-Refers to a group of upper GI disorders characterized by varying degrees of erosion of the gut wall.

Although peptic ulcer can develop in any region exposed to pepsin, ulceration is most common in the lesser curvature of the stomach and the duodenum. Most cases of PUD are caused by infection with Helicobacter Pylori, and that eradication of this bacterium not only promotes healing, but greatly reduces the chance of recurrence.

Aggressive Factors
Helicobacter pylori NSAIDS ACIDS

Defensive factors
Mucus

Bicarbonate
Blood flow Prostaglandins PEPSIN SMOKING

 Mucus is secreted continuously by cells of the GI

mucosa, forming a barrier that protects underlying cells from attack by acid and pepsin.
Bicarbonate is secreted by epithelial cells of the

stomach and duodenum. Most carbonate remains trapped in mucus layer, where it serves to neutralize any hydrogen ions that penetrate the mucus. Bicarbonate produced by the pancreas is secreted into the lumen of the duodenum, where neutralizes acid delivered from the stomach.

Sufficient blood flow to cells of

the GI mucosa is essential for maintaining mucosal integrity. If submucosal blood flow is reduced, the resultant local ischemia can lead to cell injury, thereby increasing vulnerability to attack by acid and pepsin. play an important role in maintaining defenses. These enzymes stimulate secretion of mucus and bicarbonate, and they promote vasodilation, which helps maintain submucosal blood flow. They provide additional protection by suppressing secretion of gastric

 a gram negative bacillus that can colonize the stomach and

duodenum by taking up residence in the space between epithelial cells and mucus barrier that protects these cells, the bacterium manages to escape the destruction by acid and pepsin

Promotes ulcers by:

enzymatic degredation of protective mucus layer elaboration of cytotoxin that injures mucosal cells] infiltration of neutrophils and other inflammatory cells in

response to bacteriums presence produces urease, an enzyme that forms carbon dioxide and ammonia(from urea in gastic juice): both compounds are potentially toxic to the gastric mucosa

 Inhibit the biosynthesis of prostaglandins. By doing so,

they can decrease submucosal blood flow, suppress secretion of mucus and bicarbonate, and promote secretion of gastric acid.

an absolute requirement for peptic ulcer generation: in

the absent of acid, no ulcer will form. Acid causes ulcers directly by activating pepsin, a proteolytic enzyme. Zollinger- Ellison Syndrome- the primary disorder in which hypersecretion of acid alone causes causes ulcers. The syndrome is caused by a tumor that secretes gastrin, a hormone that stimulates gastric acid production.

 pepsin is proteolytic enzyme present in gastric

juice can injure unprotected cells of the gastric and duodenal mucosa
delays ulcer healing and increases the risk of

recurrence Possible mechanisms include the reduction of the beneficial effects of antiulcer medications, reduced secretion of the bicarbonate, and accelerated gastric emptying, which would deliver more acid to the duodenum.

ANTIBIOTICS

Amoxicillin Bismuth Clarithromycin Metronidazo,e Tetracycline Tinidazole

Eradication of Helicobacter pylori

ANTISECRETORY AGENTS H2 Receptor antagonists Proton pump inhibitors Muscarinic antagonist

Cimitidine Famotidine Nizatidine Ranitidine Esomeprazole Lansop[razole Omeprazole Pantoprazole Rabeprazole Pirenzipine

Suppression of acid secretion by blocking H2 receptors on parietal cells Suppression of acid secretion by inhibiting H+,K+, -ATPase, the enzymes that makes gastric acid Suppression of acid secretion by blocking muscarinic cholinergic receptors

Misoprostol

Aluminum hydroxide Calcium bicarbonate Magnesium hydroxide Sucralfate Forms a barrier over the ulcer crater that protects against acid and pepsin

Protects against NSAIDinduced ulcers by stimulating secretion of mucus and bicarbonate, maintaining submucosal blood flow, and suppreaaing secretion of gastric acid React with gastric acid to from neutral salts

 these drugs are acid labile rapidly absorbed in the GI tract undergoes extensive metabolism in the

liver excreted in the urine

 Omeprazole, a prodrug, is converted to its

active form inside parietal cells of the stomac. The active drug then causes irreversible inhibition of H+, K+, - ATPase (proton pump), the enzyme that generates gastric acid. Because it blocks the final common pathway of gastric acid production, omeprazole can inhibit basal and stimulated acid release

 oral route, about 50% reaches the systemic

circulation undergoes hepayic metabolism followed by renal excretion T1/2 is about 1 hour. However, because omeprazole acts by irreversible enzyme inhibition, effects persist long after the drug has been cleared from the body.

