H20 and CO2 to H+ and HCO3- by carbonic anhydrase. The H+ is then pumped out of the cell and into the stomach via the H+/K+-ATPase pump.
These H+ ions combine with Cl- ions to form hydrochloric acid and decrease the pH in the stomach. Normally, the stomach is protected from the acidic environment by the mucus secreted by foveolar cells.
However, if there’s an imbalance between mucus and acid secretion, like in Zollinger-Ellison syndrome, which is caused by a gastrin secreting tumor, it could lead to damage of the stomach.

Pathology2:27–3:07

This could manifest as chronic gastritis and gastric, or peptic ulcers. Now, in the esophagus, the lower esophageal sphincter prevents most of the gastric acid from coming back up when the stomach is full or when you’re laying down.
If this sphincter is loose, the acid could reflux into the lower esophagus and erode the esophageal lining. This is called GERD, or gastroesophageal reflux disease, most commonly known as heartburn.
One way to mitigate the harmful effects of gastrin in these disorders is to decrease its acidity through medications. Let’s start with the H2 receptor antagonists like cimetidine, raNITIdine, famotidine, and nizatidine.

H2 Receptor Antagonists3:07–6:01

H2 antagonists end up with the suffix -tidine, so remember, they enable you t(w)o dine! These medications are competitive, reversible antagonists of H2 receptors, meaning they bind to these receptors so histamine can’t.
These medications are able to decrease night time and food stimulated acid secretion by over 90%. They generally take effect within an hour of ingestion and last for about 12 hours, so they can be taken one hour before meals or before bedtime, if taken once a day.
They are generally given orally, but intramuscular and IV formulas are available. Now, common indications of H2 receptor antagonists include peptic ulcers, prevention of ulcers and stress ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome, which is a rare condition caused by gastrin-secreting tumors.
But, since they are less effective than proton pump inhibitors (PPIs), they are often classified as second-line treatment.
Generally, H2 antagonists are safe medications, so side effects are rare. But, if they occur, they typically include headache, fatigue, myalgias, diarrhea, and constipation.
Now, cimetidine is a strong inhibitor of cytochrome P450 enzymes in the liver. These enzymes are responsible for the metabolism of a variety of medications and toxins in our body.
So, if taken with other medications like benzodiazepines or warfarin, cimetidine could reduce their rate of elimination and cause them to build up in the body.
Cimetidine also has anti-androgenic effects and could cause gynecomastia, sexual dysfunctions like decreased libido, and loss of hair, or alopecia.
These side effects are reversible and they typically resolve over time once the medication is discontinued. Since it crosses the blood brain barrier, it could also cause confusion and dizziness.
In kidneys, cimetidine and raNITIdine compete with creatinine for renal tubular secretion. This way, they can decrease renal excretion of creatinine and increase serum creatinine levels; therefore, individuals with renal impairment require dose reduction!
Finally, H2 antagonists can cross the placenta. But, even though there are no harmful effects for a fetus, they should be avoided during pregnancy and breastfeeding.
If necessary, the preferred medication during pregnancy is raNITIdine; and during breastfeeding is famotidine. Next we have the proton pump inhibitors, or PPIs, which include oral medications like omeprazole, lansoprazole, dexlansoprazole, and medications available in IV, like pantoprazole and esomeprazole.

Proton Pump Inhibitors6:01–8:54

The oral forms of these medications are absorbed in the small intestine in their inactive form and get metabolized in the liver.
Next, they travel through the blood to the parietal cells where the acidic environment helps protonate them so they become fully active.
These activated PPIs irreversibly bind and inhibit the H+/K+-ATPase, or proton pumps, found within the parietal cells. Since the proton pump is the terminal step in acid secretion, proton pump inhibitors are better at inhibiting acid secretion than H2 histamine receptor antagonists, with a decrease of up to 99% of gastric acid secretions.
Because of this, they are more useful for the treatment of peptic ulcers, gastroesophageal reflux disease (GERD), and Zollinger-Ellison syndrome.
On the flip side, they are equally effective in the prevention of ulcers. Furthermore, they have a weak antibacterial effect against the peptic ulcer causing Helicobacter Pylori, so they are used in combination with antibiotics like amoxicillin, clarithromycin, or metronidazole.
It takes 3-4 days for proton pump inhibitors to decrease stomach acidity, and they remain effective for 2-3 days. With continual daily dosages, an increased antisecretory effect can be achieved for up to 5 days.
Side effects of proton pump inhibitors are uncommon, but can include gastrointestinal disturbance such as nausea, abdominal pain, and diarrhea.
Also, prolonged acid suppression can decrease the absorption of iron, calcium, magnesium, and vitamin B12, or cobalamin.
When the gastric juices are less acidic, it also allows for more ingested pathogens, like Clostridioides difficile, to survive and invade the GI tract.
Therefore, individuals treated with PPIs are more susceptible to Clostridioides difficile infection; but, they are also associated with an increased risk of pneumonia.
Other side effects include headaches, rashes, and osteoporosis. Now, as far as drug interactions go, this change in the gastric pH can reduce the absorption of certain medications like digoxin and ketoconazole.
Now, omeprazole is an inhibitor of cytochrome P450 enzymes in the liver. So, if taken with other medications like warfarin, it can reduce their rate of elimination and cause them to build up in the body.
Finally, since omeprazole inhibits the enzyme CYP2C19, it can reduce the activation of the antiplatelet medication clopidogrel.
Finally, we have the antacids which are weak bases like aluminum hydroxide and magnesium hydroxide. These two medications are not well absorbed in the GI tract so once they get to the stomach, they can neutralize some of the acidity by binding to H+.

