Pharmacological Basis for Treatment of GI Disorders II

Question 1

Constipation

what is this?
what is normal bowel movement like?
consequences of rectal distension from contstipation?
what does holding off faecal matter lead to?

what causes constipation? 2 reasosn for this?

what factors improve symtoms of constipation by increasing colonic motility?

Answer 1

Constipation is a subjective complaint (differs between people) and is an obstructive problem where digested material is not coming out.

This needs to be investigated because it could be something sinister.

Normal bowel opening is 1-3x per day, if you go once this is still okay. One does not have to be regular to be physiologically adequate, no toxic substances accumulate upon prolonged constipation.

The consequences of constipation because of rectal distension include: Headache, loss of appetite, nausea, abdominal distension and stomach pain.

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.

Constipation 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.

Factors that can increase colonic motility (increase distension of the large intestine, as this helps with the motility) and improve symptoms of constipation include:

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

Question 2

Causes of constipation in elderly

3

Answer 2

o Diet
o Inactivity
o Drugs (polypharmacy), some drugs will decrease colon motility

Question 3

Alarm signs and symptoms of patients with chronic constipation include (5)

Answer 3

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

Question 4

Management of constipation

3 lifestyle changes?
2 types of drugs you can use and their effects?

effect of osmotic laxative? what can high doses lead to?

lactulose mode of action? how does it get converted into FA? effects of this? why should you drink a lot of water?

Answer 4

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

In terms of drugs
- Purgatives
o They are laxatives that act as faecal softeners and stimulant purgatives can modulate/hasten food transit in the intestine

• Bulk-forming and osmotic laxatives
  o Bulk laxatives e.g. methylcellulose
  o Plant gums which retain water in gut lumen, these promote peristalsis but take a few days to work

These increase stool’s solid content

Bloating and flatulence is associated with these

Osmotic laxatives include 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

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

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 as lactulose acts as a food for the bacteria the biomass of gut bacteria increases which means increased conversion of lactulose to fatty acids

1. 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.
2. Food will be moved along towards anus and colonic transit time is shortened.
3. It is important to drink water while on this medicine as there will be more water loss.

Question 5

Diarrhoea: Antidiarrheal agents

what do we need to try and maintain when we have diarrhoea?

when we treat diarrhoea what do we want to modify?

cause of diarrhoea?

effect of diarrhoea?
effetcs in acute diarrhoeal diseases?

Answer 5

In diarrhoea we need to try and maintain body fluids and electrolytes.

If we can identify a causal organism we can aim to treat it with antibiotics e.g. erythromycin for campylobacter jejuni = major cause of gastroenteritis.

When trying to treat diarrhoea we want to modify secretion/absorption balance

Diarrhoea is the frequent/very frequent passage of liquid faeces, causes of diarrhoea include:
o	Infectious agents (like campylobacter)
o	Toxins
o	Anxiety
o	Drugs

Effects of diarrhoea include:
Rough and discomfort. In some cases, it can lead to a medical emergency and liquid therapy is needed then.

In acute diarrhoeal diseases
- 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 6

Therapeutic Strategies to Diarrhoea Treatment

how to maintain fluid/electrolyte balance?
what is a common cause of gastroenteritis? what can we use to treat this infection?

what would we use with viral infections?

effect of anti-motility drugs?

Answer 6

To maintain fluid and electrolyte balance, we do this by oral rehydration therapy

Use of anti-infectives,
- campylobacter common cause of gastroenteritis in UK, we can use erythromycin or ciprofloxacin in severe infections
- If viral in nature, we may not need to use anti-infectives
o We can use non-microbial anti-diarrhoea agents

Use of anti-motility drugs, these are adsorbents and agents that modify fluid and electrolyte transport

Question 7

The Regulation of Peristalsis Requires Neuronal Peristalsis

Answer 7

• Relaxation is mediated by VIP

- 5-HT4 is important in motility

Question 8

Motility of GI tract

movement of substances in the gut can be modulated by ?

Agents that increase motility without above? (2)

Answer 8

The movement of substances in the gut can be modulated by
1. Purgatives, which increase passage of food through intestine

Agents that increase motility without purgation

2. Antidiarrheal drugs decrease movement
3. Antispasmodic drugs decrease movement

Question 9

Diarrhoea

loperamide? effect
codeine and loperamide? effect
bismuth chelate? effect + side effect

Answer 9

Traveller’s diarrhoea, about 3 million people travel abroad/yr and most develop diarrhoea during their travelling.

Some infections may be self-limiting, so long as you look after yourself, drink properly

• Loperamide is a selective GIT, it decreases passage of faeces and decreases duration of illness
• Codeine & Loperamide have antisecretory action which decrease intestinal motility
• Bismuth subsalicyalate (chelate) decreases fluid secretion in bowel, it is safe for young children, however may cause tinnitus and blackening of stool.