Drugs used for GIT disorders.. Prof.

Kawa Dizaye

Drugs use for GIT disorders

Drugs used for the treatment of peptic ulcer:

Peptic ulcer disease is characterized by epigastric pain, loss of appetite, and weight
loss caused by inflamed excavations (ulcers) of the mucosa and underlying tissue of
the upper gastrointestinal tract.
The ulcers result from damage to the mucous membrane that normally protects the
esophagus, stomach, and duodenum from gastric acid and pepsin.
Gastric and duodenal ulcers are peptic ulcers. Duodenal ulcers develop in the lining
of the duodenum, which is the upper part of the small intestine.
Helicobacter pylori (80% of patients with ) infection, but (NSAIDs) and other factors
may cause or contribute to peptic ulcers.
Helicobacter pylori (80% of patients with ) infection, but (NSAIDs) and other factors may
cause or contribute to peptic ulcers.

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 Drugs used for GIT disorders.. Prof. Kawa Dizaye

Antacids

Antacids are drugs, which chemically neutralize the acidity of the stomach. This raises the
gastrointestinal pH sufficiently to relieve the pain of dyspepsia and acid indigestion and enable
peptic ulcers to heal. They can be classified into either a systemic antacid or a non-systemic
antacid.

1-Systemic antacid for example NaHCO3 it interacts chemically with the gastric acid & produces
NaCl, CO2 & H2O.

NaHCO3 + HCl NaCl + CO2 + H2O

For this reason, there is an increase in Na reabsorption, so it should not be used in cardiovascular
diseases as hypertension and heart failure. NaHCO3 has a rapid onset of action & a short duration
of action.
NaHCO3 is used to alkalize the urine to promote the renal elimination of acidic drugs in acidic
drug poisoning. NaHCO3 reduces urine crystallization (for example uric acid).

2-Non-systemic antacid for example Al(OH)3, MgSO4 & CaCO3 and Mg-Trisilicate
They are called non-systemic because they are non-significantly absorbed. They have a longer
duration of action than NaHCO3. Al(OH)3 could cause constipation, while Mg(OH)2 could cause
diarrhea; therefore most antacids are the combination of Al(OH)3 & MgSO4.
Aluminum hydroxide reduces serum phosphate levels by binding with phosphate in the gut,
resulting in insoluble, and nonabsorbable aluminum phosphate, which is then excreted in feces .
Hypophosphatemia may cause bone and muscle pain,. trouble breathing, and loss of appetite.

Proton pump inhibitors

Omeprazole, Lansoprazole, Pantoprazole & Rabeparzole.
These drugs in the parietal cells & at the PH of five or below, are converted to active metabolite &
they form a covalent disulfide link with a Cysteinyl residue in the proton pump, this enables the
drug to irreversibly inhibit the proton pump & to prevent the secretion of gastric acid for an
extended period.
The drug can produce a dosa dependant inhibition of up to 95% of gastric acid secretion & a single
dose can inhibit gastric acid secretion for 1 – 2 days. These drugs are given orally, their absorption
in the stomach is affected by gastric acid, because they are destructed by gastric acid.
Clinical uses:
They are more effective than H2 receptor blockers in the treating of peptic ulcer diseases and
esophageal reflux `syndrome. They typically heal 80% to 90% of peptic ulcers in 2
weeks or less when used in combination with antibiotics, whereas H2-blocker combinations heal
70% to 80% in 4 weeks.
Proton pump inhibitors are the drug of choice for patients with Zollinger –Ellison syndrome, a
condition characterized by serer ulcers resulting from gastrin-secreting tumors (gastrinomas)*
higher `oses needed to treat this disease.
Sida effects: Nausea, diarrhea, abdominal pain & flatulence.
Omeprazole and esomeprazole act as enzyme inhibitors.
They prevent the activation of clopidogrel by inhibiting CYP2C19, leading to lower clopidogrel
levels, and these PPIs should not be used with this antiplatelet drug. Pantoprazole does not appear
to cause this interaction and can be used concurrently with clopidogrel.

