ANTI ULCERS

PREPARED BY RAHEEL AHMAD

Prepared by Raheel Ahmad (NWIHS) 1

Ulcer

 an open sore on an external or internal surface of the body, caused by a

break in the skin or mucous membrane which fails to heal. Ulcers range from
small, painful sores in the mouth to bedsores and serious lesions of the
stomach or intestine.

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 Aggressive Factor
Gastric Acid Mucous
Pepsin Bicarbonate
H.Pylori Prostaglandin

Protective Factors
NSAIDs
Histamine
Gastrin
Acetylcholine

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Gastric Acid Secretion

 Gastric acid secretion is stimulated by acetylcholine, histamine, and gastrin

 The receptor-mediated binding of acetylcholine, histamine, or gastrin results
in the activation of protein kinases, which in turn stimulates the H+/K+-
adenosine triphosphatase (ATPase) proton pump to secrete hydrogen ions in
exchange for K+ into the lumen of the stomach.

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H2 Receptor Antagonist

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H2 Receptor Antagonist

Mechanism of Action:
 By competitively blocking the binding of histamine to H2 receptors, these
agents reduce the secretion of gastric acid.
Drugs:
 Cimetidine
 Ranitidine
 Famotidine
 Nizatidine

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H2 Receptor Antagonist

Actions: These drugs

 potently inhibit basal, food-stimulated, and nocturnal secretion of gastric
acid.
 act selectively on H2receptors in the stomach
 have no effect on H1receptors.
 competitive antagonists of histamine and are fully reversible.

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H2 Receptor Antagonist

Peptic ulcers:
 But patients with NSAID-induced ulcers should be treated with PPIs, because
these agents heal and prevent future ulcers more effectively than
H2antagonists do.
Acute stress ulcers:
 intravenous infusion to prevent and manage acute stress ulcers associated
with high-risk patients in intensive care units.
 However, because tolerance may occur with these agents in this setting, PPIs
have gained favor for this indication.
 Gastroesophageal reflux disease (GERD): Low doses of H2 antagonists, are
effective for the treatment of heartburn (GERD)
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H2 Receptor Antagonist

Pharmacokinetics:
 widely throughout the body (including into breast milk and across the
placenta)
 excreted mainly in urine.
 Cimetidine, ranitidine, and famotidine are also available in intravenous
formulations.
 half-life of all of these agents may be increased in patients with renal
dysfunction, and dosage adjustments are needed

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H2 Receptor Antagonist

Adverse effects
 Cimetidinecan have endocrine effects because it acts as a nonsteroidal antiandrogen and
prolactin-stimulator. These effects include gynecomastia and galactorrhea (continuous
release/discharge of milk).
 central nervous system effects (such as confusion and altered mentation)
 Cimetidine inhibits several cytochrome P450 isoenzymes and can interfere with the
metabolism of many other drugs, such as warfarin, phenytoin, and clopidogrel.
 All H2 antagonists may reduce the efficacy of drugs that require an acidic environment for
absorption, such as ketoconazole

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Proton Pump Inhibitors
PPIs: Inhibitors of the H+/K+ -ATPase proton pump

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Proton Pump Inhibitors

The PPIs bind to the H+/K+-ATPase enzyme system (proton pump) and suppress
the secretion of hydrogen ions into the gastric lumen.
Drugs:
 Dexlansoprazole
 Esomeprazole
 Lansoprazole
 Omeprazole
 Pantoprazol
 rabeprazole

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Proton Pump Inhibitors

 These agents are prodrugs with an acid-resistant enteric coating

 The coating is removed in the alkaline duodenum,and the prodrug, a weak
base, is absorbed
 It takes about 18 hours for the enzyme to be resynthesized, and acid
secretion is inhibited during this time.
 At standard doses, PPIs inhibit both basal and stimulated gastric acid
secretion

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Proton Pump Inhibitors

 Therapeutic uses:
 The PPIs are superior to the H2 antagonists
 they are the preferred drugs for stress ulcer treatment and prophylaxis and
for the treatment of GERD, erosive esophagitis, active duodenal ulcer, and
pathologic hypersecretory conditions (for example, ZollingerEllison syndrome,
in which a gastrin-producing tumor causes hypersecretion of HCl). I.
 If an H2-receptor antagonist is needed, it should be taken well after the PPI.
 PPIs also reduce the risk of bleeding from ulcers caused by aspirin and other
NSAIDs and may be used for prevention or treatment of NSAID-induced ulcers.
 they are used with antimicrobial regimens to eradicate H. pylori

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Proton Pump Inhibitors

Pharmacokinetics:
 All effective orally.
 should be taken 30 to 60 minutes before breakfast or the largest meal of the
day.
 dexlansoprazole can be taken without regard to food
 Esomeprazole, lansoprazole, and pantoprazoleare also available in
intravenous formulations.
 Metabolites of these agents are excreted in urine and feces.

