This document summarizes anti-ulcer drugs. It discusses the causes of ulcers including H. pylori infections and NSAID use. The main types of ulcers are described along with signs and symptoms. Treatment includes eradicating H. pylori, decreasing acid secretion through proton pump inhibitors or H2 receptor blockers, and protecting the stomach lining with drugs like misoprostol or sucralfate. Proton pump inhibitors are now the most potent way to decrease acid production and promote ulcer healing.

1. ANTI-ULCER DRUGS
M.ASIYABI
M.PHARM – 1st YEAR
DEPARTMENT OF PHARMACOLOGY
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2. INTRODUCTION
• From ancient time stomach ulcer has been
recognised and also therapy established
according to their knowledge.
• A Roman emperor Marcus Aurelius was died due
to perforated ulcer.
• More than 12 centuries ago, Paulus Aeginata
recognised the acid neutralisation was the
effective treatment.
• Later on 19 th century, lot of research has been
developed for treatment of ulcer.

3. Cont…..
• After period of time it has been identified that
bacteria can cause the ulcer. (Mainly
Helicobacter pylori)
• The main goal of Anti-ulcer drug is that to
decreasing the level of gastric acidity or
enhancing mucosal protection.
• For infectious agent new approach was found
to prevent or to kill micro organisms.

4. ULCER
• Stomach ulcers are painful sores that can be
found in the stomach lining or small intestine.
• They occur when the thick layer of mucus that
protects your stomach from digestive juices is
reduced, thus enabling the digestive acids to
eat away at the lining tissues of the stomach.
• A stomach or gastric ulcer is a break in the
tissue lining the stomach.

5. CAUSES
• An infection with the bacterium Helicobacter
pylori (H. pylori)
• Long-term use of nonsteroidal anti-inflammatory
drugs, such as aspirin and ibuprofen.
• Many people take NSAIDs without having any
side effects, but there's always a risk the
medication could cause problems, such
as stomach ulcers, particularly if taken for a long
time or at high doses.
• Cancer: stomach cancer can present as an ulcer,
particularly in older people.

6. CAUSES BY LIFESTYLE FACTORS
• Not eating food on time (Eating Late)
• Too much of spicy foods
• Stress
• Drink too much of alcohol
• Ciggarette smoking.

7. SIGNS AND SYMPTOMS
• Burning sensation
• Abdominal pain just below the ribcage
• Bloating
• Bright or altered blood present in vomit or bowel
motions
• Burping or acid reflux
• Dark blood in stools or stools that are black or
tarry
• Heartburn (burning sensation in the chest)

8. Cont….
• Indigestion
• Nausea
• Loss of appetite
• Symptoms of anemia, such as light-headedness
• The vomiting of blood — which may appear red
or black
• Shock due to blood loss which require medical
attention (medical emergency).
• Weight loss

11. • Gastric secretions of the stomach strive to keep
a pH of 2 to 5.
• Pepsin-a digestive enzyme is activated at a pH of
2, the acid-pepsin complex of gastric secretions
can cause mucosal damage
• If the pH inc. to 5 - the activity of pepsin declines
• Gastric Mucusal Barrier (GMB) - thick, viscous,
mucous material that provides a barrier between
the mucosal lining & the acidic gastric secretions -
defense against corrosive substances, maintains
integrity of the gastric mucosal lining

12. Possible areas of ulcer in Stomach

13. SPINCHTER MUSCLES
• Two sphincter muscles:
- Cardiac - located at the upper portion of the
stomach - prevents reflux of acid into the
esophagus
- pyloric - located at the lower portion of the
stomach - prevents reflux of acid into the
duodenum

14. TYPES OF ULCER
* Esophageal ulcers  reflux of acidic gastric
secretion into the esophagus d/t a defective
or incompetent cardiac sphincter
* Duodenal ulcers  hypersecretion of acid
from the stomach that passes to the
duodenum
* Gastric ulcer  breakdown of GMB (gastric
mucosal barrier)
* Pyloric ulcer

15. PATHOPHYSIOLOGY
There is imbalance between aggressive factors
(acid & pepsin) and
defensive factors(e.g. prostaglandins,
mucus & bicarbonate layer).

16. Cont…
1. Hydrochloric acid and pepsin destroy gastric
and duodenal mucosa.
2. Mucus and bicarbonate ion secretions
protect mucosa
3. Prostaglandins protect mucosa by enhancing
mucus and bicarbonate production and by
enhancing mucosal blood flow

17. Regulation of gastric secretions
Parietal cells secrete acid in response to:
1. Histamine (local hormone): H2 receptors
2. Gastrin (hormone): CCK2 receptors
3. Ach (neurotransmitter): M3 receptors
4. Proton pump (H+/ K+ ATPase)

21. TREATMENT
 Eradication of H. pylori infections
 Hyposecretory drugs.
 H2 receptor blockers
 Antimuscarinic drugs
 Proton pump inhibitors
 Mucosal cytoprotective agents.
 Prostaglandin analogues
 Sucralfate (CarafateR)
 Neutralizing agents (antacids).

23. Gastric hyposecretory drugs
Include:
 H2 receptor blockers
 Proton pump inhibitors
 Antimuscarinic drugs
 Hyposecretory drugs decrease gastric acid
secretion Promote healing & relieve
pain.

24. Proton pump inhibitors (PPI’S)
Omeprazole – Lansoprazole
Pantoprazole -Raprazole
Acts by irreversible inhibition of proton pump
(H+/ K+ ATPase) that is responsible for final
step in gastric acid secretion from the parietal
cell.

25. PHARMACODYNAMICS
 They are the most potent inhibitors of acid
secretion available today.
 Produce marked inhibition of basal & meal
stimulated-acid secretion (90-98%).
 Reduce pepsin activity.
 Promote mucosal healing & decrease pain
 Proton pump inhibitors heal faster the ulcers
than H-2 blockers, and have H.pylori
inhibitory properties How?.

