Anti-Ulcer drugs


Antiulcer drugs are a class of drugs, exclusive of the antibacterial agents, used to treat ulcers in the stomach and the upper part of the small intestine.

Purpose:
The Anti Ulcer Drugs are used as part of the treatment for ulcers. Ulcers are sores or raw areas that form in the lining of the stomach or the duodenum (the upper part of the intestine). Those that form in the stomach are called Gastric Ulcers; in the duodenum, they are called Duodenal Ulcers. Both types are referred to as Peptic Ulcers. For a long time, physicians thought that stress and certain foods caused ulcers.

Now they know that most ulcers are caused either by infection with a bacterium called Helicobacter Pylori or by long-term use of aspirin or other Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), such as Ibuprofen. In either case, something damages the barrier of mucus that normally protects the stomach and duodenum from the powerful acids and enzymes that the body produces to digest food. When that happens, the acids and enzymes begin to eat away at the unprotected tissue, causing ulcers.

Ulcers do not always cause symptoms. When they do, they usually cause a gnawing or burning pain - something like hunger pangs - between the breastbone and the navel. The pain often occurs early in the morning or between meals and may be temporarily relieved by eating or by taking Antacids. Nausea, vomiting, loss of appetite and weight loss are other symptoms of ulcers. If ulcers bleed, the blood may show up in the form of black, tarry stools.

The proton pump inhibitors block the secretion of gastric acid by the gastric parietal cells. The extent of inhibition of acid secretion is dose related. In some cases, gastric acid secretion is completely blocked for over 24 hours on a single dose. In addition to their role in treatment of gastric ulcers, the proton pump inhibitors are used to treat syndromes of excessive acid secretion (Zollinger-Ellison Syndrome) and gastroesophageal reflux disease (GERD). Histamine H-2 receptor blockers stop the action of histamine on the gastric parietal cells, inhibiting the secretion of gastric acid. These drugs are less effective than the proton pump inhibitors, but may achieve a 75-79% reduction in acid secretion. Higher rates of acid inhibition may be achieved when the drug is administered by the intravenous route. The H-2 receptor blockers may also be used to treat heartburn and hypersecretory syndromes. When given before surgery, the H-2 receptor blockers are useful in prevention of aspiration pneumonia. Sucralfate (Carafate), a substituted sugar molecule with no nutritional value, does not inhibit gastric acid, but rather, reacts with existing stomach acid to form a thick coating that covers the surface of an ulcer, protecting the open area from further damage. A secondary effect is to act as an inhibitor of the digestive enzyme pepsin. Sucralfate does not bind to the normal stomach lining. The drug has been used for prevention of stress ulcers, the type seen in patients exposed to physical stress such as burns and surgery. It has no systemic effects.


INDICATIONS:

  • Duodenal Ulcer- A peptic ulcer occurring in the wall of the duodenum, the first portion of the small intestine.
  • Benign Gastric Ulcer- A non- cancerous gastric ulcer is a break in the normal tissue that lines the stomach.
  • Reflux oesophagitis- Reflux oesophagitis, also known as gastrooesophageal reflux disease (GERD), occurs when the lower oesophageal sphincter (LES) does not close properly and stomach contents leak back, or reflux, into the oesophagus. The LES is a ring of muscle at the bottom of the oesophagus that acts like a valve between the oesophagus and stomach. The oesophagus carries food from the mouth to the stomach.
  • Dyspepsia- a condition in which there are upper abdominal symptoms which may include upper abdominal pain, bloating (a feeling of abdominal fullness without objective abdominal distention), early satiety (a feeling of unusual fullness with very little intake of food), nausea, or belching. The symptoms often are provoked by eating.
  • Aerophagia- swallowing air (usually followed by belching and discomfort and flatulence)
  • Gastric hypomotility- a state of diminished motility or loss of power to move about
  • Gastro- intestinal distress
  • In Zollinger-Ellison syndrome (ZES), a tumor (a gastrinoma) secretes the hormone gastrin, which stimulates the secretion of gastric acid. This leads to the development of ulcers in the stomach and duodenum (the first part of the small intestine).

TYPES OF ANTI- ULCER DRUGS

1. Antacids

Antacids are medicines that neutralize stomach acid.