 approved for short- term therapy

of Duodenal ulcers, Gastric ulcers, erosive esophagitis, and GERD; and long-term therapy of hypersecretory conditions (eg, Zollinger-Ellison Syndrome)

 headache diarrhea nausea

Vomiting

tumor generation is related to hypersecretion of gastrin, which occurs in response to omeprazole- induced suppression of gastric acidity. Gastrin stimulates hyperplasia of gastric epithelial cells, whose growth may ultimately result in gastric carcinoid tumor

Long term therapy, especially in high doses, may increase the risk of osteoporosis and fractures. How? By reducing acid secretion, omeperazole may decrease absorption of Calcium and thereby promote osteoporosis.

 nearly identical to omprazole

Structurally esomeprazole is the S- isomer

of omeprazole (which is a mixture of S- and R- isomers). The S- isomer (esomeprazole is metabolized slowly than the R- isomer, and hence esomeprazole achieves higher blood levels than omeprazole, and its effects last somewhat longer.

 erosive

headache

Esophagitis GERD Duodenal ulcers associated with H. pylori infection prophylaxis of NSAID- induced ulcers

diarrhea
nausea flatulence abdominal pain dry mouth

 very similar to omeprazole

both drugs can cause prolonged

inhibition of H+, K+, - ATPase. Hence suppression of acid secretion is sustained well- tolerated

 is much like similar to omeprazole and

lansoprazolein actions, uses, and adverse effects Like other PPIs rabeprazolesuppresses acid secretion by inhibiting H+, K+, - ATPase in parietal cells. However, the drug causes reversible inhibition of H+, K+, - ATPase, and hence its effects are less durable. has an antibacterial activity

 Antacids react with gastric acid to produce

neutral salts or salts of low acidity. By neutralizing acid, these drugs destruction of the gut wall. In addition, if treatment raises gastric Ph above 5, these drugs will release pepsin as well. Antacids may also enhance mucosal protection by stimulating production of prostaglandins. These drugs do not coat the ulcer crater to protect it from acid and pepsin.

Classification of ANTACIDS
Aluminum Compounds
Aluminum Hydroxide Aluminum Carbonate Aluminum Phosphate Drihydroxyaluminum sodium carbonat

Magnesium Compounds
Magnesium Hydroxide (Milk of Magnesia) Magnesium oxide

Cacium Compounds
Calcium Carbonate

Sodium Compounds
Sodium bicarbonate

Other
Magaldrate ( a complex of magnesium and aluminum compounds)

 rapid acting antacid the liquid formulation of magnesium

hydroxide is often referred to as the milk of magnesia The most prominent adverse effect is diarrhea, which results from retention of water in the intestinal mucosa. To compensate for this effect, magnesium hydroxide is usually administered in combination with aluminum hydroxide, an antacid that promotes constipation.

 has relatively low ANC, slow acting, but produces

effects of long duration used in combination with magnesium Hydroxide

most common adverse effect is constipation can cause hypophosphatemia ( drug has high affinity to phosphate; by binding to phosphate, the drug can reduce phosphate absorption)

can also bind to pepsin which may facilitate

ulcer healing

 rapid acting, high ANC, produces effects of long

duration may cause acid rebound principal adverse effect is constipation palatability of the drug is low and can detract from adherence releases CO2 in the stomach and can cause flatulence and eructation (belching)

 Rapid onset but effects are short lasting Liberates CO2 , thereby increasing intra-abdominal

pressure and promoting eructation and flatulence Absorption of sodium can exacerbate hypertension and renal failure. Because of its brief duration, high sodium content, an ability to cause alkalosis, drug is inappropriate for treating PUD. This drug is useful for treating acidosis and elevating urinary pH to Promote excretion of acidic drugs following overdose.

Potency
Antacid potency is expressed as acid-

neutralizing capacity (ANC). ANC is defined as the number of milliequivalents of HCL that can be neutralized by a given weight or volume of antacid.

Dosage
Antacids should be taken on a regular

schedule, not just in response to discomfort. In its usual dosage period antacids are given 7 times daily: 1 to 3 hours after each meal and at bed time. Dosage recommendations should be based on ANC and not on weight and volume of antacid. the ANC of a single dose usually ranges

 Peptic Ulcer Disease

GERD
Prophylaxis against stress- induced ulcer

Constipation and Diarrhea Sodium Loading