PHARM - Ulcers and Reflux

Question 1

2 antisecretory agents

Answer 1

• histamine receptor antagonists
• proton pump inhibitors

Question 2

4 examples of cytoprotective agents and mucosal strengtheners

Answer 2

• sucralfate
• prostaglandins
• bismuth
• antacids

Question 3

histamine receptor antagonists
- MOA
- use
- what happens on withdrawal?
- e.g.

Answer 3

• inhibits histamine (H2) receptor = decreased gastric HCl secretion
• promote healing of duodenal ulcers
• relapse on withdrawal b/c reversible
• e.g. ranitidine

Question 4

proton pump inhibitors (PPIs)
- MOA
- use
- optimum pH
- e.g.

Answer 4

• irreversibly inactivates H+/K+ ATPase pump at the parietal cell luminal surface to decrease HCl secretion (need new pumps to resume secretion)
• most effective anti-ulcer therapy b/c blocks common pathway
• inactive at neutral pH, activated in acidic environment in canaliculi (channels) of parietal cells
• e.g. esomeprazole (Nexium)

Question 5

PPI
- mode and time of administration
- what is it NOT used with

Answer 5

• administered 1h before meals as enteric coated oral capsules to make sure they reach site of action
• not used with other acid-suppressing agents e.g. antacids

Question 6

PPI A/Es

Answer 6

• generally extremely safe
• minor - headaches, skin rashes, dizziness
• rare - gynaecomastia, renal impairment
• inhibit CYP450

Question 7

sucralfate
- MOA
- how should it be taken
- interactions

Answer 7

• adheres to surface of ulcers to act as a barrier to aggressive luminal factors (viscous at acidic pH) e.g. acid, pepsin, bile salts
• stimulates mucosal protecting mechanisms e.g. mucus
• taken on empty stomach 1h before meals (4 per day)
• don’t take antacids or meals within 30 mins as they can raise pH and alter its properties

Question 8

prostaglandin analogues MOA

Answer 8

• prostaglandins PGI2 and PGE2 are protective in GIT: inhibit gastric acid secretion, increase mucosal blood flow and mucus and protects mucosa

Question 9

misoprostol
- class
- indication
- AEs
- CI

Answer 9

• prostaglandin analogue, similar efficacy to histamine antagonists
• indicated only in Pts using NSAIDs with high ulcer risk
• AEs: diarrhoea, nausea, headache, dizziness
• C/I: pregnancy b/c causes uterine contractions

Question 10

bismuth chelate
- class
- indication
- MOA
- AEs
- contraindications

Answer 10

• prostaglandin analogue
• not first line, used in combination therapy
• coats ulcer base, forms barrier to aggressive factors in gastric juice
• also moderates direct activity against H. pylori
• AEs: blackening of stools and tongue, bismuth toxicity (kidneys and CNS - not used for long periods)
• C/Is: not to be taken with meals or ANY other meds

Question 11

antacids
- MOA
- indication
- duration of action
- e.g.s

Answer 11

• weak bases that neutralise acid, raising gastric pH and inhibits pepsin activation
• more effective against duodenal ulcers than gastric, OTC relief of indigestion
• 30 min duration on empty stomach, 2h when taken w/ meal
• e.g. Al(OH)3, Mg(OH)2

Question 12

H. pylori

Answer 12

• gram -ve bacteria
• major cause of gastric and duodenal ulcers + class 1 carcinogen for gastric cancer

Question 13

antibiotics/agents against H. pylori and what is first and 2nd line Tx

Answer 13

• bismuth and penicillin: disrupts cell wall
• macrolides or tetracycline: inhibits protein synthesis
• metronidazole: used for resistance to amoxicillin and tetracycline (very common)
• FIRST LINE: PPI + amoxicillin + clarithromycin (triple therapy)
• SECOND LINE (not commonly used, only for clarithromycin resistance): PPI, bismuth, metronidazole, tetracycline

Question 14

why is the pH of venous blood more alkaline than arterial blood

Answer 14

• bicarbonate (weak base), is exchanged with Cl- on the plasma (basolateral) side of the parietal cell, which is where the blood vessels are located