Peptic Ulcer Disease

~ By Roll no.14,15 and 16

INTRODUCTION
• Peptic ulcer occurs in that part of the gastrointestinal tract (g.i.t.) which is
exposed to gastric acid and pepsin, i.e. the stomach and duodenum

• Etiology- not clearly known

• It results probably due to an imbalance between the aggressive (acid, pepsin,

bile and H. pylori) and the defensive factors(mucus,bicarbonate,prostaglandins)

Note- Peptic ulcer(especially duodenal) is a chronic remitting and relapsing

disease lasting several years
Aetiology
Symptoms
Treatment
1.Gastric acid secretion inhibitors
■ Proton pump inhibitors
● Proton pump inhibitors are ir- reversible drugs
● They are type of Hit and Run drugs
● Strongest acid inhibitor
● PPIs are acid labile thats why they’re given with acid resistant coating
(Enteric coating )
● Coat dissolve in Alkaline medium in intestine
● Oral bioavailability is ~50% due to acid labilty
● Highly protien bound metabolized in liver by CYP2C19 and CYP3A4.
● Bioavailability of all PPIs is reduced by food; they should be taken in empty
stomach, followed 1 hour later by a meal to activate the H*K* ATPase and make
it more susceptible to the PPI.
● The metabolites are excreted in urine. No dose modification is required in elderly
or in patients with renal/hepatic impairment.
 Proton pump inhibitors
○ Mode of action – ● PPI absorb from intestine into blood
⬇️
Goes to parietal cell
⬇️
Act on proton pump (H+ - K+ pump)
⬇️
Inhibition
⬇️
Reduction in gastric acid secretion

Drugs: Omeprazole,
Pantoprazole,
Lansoprazole,
Esomeprazole
 Proton pump inhibitors
○ Uses - ● Drug of choice in peptic ulcer
● Bleeding peptic ulcer
● Stress ulcers
● GERD
● Zollinger-Ellison syndrome
● Aspiration pneumonia

○ Drug interaction -
● Clopidogrel - PPI can reduce the activation of clopidogrel by
Inhibiting CYP2C19

● Warfarin and Diazepam - Omeprazole inhibits CYP2C19,which

may reduce metabolism of these drugs
 Proton pump inhibitors
○ Side effect - ● Headache ● Abdominal pain

● Nausea ● Diarrhea / constipation

▪︎In long term use it causes -

● Vit- B12 deficiency ( Megaloblastic anemia )

● Calcium deficiency ( Osteoporosis )

( Increase risk of Bone fracture )

□ So, when we give PPIs for long term to any patient we give
Ca+2 & Vit- B12 supplements
H2 Receptor Blockers
• includes cimetidine, ranitidine, famotidine

• MOA - Histamine stimulates specific receptors on stomach parietal cells to increase

gastric acid secretion. These histamine receptors are classified as H2 receptors. H2
antagonists, or blockers, prevent the histamine activated release of gastric acid.

• Pharmacokinetics -

i. Given orally

ii. Absorption is not affected by food iii. Distributed widely throughout the body

iv. Cleared by a combination of hepatic metabolism, glomerular filtration

and renal tubular secretion

V. Dosage must be reduced in hepatic or renal failure

H2 Receptor Blockers
Therapeutic uses - PUD, GERD, gastritis, Zollinger-Elison syndrome

• Adverse effects

i. Headache, dizziness, diarrhea, muscular pain, dry mouth

ii. CNS: confusion, restlessness

iii. Cimetidine can also have endocrine effects because it acts as a nonsteroidal
antiandrogen. These effects include gynecomastia, impotence - in men, and galactorrhea,
menstrual irregularities - in women.

• Drug interactions - Cimetidine inhibits several CYP-450 isoenzymes and reduces

hepatic blood flow, so inhibits metabolism of many drugs like theophylline, metronidazole,
phenytoin, imipramine etc. Also, antacids reduce the absorption of all H2 blockers.
 Anticholinergics

• includes pirenzepine, telenzepine

• MOA - Reduce meal stimulated HCI secretion by reversible blockade of

muscarinic (M1) receptors on the cell bodies of the intramural cholinergic ganglia.

• Unpopular as a first choice because of high incidence of anticholinergic side

effects (dry mouth and blurred vision).
Prostaglandin Analogues
• includes misoprostol

• MOA - Enhance local production of mucus or bicarbonate. These inhibit gastrin

production, increase mucosal blood flow.

• Therapeutic use - Prevention of NSAID induced mucosa injury (Rarely used

because it needs frequent administration - 4x daily).

• ADRs - diarrhea, abdominal cramps, uterine bleeding, abortion, exacerbation

inflammatory bowel disease

• Contraindications - inflammatory bowel disease, pregnancy.

