Ulcers

Question 1

Parietal Cell Stimulation

Answer 1

Gastrin-G Cells
Histamine-ECL
Ach-Vagus

Question 2

Aggressive Factors

Answer 2

H. Pylori
Acid/Pepsin
NSAIDs
Bile Salts
Smoking

Question 3

Defensive Factors

Answer 3

HCO3-
Mucousa
Blood Flow
Phospholipids
Free radical scavengers

Question 4

H. Pylori

Answer 4

Thrives under low pH
Binds surface epithelium
Decreases HCO3- production
Secretes immunogenic proteins
Immune cell invasion and inflammation

Question 5

H2 Antagonists

Answer 5

Cimetidine, ranetidine
Structurally similar to Histamine
Blocks Histamine at H2 receptors on Parietal Cells
Heals 70-80% in 4-8 weeks (90% relapse 1 year)
Use: Prevention, healing, Zollinger-Ellison Syndrome
Oral-OTC and Rx

Question 6

H2 Antagonists- Kinetics and SEs

Answer 6

Well absorbed by gut, food and antacids reduce this
Metabolised by liver, excreted in urine
Inhibits CYP450- Warfarin, lignocaine, phenytoin
SE: Headache, diarrhoea, rash

Question 7

PPIs

Answer 7

Omeprazole, Lansoprazole, Rabeprazole
Acid labile prodrug
Disulfide covalent bonds with H/K ATPase
Irreversible inhibition (95% secretion for 1-2 days)

Question 8

PPIs Use

Answer 8

NSAID ulcers
Gastric ulcers
H. Pylori eradication
Zollinger-Ellison Syndrome
GORD

Question 9

PPIs Kinetics

Answer 9

Oral- enteric-coated form to bypass stomach
Dissolved and absorbed in small intestine
Highly protein bound
Extensively metabolised by liver and eliminated in urine
Interfere with low pH dependent absorption
Interfere with metabolism of diazepam, phenytoin

Question 10

PPIs Side Effects

Answer 10

Abdominal pain
Diarrhoea-C. Diff
N and V
Hypomagnesia
Osteoperosis
Pneumonia

Question 11

Anticholinergics

Answer 11

Pirenzepine
Muscarinic M1 antagonist
Block Ach mediated histamine release from gastric paracrine cells
Original anti-ulcer drug
Used in PUD
Other anticholinergics have too many side effects

Question 12

Antacids

Answer 12

Aluminium and Magnesium Hydroxides, Sodium Bicarbonate
MOA: Chemical antagonism
Al3+ and Mg2+ bind and neutralise pepsin
Use: to relieve pain and promote healing in PUD
To relieve symptoms of acid indigestion, heart burn, GORD, dyspepsia

Question 13

Antacids Kinetics and SEs

Answer 13

Liquids more effective than tablets
Distributed throughout GIT, eliminated in faeces
All antacids can interfere with the absorption of oral drugs given at same time
SE: Aluminium- Constipation. Magnesium- Diarrhoea
Give them together

Question 14

Mucosal protectant-Sucralfate

Answer 14

MOA: Viscous polymer at pH<4 of sucrose octasulphate and Al hydroxide
Adheres to necrotic ulcer tissue- pos glycoproteins
Forms protective barrier to acid, pepsin and bile
May stimulate PG synthesis, increasing mucus and bicarbonate
Use: PUD

Question 15

Sucralfate Kinetics and SEs

Answer 15

Protective barrier-6 hours
Not absorbed- good for liver disease patients
Can bind other medications-digoxin
SE: Constipation

Question 16

Mucosal Protectant- Colloidal Bismuth

Answer 16

MOA: Selective binding to ulcer crater protecting it from acid and pepsin
May inhibit activity of pepsin, stimulate mucus production
Toxic to H. Pylori
Use: PUD
Few SEs

Question 17

Mucosal Protectants- Misoprostol

Answer 17

MOA: Synthetic Prostaglandin E1
Protects gastric lining- inhibiting acid and promoting mucus and HCO3-
Use: Prevention of NSAID induced ulcers
SE: Diarrhoea, uterine contractions

Question 18

Tests for Initial Diagnosis of H. Pylori

Answer 18

Urea breath test and Stool Assay- Non-invasive, sensitive, specific. PPIs can interfere with Breath Test, not Stool
Serology: Fairly sensitive and specific
Endoscopy: antral and fundal biopsy- not reqired for diagnosis. May check for cancer

Question 19

H. Pylori Treatment

Answer 19

Triple- 1-2 weeks, PPI, Amoxicillin, Clarithromycin
Quad- Tetracycline, metronidazole(resistance), PPI, bismuth
Dual- PPI and Amoxicillin/Clarithromycin
90% eradication
SE- too many to list

Question 20

Success For H. Pylori

Answer 20

Compliance
Antibiotic resistance
Duration of Therapy
Correct dosing

Question 21

Diseases Associated with H. Pylori

Answer 21

PUD- 60% reoccurrence if not eradicated
Bleeding duodenal ulcer- 30% rebleeding in 1 year
Gastric cancer- justified in early cancer, 9% recurrence of tumor in untreated control