2. PEPTIC ULCER
An Ulcer is …
Erosion in the lining of the stomach or the first part of the small intestine, an
area called the duodenum.
Ulcers damage the mucosa of the alimentary tract, which extends through
the muscularis mucosa into the sub mucosa or deeper.
3. Ulcers that form in the stomach are called gastric ulcers;
in the duodenum, they are called duodenal ulcers. Both
types are referred to as peptic ulcers.
5. PATHOGENESIS OF PEPTIC
ULCER DISEASE
IMBALANCE:
AGGRESSIVE
FACTORS
Acid
Pepsin
Helicobacter pylori
NSAIDS
DEFENSIVE FACTORS
Prostaglandins
Mucosal blood flow
Mucous gel layer
HCO3
Epithelial junctions
Regeneration of the epithelial
layer
Epidermal growth factor
6. APPROACHES FOR THE
TREATMENT OF ULCER
1. Reduction of gastric acid secretion
A) H2 antihistaminics:
Cimetidine, ranitidine, famotidine, roxatidine
B) Proton pump inhibitors:
Omeprazole, esomeprazole, lansoprazole,
pantoprazole, rabeprazole, dexrabeprazole
C) Anti cholinergic drugs:
Pirenzapine, propantheline, oxyphenomium
D) Prostaglandin analogue:
misoprostol
7. 2. Neutralization of gastric acid
A) Systemic : Sodium bicarbonate, sodium citrate
B) Non systemic: Magnesium hydroxide, mag trisilicate, aluminium hydroxide gel,
magaldrate, calcium carbonate
3. Ulcer protective :
Sucralfate, colloidal bismuth subcirtrate
4. Anti H-pylori drugs:
Clarithromycin, metronidazole, amoxicillin, tinidazole, tetracycline
8. PHYSIOLOGY OF
GASTRIC ACID
SECRETION
Gastric acid secretion is a complex, continuous process in
which multiple central and peripheral factors contribute to a
common endpoint secretion of H⁺ by parietal cells.
Neuronal(acetylcholine,Ach),paracrine(histamine), and
endocrine (gastrin) factors all regulate acid secretion.
Their specific receptors (M3,H2,and CCK2 receptors,
respectively)are on the basolateral membrane of parietal cells
in the body and fundus of the stomach.
9. The H2 receptor is a GPCR that activates the Gs- adenyl
cyclase –cyclic AMP-PKA pathway.
Ach and gastrin signal through GPCRs that couple to the Gq-
PLC-IP3-Ca2+
pathway in parietal cells .
In parietal cells , the cyclic AMP and the Ca2+
dependant
pathways activate H+
,K+
-ATPase (the proton pump), which
exchanges hydrogen and potassium ions across the parietal
cell membrane
12. HISTAMINE ANTAGONIST
First class of highly effective drugs for acid peptic disease but
surpassed by proton pump inhibitors
Cimetidine was the first to introduce in the market and described
as prototype
Pharmacological actions:
1.H2 blockade:
Block histamine induced gastric secretion, cardiac stimulation,
uterine relaxation
No effect on H1 responses because they are selective
13. 2. Gastric secretion:
Marked inhibition of gastric secretion
All phase are suppressed dose dependently.
Secretory response to not only histamine but also Ach,
gastrin, insulin, alcohol, food are attenuated
The volume, pepsin content and intrinsic factor secretion
are reduced
They don’t have any direct action on gastric or
oesophageal motility or on LES tone
14. PHARMACOKINETICS
Adequately absorbed orally,
Bioavailability is 60-80%
Undergoes first pass metabolism
No interference by presence of food
Crosses placenta and reaches milk
Poor BBB penetration
About 2/3 of dose is excreted unchanged in urine/bile
Elimination t1/2 is 2-3hr
Dose reduction is needed in renal failure
15. CIMETIDINE
SIDE EFFECTS;
It include constipation, diarrhea, fatigue, headache, insomnia,
muscle pain, and vomiting.
Major side effects:
Bowel upset,
Dry mouth,
Rashes,
Gynaecomastia,
Impotence,
Loss of libido,
Decrease in sperm count
16. USES: It is used in treatment of
Duodenal ulcer,
Gastric ulcer,
Stress ulcer,
GERD,
Zollinger ellison syndrome
Prophylaxis of aspiration pneumonia
17. PROTON PUMP INHIBITORS
Proton pump inhibitors act by irreversibly blocking
the hydrogen/potassium adenosine triphosphatase enzyme
(H+K+ATPase) system of the gastric parietal cells.
The proton pump is the terminal stage in gastric acid secretion
18. PROTON PUMP
INHIBITORS
(OMEPRAZOLE)
Prototype member of this category
Overtaken H2 blockers for acid peptic disorders
Dose dependant suppression of gastric secretion
No anticholinergic/ antihistaminergic
Powerful inhibitor of gastric acid secretion both resting and as
well as stimulated
No much action on pepsin, juice volume and gastric motility
19. MECHANISM OF ACTION
Inactive at neutral pH, but at <5 it rearranges to two charged
cationic forms
React covalently with SH groups of H+K+ATPase enzyme and
inactivate it irreversibly
After absorption if diffusion and concentrate in parietal cell and
then in acidic pH of canaliculi
Binds tighly covalently with enzyme of parietal cell confer high
degree of selectivity
Acid secretion resumes only when new H+K+ATPase
molecules are synthesized
20. PHARMACOKINETICS
All PPIs are administered enteric coated
Oral bioavailability is 50% due to acid lability
Food interferes with absorption
Should be taken 1 hour prior to meal
Highly plasma protein binding
Metabolised byCYP2C19 and CYP3A4
Plasma t1/2 is1 hour
Metabolites are excreted in urine
No dose modification is required in any impairment
22. HELICOBACTER PYLORI
1981 - Robin Warren, M.D.,
an Australian pathologist,
discovered numerous
bacteria living in tissue taken
during a stomach biopsy.
