Proton Pump Inhibitor Function and Ulceration Management

1. Presentation on
GI System, Ulceration Management &
Role of PPI
Md. Mustafizur Rahman Sonnet
B.Pharm, M.Pharm

2. Management of Ulceration and Role of Proton
Pump Inhibitors(PPI)
Gastrointestinal System
Ulceration

3. 1.Oral Cavity
-Grinding Food, Absorb specific molecule
2.Pharynx
-Transfer food/Drug to esophagus
3.Esophagus
-Carries food/drug into Stomach
4.Stomach
-Digestion and absorption
5.Duodenum
-Breakdown food using enzyme
6.Liver, Gallbladder, Pancreas
-Production and storage of enzyme
7.Small intestine
-Digestion and Absorption
8.Large Intestine
-Breakdown and absorb food
9.Rectum
-Store feces and absorption.
Components of GI System:
Gastrointestinal System

4. 1. Stomach
-pH 1.5-3.5 (Acidic)
-Pepsinogen—Pepsin (Converted by HCl)
-Prorenin—Renin (Converted by HCl)
-Mucus layer(First line defense)
-Parietal Cell (Contain Proton Pump)
-Proton Pump (Produce H+)
-Gastric emptying time 1-2 hours
Critical Areas of GI System (Responsible for Ulceration and PPI Activities)

5. 2. Small Intestine
-Duodenum (ph 6)
-Bile salt, pancreatic juice
-Ph 6-7.4(Basic)
-Villi (Each Square inch mucusa contain 20000 villi)
-Micro-Villi(Each Square inch mucusa contain 130 billion microvilli)

6. Ulceration or Peptic Ulcer Disease(PUD):
PUD is a break in the lining of the stomach(Gastric Ulcer), first part of the small
intestine(Deodenal Ulcer), or occasionally the lower esophagus(Esophageal Ulcer).
Ulceration of the gastrointestinal mucosa occurring in areas exposed to acid and
pepsin and most often caused by Helicobacter pylori infection.
(Infects mucosa of stomach > inflammatory response > gastritis > increased gastrin
secretion > gastric metaplasia > damage to mucosa > ulceration).

7. • Helicobacter Pylori
• Non Steroidal Anti-inflammatory Drugs
• Steroid therapy
• Smoking
• Excess alcohol intake
• Genetic factors
• Zollinger Ellison syndrome – rare syndrome caused by gastrin-
secreting tumor
• Blood group O
• Hyperparathyroidism
Risk Factors of PUD

8. • Epigastric tenderness
– Gastric: epigastrium; left of midline
– Duodenal: mid to right of epigastrium
• Sharp, burning, aching, gnawing pain
• Dyspepsia (indigestion)
• Nausea/vomiting
• Belching
General Symptom of PUD

9. Complications of PUD:
Hemorrhage
– Blood vessels damaged as ulcer erodes into the muscles of
stomach or duodenal wall
Perforation
– An ulcer can erode through the entire wall
– Bacteria and partially digested food spill into
peritoneum=peritonitis
Narrowing and obstruction (pyloric)
– Swelling and scarring can cause obstruction of food leaving
stomach=repeated vomiting

10.  Antacids
-neutralize stomach acid.
 Histamin-2 Antagonist
-reduce acid production.
 Muscarin-1 Antagonist
-reduce acid production.
 Cytoprotective Drug
-protect the lining of your stomach and small intestine.
 Proton Pump Inhibitor (PPI)
-block acid production and promote healing(End time protection).
 Antibiotic
-kill H. pylori.
Over the years a variety of therapies have been developed to treat acid-related
conditions. For example –
GI Acid Controlling Agents

11. HCl + Antacid [Al(OH)3+Mg(OH)2] = Neutralize HCl
-Used for symptomatic relief
-Not used to Healing ulcer
Antacid:

12. Histamin-2 Receptor Antagonist (H2RA):
-Reduce Gastric juice Secretion
-Relieve persistent GERD symptoms
-Not used for healing ulcer
H2RA Agents:
 Ranitidine
 Femotidine
 Cimetidine
 Nizatidine

13. Cytoprotective drugs: Sucralfate, Misoprostol
Sucralfate:
-Give physical barrier to prevent degradation of mucus by acid
-Give protective barrier to ulcered area from further acid exposure
Misoprostol:
-Reduce HCl production by blocking PG receptor
-Used in prevention of NSAID-induced gastric ulcers
-Stimulate mucus production

14. Antibiotic:
Antibiotic + Helicobacter Pylori= Kill H. Pylori
Antibiotics:
 Amoxicillin
 Tetracycline
 Clarithromycin
 Metronidazole
-Most common cause of gastric and deodenal ulcer.
-Antibiotic kills the pathogen.
-Need combination therapy with PPI for acid suppression.

15. Proton Pump Inhibitor:
PPI
-The most potent drugs that reduce gastric acid production
-Inhibit the final step of gastric acid production
-Common drug for PUD
PPI Agent:
Omeprazole
Lansoprazole
Dexlansoprazole
Rabeprazole
Pantoprazole
Esomeprazole
Ilaprazole

16. How Proton Pump Works:
PPI blocks H+/K+ ATPase receptor to terminate all proton production
from each Parietal cell

17. Management of Peptic Ulcer Disease (PUD):
NSAID-induced ulcers:
PPI+ Misoprostol
When NSAID must be continued
PPI + COX-2 selective inhibitor/ low dose NSAID/ less toxic NSAID
Bleeding PUD:
Only PPI
H. Pylori induced ulcer:
PPI + Amoxicillin + Clarithromycin
or
PPI + Clarithromycin + Metronidazole
or
When normal medication is failed
PPI + Bismuth + Tetracycline + Metronidazole
Only PPI Can Suppress 80-98% HCl Production
Irreversibly Blocks Most Of The Proton Pumps

18. Common Adverse Effects of PPI:
 Headache
 Diarrhea
 Abdominal Pain
 Nausea
Vomiting
 Carcinoid Tumor(prolong use)
 Bone fraction

19. Comparison of Proton Pump Inhibitors

20. Bioavailability:

21. Time for Plasma Peak Level:

22. Duration of Action of PPI:

23. Chance of ulceration when used with NSAIDs

24. Thank You