Pharmacology of ulcers & inflammation

Question 1

What is a peptic ulcer, what are the symptoms?

Answer 1

erosion of a small patch of the lining of the stomach
- gastric irritation, abdominal pain, inflammation of mucosa, bleeding, perforation

Question 2

what are some features that protect and attack mucosal integrity?

Answer 2

Protective factors - surface mucus layer, HCO3- secretion, good mucosal blood flow, protective prostaglandins (PGE2 & PGF-2a), epithelial regeneration and epithelial tight junctions

factors that attack gastric mucosa - acid and pepsin, gastrin, bile secretion + delayed gastric emptying, microvascular constriction, absence of protective prostaglandins, failure of epithelial regeneration and stress, alcohol, smoking

Question 3

Explain the mechanism of PGE2 - its protective role?

Answer 3

PGE2 stimulates HC03- and mucus secretion - buffers the acidification

PGE2 also acts on EP receptors on parietal cells - inhibits histamine pathway which stimulates acid secretion

Question 4

Explain mechanism of acid stimulators?

Answer 4

Histamine - acts on H2 receptors on parietal cells, activates cAMP, stimulates H+/K+ ATPase pump - increases H+ secretion

gastrin also activates pump

ACh acts on muscarinic receptors, activates calcium mediated mechanism which stimulates the pump

Question 5

What is the general treatment strategy?

Answer 5

relive pain - antacids

allow healing - antisecretory agents + mucosal strengtheners - ACID MODIFYING

prevent relapse - maintenance treatment + lifestyle change

surgery - not used anymore

Question 6

What are the diff types of acid modifying drugs?

Answer 6

antihistamines
PPIs
antimuscarinics
mucosal strengtheners

Question 6

Role of Antacids?

Answer 6

OTCs - MgCO3, NaHCO3 - provide rapid pain relief as acid is neutralised chemically

given when pain is expected - b/w meals or for acute pain

-VE: as pH rises, more acid is secreted - acid rebound + Mg - diarrhoea, Al - constipation

Question 7

Role of Antihistamines/H2 antagonists?

Answer 7

Ranitidine, cimetidine, famotidine

will bind to H2 receptors on parietal cells and block them (H2 antagonists)

inhibits cAMP activation, inhibits H+/k+ pump, reduces acid secretion

Question 8

Role of PPIs?

Answer 8

omeprazole, lansoprazole

chemically alter the structure of the ATPase pump - reduces H+ secretion -

provide long lasting acid suppression

can lead to acid rebound

Question 9

Role of antimuscarinics?

Answer 9

Pirenzepine - discontinued now

as muscarinic receptors widely distributed throughout body - results in non selective, many S.Es - blurred vision, dry mouth

Question 10

Role of mucosal strengtheners?

Answer 10

Bismuth chelate - coats ulcer area, can lead to black tongue/stool

Sucralfate - protects ulcer area + stimulates mucus secretion

Question 11

Role of Prostaglandin analogues?

Answer 11

e.g. misoprostol

mimic endogenous PGE1and2 - they act on EP receptors - EP agonist

act on EP receptors on epithelial cells - for HCO3- and mucus secretion

on parietal cells for inhibiting cAMP + ATPase pump leading to reduced acid secretion

can be used prophylactically for NSAID associated ulcers - effective when patient is taking NSAID as they inhibit endogenous prostaglandins

Question 12

What are the current treatments for IBD?

Answer 12

Treatment strategies - anti-inflammatory agents + anti-cytokine agents

• corticosteroids - inhibit phospholipase activity and arachidonic acid PG cascade
  e.g. hydrocortisone, prednisolone
• immunosuppressive - reduce T cell number/cell signalling
  e.g. ciclosporin
• Monoclonal TNFa antibodies - inhibit actions of TNF-alpha
• aminosalicylate - inhibit inflammation, maintain remission of UC