What is the difference between antacids, H2 receptor blockers and proton pump inhibitors❓❓❓

Gastrointestinal diseases are common diseases in daily life, and there are many types of treatment drugs, such as gastric acid secretion inhibitors, antacids, gastric mucosal protective drugs, and gastrointestinal motility drugs. They have their own characteristics, different mechanisms of action, indications and usage. Therefore, we must learn to choose more accurately and use drugs rationally according to the characteristics of stomach diseases. Gastric acid secretion inhibitors and antacids are two drugs that are frequently used in digestive tract diseases. Here we briefly describe the differences in their pharmacological mechanisms, indications, usage and dosage, adverse reactions and precautions.

1. Pharmacological mechanisms

Gastric acid secretion inhibitors

    H₂ antagonist:

• It can block H₂ receptors of parietal cells. It inhibits basic gastric acid and nocturnal gastric acid secretion. It also inhibits gastric acid secretion caused by gastrin and M receptor agonists. Studies have shown that H₂ antagonist has a significant inhibitory effect on gastric acid secretion at night, but it has a poor control effect on gastric acid secretion during the day.
• Commonly used drugs: cimetidine, famotidine, ranitidine.
•  Acid suppression strength: famotidine > ranitidine > cimetidine.

    Proton pump inhibitor (PPI)

• It is an H⁺/K⁺-ATPase inhibitor that can inhibit central or peripheral gastric acid secretion. It can effectively inhibit basic gastric acid secretion or various forms of stress-induced gastric acid secretion.
• Commonly used drugs: Esomeprazole, Lansoprazole, Omeprazole, Pantoprazole, Rabeprazole.
• Acid suppression strength: esomeprazole > rabeprazole > pantoprazole > lansoprazole and omeprazole.

Antacids

• They are weakly alkaline substances, which directly neutralize gastric acid in the stomach after oral administration and increase the pH of the gastric juice to reduce the activity of pepsin (when the pH of the gastric juice is 1.5-2.5, the most active). Antacids such as aluminum hydroxide neutralize gastric acid and cover the gastric mucosa to form a gel-like protective layer to prevent gastric acid and pepsin from invading again.
• Commonly used drugs: aluminum hydroxide, aluminum phosphate, magnesium hydroxide, sodium bicarbonate.

2. Indications

Gastric acid secretion inhibitors

• Acute gastric mucosal disease, gastroesophageal reflux disease, peptic ulcer or bleeding, prevention of stress mucosal injury of upper gastrointestinal tract. PPI can be combined with antibacterial drugs to eradicate Helicobacter pylori.

Antacids

• Relieve stomachache, acid reflux and heartburn caused by hyperacidity. It can be used for functional dyspepsia, chronic gastritis, peptic ulcer or bleeding, acute gastric mucosal lesions and reflux esophagitis.

Different

• Antacids directly neutralize gastric acid and have a quick effect. However, as the stomach empties and cannot neutralize the continuously secreted gastric acid, the duration of action is very short. PPI has a strong, complete and long-lasting acid-inhibiting effect, and its acid-inhibiting ability greatly exceeds that of H₂ antagonist. Usually, the time for antacids to make the stomach pH> 4 is only 4 hours, H₂ antagonist is 8 hours and PPI can reach 18 hours.

3. Dosage

Classification	Drug name	Dosage	Taking time
H2 antagonist	Cimetidine	0.2g/time, 2 times/day, daily dose ≤0.8g	During meal and before bedtime
	Famotidine	20mg/time, 2 times/day, the daily dose is 40mg.	After breakfast, dinner or before bedtime.
	Ranitidine	0.15g/time, 2 times/day	Early morning and before bed
PPI	Esomeprazole	20-40mg/time, 1-2 times/day	1h before meal
	Ilaprazole	5-10mg/time, 1-2 times/day	Take it on an empty stomach in the morning
	Lansoprazole	30mg/time, 1-2 times/day	0.5h before meal
	Omeprazole	20mg/time, 1-2 times/day 0.5h before meal	0.5h before meal
	Pantoprazole	20-40mg/time, 1-2 times/day	1h before meal
	Rabeprazole	10-20mg/time, 1-2 times/day	0.5h before meal
Antacids	Aluminum hydroxide	0.6-0.9g/time, 3 times/day	1h before meal
	Aluminum Phosphate Gel	1-2 packs/time, 2-3 times/day	0.5h before meal
	Sodium bicarbonate	0.3-1g once, 3 times a day.	Before meal

H₂ antagonist has no obvious irritation to gastric mucosa, and its absorption and utilization are basically not affected by gastric contents. Generally, it can be taken after a meal or before going to bed.

Since PPI has an inhibitory effect on the "active pump" on the cell membrane of the gastric parietal cell, it has no effect on the "rest pump" in the cytoplasm, and the proton pump regeneration is mainly completed at night, so the best effect is to take the drug in the morning. PPI can only obtain the maximum acid suppression effect when it acts on food to stimulate the gastric parietal cells to be active. Therefore, it is recommended that PPI be taken 15 to 60 minutes before a meal in the morning.

