S2: Pharmacological Basis for Treatment of GI Disorders II

Question 1

Describe constipation

Answer 1

• Subjective complaint as it differs between people as we all have different bowel habits
• Obstructive problem where digested material is not coming out
• No toxic substances accumulate upon prolonged constipation

Question 2

Consequences of constipation as a result of rectal distension

Answer 2

• Headache
• Loss of appetite
• Nausea and abdominal distension
• Stomach pain

Question 3

What does holding of faecal matter lead to?

Answer 3

Holding of faecal matter leads to increased water loss from the faeces leading to a drier faeces. As a result it can make it more painful and harder to defecate.

Question 4

What is constipation caused by?

Answer 4

It is caused by decreased motility of the large intestine

This is often a product of old age or damage to the enteric nervous system of the colon.

Question 5

List factors that increase colonic motility

Answer 5

These increase distension of large intestine, as this helps with motility. It also improves symptoms of constipation.

• Increased fibre, cellulose and complex polysaccharides
• Bran, some fruits and vegetables with high fibre
• Laxatives but excessive use will lead to decreased responsiveness to them
• Mineral oil lubricates faeces
• Castor oil, stimulates motility of the colon

Question 6

Causes of constipation in the elderly

Answer 6

• Diet
• Inactivity
• Drugs (polypharmacy) - some drugs will decrease colon motility

Question 7

Alarm signs and symptoms of patients with chronic constipation

Answer 7

• Acute onset constipation in older individuals
• Weight loss
• Blood in stool
• Anaemia
• Family history of colon cancer or inflammatory bowel disease

Question 8

Management of constipation

Answer 8

Lifestyle changes
- Diet, fluid intake and exercise (more appealing)
- Increase fibre intake (can lead to bloating and flatulence which may not be appealing)
- Increase water intake which softens faecal matter for evacuation

Question 9

Drugs to treat consitipation

Answer 9

• Purgatives

- Bulk forming and osmotic laxatives

Question 10

What are purgatives?

Answer 10

They are laxatives that act as faecal softeners and stimulant purgatives can modulate/hasten food transit in the intestine

Question 11

What are bulk forming laxatives?

Give example

Answer 11

e.g. Methylcellulose
Plant gums

Plant gums retain water in gut lumen which promote peristalsis but take a few days to work. These increase stool’s solid content.

Question 12

What are osmotic laxatives?

Give example

Answer 12

e.g.lactulose

This increases and maintains the volume of fluid in the lumen of the bowel by osmosis, it increases the transfer of gut contents into the intestine.
It increases the volume of gut content entering the colon which causes a big distension leading to purgation in one hour (therefore user should be close to a bathroom)

However, high doses can lead to flatulence, cramps, diarrhoea, vomiting and tolerance

Question 13

Describe mode of action of lactulose inconstipation

Answer 13

Lactulose that you take reaches colon unchanged, once it reaches it gets broken down by friendly bacteria. These break it down into short chain fatty acids, while this occurs the osmotic pressure increases and also as lactulose acts as a food for the bacteria the biomass of gut bacteria increases which means increased conversion of lactulose to fatty acids!
Effect of these is that there is softening of the stool and volume of stool increases, this increased volume will stimulate peristalsis via vagal nerves.
Food will be moved along towards anus and colonic transit time is shortened.
It is important to drink water while on this medicine as there will be more water loss.

Question 14

What is the aim of treatment for diarrhoea?

Answer 14

• Maintain body fluids and electrolytes

Question 15

Name a bacteria that is major cause of gastroenteritis

Treatment for this

Answer 15

Campylobacter jejuni

We can use erythromycin or ciprofloxacin in severe infections

Question 16

What is diarrhoea?

Answer 16

Diarrhoea is the frequent/very frequent passage of liquid faeces

Question 17

Causes of diarrhoea

Answer 17

• Infectious agents (like campylobacter)
• Toxins
• Anxiety
• Drugs

Question 18

Describe the consequence of diarrhoea

Answer 18

There is increased gut movement, increased secretion and decreased absorption of fluid – this means decreased electrolyte (Na+) and water levels
Cholera toxins can lead to a massive loss of gut contents

Question 19

Describe Therapeutic Strategies to Diarrhoea Treatment

Answer 19

• To maintain fluid and electrolyte balance there is oral rehydration therapy
• Non-microbialanti-diarrhoea agents
• Use of anti-motility drugs, these are adsorbents and agents that modify fluid and electrolyte transport

Question 20

How do VIP and 5-HT4 affect peristalsis?

Answer 20

Relaxation is mediated by VIP

5-HT4 is important in motility

Question 21

Mechanism of action of Loperamide

Answer 21

• An opioid receptor agonist
• Exerts effects on the u-opioid receptor of the myenteric plexus of the large intestine
• A spasmolytic agent which reduces smooth muscle activity in the GIT and thus reduces the passage of faeces
• Reduces force and speed of colonic movement (increases haustral mixing of proximal colon and inhibits propulsive mass movement of the distal colon).
• Does not cross BBB
• Stimulation of the u-opioid receptor by loperamide inhibits gastric emptying, increases sphincter tone, induces stationary motor patterns and blocks peristalsis