Spiral urease-producing, Gram-
negative bacteria always
accompanied changes in the
stomach lining
23. HELICOBACTER PYLORI
Gram negative, Spiral bacilli
Spirochetes
Do not invade cells – only mucous
Breakdown urea - ammonia
Break down mucosal defense
Chronic Superficial inflammation
24. SYMPTOMS OF H. PYLORI
Abdominal pain
Feeling of Fullness
Indigestion
Feeling very hungry 1 to 3 hours after
eating
Mild nausea
Pain Starts 2/3 hours after meals, or in the
middle of the night
26. DIAGNOSIS
Endoscopy:
Flexible tube fitted with camera is
threaded down the esophagus in to
stomach to see the ulcer by physician
Bariummeal:
Barium liquid is drunk making ulcer
visible on X-ray
27. Test fordiagnosing H.pylori
Breath test :by measuring the amount of co2 in exhaled
breath.
Blood test: by identifying H.pylori antibodies by ELISA test.
Stool test :stool sample tested with H.pylori antigen.
28. ACETYL CHOLINE
ANTAGONIST
PIRENZEPINE
MECHANISM:
It selectively block M1 muscaranic recptors and inhibits
gastric secretion.
Because of their relatively poor efficacy, side effects, and risk
of blood disorders, they are rarely used today
29. AGENTS THAT ENHANCE
MUCOSAL DEFENSE
Prostaglandin Analogs:
prostaglandins are produced in the gastric
mucosa and appear to serve a protective role by inhibiting acid
secretion and promoting mucus
and bicarbonate secretion.
In addition, PGs inhibits gastrin production, increase mucosal
blood flow and probably have an ill defined cytoprotective
action.
DRUGS: Misoprostol
30. MISOPROSTOL
MECHANISM:
Misoprostol acts upon gastric parietal cells, inhibiting the
secretion of gastric acid via G-protein coupled receptor-mediated
inhibition of adenylate cyclase, which leads to decreased intracellular
cyclic AMP levels and decreased
pump activity at the apical surface of the parietal cell
Side effects
Diarrhea.
Other common side effects include: abdominal pain, nausea,
flatulence, headache, dyspepsia, vomiting, and constipation.
31. ULCER PROTECTIVES
SUCRALFATE
MECHANISM:
Sucralfate is a locally acting substance that in an acidic environment
(pH < 4),
reacts with hydrochloric acid in the stomach to form a cross-linking,
viscous, paste-like material capable of acting as an acid buffer for as
long as 6 to 8 hours after a single dose.
It also attaches to proteins on the surface of ulcers, such as albumin and
fibrinogen, to form stable insoluble complexes.
These complexes serve as protective barriers at the ulcer surface,
preventing further damage from acid, pepsin, and bile.
32. Side effects
The most common side effects seen are constipation. Less
commonly reported include flatulence, cephalalgia (headache),
xerostomia (dry mouth).
USES:
It is used in treatment of
Gastritis,
Stress ulcers.
33. ANTACIDS
Basic substances which neutralize the gastric acid and
increase pH
Peptic activity is indirectly reduced if pH increase above 4
which dissociates below 5
Do not decrease acid production rather increase acid antral pH
>4
Potency is generally expressed in term ANC
Acid ne utraliz ing capacity : no o f m Eq o f 1 NHClthat are
brought to pH 3.5 in 15 mins by a unit dose of antacid
34. ANTACID
SYSTEMIC ANTACIDS
Sodiumbicarbonate It is watersoluble, acts instantaneously, but
the duration of action is short. It is a potent neutralizer (1 g → 12
mEq HCl), pH may rise above 7. However, it has several
demerits:
(a) Absorbed systemically: large doses will induce alkalosis.
(b) Produces CO2 in stomach → distention, discomfort, belching,
risk of ulcer perforation.
(c) Acid rebound occurs, but is usually short lasting.
35. NON SYSTEMIC
ANTACIDSInsoluble and poorly absorbed basic substance react in
stomach to form corresponding chloride salts
The chloride salts reacts with intestinal bicarbonate so that
HCO3 in spread for absorption- no acid basic disturbances
occurs
Magnesium hydroxide ( milk of magnesia) with 30mEq HCl
Magnesium trisilicate :mg salts are having laxative action
generation osmotically active MgCl2 induced cholecystokinin
hormone
36. Alluminium hydroxide:
It ANC depends upon storage, it activity decline as storage time
increases
Alum. hydrox. binds phosphate in the intestine and prevents its
absorption—hypophosphatemia occurs on regular use. This may:
(a) cause osteomalacia
(b) be used therapeutically in hyperphosphatemia and phosphate
stones.
Small amount of Al3+ that is absorbed is excreted by
kidney. This is impaired in renal failure—aluminium
toxicity(encephalopathy, osteoporosis) can occur.
37. SODIUM BICARBONATE
(ANTACID)
It is water soluble, acts instantaneously,
but duration of action is short. It is a potent
neutralizer, pH may raises above 7.
Adverse reactions
It causes systemic alkalosis, gastric
distention, rebound acidity and milk-alkali
syndrome
Uses
It is restricted to casual treatment of
heartburn and to treat acidosis