Presentation on GI System, Ulceration Management &

Role of PPI

Md. Mustafizur Rahman SonnetB.Pharm, M.Pharm

Management of Ulceration and Role of Proton Pump Inhibitors(PPI)

Gastrointestinal System

Ulceration

1.Oral Cavity-Grinding Food, Absorb specific molecule2.Pharynx-Transfer food/Drug to esophagus3.Esophagus-Carries food/drug into Stomach4.Stomach-Digestion and absorption5.Duodenum-Breakdown food using enzyme6.Liver, Gallbladder, Pancreas-Production and storage of enzyme7.Small intestine-Digestion and Absorption8.Large Intestine -Breakdown and absorb food9.Rectum-Store feces and absorption.

Components of GI System:

Gastrointestinal System

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)

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)

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).

• 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

• 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

Complications of PUD:

Hemorrhage– Blood vessels damaged as ulcer erodes into the muscles of

stomach or duodenal wallPerforation

– An ulcer can erode through the entire wall– Bacteria and partially digested food spill into

peritoneum=peritonitisNarrowing and obstruction (pyloric)

– Swelling and scarring can cause obstruction of food leaving stomach=repeated vomiting

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

HCl + Antacid [Al(OH)3+Mg(OH)2] = Neutralize HCl

-Used for symptomatic relief -Not used to Healing ulcer

Antacid:

Histamin-2 Receptor Antagonist (H2RA):

-Reduce Gastric juice Secretion -Relieve persistent GERD symptoms-Not used for healing ulcer

H2RA Agents: Ranitidine Femotidine Cimetidine Nizatidine

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

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.

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

How Proton Pump Works:

PPI blocks H+/K+ ATPase receptor to terminate all proton production from each Parietal cell

Management of Peptic Ulcer Disease (PUD):

NSAID-induced ulcers:PPI+ MisoprostolWhen 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 + ClarithromycinorPPI + Clarithromycin + MetronidazoleorWhen normal medication is failedPPI + Bismuth + Tetracycline + Metronidazole

Only PPI Can Suppress 80-98% HCl ProductionIrreversibly Blocks Most Of The Proton Pumps

Common Adverse Effects of PPI:

Headache Diarrhea Abdominal Pain NauseaVomiting Carcinoid Tumor(prolong use) Bone fraction

Comparison of Proton Pump Inhibitors

Bioavailability:

Time for Plasma Peak Level:

Duration of Action of PPI:

Chance of ulceration when used with NSAIDs

Thank You