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Proton Pump Inhibitors

 Adverse effects: The PPIs are generally well tolerated.

 Omeprazoleand esomeprazolemay decrease the effectiveness of clopidogrel because
they inhibit CYP2C19 and prevent the conversion of clopidogrelto its active metabolite.
 PPIs may increase the risk of fractures, particularly if the duration of use is 1 year or
greater
 Prolonged acid suppression with PPIs (and H2antagonists) may result in low vitamin B12
because
 acid is required for its absorption in a complex with intrinsic factor.
 Elevated gastric pH may also impair the absorption of calcium carbonate.
 Calcium citrateis an effective option for calcium supplementation in patients on acid
suppressive therapy, since absorption of the citrate salt is not affected by gastric pH.
 Diarrhea and Clostridium difficilecolitis may occur in community patients receiving PPIs.
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Prostaglandins

Prepared by Raheel Ahmad (NWIHS) 20

Prostaglandins

 Prostaglandin E, produced by the gastric mucosa, inhibits secretion of acid

and stimulates secretion of mucus and bicarbonate (cytoprotective effect).
 Misoprostol an analog of prostaglandin E1 , is approved for the prevention of
NSAID-induced gastric ulcers
 Prophylactic use of misoprostol should be considered in patients who are
taking NSAIDs and are at moderate to high risk of NSAID-induced ulcers,
 Misoprostolis contraindicated in pregnancy, since it can stimulate uterine
contractions and cause miscarriage.

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Antacids

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Antacids

 Antacids are weak bases that react with gastric acid to form water and a salt
to diminish gastric acidity.
 Because pepsin (a proteolytic enzyme) is inactive at a pH greater than 4,
antacids also reduce pepsin activity.
 The efficacy of an antacid depends on its capacity to neutralize gastric HCl
and on whether the stomach is full or empty (food delays stomach emptying
allowing more time for the antacid to react).
 Commonly used antacids are combinations of salts of aluminum and
magnesium, such as aluminum hydroxideand magnesium hydroxide[Mg(OH)2].
 Calcium carbonate[CaCO 3] reacts with HCl to form CO2 and CaCl 2 and is
also a commonly used preparation.

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Antacids

 Systemic absorption of sodium bicarbonate[NaHCO] can produce transient

metabolic alkalosis. Therefore, this antacid is not recommended for long-
term use
 They should be administered after meals for maximum effectiveness.
 Calcium carbonate preparations are also used as calcium supplements for the
treatment of osteoporosis.
 Aluminum hydroxidetends to cause constipation, whereas magnesium
hydroxidetends to produce diarrhea.
 Preparations that combine these agents aid in normalizing bowel
 function.

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Mucosal protective agents

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Mucosal protective agents

 Also known as cytoprotective compounds, these agents have several actions

that enhance mucosal protection mechanisms, thereby reventing mucosal
injury, reducing inflammation, and healing existing ulcers

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Sucralfate

 This complex of aluminum hydroxideand sulfated sucrose binds to positively

charged groups in proteins of both normal and necrotic mucosa.
 By forming complex gels with epithelial cells, sucralfate creates a physical
barrier that protects the ulcer from pepsin and acid, allowing the ulcer to
heal.
 it requires an acidic pH for activation, sucralfate should not be administered
with PPIs, H2antagonists, or antacids.
 Sucralfateis well tolerated, but it can interfere with the absorption of other
drugs by binding to them.
 This agent does not prevent NSAID-induced ulcers, and it does not heal gastric
ulcers

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Bismuth subsalicylate

 This agent is used as a component of quadruple therapy to heal peptic

ulcers.
 In addition to its antimicrobial actions, it inhibits the activity of pepsin,
increases secretion of mucus, and interacts with glycoproteins in necrotic
mucosal tissue to coat and protect the ulcer.

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Anti Microbial Therapy

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Anti Microbial Therapy

 Patients with peptic ulcer disease (duodenal or gastric ulcers) who are
infected with H. pylorirequire antimicrobial treatment.
 Infection with H. pyloriis diagnosed via endoscopic biopsy of the gastric
mucosa or various noninvasive methods, including serology and urea breath
tests
 triple therapy consisting of a PPI combined with amoxicillin (metronidazole
may be used in penicillin-allergic patients) plus clarithromycin is the therapy
of choice.
 Quadruple therapy of bismuth subsalicylate, metronidazole, and tetracycline
plus a PPI is another option.
 Quadruple therapy should be considered in areas with high resistance to
clarithromycin.
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