S2: Pharmacological Basis for Treatment of GI Disorders II Flashcards
Describe constipation
- 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
Consequences of constipation as a result of rectal distension
- Headache
- Loss of appetite
- Nausea and abdominal distension
- Stomach pain
What does holding of faecal matter lead to?
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.
What is constipation caused by?
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.
List factors that increase colonic motility
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
Causes of constipation in the elderly
- Diet
- Inactivity
- Drugs (polypharmacy) - some drugs will decrease colon motility
Alarm signs and symptoms of patients with chronic constipation
- Acute onset constipation in older individuals
- Weight loss
- Blood in stool
- Anaemia
- Family history of colon cancer or inflammatory bowel disease
Management of constipation
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
Drugs to treat consitipation
- Purgatives
- Bulk forming and osmotic laxatives
What are purgatives?
They are laxatives that act as faecal softeners and stimulant purgatives can modulate/hasten food transit in the intestine
What are bulk forming laxatives?
Give example
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.
What are osmotic laxatives?
Give example
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
Describe mode of action of lactulose inconstipation
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.
What is the aim of treatment for diarrhoea?
- Maintain body fluids and electrolytes
Name a bacteria that is major cause of gastroenteritis
Treatment for this
Campylobacter jejuni
We can use erythromycin or ciprofloxacin in severe infections
What is diarrhoea?
Diarrhoea is the frequent/very frequent passage of liquid faeces
Causes of diarrhoea
- Infectious agents (like campylobacter)
- Toxins
- Anxiety
- Drugs
Describe the consequence of diarrhoea
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
Describe Therapeutic Strategies to Diarrhoea Treatment
- 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
How do VIP and 5-HT4 affect peristalsis?
Relaxation is mediated by VIP
5-HT4 is important in motility
Mechanism of action of Loperamide
- 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
