Physiology and Pharmacology of the Large Intestine

Question 1

Describe the gastroileal reflex and what controls it

Answer 1

The gastroileal reflex is stimulated by gastric distention and it involves the opening of the ileocaecal valve
The reflex is under the control of CN X, sympathetic nerves and enteric neurones

Question 2

What are the functions of the ileocaecal sphincter?

Answer 2

Allows digested contents of small intestine to enter the caecum
Prevents colonic bacteria from proliferating into the ileum
Produces an urge to defaecate

Question 3

What does the motility of the large intestine consist of?`

Answer 3

Mass movements - strong peristaltic contractions of the circular muscles in large parts of the colon, drives faeces into distal regions
Haustration - non-propulsive segmentation caused by contraction of smooth muscle
Defaecation reflex - spinal reflex triggered by distention of the rectum

Question 4

Outline what happens in the defaecation reflex

Answer 4

Rectum fills with faecal matter → Rectal stretch receptors activated → Afferents to brain activated (urge to defaecate) → Altered firing in efferents to spinal cord → Skeletal muscle of external anal sphincter relaxes → Defaecation

Question 5

Outline the different functions of colonic flora

Answer 5

Increasing intestinal immunity
Promoting motility and helping to maintain mucosal integrity
Synthesising Vitamin K2 and free fatty acids
Activating some drugs
Having a role in enterohepatic cycling of compounds

Question 6

What are the main pharmacological agents used to treat IBD?

Answer 6

Aminosalicyates
Glucocorticoids
Immunosuppressants
Biological agents

Question 7

Explain the use of sulfasalzine in IBD

Answer 7

Sulfasalazine is an aminosalicyate that is a combination of 5-ASA and sulfapyridine. 5-ASA reduces inflammation by inhibiting COX and LOX
Sulfapyridine causes adverse side effects such as rashes and arthralgias. Folic acid is advised during its use

Question 8

What drug is used to avoid the side effects of sulfasalazine?

Answer 8

Mesalazine

Question 9

Explain when a glucocorticoid would be prescribed and give examples

Answer 9

Glucocorticoids are used in acute UC and Crohn’s. Examples include prednisolone and budesonide

Question 10

When are immunosuppressants used in IBD and how do they work?

Answer 10

Immunosuppressants are used in patients not responding to glucocorticoid. They inhibit T cell function

Question 11

Give examples of immunosuppressants and any side effects/advantages

Answer 11

Azathioprine - most commonly used but causes some hepatotoxicity
Ciclosporin - short course drug but causes renal toxicity
Methotrexate - limited role but only taken once weekly

Question 12

Describe the use of biological agents and give examples

Answer 12

Biological agents are monoclonal antibodies used in severe IBD. They block TNF-alpha, and examples include:
Infliximab
Adalimumab
Vedolizumab
Golimumab

Question 13

What drugs are used to treat IBS?

Answer 13

Antispasmodics
Laxatives
Antimotilities