Dyspepsia

Question 1

Define GORD

Answer 1

Gastro oesophageal reflux disease- reflux of gastric contents into stomach leading to oesophagitis. May be due to Obesity Pregnancy Drug induced

Question 2

Define peptic ulceration

Answer 2

Gastric or duodenal - erosion, damage, bleeding (which may lead to anaemia).

Question 3

Zollinger- Ellison syndrome

Answer 3

Rare gastric secreting tumour of D - cells of the pancreas. Excessive acid production, consequent GI mucosal ulceration.

Question 4

Define gastritis

Answer 4

Inflammation of the stomach

Question 5

Peptic Ulceration - S&S (5)

Answer 5

Epigastric pain, may be precisely located by pointing (relationship to food is variable). Gastric ulcers - pain during eating Duodenal ulcers - pain on hunger, relived by eating (pyloric sphincter closes so acid doesn’t reach the duodenum). Night pain- relieved by food, milk, antacids Waterbrash - appearance of water in the mouth Nausea, less frequently vomiting Vomiting blood

Question 6

Peptic ulceration cause

Answer 6

H. Pylori. 80-90% duodenal ulcers (gram negative) 70% gastric ulcers (remainder mostly NSAID induced) Infection may lead to chronic inflammation and gastric damage (gastritis) leading to ulceration.

Question 7

H. Pylori Tests

Answer 7

13C Urea breath test. Patient given 13C urea and bacterial ureases convert it to 13CO2, which is absorbed and exhaled from the lungs. H. Pylori antigens/ antibodies in blood, saliva, stools.

Question 8

Dyspepsia WARNING SIGNS (9)

Answer 8

Age > 55 Weight loss Iron deficiency anaemia Dysphagia (difficulty swallowing) Haematemesis Melaena (tarry stools) Upper abdominal masses Persistent symptoms with repeat requests for OTC remedies Onset of NEW symptoms

Question 9

Control of acid secretion Increase & Decrease

Answer 9

INCREASE ACID SECRETION (up activity proton pump H+ out cells) Histamine (via H2 receptors) Gastrin (via CCK receptors) ACh (via M3 receptors) All receptors on parietal cells (stomach). DECREASE ACID SECRETION Prostaglandins (E2 & I2) Also cytoprotective via bicarbonate and mucus release

Question 10

Goals of treatment (5)

Answer 10

Symptomatic relief or cure. Symptomatic relief may involve lifestyle changes: Avoidance of causative drugs and food. GORD- propping up bed and removing belts Suppression of acid release/ activity, and mucosal protection. Cure may involve suppression of acid release to allow natural healing and, if appropriate, eradication of H. pylori infection. Later goal reduce chance of developing gastric carcinomas, as H. Pylori is regarded as a carcinogen.

Question 11

ANTACIDS. MOA

Answer 11

Widely available OTC and raise pH. Rapid relief but not cure. Sodium bicarbonate, simplest. HCO3- + H+ –> CO2 + H2O Magnesium hydroxide and aluminium hydroxide also used. Al(OH)3 + 3HCl –> AlCl3 + 3H2O Calcium salts - gastric release.

Question 12

Alginates. MOA

Answer 12

May be combined with antacids. Like in Gaviscon. The alginic acid when combined with saliva, forms a viscous foam which floats on the gastric contents forming a raft which protects the oesophagus during reflux.

Question 13

Histamine H2 Antagonists. MOA

Answer 13

Cimetidine, Tagamet Ranitidine, Zantac Famotidine, Pepcid Low dose OTC for short term relief. High dose prescription only. H2 receptors, coupled via adenyl cyclase to increase cAMP which activates the proton pump. Inhibit H2 –> inhibit pump.

Question 14

H2 antagonist. Effects. (5)

Answer 14

Reduce gastric acid secretion Provide symptomatic relief Best given at night Promote ulcer healing (relapse on discontinuation) Reduced the need for surgery in ulceration

Question 15

Define dyspepsia

Answer 15

“Indigestion” - painful, difficult or disturbed digestion which may be accompanied by symptoms such as N&V, heartburn, bloating and/or stomach discomfort.

Question 16

Cimetidine. Class and interactions

Answer 16

H2 antagonist Inhibits cytochrome p450 and therefor other drug metabolism resulting in numerous interactions e.g. Oral anticoagulants Phenytoin Carbamazepine TCAs NB. Ranitidine does not interact in this way and is thus favoured.

Question 17

PPIs . MOA

Answer 17

E.g. Omeprazole, pantoprazole, lansoprazole Widely used, act via irreversible inhibition of the proton pump H+/K+-ATPase Activated by acid pH Inhibit acid secretion by >90%, may lead to achlorhydria Increased risk of CAMPYLOBACTER infection (food poisoning) due to increased pH Omeprazole is now OTC

Question 18

Pro kinetic drugs. Types and MOA.

Answer 18

CAUSE GASRIC EMPTYING Movement of gastric contents from stomach to duodenum. These drugs are benefit in GORD. DOMPERIDONE. Increased closure of oesophageal sphincter (good for reflux disease) and opens lower sphincter. METOCLOPRAMIDE. Acts locally to increase gastric motility and emptying (combined with analgesics to accelerate absorption).

Question 19

Helicobacter Pylori eradication. Treatment.

Answer 19

Eradication is most effective treatment for long term cure of ulcers with low relapse rates. TRIPLE THERAPY. 2 Antibiotics - (metronidazole, amoxicillin, clarithromycin) 1 PPI/ H2 antagonist Sometimes BISMUTH CHELATE: kills H. Pylori, coats the ulcer, absorbs pepsin (chief protease in stomach), increase prostaglandin production, increases HCO3- secretion.

Question 20

Non H. Pylori dyspepsia. Approach.

Answer 20

A stepped approach (up or down as appropriate) used in absence of proven H. Pylori infection. Step 1. Antacid OR Antacid & Alginate. Step 2. H2 Antagonist Step 3. PPI

Question 21

NSAIDS (and oral steroids) - Ulcerogenic effects

Answer 21

Oral NSAIDS (commonly) and corticosteroids (less commonly but esp in combo with NSAIDs) are associated with peptic damage / ulceration. Very important ADR Annually: 10,000 admissions and 2,000 deaths Ibuprofen - low incidence of GI side effects.

Question 22

Arachidonic Acid Pathway

Answer 22

Membrane phospholipids –> (PLA2) –> Arachidonic Acid –> Leukotrienes –> (COX) –> Prostaglandins Steroids -> Lipocortin inhibits PLA2 NSAIDs inhibit COX

Question 23

Cyclooxygenases - types and damage

Answer 23

2 isoforms. COX1 - physiological form, involve din gastric protection COX2 - pathological, inflammation Most inhibits inhibit both therefore DAMAGE COX2 selective inhibitors (celecoxib) have less GI side effects

Question 24

How to minimise GI damage (3)

Answer 24

Prophylaxis with PPI H2 antagonists less or ineffective Give in combination with misoprostol - a stable PGE1 analogue, acts on prostanoid receptors to inhibit gastric H+ secretion.

Question 25

Dyspepsia pathway

Answer 25