· Peptic ulcer is gastrointestinal disorder which is exposed to gastric acid and pepsin on the lining of the esophagus, stomach and small intestine.
· There are two type of peptic ulcer
1. Gastric ulcer (lining of the stomach)
2. Duodenal ulcer (from in the upper part of the small intestine)
PARTS OF THE STOMACH
· It is a muscular tube links the throat to the stomach.
Lower esophageal sphincter
· LES open to allow the food particle to the stomach and then closes quickly to prevent back into the esophagus.
· Stores gases produce during digestion.
· Volume is 50 ml when empty, then expand up to 1 liter.
· Contain arteries and vein which delivered and return blood to the liver
· It produces chyme
· Strong wave like muscle (strong peristaltic contraction).
· The chyme is pushed depends upon the strength of the peristaltic contraction.
· The chyme is mixed with digestive enzyme and bile in the duodenum.
· Contains 25-38 cm (small intestine), where nutrients absorption begins.
PHASES OF GASTRIC ACID SECRETION
1. Cephalic phase
· Cephalic phase is activated by the thought, taste, smell and sight of food, and swallowing, mediated mostly by cholinergic/vagal mechanisms.
2. Gastric phase
· Gastric phase is due to the chemical effects of food and distension of the stomach
3. Intestinal phase
· Intestinal phase only a small proportion of the acid secretory response to a meal; its mediators remain unknown.
REGULATION OF GASTRIC ACID SECRETION
· Histamine, Ach and Gastrin have their own receptors located on the basolateral membrane.
· The primary action is that to secrete H+ ion in the apical canaliculi of parietal cell through the enzyme H+ K+ ATPase.
· Gastrin and Ach act partly directly and to a greater extent indirectly by releasing histamine from paracrine enterochromaffin-like (ECL) cells called “histaminocytes” located in the oxyntic glands.
· While H2 receptors activate H+ K+ ATPase by generating cAMP, muscarinic and gastrin/cholecystokinin (CCK2) receptors through the phospholipase C (IP3–DAG) pathway that mobilizes intracellular Ca2+.
· Prostaglandins have a “cytoprotective” role in the gastric mucosa by secreting mucus and bicarbonate.
· Somatostatin blocks the action of histamine, Gastrin and also the HCl production.
1) Reduction of gastric acid secretion
(a) H2 antihistamines:
(b) Proton pump inhibitors:
(c) Anticholinergic drugs:
(d) Prostaglandin analogue:
2) Neutralization of gastric acid (Antacids)
· Sodium bicarbonate
· Sod. citrate
· Magnesium hydroxide
· Mag. Trisilicate
· Aluminium hydroxide gel
· Calcium carbonate
3) Ulcer protectives:
· Colloidal bismuth subcitrate (CBS)
4) Anti-H. pylori drugs:
MECHANISM OF ACTION
· Gastric acid secretion is stimulated by Ach, Histamine and Gastrin, which activate protein kinase (PKA) turn stimulates H+ K+ ATPase (proton pump).
· Dicyclomine and Cimetidine binds to the cholinergic and histamine receptor to inhibit the activation of adenylyl cyclase.
· Omeprazole inactive the proton pump.
· Prostaglandin shows inhibitory action to produce inactive the adenylyl cyclase. This action is blocked by Mesoprostol.
REDUCTION OF GASTRIC ACID SECRETION
· Act selectively on H2 receptor.
· They are competitive antagonist (Reversible).
· Inhibit CYP450
· Produce endocrine effect like Gynecomastia and galactorrhea (anti-androgenic effect).
Ranitidine & Famotidine
· No anti-androgenic effect.
· ↑more bioavailability
· Widely distributed throughout the body (including breast milk and across the placenta).
· Excreted in urine.
· Available in i.v. formulation.
· Peptic ulcer
· Zollinger Ellison syndrome (ZES)
· Inhibit H+ K+ ATPase (proton pump)
· Inhibit irreversibly
· It has enteric coated that absorbed in small intestine and diffuse to the blood then it diffuses back to the parietal cell.
· Effective orally
· Food interaction ↓se absorption.
· Administration 30 min before food.
· Highly plasma bound
· Available in parenteral.
· ↓se vit. B12 absorption.
· Gastric tumor
· Inhibit CYP2C19 (inhibit effectiveness of clopidogrel).
· DOC → GERD
· Peptic ulcer
· Used with antimicrobials to treat H. pylori.
· Selective for M1 receptor.
· Not usually used because ↓se efficacy and shows serious side effects.
· ↓se gastric acid secretion.
· ↑ secretion of mucus.
· ↑ bicarbonate
· ↑ HCO3– these effect shows the cytoprotective effect.
· During pregnancy produce uterine contraction and abortion.
Acid Neutralizing Agents
Anti-H. Pylori Agent
· Sucralfate in acidic medium get polymerized and stick on the ulcer area.
· Also, protein ppt at the site of the damage.
· Epidermal growth factor
· ↑ HCO3– secretion
· Taken one hour before meal
· It needs acidic pH to work so, Antacid, PPIs should not give along with this.
· Used in GERD
· Magnesium hydroxide, Aluminium salts, magnesium salts, calcium carbonate reacts with HCl to form salts.
· Sodium bicarbonate and sodium citrate
· Having short acting and rapid absorption.
· Release CO2
· Produce alkalosis
· Rebound acidity
· BP ↑se, CHF due to retention of Na+.
↓ H. Pylori
CO2 + NH3
· CO2 is dissolved in the blood and transported to the lungs.
· Exhaled CO2 is analyzed the presence of H. Pylori results in an ↑se in the ratio of CO2.
2. Amoxicillin (Mtz may be used in penicillin-allergic patients.)
Hi….!! My name is Smrutiranjan Dash, From Odisha, India. Professionally I am Assistant Professor at The Pharmaceutical College, Barpali, Odisha, department of Pharmacology.