L2-L7

Question 1

Peptic Ulcer Disease
- lesion on wall of stomach or intestine

Answer 1

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

Question 2

Stomach Protection Barriers
- alkaline mucous
- tight junctions

Answer 2

alkaline mucus - epithelial cells secrete bicarbonate, neutralising some acid

Tight Junctions - between epithelial cells making it hard for molecules (like acid) to seep out

Question 3

Causes of Peptic Ulcer Disease

Answer 3

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

Question 4

Symptoms of Peptic Ulcer Disease

Answer 4

abdominal pain, discomfort
- pain doesnt radiate, stays local

burning pains in upper abdomen

Question 5

Helicobacter Pylori and Peptic Ulceration
- 40% individuals Peptic Ulcers

Answer 5

in gastric ulcer patients, 95% have H. Pylori
H. Pylori damages protective layer of stomach increasing chance of ulceration
1.Infects lower part of stomach and allows acid & pepsin to attack the stomach(leading to ulcers)
2.produces enzyme urease, degrades urea to make ammonia + CO2 which helps bacteria survive
3.Uses adhesion molecules to stay on stomach wall

Question 6

Diagnostic Testing for H. Pylori

serological
UBT
SAT

Answer 6

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

Question 7

ECL Cells
- in gastric mucosa

Answer 7

secrete histamine as paracrine stimulant
leads to increased acid secretion from parietal cells

Question 8

Acid Secretion in Stomach
- in parietal cell

Answer 8

1.Muscarinic , h2 , and gastrin receptors promote acid production on parietal cell.
2.Carbonic Anhydrase combines CO2 with carbonic acid to make bicarbonate and H+
3.Bicarbonate exchanged for Cl- which enters lumen
4.Proton HCl pumped into lumen by H+/K+ ATPase allowing K+ inside and stomach acid to be secreted

Question 9

H2 Antagonists
(Cimetidine, Ranitidine, Nizatidine, Famotidine)

Answer 9

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

Question 10

PPI’s
- omeprazole, esomeprazole, lansoprazole

Answer 10

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

Question 11

Eradication of H. Pylori Infection
- PUD H. Pylori gets triple therapy

Answer 11

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

Question 12

Cytoprotective Agents
- Misoprostol (prostaglandin analogue)

Answer 12

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

Question 13

Zollinger Ellison Syndrome
- gastronome in pancreas OR duodenum

Answer 13

Large gastrin secreting tumour (Gastronome) in pancreas or duodenum
- causes gastric acid hypersecretion

removal of tumour is effective treatment

Question 14

GORD reflux disease
- treatment

Answer 14

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

Question 15

Barrets Oesophagus
- pink colour at bottom of oesophagus

Answer 15

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

Question 16

Making Omperazole
- prodrug becoming sulfenamide

Answer 16

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

Question 17

Omeprazole mode of action

ion trapping

Answer 17

1.uncharged om absorbed from small intestine and diffuses into parietal cell
2.conversion to sulphenamide due to steep proton gradient caused by H+/K+ ATPase
3.sulphonamide reacts with thiol groups in H+/K+ ATPase enzyme creating disulphide bridge
4.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

Question 18

Omeprazole Dosing Requirements

Answer 18

20mg daily for 2-4 weeks to treat duodenal ulcers
8 weeks for gastric ulcers

Question 19

Other Treatment Options for GORD
- Chelates, Prostaglandin Analogues & Pro-Kinetic Drugs

Answer 19

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

Question 20

H2 Receptor Antagonist
-ranitidine, cimetidine, famotidine

Answer 20

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

Question 21

Inflammatory Bowel Disease
- Ulcerative Colitis + Crohn’s Disease

Answer 21

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

Question 22

Diagnosis of IBD
- blood tests for anaemia, vitamin deficiencies or inflammation

Answer 22

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

Question 23

Corticosteroids
- hydrocortisone
- beclamethasone

Answer 23

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

Question 24

Aminosalicylates
- balsalazide
- mesalazine
- sulfalazine

Answer 24

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

Question 25

Treating IBD

Cytokine Modulators

Answer 25

inhibits pro-inflammatory cytokine
- administered as subcutaneous injection - infliximab, adalimumab, golimumab

stop the expansion of activated T cells by interrupting the calmodulin-calcineurin cascade

Question 26

Immunosuppressants
-formulations
-side effects

Answer 26

administered orally or by injection
- azathioprine, ciclosporin, methotrexate

blood and liver toxicity so require regular monitoring of blood counts and organ function for safe use

Question 27

Methotrexate (immunosuppressant)

dosing and danger symptoms

Answer 27

weekly dose
- only use 2.5mg tablets
- follow up dose of folic acid to reduce side effects

report sore throat, bleeding, bruising, mouth ulcers

Question 28

Sulfalazine
- treats GIT inflammation

Answer 28

Sulfalazine is a pro-drug and contains Sulphonamide
- becomes mesalazine
- site of action in colon

inhibits inflammatory modulators , Prostaglandin and Leukotriene
site of absorption is colon
Sulfasalazine two components:
- AZO bond is cleaved to make 5-ASA
- sulfapyridine (responsible for side effects)

Question 29

Sulfasalazine Administration & Formula

Answer 29

Administered as oral coated tablet disintegrating at pH=7 in the intestine or suspension
- can also be given rectally

FOR BASE
pH <2 pKa = 100% ionisation
pH >2 pKa = 100% unionisation

ACID
pH <2 pKa = 100% unionisation
pH >2 pKa = 100% ionisation

Question 30

Particle Size Reduction
- Mechanical Methods
- Milling (step 1 of size reduction)

Answer 30

1.Cutter method - material cut by one or more blades and passes through sieve when small enough
2.Compression method - pressure is applied usually in dry state. ex. rolling mill, 2 wheels crushing material
3.Impact method - particles hit by moving surface and moving particles hit surfaces. tends to produce particles of narrow size distribution. ex. hammer mill
4.Attrition method - pressure + friction so unlike compression, wheels would move at different speeds to create friction. ex. roller mills
5.Impact + Attrition - Ball Mill, heavy balls rotated round spinning basin to fall onto material and break it up

Question 31

Analysing Particle Size
- Light Scattering

Answer 31

Laser light interacts with particles

light is shone and diffracts off particles at an angle inversely proportional to volume of the particles
detector analyses radiation emitted by diffracting light
helium + neon laser most common