Presented by: Mohd akhtar M.Pharm. (Pharmacology)
Jul 16, 2015
Presented by:Mohd akhtar
M.Pharm. (Pharmacology)
Anatomy of Stomach Acid Peptic Disorders Peptic ulcer disease Comparison of Gastric & Duodenal ulcers Risk factors Symptoms Physiology of Acid secretion Treatment of peptic ulcer Summary
MuscularisSerosa
MucosaSubmucosa
Fundic Fundic regionregion
Esophagus
Duodenum
AntrumAntrum
Layers
Parietalcells
BodyBody
Pyloricsphincter
Chief cells
Gastric pit
Peptic Ulcers• Gastric ulcer• Duodenal Ulcer
Gastro Esophageal Reflux Disease (GERD) Dyspepsia Stress Ulcers Gastric Cancers
Peptic ulcer refers to an erosion of the mucosal layer anywhere in the GI tract; however, it usually refers to erosions in the stomach or duodenum.
Over 80% of peptic ulcers are caused by Infection with the bacterium Helicobacter pylori.
Pathophysiology of Peptic Ulcer Pathophysiology of Peptic Ulcer Disease (PUD)Disease (PUD)
Mucosal Defenses
• Bicarbonate
• Mucus
• Prostaglandin
• Growth factor
• Mucosal regeneration
Luminal Aggressors
• H. pylori
• NSAIDs
• Acid
• Pepsin
DUODENAL GASTRIC
INCIDENCE More common Less common
ANATOMY First part of duodenum – anterior wall
Lesser curvature of stomach
DURATION Acute or chronic Chronic
MALIGNANCY Rare Benign or malignant
HELICOBACTER PYLORI Infection Non Steroidal Anti-inflammatory Drugs Steroid therapy Smoking Excess alcohol intake Genetic factors Zollinger Ellison syndrome – rare syndrome caused by
gastrin-secreting tumour Blood group O Hyperparathyroidism
Nausea – Vomiting – Anorexia Epigastric pain after meal and during meal Intolerance of fatty food Heartburn Loss of weight Oral flatulence, bloating Pain radiating to the back
Feldman: Sleisenger & Fortran’s Gastrointestinal and Liver Disease, 7 th ed.
Gastrointestinal hemorrhage Chronic iron deficiency anemia
Pyloric stenosis Perforation
peritonitis
Bacteria Gram Negative spiral bacterium 40% of patients >60 years are +ve for H.pylori Transmitted: possibly person to person Most common cause of antral gastritis
Mechanism of gastric injury Adherence to epithelial cells Infects mucosa of stomach > inflammatory response >
gastritis > increased gastrin secretion > gastric metaplasia > damage to mucosa > ulceration
Cytotoxin
Inhibits prostaglandin synthesis (COX inhibition)
Disrupts functional mucosal integrity
↓ mucosal blood flow ↓ cell regeneration Direct GI irritation Antiplatelet effect
(causing bleeding) ↑ acid (basal and
maximal stimulation) secretion
ProglumideACh
PGE2
Histamine Gastrin
Adenyl cyclase
_+
ATP cAMP
Protein Kinase (Activated)
Ca++
+
Ca++
Proton pump
K+ H+
Gastric acid
Parietal cell
Lumen of stomach
AntacidOmeprazole
Ranitidine
H2M3
Misoprostol
_
__
_
+
PGE receptor
+
+
Gastrin receptor+
+
+
Cl- K+
Promotion of ulcer healing.Symptomatic relief of pain.
Prevention of recurrence (relapse).Prevention of complications
I. Gastric hyposecretory drugs Proton pump inhibitors H2 receptor blockers Muscarinic receptor blockers
II. Eradication of H. pylori infections To prevent relapse
III. Mucosal cytoprotective agents Sucralfate Colloidal bismuth Prostaglandin analogues
IV. Neutralizing agents (antacids)
1. Proton pump inhibitors2. H2 receptor blockers3. Muscarinic receptor blockers
Mechanism of actionIrreversible inhibition of proton pump (H+/ K+ ATPase) that is responsible for final step in gastric acid secretion from the parietal cell.
PP inhibitors include: Omperazole Lansoprazole Pantoprazole Rabeprazole
They are prodrugs – taken orally. Are given as enteric coated capsules
They are activated in the acidic medium of the secretory parietal cell canaliculus.
They are inactivated if (combined with H2 receptor blockers).
Have long duration of action (> 18 -24 hr). Bioavailability is reduced by food. Given 1 hr before meal.