26. PHARMACODYNAMICS
 They are the most potent inhibitors of acid
secretion available today.
 Produce marked inhibition of basal & meal
stimulated-acid secretion (90-98%).
 Reduce pepsin activity.
 Promote mucosal healing & decrease pain
 Proton pump inhibitors heal faster the ulcers
than H-2 blockers, and have H.pylori
inhibitory property.

27. PHARMACOKINETICS
 Given orally as enteric coated capsules
(unstable in acidic medium in stomach).
 Are pro-drugs
 rapidly absorbed from the intestine.
 Activated in the acidic medium of parietal
cell canaliculi. Therefore,
 Should not be combined with H2 blockers or
antacids.
 Inactivated if at neutral pH.

28. Cont….
 Have long duration of action (> 12 h-24 h).
 Once daily dose is sufficient
 Given 1 h before meal.
 Bioavailability is reduced by food.
 metabolized in the liver by Cyt-P450.
 Dose reduction is required in severe liver
failure.

29. USES
Eradication of H. pylori (combined with
antimicrobial drugs).
Resistant severe peptic ulcer ( 4-8 weeks).
 Reflux esophagitis.
Hypersecretory conditions as Zollinger
Ellison syndrome and gastrinoma (First
choice).

30. ADVERSE EFFECTS
Headache, diarrhea & abdominal pain.
 Achlorhydria
 Hypergastrinaemia.
 Gastric mucosal hyperplasia.
- Increased bacterial flora
- increased risk of community-acquired
respiratory infections & nosocomial pneumonia
 Long term use:
 Vitamin B12 deficiency
 increased risk of hip fractures

31. H2 receptor blockers
-Cimetidine - Ranitidine
- Famotidine - Nizatidine
Mechanism of action
 They competitively and reversibly block
H2 receptors on the parietal cells.

32. PHARMACOKINETICS
 Good oral absorption
 Given before meals.
 Famotidine is the most potent drug.
 Exposed to first pass metabolism (except
nizatidine that has 100 % bioavailability).
 Duration of action (4-12 h).
 Metabolized by liver.
 Excreted mainly in urine.
 Cross placenta & excreted in milk (should
not be given in pregnancy unless it is necessary).

34. PHARMACODYNAMICS
 Reduce basal and food stimulated-acid
secretion
 Block 90% of nocturnal acid secretion
(which depend largely on histamine) & 60-
70% of total 24 hr acid secretion.
Therefore, it is better to be given before
night sleep.
 Reduce pepsin activity.
 Promote mucosal healing & decrease pain

35. USES
GERD ((heartburn/ dyspepsia).
Acute ulcer healing in moderate cases
Duodenal Ulcer (6-8 weeks).
Benign gastric ulcer (8-12 weeks).
Pre-anesthetic medication (to prevent aspiration
pneumonitis).
Prevention of bleeding from stress-related gastritis.
Post–ulcer healing maintenance therapy.
Together with NSAIDs to prevent ulcers

36. ADVERSE EFFECTS
 GIT disturbances (Nausea & Vomiting).
 CNS effects: Headache - confusion
(elderly, hepatic dysfunction, renal
dysfunction).
 Bradycardia and hypotension (rapid I.V.)
 CYT-P450 inhibition (Only Cimetidine)
decrease metabolism of warfarin,
phenytoin, benzodiazepines.

37. Cont…
Endocrine effects (Only Cimetidine)
 Galactorrhea (Hyperprolactinemia )
 Antiandrogenic actions (gynecomasteia –
impotence) due to inhibition of
dihydrotestosterone binding to androgen
receptors.
Precautions
Dose reduction of H2 RAs in severe renal or
hepatic failure and elderly.

38. ANTACIDS
These drugs are mainly inorganic salts
e.g.: NaHCO3; Ca CO3; Al (OH)3; Mg (OH)2
acts by direct chemical neutralization of
HCL and as a result may decrease pepsin
activity.
 used to relief pain of peptic ulcer & for
dyspepsia.
 All antacids  absorption of some drugs as
tetracycline, fluoroquinolones, iron.

39. Cont….
NaHCO3: Systemic alkalosis; CaCO3 : milk
alkali syndrome (hypercalcemia, renal failure)
Al (OH)3 : constipation; Mg (OH)2 : Diarrhea
Therefore, combination of Mg (OH)2 plus
Al (OH)3 commonly used.

40. MISOPROSTOL
Prostaglandin analogues (PGE1 )
  HCL secretion.
  protective measures (mucous/bicarbonate
& gastric mucosal blood flow).
Orally, must be taken 3-4 times/day.
Used for NSAIDS-induced peptic ulcer but H2
blockers or proton pump inhibition are better.
Adverse effects:
Abdominal cramps; diarrhea
Uterine contraction (dysmenorrhea or abortion);
Vaginal bleeding.

41. If H. pylori infection is diagnosed in the
presence of peptic ulcer disease
• Eradication with most commonly "triple
therapy" with a PPI, clarithromycin,
and amoxicillin +/- metronidazole for 7-14
days (Cure rates of 70% to 90% ).
• Pentaprazole 40 mg BID
• Amoxicillin 1000 mg BID
• Clarithromycin 500 mg BID

42. SUCRALFATE
–Is a sucrose sulfate-aliminium complex
works as an oral cytoprotective agent via
binding to the duedenal mucosa and thus
creating physical barrier. Also, may
stimulate bicarbonate secretion
–USES : Mainly as an addition for resistance
gastritis or GERD

43. FOR BETTER UNDERSTANDING WATCH
THIS VIDEO WITH PASSION

44. ANY QUERIES…???