Antacids8:54–11:18

In general, they are less effective in raising the pH of gastric acid when compared to H2 receptor antagonists and PPIs, and are mainly used for symptomatic relief in GERD.
Antacids also include calcium carbonate and sodium bicarbonate, but these medications are less popular since they are well absorbed from the GI tract and associated with severe systemic side effects, such as milk-alkali syndrome.
This syndrome is associated with metabolic alkalosis, hypercalcemia, and renal insufficiency. For side effects, aluminum hydroxide inhibits smooth muscle contraction in the GI tract, leading to constipation.
Magnesium hydroxide on the other hand, works as a laxative by drawing water from surrounding tissue, leading to diarrhea.
In rare cases, this could also lead to hypotension. Now, in healthy individuals, absorption of small amounts of aluminum and magnesium is not associated with serious side effects; but in individuals with renal insufficiency, they can accumulate and cause serious side effects.
Moreover, aluminum hydroxide can cause hypophosphatemia, proximal muscle weakness, osteoporosis, and even seizures; while magnesium hydroxide can cause hypermagnesemia, hyporeflexia, and cardiac arrest.
Finally, all antacids can cause hypokalemia. Now, as far as drug interactions go, antacids can affect absorption, bioavailability, and urinary excretion of other medications, primarily by changing gastric and urinary pH.
Moreover, they can increase oral absorption of medications that are weak bases, such as quinidine; and decrease the oral absorption of medications that are weak acids, such as warfarin.
Also, antacids can chelate other medications in the GI tract, thereby forming complexes that are not absorbable. This is especially common with medications such as tetracyclines.
Finally, antacids can delay gastric emptying.Now, we want to make a simple and fun mnemonic that’ll help you efficiently memorize and retain all these pharm facts!
The H2 receptor antagonists that ends in “-tidine” will be represented by a fancy man with a black bowtie carrying his dinner under a plate cover.

Memory Palace11:18–13:55

When he opens it, there’s a live snake going “hissss” for histamine. He’s got blocks of cement on his feet to represent cimetidine, and he’s crushing a poor chrome colored cell, to help you remember the cytochrome P450 inhibition.
Cimetidine also has anti androgenic side effects, so let’s have him crush a ♂ symbol under his other foot. This medication also causes decreased renal secretion of creatinine.
So let’s have a bunch of tiny crates surrounding him to represent a creatinine build up in the blood. Next up are the proton pump inhibitors, so let’s have a gas pump, where the hose is tied into a pretzel shape since these drugs end in “-prazole,” like omeprazole and esomeprazole.
Waiting to refuel, is a zeppelin for Zollinger-Ellison syndrome, and a helicopter piloted by a bacteria for helicobacter pylori.
For side effects, let’s put a dusty closet full of bacteria, for clostridioides difficile infection, next to the gas pump.
On the ground next to it are the things that do not get absorbed by the GI, so we have a bottle of milk for calcium, some half eaten cobbler for cobalamin, a dumbbell for iron, and a magnet for magnesium.
Omeprazole is also a CYP450 inhibitor so let’s have a chrome colored cell om-nom-noming the pretzel shaped hose. Speaking of magnets, let’s look at the antacids.
Let’s have a metal outhouse for these drugs, since they both contain metal. Now, magnesium hydroxide is a laxative, so let’s put a giant magnet on top of the toilet in the outhouse.
Aluminum hydroxide on the other hand, causes constipation so let’s have a roll of aluminum foil outside. This medication can cause osteoporosis, so someone even made a bone out of the aluminum foil but it’s not as strong as a real bone.
For the less popular antacids, we have calcium carbonate, represented by a glass of milk that’s carbonated and bubbling, and sodium bicarbonate, a container of salt and baking soda.
These can cause milk-alkali syndrome so we can put a cow licking a giant alkaline battery and getting zapped! The cow kicks behind it and knocks over a bottle of various pills to help you remember that these antacids will interfere with the absorption, bioavailability and renal excretion of other medications.
All right, as a quick recap… Antacids are weak bases that neutralize the acids in the stomach. Antisecretory medications like H2 receptor antagonists and proton pump inhibitors act on the parietal cells to decrease H+ secretion.
All 3 types of medication reduce the acidity in the stomach, which help treat or relieve the symptoms of peptic and gastric ulcers, gastritis, and GERD.
But wait, there's more: Here's a mind map with all of the mnemonics from the video. Go ahead and pause the video so you can test yourself to see what you remember.

Review13:55–14:22

Stay tuned for the answers at the end. pump inhibitors act on the parietal cells to decrease hydrogen ion secretion All three types of medication reduce the acidity in the stomach which helped treat or relieve the symptoms of peptic and gastric ulcers gastritis and guard but wait there's more here's a mind map with all the pneumonic from the video go ahead and pause the video so you can test yourself to see what you remember stay

Mind Map14:22–14:32