L2 - L7 Flashcards
Peptic Ulcer Disease
- lesion on wall of stomach or intestine
- stomach ulcer = gastric, intestinal = duodenal
- causes breach of lining and gastric acid will damage cells/tissue
- breach needs surgically fixed or patient could get sepsis
Stomach Protection Barriers
- alkaline mucous
- tight junctions
alkaline mucus - epithelial cells secrete bicarbonate, neutralising some acid
Tight Junctions - between epithelial cells making it hard for molecules (like acid) to seep out
Causes of Peptic Ulcer Disease
Helicobacter Pylori
- stimulates stomach acid production causing impaired mucosal defence. leads to ulcers
NSAIDS
- prevent AA from producing prostaglandins (which stimulate bicarbonate to neutralise acid)
- this causes there to be more acid in stomach
Smoking/Genetic Factors
Symptoms of Peptic Ulcer Disease
abdominal pain, discomfort
- pain doesnt radiate, stays local
burning pains in upper abdomen
Helicobacter Pylori and Peptic Ulceration
- 40% individuals Peptic Ulcers
- in gastric ulcer patients, 95% have H. Pylori
- H. Pylori damages protective layer of stomach increasing chance of ulceration
- Infects lower part of stomach and allows acid & pepsin to attack the stomach(leading to ulcers)
- produces enzyme urease, degrades urea to make ammonia + CO2 which helps bacteria survive
- Uses adhesion molecules to stay on stomach wall
Diagnostic Testing for H. Pylori
- serological
- UBT
- SAT
Serologic - blood test, but will be positive if you have have H. Pylori any time in the past
UBT (Urea Breath Test) - takes urea capsule and if they have H. Pylori, higher amount of CO2 will be exhaled
SAT (stool antigen test) - detects antigens from stool and shows i there is current infection
ECL Cells
- in gastric mucosa
- secrete histamine as paracrine stimulant
- leads to increased acid secretion from parietal cells
Acid Secretion in Stomach
- in parietal cell
- Muscarinic , h2 , and gastrin receptors promote acid production on parietal cell.
- Carbonic Anhydrase combines CO2 with carbonic acid to make bicarbonate and H+
- Bicarbonate exchanged for Cl- which enters lumen
- Proton HCl pumped into lumen by H+/K+ ATPase allowing K+ inside and stomach acid to be secreted
H2 Antagonists
(Cimetidine, Ranitidine, Nizatidine, Famotidine)
- act competitively on H2 muscarinic receptor of parietal cells
- reduce basal acid secretion by 60%
- treats both duodenal and gastric ulcers
Side Effects: Diarrhoea, headache, Confusion in elderly
cimetidine - interacts with warfarin & cause gynaecomastia
PPI’s
- omeprazole, esomeprazole, lansoprazole
Inhibition of proton pump blocks acid secretion irreversibly
- return of acid secretion by synthesis of new pump protein H+/K+ ATPase
- acid secretion reduced by 90% after dose
Side Effects - GI upset, diarrhoea, skin rashes
increase risk of fracture
Eradication of H. Pylori Infection
- PUD H. Pylori gets triple therapy
PPI + Amoxicillin + Clarithromycin/Metronidazole
- if penicillin allergic give both Clarithromycin & Metronidazole
triple therapy because H. Pylori is known to become resistant so it has to be completely destroyed
Cytoprotective Agents
- Misoprostol (prostaglandin analogue)
- misoprostol mimic action of prostaglandins to protect stomach.
- take with NSAID to protect stomach
- enhances duodenal bicarbonate production & weakly inhibits gastric acid secretion
- cant be used during pregnancy
Zollinger Ellison Syndrome
- gastronome in pancreas OR duodenum
Large gastrin secreting tumour (Gastronome) in pancreas or duodenum
- causes gastric acid hypersecretion
removal of tumour is effective treatment
GORD reflux disease
- treatment
- dysfunctional lower oesophageal sphincter allows reflux of stomach acid and pepsin
Treatment: antacids, PPI, H2 antagonist
Detection: probe with pH reader to determine acid in oesophagus
Barrets Oesophagus
- pink colour at bottom of oesophagus
irreversible, common in long-term GORD patients
- Will lead to oesophageal cancer – adenocarcinoma
treatment: replace stratified squamous epithelium with columbar epithelium that has goblet cells
Making Omperazole
- prodrug becoming sulfenamide
H159/69 had ester which was changed for an Ether, making it more stable
- Ether allows omeprazole to diffuse through fatty secretory canals of parietal cell wall
Omeprazole mode of action
- ion trapping
- uncharged om absorbed from small intestine and diffuses into parietal cell
- conversion to sulphenamide due to steep proton gradient caused by H+/K+ ATPase
- sulphonamide reacts with thiol groups in H+/K+ ATPase enzyme creating disulphide bridge
- omeprazole and sulphenamide are ionised upon entry into cell, trapping them
given in gelatine capsule to make it activate in intestinal pH and not activate in stomach
Omeprazole Dosing Requirements
20mg daily for 2-4 weeks to treat duodenal ulcers
8 weeks for gastric ulcers
Other Treatment Options for GORD
- Chelates, Prostaglandin Analogues & Pro-Kinetic Drugs
Chelates : sucralfate(1000mg),
- coat ulcer surface by adhesive complex, protecting it from more acid damage
Prostaglandin Analogues : misoprostol (200mcg)
- mimic prostaglandins to cause bicarbonate production
H2 Receptor Antagonist
-ranitidine, cimetidine, famotidine
Suppresses stomach acid production by antagonising H2 receptors on parietal cells
side effects: masks symptoms of cancer like ulcers by treating them
diarrhoea, dizziness/confusion in elderly
- Cimetidine increases plasma conc. of erythromycin and has interactions with warfarin
Inflammatory Bowel Disease
- Ulcerative Colitis + Crohn’s Disease
Ulcerative Colitis
- only affects large bowel and inflammation is on large intestine lining and rectum area
Crohn’s Disease
- affects all areas of GI and all tissues can be inflamed
- inflammatory conditions with swelling and ulceration of intestinal tissue. Chronic with periods of remission
- stomach pain, weight loss, diarrhoea
Diagnosis of IBD
- blood tests for anaemia, vitamin deficiencies or inflammation
anaemia - due to loss of blood
Vit Deficiencies - from diarrhoea / inadequate absorption
CT + MRI scans
Sigmoidoscopy - camera inserted to view lower rectum
Colonoscopy - similar but camera extends up colon
Small Bowel Enema
- varium put in patient to highlight inflammation on X-ray
Corticosteroids
- hydrocortisone
- beclamethasone
- given to reduce inflammation and suppress immune system
Cautions : congestive heart failure, hypothyroidism, osteoporosis
Side Effects : insomnia, dyspepsia, Cushing’s syndrome
Interactions : grapefruit juice increases plasma conc. of budesonide
Aminosalicylates
- balsalazide
- mesalazine
- sulfalazine
Administered orally or rectally
- MR tabs/caps, granules, suspensions or foam, suppository, enemas
Side Effects : blood disorders, sore throat, fever
Interactions :
- sulfalazine clouds urine & decreases conc. of digoxin & decreases absorbance of folates