PPIs are quite safe but may occur:GIT disturbances: nausea, vomiting, diarrhoea
Achlorhydria: increase the risk of enteric infections due to Shigella, salmonella
Hypergastrinaemia Gastric hyperplasia
Mechanism of actionThey competitively and reversibly block to H2 receptors on the parietal cells thus reduce gastric secretion. They include:
H2 Receptor inhibitors include: Cimetidine Ranitidine
Famotidine Nizatidine
Good oral absorption Plasma half life (1-3 h). Duration (4-12 h). First pass metabolism (50% Except Nizatidine
100 % bioavailability). Given before meals. Metabolized by liver. Excreted mainly in urine. Cross placenta & excreted in milk
These are extremely safe drugs but may occur: nausea, vomiting, bradycardia and hypotension (rapid
I.V.) Gynecomasteia, impotence in male Galactorrhea in female on long term use
of cimitidine Decrease metabolism of oral anticoagulant,
phenytoin, benzodiazepines.
Acid (control)H2 BlockPPI
Mechanism of action Blocks M3 receptors on the parietal cells. Selectively inhibit gastric acid secretion Decreased gastric motility Delayed gastric emptying
Muscarinic blockers: Oxyphenonium Dicyclomine Pirenzepine Telenzepine
TreatmentCombined therapy is usually used.
Clarithromycin, tetracycline, amoxicillin Proton pump inhibitors or H2 receptor
blockers Bismuth compounds Metronidazole
Resistance may develop to antibiotics so the better eradication is obtained using proton pump inhibitors, clarithromycin & Amoxicillin.
The BEST among all the Triple therapy regimen is
Omeprazole/Lansoprazole - 20/30 mg bd
Clarithromycin - 500 mg bd
Amoxycillin/Metronidazole -1gm/500 mg bd
Given for 14 days followed by P.P.I for 4 – 6 weeks.
Short regimens for 7 – 10 days not very effective.
REGIMEN DOSE DURATION
BismuthMetronidazole
Tetracycline
525 mg qid250 mg tid500 mg qid
2 weeks
omeprazoleMetronidazole
Clarithromycin
20 mg bid500 mg bid500 mg bid
1 week
omeprazoleAmoxacillin
Clarithromycin
20 mg bid500 mg qid500 mg bid
1 week
omeprazoleBismuth
MetronidazoleAmoxacillin or /
Tetracycline
20 mg bid525 mg qid500 mg qid500 mg qid
week
1. Sucralfate2. Prostaglandin analogs3. Colloidal bismuth
Bismuth subcitrate Tripotassium dicitrato bismuthate
Sucralfate (aluminum hydroxide + sucrose) Form a sticky like gel over ulcer crater to
protect gastrointestinal mucosa and stimulates prostaglandin synthesis
It promote mucosal repair and ulcer healing It has no acid neutralising action and delay
gastric emptying Dose: 1 g QID
Misoprostol is a prostaglandin E1 analog that stimulates the secretion of mucus and bicarbonates and inhibits acid secretion to a minor degree.
The drug has significant side effects, primarily mild to moderate diarrhoea
Is too costly to be used by most patients.
Drugs used to relief gastric pain associated with hypersecretion of HCL and neutralize the gastric acid.
Mechanism of ActionNeutralization of HCL
Inhibition of pepsin (inactive at PH 5)
1. Systemic AntacidsSodium bicarbonate Calcium Carbonate
2. Non Systemic AntacidsAluminum Hydroxide GelMagnesium Trisilicate
Sodium bicarbonate Calcium Carbonate
NaHCO3 + HCL → NaCL + CO2
Disadvantages Rebound hyperacidity Stomach distension due to CO2 liberation
→ pain sensation
Sodium load → salt and water retention
( # in cardiac patients) Systemic alkalosis
Aluminum Hydroxide Gel Magnesium Trisilicate
Al (OH)3 + HCL → HCL3 + H2O
Advantages Longer duration of action. Gradual neutralization of HCL → No rebound
hyperacidity. Adsorbs pepsin. No stomach distention
Due to the benign nature of duodenal ulcers When patients with duodenal ulcers require
surgery, it is usually one of three procedures:
Vagotomy,Vagotomy with antrectomy,Pyloroplasty
A peptic ulcer is a break in superficial epithelial cells penetrating down to muscularis mucosa
Duodenal > gastric ulcers H pylori is a predominant risk factor H pylori diagnosed by c urea breath test, stool
antigen or if validated serology, treated with PAC500 or PMC250 regimen
Complications of PUD can lead to acute emergency of upper GI bleed