Antacids are used to relieve acid indigestion, upset stomach, sour stomach, and heartburn. Additional components of some formulations include dimethicone, to reduce gas pains (flatulence) and alginic acid, which, in combination with antacids, may help manage GERD (gastro-esophageal reflux disease). Antacids should not be confused with gastric acid inhibitors, such as the H-2 receptor blockers (cimetidine, ranitide and others) or the proton pump inhibitors (lansoprazole, omeprazole and others). Although all three classes of drugs act to reduce the levels of gastric acid, their mechanisms are different, and this affects the appropriate use of the drug. Antacids have a rapid onset and short duration of action, and are most appropriate for rapid relief of gastric discomfort for a short period of time.Antacids may be divided into two classes, those that work by chemical neutralization of gastric acid, most notably sodium bicarbonate; and those that act by adsorption of the acid (non-absorbable antacids), such as calcium and magnesium salts.The chemical antacids show the most rapid onset of action, but may cause "acid rebound," a condition in which the gastric acid returns in greater concentration after the drug effect has stopped. Also, since these antacids may contain high concentrations of sodium, they may be inappropriate in patients with hypertension.Calcium and magnesium salts act by adsorption of the acid, and are less prone to the rebound effect, but may have other significant disadvantages. These antacids are particularly prone to drug interactions, and patients taking other medications must often avoid simultaneous administration of the medications. These antacids are more effective in liquid formulations than in tablet or capsule form, and so may be inconvenient for routine dosing.The non-absorbable antacids may have additional uses beyond control of hyperacidity. Calcium salts may be used as diet supplements in prevention of osteoporosis. Aluminum carbonate is useful for binding phosphate, and has been effective in treatment and control of hyperphosphatemia or for use with a low phosphate diet to prevent formation of phosphate urinary stones. This application is particularly valuable in patients with chronic renal failure. Antacids with aluminum and magnesium hydroxides or aluminum hydroxide alone effectively prevent significant stress ulcer bleeding in post-operative patients or those with severe burns.

2. Histamine 2 (H2)
Histamine 2 antagonists are drugs that block the production of acid in the stomach.

Histamine 2 antagonists are used to treat the precancerous condition of Barrett's esophagus. They are also used to treat Zollinger-Ellison syndrome and multiple endocrine neoplasia, rare cancerous conditions in which the stomach makes too much acid and to prevent the development of gastric (stomach) and duodenal (upper part of the small intestine) ulcers.

Histamine 2 blockers are familiar to most people as the over-the counter heartburn medications Tagamet (cimetidine), Pepcid, (famotidine), and Zantac (ranitidine). Axidnizatidine) is less well known. These drugs also come in prescription strengths. Histamine 2 blockers work by reducing the amount of acid the stomach produces.

The esophagus is a tube 10-13 inches long and about 1 inch wide that carries food from the mouth to the stomach. Normally, the esophagus is lined with cells that are similar to skin cells and look smooth and pinkish-white.
The stomach makes acid to help digest food. A different type of cell that is resistant to acid lines the stomach. These cells look red and velvety. At the place where the esophagus meets the stomach, there is a ring of muscle called a sphincter that normally keeps acid stomach juices from backflowing into the esophagus. When this sphincter is not working correctly, stomach acid enters the bottom portion of the esophagus. This backflow is called reflux or heartburn. When reflux occurs frequently over an extended period of time, it is called gastroesophageal reflux disease (GERD).

Barrett's esophagus is pre-cancerous condition in which normal cells lining the esophagus are repeatedly exposed to stomach acid and are replaced with abnormal cells that, in some people, develop into a type of cancer of the esophagus called adenocarcinoma. Histamine 2 blockers are given to reduce acid in the stomach and eliminate exposure of the esophagus cells to acid.

Histamine 2 blockers are also used to treat two rare cancerous conditions: multiple endocrine neoplasia (MEN) and Zollinger-Ellison syndrome, both of which can cause the stomach to produce too much acid. In MEN, an inherited form of cancer, tumors form in more than one gland. Depending on which glands are affected, the stomach may be stimulated to produce excess acid. In Zollinger-Ellison syndrome, a tumor in the digestive tract secretes a hormone called gastrin that stimulates the production of stomach acid. These tumors are malignant (cancerous) in 50% to 65% of people with Zollinger-Ellison syndrome.

Histamine 2 blockers are sometimes given in advance of chemotherapy to help reduce the gastrointestinal side effects of chemotherapy drugs. Cimetidine was the first histamine 2 blocker approved by the United States Food and Drug Administration (FDA) in 1976.

Recommended dose varies depending on how much stomach acid is produced. Histamine 2 blockers are available in low doses without a prescription and in higher doses with a prescription. They are available in tablet, chewable tablet, liquid, and injectable liquid form. If histamine 2 inhibitors are unsuccessful in controlling acid reflux, proton pump inhibitors (Prevacid, Prilosec) are usually given as an alternative.
People who have trouble with heartburn should stay away from acidic foods such as orange, grapefruit, and tomato juice, coffee, and carbonated drinks (sodas) because these all increase stomach acid. Although animal studies show that histamine 2 blockers appear to be safe during pregnancy, these drugs do pass into breast milk and should not be taken by nursing mothers.

Histamine 2 blockers have few side effects. These drugs are excreted by the kidney, and may slow the excretion of other drugs excreted by the kidney. People with reduced kidney function may need a reduced dose of histamine 2 blockers.
Rare cases of irregular heart rhythms and high blood pressure have been reported when histamine 2 blockers are given intravenously (IV, injected directly into a vein). Mild diarrhea has been reported by some people taking these drugs.