The purpose of taking antacids is to neutralize excessive stomach acid, so it is generally best to take it half an hour before a meal or when stomach pain occurs.

4. Course of treatment

H₂ antagonist is generally taken continuously for no more than 12 weeks.

PPI is used for gastric ulcer medication for 6 to 8 weeks and duodenal ulcer is 4 weeks. The course of anti-Helicobacter pylori treatment is 10 to 14 days. The course of treatment for gastroesophageal reflux disease should be at least 8 weeks. Preventive use of PPI, elective surgery: Use one dose before surgery and use ≦ 24h after surgery. Fasting or parenteral nutrition: After establishing enteral nutrition, consider stopping PPI.

Antacids are generally taken for no more than 7 consecutive days.

5. Adverse reactions

Gastric acid secretion inhibitors

H₂ antagonist may induce rapid drug resistance during use and may cause gastric acid rebound after stopping. Others include nausea, vomiting, diarrhea, leukopenia, elevated serum transaminase, male sexual dysfunction and breast enlargement, galactorrhea and neuropsychiatric symptoms such as headache, dizziness, hallucinations, mania, etc.

Adverse reactions caused by short-term use of PPI are rare, such as headache, diarrhea, nausea, gastrointestinal flatulence, abdominal pain, constipation, dizziness, itching, and rash, etc., which are generally mild. Long-term treatment (>1 year), long-term overdose (>1.75 times the standard dose) may cause serious adverse reactions, such as osteoporosis and fractures, pneumonia, intestinal infections, iron deficiency anemia, vitamin B12 deficiency, hypomagnesemia and gastric mucosal lesions.

Antacids

Long-term use of aluminum hydroxide can cause severe constipation and even intestinal obstruction. Long-term use of aluminum hydroxide in the elderly can affect the intestinal absorption of phosphate, which can lead to osteoporosis. Large doses of aluminum phosphate can also cause mild constipation. Aluminum salt is absorbed and deposited in the brain, which can cause senile dementia.

Magnesium hydroxide can easily cause diarrhea.

Repetitive use of large doses of sodium bicarbonate can easily cause abdominal distension, sodium retention and secondary gastric acid secretion. Eating dairy products during medication may cause milk-alkali syndrome (manifested by nausea, vomiting, weakness, polyuria, and muscle pain).

6. Precautions

Gastric acid secretion inhibitors

    H₂ antagonist

• Antacids can reduce the concentration of gastric acid and form a protective film on the surface of the ulcer, thereby hindering the absorption and function of H₂ antagonist. Therefore, H₂ antagonist should not be combined with antacids.
• Avoid the combination of H₂ antagonist and PPI unless there is a nighttime acid breakthrough (taking PPI during the day and taking H₂ antagonist before going to bed can significantly reduce the incidence).
• Cimetidine can inhibit the activity of liver cytochrome P450 and can interact with warfarin, phenytoin and other drugs. The dose needs to be adjusted when combined. Ranitidine has a weak effect on liver drug enzymes and famotidine has almost no effect.
• In order to reduce the occurrence of the rebound phenomenon of H₂ antagonist withdrawal, it is generally advocated to stop the drug by the decrement method, such as changing from 2 times a day to once a day, then to once every other day after 1 week, and gradually stop the drug.

    PPI

• PPI needs to be combined with H⁺. It activated in an acidic environment and irreversibly combined with the sulfhydryl group of the proton pump through the disulfide bond. It causes the proton pump is permanently inactivated. Therefore, PPI should not be combined with antacids.
• It has liver enzyme inhibitory effect. Combining with clopidogrel can reduce the efficacy of the latter. Among them, omeprazole has the most obvious inhibitory effect, and PPI with weaker CYP inhibition (such as pantoprazole) may be a better choice.
• Mucosal protective agents such as sucralfate need to form a protective film in an acidic environment. Acid inhibitors increase the pH of the stomach and reduce the efficacy of such drugs. Since mucosal protective agents are attached to the surface of the gastric mucosa, they can affect the activation of PPI. Therefore, the two types of drugs should not be used in combination, and the two should be taken separately.

Antacids

• The main factors affecting the efficacy of antacids include drug neutralization ability, gastric acid secretion and emptying rate. Prolonging the action time of the drug in the stomach can enhance the curative effect, and the prokinetic drug will shorten the residence time of the antacid in the stomach when promoting intestinal motility. Therefore, it is not recommended to take the prokinetic drug and antacid at the same time. In addition, the effect of increasing the frequency of administration is better than increasing the single dose.
• Aluminum can affect the absorption of certain drugs, such as tetracycline, iron, digoxin, cimetidine, etc., when the two are used together, an interval of 1-2h is required.