Peptic ulcer disease arises from the imbalance between defensive factors(mucus, bicarbonate and mucosal blood flow)

and aggressive factors(acid, pepsin, NSAIDs and H.pylori).

Hydrochloric acid is secreted by gastric parietal cells

due to stimulation of H+K+ATPase(proton pump).

Histamine(through H2 receptors),

acetylcholine(through M1 and M3 receptors) and

gastrin through CCK receptors are important stimulators of proton pump.

Antral G cells produce gastrin on stimulation by dietary peptides.

Gastrin mainly stimulates release of histamine from enterochromaffin (ECL) cell

and weakly stimulates proton pump itself.

Parietal cells secrete H+ in the lumen through H+K+ATPase.

Vagus nerve(via Ach) help in increasing acid by three mechanism:

direct stimulation of proton pump,

stimulation of ECL cells to release histamine,

direct release of gastrin(by action of G-cells)

and inhibition of somatostatin by action on D-cells(latter inhibits the release of gastrin).

these drugs are weak bases that neutralize gastric acid(donot increase the volume of acid secreted.)

Their major role in peptic ulcer is to provide prompt relief from ulcer pain.

Antacids may be systemic(absorbed from the GIT) or local(poorly absorbed).

Sodium bicarbonate is rapidly acting systemic antacid.

It is not indicated for long term use because

it releases CO2 that can cause belching and gastric distension(ulcer perforation can occur).

Aluminium hydroxide, magnesium trisilicate, magaldrate and magnesium hydroxide

are non systemic antacids.

These are slower but longer acting drugs.

Rebound acidity doesn’t occur.

Simethicone is a water repellent, pharmacologically inert anti-foaming agent.

It reduces flatulence

and can also be used to prevent bed sores.

Antacids decrease the absorption of acidic drugs

(acidic drugs are ionized in alkaline medium)

and tetracyclines by forming complexes.

Milk alkali syndrome(hypercalcemia, renal insufficiency and metabolic alkalosis)

may be caused by excessive doses of Na2CO3 or CaCO3 with calcium containing foods like milk.

these are prodrugs(active moiety is sulfenamide)

and act by irreversibly inhibiting H+K+ATPase in gastric parietal cells.

The drugs in this group include omeprazole, pantoprazole, esomeprazole, lansoprazole and rabeprazole.

MOA: On reaching parietal cells, active moiety(sulfenamide) is formed and gets trapped.

These can inhibit both basal acid output(nocturnal acid secretion)

as well as meal stimulated acid output(maximal acid output).

PPIs are given orally in early morning empty stomach(just before breakfast),

pantoprazole, esomeprazole and lansoprazole can be given IV.

These drugs have short t1/2 but can inhibit acid secretion for more than 24 hours

(hit and run drugs inhibit proton pump irreversibly).

In patients with nasoenteric tube, immediate release omeprazole by nasogastric tube is currently preferred.

PPIs are quite safe drugs and have diarrhea, headache and abdominal pain as adverse effects.

These have shown to be carcinogenic in rodents but no such case has been reported in humans.

Long term use of PPI is associated with subnormal vitamin B12 levels (reduced absorption),

increase in risk of hip fractures(reduced Ca2+ absorption),

increased risk of enteric bacterial infections like C.difficle infections, bacterial gastroenteritis and pneumonia.

these drugs competitively inhibit H2 receptors in parietal cells, thus inhibiting the acid secretion.

Ach and gastrin act partly by causing the release of histamine,

therefore acid secreting capacity of these agents is decreased by H2 blockers.

These drugs are more effective for reducing basal(nocturnal) acid secretion(histamine mediated)

than stimulated acid secretion(stimulated by gastrin, Ach as well as histamine).

These drugs can be used for GERD, PUD, ZES and prevention of stress induced ulcers.

because:

it can cross blood brain barrier and result in mental state changes.

It inhibits binding of dihydrotestosterone to androgen receptors that can manifest as impotence in males.

Famotidine is the most potent H2 blocker.

All H2 blockers except famotidine inhibits the gastric first pass metabolism of ethanol.

Loxatidine is a non-competitive blocker of H2 receptors.

Nizatidine also possess anti-ACHE activity and can cause bradycardia and enhanced gastric emptying.

non selective antimuscarinic drugs like propantheline and oxyphenonium

can be used for decreasing gastric acid secretion.

However by increasing gastric emptying time,

these drugs prolong the exposure of ulcer bed to gastric acid.

Acid suppressing agents like PPIs, H2 blockers can result in tolerance

and rebound hyperacidity due to secondary hypergastrinemia.

PGE1, PGE2 and PGI2 acts as anti-ulcer drugs by increasing the release of mucus and bicarbonate

and by increasing the mucosal blood flow.

PGs also inhibit H+K+ATPase and decrease the acid production.

these drugs form a protective covering over the ulcer bed that prevents its exposure to gastric acid.

Sucralfate and colloidal bismuth subcitrate are two important ulcer protective drugs.

it is an aluminium salt of sulphated sucrose.

At pH below 4, its molecules polymerize to form a sticky layer that covers the ulcer base

and acts as a physical barrier to prevent acid exposure.

it also forms an acid resistant coating over the ulcer.

It also dislodges H.pylori from the surface of gastric mucosa and kills it.

Adverse effects: blackening of tongue and bismuth toxicity(osteodystrophy and encephalopathy).

are cytoprotective drugs act by increase in PG generation

and by scavenging reactive oxygen species.

carbenoloxone is obtained from the roots of licorice.

It causes epithelialisation of ulcer without decreasing acid production.

It can displace aldosterone from plasma protein binding sites

and result in hypertension, sodium and water retention and hypokalemia.

H.pylori infection can be detected by urea breath test.

It is responsible for relapse of PUD.

Drugs used in the treatment of H.pylori include:

metronidazole/tinidazole, amoxicillin, clarithromycin, tetracycline, colloidal bismuth subcitrate and omeprazole/lansoprazole.

Bismuth subcitrate is used for peptic ulcer

whereas another salt, bismuth subsalicylate is used in travellers diarrhea.

It reduces stool frequency by inhibiting PG synthesis and chloride secretion

apart from having antimicrobial and gastroprotective effects.

Clarithromycin 500mg + amoxycillin 1g(metronidazole 500mg) if penicillin allergy + lansoprazole 30mg twice daily for 14 days