18. Drugs in the GI Tract

Question 1

28yo male, builder, bloody diarrhoea for 4/52, recently stopped smoking, recently on walking holiday in Oman, father has UC, examination normal, rigid sigmoidoscopy below.
What are your differential dx?

Hb 12, CRP 15, stool microscopy and culture neg
What would you start treatment with?

Answer 1

• *IBD** - ulcerative colitis, Crohn’s disease.
• *Infection** - C. diff, camphylobacter, salmonella etc.

5-aminosalicyclic acid (5ASA) e.g. sulphasalazine, mesalazine, olsalazine, balsalazine. NB. similar structure to aspirin, both anti-inflammatory and anti-cancer, and pts allergic to aspirin may be allergic to 5ASA, but 5ASA is not damaging to upper GIT and works in IBD by diff mechanisms

Question 2

What are 5ASAs indicated for?

What is the 5ASA mechanism of action?

What is the route of 5ASA?

Answer 2

• *Mild/moderately active UC**.
• *Maintenence of UC** - reduces inflammation and risk of colorectal cancer

Poorly absorbed (when coated) - topical effect/oral or rectal
Unknown MoA - **antioxidant**, **inhibits prostaglandin and leukotriene synthesis**, modulates cytokine profile, PPARγ agonist. Scavengers of RoS

Oral tablets given special coating so tablets go straight to gut. Can also be given via enema. Route depends on extent of UC

Question 3

List some SEs of 5ASAs.

What is the dose, and is it safe for pregnacy/breast feeding?

The pt was given 5ASA, 2w later: BO 8x day, blood with stool half the time, no longer able to work. Stool culture negative for infection incl. C. diff.
What would you give next?

Answer 3

5ASAs - uncommon: nausea + GI upset, worsening colitis (v. rare)
Sulphasalazine (SE due to sulphonamide): BM supression, haemolytic anaemia, hepatitis, male infertility.

2 - 4.8g/d, safe for pregnancy/breast feeding

Corticosteroids (glucorticoids): prednisolone, hydrocortisone, budesonide (avoids 1st part of metabolism)

Question 4

What are the indications for steroid use in this case?

What is the steroidal mechanism of action?

What are the routes steroids can be given via?

List some side effects.

Answer 4

Induction of remission in UC and CD. NO role in maintenance.

Immunosuppressive, mediated via glucocorticoid receptor, regulates transcription of 100+ genes, reduces IL-1, TNFa, IL-8, prevents leucocute migration, reduces NO

Oral, IV, enemas, suppository

Diabetes, acne, purpura, growth failure, sepsis, moon face, osteoporosis etc. [Pic]

Question 5

What is budesonide used for?

What is its mechanism of action?

4w later: pt (on 20mg prednisolone, 4.8g Asacol with otc NSAIDs for joint pains)
Admitted with haematemesis/melaena. BP 90, P140, Hb 7.6, urease test for H. pylori negative. Gastroscopy image below.
What can you see in the gastroscopy?

What is a urease test?

Answer 5

Terminal ileal Crohn’s

Glucocorticoid (agonist), formulated for local mucosal release in TI, extensive 1^st pass metabolism (only 2% enters systemic circulation), fewer side-effects. Controls rate of protein synthesis, depresses migration of polymorphonuclear leukocytes and fibroblasts

Duodenal ulcer (caused by NSAIDs? Opioids?)

H. pylori in biopsy breaks down urea on disc to NH₃ and CO₂.
NH₃ raises pH of disc and turns phenol red

Question 6

What are the causes of:

a) duodenal ulcer
b) gastric ulcer

How would you treat the pt with a peptic ulcer and BP 90, P140, Hb 7.6?

Answer 6

a) H. pylori
b) H. pylori, NSAIDs and steroids [Pic]

1. Resus - blood transfusion
2. Stop NSAIDs
3. Eradicate H. pylori
4. Anti-secretory drugs (PPIs/H₂ receptor antagonists)

Question 7

Give the classes and names of anti-secretory therapy drugs.

What are the indications for anti-secretory therapy?

What is the mecahnism for anti-secretory threrapy?

Answer 7

1. Class: PPIs. Names: omeprazole, lanzoprazole, pantoprazole, rabeprozole, esomeprazole
2. Class: H₂ receptor antagonists. Names: ranitidine, cimetidine

PUD (peptic ulcer disease), H. pylori eradication ( + 2 abx: amoxicillin + clarithromycin), GORD, prevention of ulcers in pts on NSAIDs, Zollinger-Ellison syndrome (tumours cause stomach to produce too much acid -> peptic ulcers)

PPIs: irreversibly inhibit H⁺/K⁺-ATPase in gastric parietal cells - suppresses gastric acid secretion almost completely
H₂ receptor antagonists: histamine regulates the proton pump of the gastric parietal cell. However the proton pump can be stimulated by other pathways so H₂ blockers cannot completely suppress gastric acid secretion
[Pic]

Question 8

What are the routes and side effects of anti-secretory therapy?

48h after endoscopy the pt has had 4 units of blood, endoscopy (vessel cliped, adrenaline), Hb 12.5, IV PPI. He has abdominal pain and nausea + vomited on 2 occasions.
What could be the cause of the abdo pain and nausea + vomiting?

What is the chemotactic trigger zone, and thus the emetic pathways and efferents?

Answer 8

Routes: oral, IV
SEs: diarrhoea (most common), GI upset, headache, increases risk of C.diff, weak cytochrome P450 inhibitors (care with phenytoin, warfarin, theophyline)

Opiate-related/chemical imbalance

Area of medulla oblongata that receives input from blood-bourne drugs or hormones, and communicates with other structures in the vomiting centre to initiate vomiting.
Emetic paths: medulla, afferents (labyrinth, vagus, systemic circulation)
Efferents: oesophagus, stomach, abdo wall [Pic]

Question 9

State the indication, class, mechanism and SEs of the following anti-emetics:

a) cyclizine
b) metoclopramide
c) ondansetron

Answer 9

[Table] - most SEs neurological!

Question 10

What is the BSS?

Answer 10

Bristol stool chart [Pic]

Question 11

State the indication, class, mechanism and SEs of the following laxatives:

a) fybogel
b) senna
c) arachis oil
d) lactulose

What could you give to treat diarrhoea and bloating?

Answer 11

[Table]

Diarrhoea: Imodium (loperamide, anti-diarrhoeal)
Bloating: anti-spasmodics, dietary advice (high fibre diet = bloating)