How does loperamide exert its anti-diarrhoea action?
GI opioid receptor agonist μ opioid receptor.
Activation of this receptor leads to decreased motility of bowel and increased tone of anal sphincter.
Where does apoptosis occur in the villi?
In areas adjacent to the stem cell population.
What are the main cell types found in the small intestine?
- Brush border enterocytes
- Goblet cells
- Endocrine cells
- Paneth cells
What happens to indigestible carbohydrates in the Large Intestine?
The carbohydrates are fermented by colonic flora, producing short chain fatty acids, such as butyrate and acetate.
These SCFA can then be abosrbed by the colonic mucosa.
When should loperamide be given?
- Acute diarrhoea - symptomatic treatment in conjunction with ORS
- Chronic diarrhoea
- Limited indications in children
In which section are the majority of macronutrients absorbed?
95% of the macronutrients are absorbed from the jejunum
What is the optimal treatment for diarrhoea?
Oral rehydration solution (ORS).
What are the symptoms of clinical dehydration?
- Great thirst
Roughly how much indigestible carbohydrate can be converted SCFAs per day?
Around 80g per day
What is the unstirred layer?
It is a continous layer on the surface of epithelium, consisting of:
- Secreted IgA
Name 3 mechanisms of inflammatory diarrhoea.
- Inflammatory bowel disease - Crohn's, Ulcerative colitis
- Dysentery - Shigella, Campylobacter
- Other - Radiation enteritis
Diseases of which organ(s) commonly cause steatorrhoea?
- Small intestine - Coealic
What is in the intestinal chyme in the ileum?
- Indigestible carbohydrates
- Bile acids
- Vitamin B12 bound to intrinsic factor.
Where are bile acids and Vit B12.IF absorbed?
The terminal 50cm of the ileum; if this section is removed, patients can develop pernicious anaemia.
Diseases of which part of the GIT can cause large volume diarrhoea?
What are the differences in the villi between the jejunum and ileum?
- The jejunal villi are finger-like in appearance
- The villi in the iluem have a characteristic leaf shape
List 5 groups of drugs that can cause diarrhoea, with examples.
- Antibiotics; alters gut flora and gut motility
- NSAIDs; irritate and inflame the GIT
- Digoxin; imbalance of ions in the GIT
- Orlistat; fat in the gut
- Magnesium; osmotic effect.
What are the symptoms of inflammatory diarrhoea?
- Mucoid stools
- Weight loss.
What is the definition of diarrhoea?
3 or more loose or watery stools (taking the shape of the container) in a 24 hour period.
What are the types of diarrhoea?
What are the side effects of loperamide?
- Abdominal cramps
- Skin reactions, including urticaria.
How would you treat hypernatraemic dehydration?
- Give 20mls/Kg 0.9% NaCl over 48 hours as opposed to 24 hours in normal treatment of shock.
What are the functions of the intestinal flora?
- Assist in fermentation of the faecal material
- Suppress over growth of pathogens
- Affect hydration status and weight
- Alters stool pH
- Degrades intestinal mucins
Which route of entry is loperamide given?
Orally; syrup, tablets or capsules.
What are the possible consequences of diarrhoea?
- Excess loss of fluid - dehydration
- Loss of electrolytes
- Loss of nutrients - malnutrition
- Excessive energy consumption - weight loss
- Mucosal damage - haemorrhage, perforation, gut derived sepsis.
What are the symptoms of severe acute malnutrition (SAM)?
- Muscle wasting and reduced subcutaneous fat
- Angular stomatitis
- Smooth tongue
- Conjunctival and palmar pallor
- Hypo- and hyper-pigmentation.
What are the cell types found in the large intestine?
- Brush bordered coloncytes
- Goblet cells
- Endocrine cells
- Paneth cells (only in right side of colon).
What are the alternative treatment options to loperamide?
- Rehydration alone
- Treatment for cause.
What is dysentery?
A gastrointestinal disease characterised by severe, often bloody diarrhoea, usually caused by infection with bacteria or parasites.
Where does most of the fluid get reabsorbed from the GIT?
What interactions does loperamide have, if any?
Avoid where inhibition of peristalsis should be avoided, such as infective cause, active colitis and antibiotic associated colitis.
There are no significant interactions with other medications.
Why is apoptosis important in the small intestine?
It prevents abnormal cell growth, and therefore the number of small intestinal tumours is very low
Where are stem cells found in the small intestine?
In the crypts of Lieberkuhn, between the villous cells and the Paneth cells.
What are the symptoms of over-hydration?
- Increased HR
- Respiratory distress/cough
- "Crackles" in the lung fields
What should be monitored during treatment with loperamide?
- Hydration status
- U & E's
- Visible signs.
How long should loperamide be given for?
Until the symptoms are controlled; or if on-going, lower dose in chronic diarrhoea.
What are the symptoms of shock?
- Cold sweaty skin
- Weak rapid pulse and Irregular breathing
- Dry mouth and dilated pupils
- Decreased level of consciousness
- Reduced urine output
What would make you suspect hypernatraemic dehydration?
- Jittery movements
- Increased muscle tone
What class of drug is Loperamide?
An antimotility drug
What is the immediate treatment for shock?
- Establish IV line
- Give 20mls/Kg 0.9% Fluid (Hartmann's, NaCl 0.9%)
- Frequent monitoring and repeat if shock persists.
What is the maximum resorptive capacity of water in the colon?
Approximately 4L per 24 hours.
What is the normal osmolarity of the blood plasma?
Name 3 mechanisms that cause osmotic diarrhoea, and give an example of each.
- Malabsorption of CHO/protein - Lactose intolerance
- Rapid gut transit - IBS, Toddler's diarrhoea and stimulant laxative
- Osmotic laxative - Lactulose, PEG
What are some common causes of secretory diarrhoea?
Infections such as Cholera, rotavirus and ETEC