2.ANTACIDS
• Systemic - Sodium bicarbonate, Sodium citrate

• Non-systemic - Magnesium hydroxide, Magnesium trisilicate, Aluminum

hydroxide gel, Magaldrate (hydrated hydroxy magnesium aluminate)

• MOA - They're weak bases that neutralize gastric acid and raise pH of gastric
content. Also inhibits the formation of pepsin.

Sodium bicarbonate - Reacts rapidly with HCl to produce CO2 and NaCl

Side effects: Distension and belching, metabolic alkalosis, fluid retention, acid
rebound.
ANTACIDS
Magnesium hydroxide and Aluminum hydroxide - reacts slowly with HCl, no
belching, no metabolic acidosis.

ADR of Mg salts - diarrhea, of Al salts - constipation.

So both are administered together.

• Drug interactions - By raising gastric pH & forming insoluble complexes, it

decreases absorption of many drugs including tetracyclines, iron salts, H2
Blockers, diazepam, phenytoin, isoniazid, ethambutol.
Antacids Combinations
A combination of two or more antacids is frequently used. These may be superior
to any single agent on the following accounts:

(a) Fast (Mag. hydrox.) and slow (Alum. hydrox.) acting components yield prompt
as well as sustained effect.

(b) Mag. salts are laxative, while alum. salts are constipating: combination may
cancel each other's action and bowel movement may be least affected.

(c) Gastric emptying is least affected; while alum. salts tend to delay it, mag./cal.
salts tend to hasten it.

(d) Dose of individual components is reduced; systemic toxicity (dependent on

fractional absorption) is minimized.
3.ULCER PROTECTIVE DRUGS
SUCRALFATE
• MOA - At acidic pH < 4, it undergoes extensive polymerization by cross linking
molecules to form a sticky gel over the ulcer base protects it.

• Therapeutic uses - PUD, bile reflux gastritis, topically - burns, bedsore ulcers,
excoriated skins.

• ADRs - Constipation, hypophosphatemia

• Drug interactions - absorbs many drugs and interferes with the absorption
tetracyclines, fluoroquinolones, cimetidine, phenytoin and digoxin. Antacids given
concurrently reduce the efficacy of sucralfate.
 ULCER PROTECTIVE DRUGS
Colloidal Bismuth Subcitrate
It is a colloidal bismuth compound; water soluble but precipitates at pH < 5. It is
not an antacid but heals 60% ulcers at 4 weeks and 80-90% at 8 weeks. The
mechanism of action of CBS is not clear; probabilities are:

• May increase gastric mucosal PGE2, mucus and bicarbonate production.

• May precipitate mucus glycoproteins and coat the ulcer base.

• May detach and inhibit H.pylori directly.

Side effects: blackening of tongue, stools, dentures. Prolonged use may cause
osteodystrophy and encephalopathy, diarhea, headache, dizziness.
4.ANTI H.PYLORI DRUGS
• Helicobacter pylori - a gram -ve bacilli that attaches beneath the mucus and
causes back diffusion of H+ ions. It's present in 90% of cases with Peptic ulcers.

• Anti-H. pylori drugs includes antimicrobialss like amoxicillin, clarithromycin,

metronidazole, tetracycline
H.Pylori Treatment Regimen
• PPI, clarithromycin, either amoxicillin or metronidazole (ppi based triple therapy) for 10 to 14 days

• Amoxicillin based regimen is first choice because bacterial resistance to amoxicillin is almost absent
and has fewer adverse effects.

-In pencillin allergic patients, metronidazole is taken instead of amoxicillin.

• Sequential therapy - is a form of eradication therapy in which the antibiotics are administered in a
sequence rather than together.

• The basis of this therapy is to initially treat with antibiotics that rarely promote resistance (eg;
amoxicillin) to reduce the bacterial load and pre existing resistant organisms that are susceptible.

• The second sequence follows with different antibiotics (clarithromycin and metronidazole) to kill
any remaining organisms.

• Treatment typically consist of a PPI and amoxicillin for 5 days followed by a PPI, clarithromycin and
metronidazole for an additional 5 days.
■ Triple Drug Therapy -
Used for H.pylori associated PUD

● 1 PPI + 2 Anti microbials

[ Omeprazole + Clarithromycin + Amoxycillin ]

■ Bismuth- based Quadruple Therapy -

● 1 PPI + Bismuth + 2 Anti microbials

[ Omeprazole + Bismuth + Metronidazole + Tetracycline ]

■ Non-bismuth therapy -
[ Omeprazole + Clarithromycin + Amoxycillin + Metronidazole ]
 Management of Peptic Ulcer Disease -

• Non-pharmacological therapy
• Patient should eliminate or reduce stress, cigarette smoking and use of NSAIDS.

• Avoid spicy and fatty foods, caffeine, alcohol as these generally irritate the lining
of the stomach.

• Vagotomy inhibits vagal stimulation of gastric acid.

• Use acetaminophen as alternative agent for pain.

Thank You