Histamine 2 blockers are reported to have few interactions with other drugs. However, because they reduce the level of acid in the stomach, they may inhibit the uptake of drugs such as ketoconazole that depend on an acid environment in the stomach to work. These drugs should be administered at least two hours before histamine 2 blockers are taken. Prior to starting any over-the-counter medications, herbal medications, or new medications, patients should notify their physician and check with their pharmacists for any potential drug interactions.

3. Proton Pump


A proton pump is an integral membrane protein that is capable of moving protons across the membrane of a cell, mitochondrion, or other subcellular compartment.
In cell respiration, the pumps grab protons from the matrix (the space enclosed by the two membranes) within the organelle and release the protons into the inter-membrane space. The confined protons create a difference or gradient in both pH and electric charge (ignoring differences in buffer capacity) and establish an electrochemical potential that acts as a kind of battery or reservoir of stored energy for the cell. The inner cell membrane functions in a similar way to a dam in a river. It blocks protons from drifting back into the matrix. Since the pumping action is against the gradient, it requires work (energy). The process is directly analogous to bicycling uphill or charging a battery (storing up potential energy). It is important to remember that the proton pump does not create energy. Instead, the gradient stores energy for the appropriate time.



Brand name
Specific Class
Common Side effect
Available dosage forms
Contraindication
Pregnancy category
Axid (nitzatidine)
H2 blockers
Diarrhea, headache, nausea and vomiting, sore throat
Tablet
130 GM
300 GM
Hypersensitivity to drug or other H2-receptor antagonists.
Category B
Carafate (sucralfate)
Gastrointestinal Agents / Miscellaneous GI Agents
Constipation, insomnia, hives, upset stomach, vomiting
Tablet
1 GM

Suspension
1 GM/ mL
No known contraindications
category B
Cytotec (misoprostol)
Gastrointestinal Agents / Miscellaneous GI Agents
Cramps, diarrhea, nausea, gas, headache, menstrual disorders (including heavy bleeding and severe cramping)
Tablet
200 GM
100 GM
Cytotec should not be taken by pregnant women to reduce the risk of ulcers induced by nonsteroidal anti-inflammatory drugs (NSAIDs).
Cytotec should not be taken by anyone with a history of allergy to prostaglandins.
Category X
Pepcid (famotidine)
H2 blockers
Constipation or diarrhea, dizziness, fatigue, fever
Tablet
20 GM
40 GM
Hypersensitivity to any component of these products. Cross sensitivity in this class of compounds has been observed. Therefore, PEPCID should not be administered to patients with a history of hypersensitivity to other H2-receptor antagonists.
Category B
Prilosec (omeprazole)
proton pump inhibitors
Nausea and vomiting, headache, diarrhea, abdominal pain
Capsule
40 GM
20 GM
10 GM
Omeprazole is contraindicated in patients hypersensitive to it. Omeprazole should be used when the benefits outweigh the risks in patients with hepatic disease or a history of hepatic disease, as the drug’s half life may be prolonged and dosage adjustment may be necessary.

Omeprazole’s safety during pregnancy has not been established, but a study done in rats at doses of up to 345 times those recommended did not demonstrate any teratogenic ef­fects. Increased embryo-lethality has been noted in lab animals at very high dosages. It is unknown whether omeprazole is excreted in milk.
category C
Tagamet (cimetidine)
H2 blockers
Headache, breast development in men, depression and disorientation
Tablet
800 GM
400 MG
300 MG
Cimetidine is contraindicated in patients with known hypersensitivity to the drug.

Cimetidine should be used cautiously in geriatric patients and in patients with significantly impaired hepatic or renal function. In humans meeting these criteria, increased risk of CNS (confusion) effects may occur; dosage reductions may be necessary.
category B
Zantac
(ranitidine hydrochloride)

H2 blockers
Headache, constipation or diarrhea, joint pain
Capsule
300 MG
150 MG

Syrup
15 MG/ mL (mint)

Geldose Capsule
300 MG
150 MG

Injectional Vial
25 MG/ mL
ZANTAC is contraindicated for patients known to have hypersensitivity to the drug or any of the ingredients
Category B
methylprednisolone
Medixon®

Glucocorticoid/ Miscellaneous GI Agents
Fluid & electrolyte disturbances, muscle weakness, impaired wound healing, increased BP, posterior subcapsular cataracts, growth suppression in childn, adrenal insufficiency, Cushing's syndrome, osteoporosis & peptic ulcer.
Tablet
Systemic fungal infections, peptic ulcer, severe osteoporosis & patients w/ history of psychoses, herpes & those who undergo immunization procedures.

Category C.



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89/100 = lack brand names