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 Drugs used for GIT disorders.. Prof. Kawa Dizaye

Histamine H2 Receptor Antagonists

Cimetidine, Famotidine, Ranitidine, Roxatidine

Indications:
peptic ulcer disease, and gastroesophageal reflux disease (GERD) used in combination with
an H1 blocker for the treatment of allergic reactions that do not respond when an H1 blocker
is used alone.
The usual ulcer healing doses produce 60–70% inhibition of 24 hr acid output.
Cimetidine is adequately absorbed orally, though bioavailability is 60–80% due to first-pass
hepatic metabolism. Food does not interfere with its absorption. It crosses the placenta and
reaches milk. About 2/3 of a dose is excreted unchanged in urine and bile, the rest as
oxidized metabolites. The elimination t½ is 2–3 hr. Dose reduction is needed in renal
failure.
Cimetidine has antiandrogenic action (displaces dihydrotestosterone from its cytoplasmic
receptor), it increases plasma prolactin and inhibits degradation of estradiol by liver. High
doses given for long periods have produced gynaecomastia, loss of libido, impotence and
temporary decrease in sperm count.
Cimetidine inhibits several cytochrome P-450. isoenzymes and reduces hepatic blood flow.
e.g. theophylline, phenytoin, carbamazepine, phenobarbitone,
Ranitidine is about 5 times more potent than cimetidine and the duration is longer. It does
not inhibit metabolism of other drugs and it has no antandrogenic activity..
Famotidin is 5–8 times more potent than ranitidine and antiandrogenic action is absent.

Muscarine receptor antagonists

Propantheline, Pipenzoahate.
These drugs inhibit gastric motility & prolong the gastric emptying time, these drugs
increase the stay of antacid in the stomach " increase its effectiveness, these drugs decrease
gastric acidity but they need large doses, which may cause anticholinergic like syndrome
(constipation, urinary retention & visual disturbances).

Pirenzepin & Tehenzepin: these are M1 receptor blockers; they can decrease gastric
acidity with few anticholinergic side effects.

Cytoprotective drugs
1-Misoprostol
It is prostaglandin analogs. The drug exerts a cytoprotective effect by inhibiting gastric
acid secretion & promoting secretion of mucus & H2CO3, it is primarily indicated for the
prevention of gastric & duodenal ulcers in patients who are taking NSAIDs as
Indomethacin diclofenac, and aspirin on a long term basis for the treatment of arthritis &
other conditions.
Because Misoprostol is expensive, it is usually reserved for patients at high risk of NSAIDs
induced ulcers including the elderly & those with a history of peptic ulcer disease.
It is administered orally four times daily with food for the duration of NSAD therapy.

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 Drugs used for GIT disorders.. Prof. Kawa Dizaye

Side effects:
Diarrhea & abdominal pain are the most common adverse effects, Misoprostol can
stimulate uterine contraction & induce labor in pregnant women, so it is contraindicated
during pregnancy.

2-Sucralfate:
It is a combination of octasulfate and aluminum hydroxide. This sulfated polysaccharide
adheres to ulcer craters and epithelial cells and inhibits pepsin-catalyzed hydrolysis of
mucosal proteins. Sucralfate also stimulates prostaglandin synthesis in mucosal cells. These
actions form a protective
barrier to acid and pepsin and facilitate the healing of ulcers.

Antiemetics
Vomiting is initiated by a nucleus of cells located in the medulla that is called the vomiting
or emesis center.The vomiting center can be activated by afferent fibers arising from the
gut, chemoreceptor trigger zone (CTZ), cerebral cortex, or vestibular apparatus.
Emetic substances activate the CTZ via stimulation of serotonin 5-HT3, dopamine D2, or
muscarinic M1 receptors.
Most antiemetic drugs act by blocking dopamine, serotonin, muscarinic, or histamine
receptors.

Serotonin receptor antagonist:

Ondansetron, Granisetron. Palonosetron;
These drugs are structurally related to serotonin( so they competitively inhibit serotonin
receptors which locate` on the visceral afferent nerves in the GIT & chemoreceptor trigger
zone, these drugs can be given orally or parenterally, they are primarily used for prevention
& treatment of cancer chemotherapy-induced emesis. Also, they are useful for the treatment
of postoperative emesis, these two drugs are expensive; therefore they are not used for
simple emesis & vomiting.

Dopamine D2 Receptor Antagonists:

Metoclopramide, Prochlorperazine

H1 antagonists:
Diphenhydramine, meclizine, promethazine

Muscarinic antagonists:
Scopolamine

Dronabinol
It is a cannabinoid derivative. It is used to treat severe nausea and vomiting caused by
cancer chemotherapy. cancer chemotherapy-induced emesis Dronabinol is It is also used to
treat loss of appetite that causes weight loss in people with AIDS.