Constipation& Diarrhoea

Question 1

Definition for constipation

Answer 1

Frequency of bowel movements less than 3 times a week
Primary -chronic constipation without known cause
Secondary- caused by a drug (diarrhoea drug loperamide?)or medical condition

Question 2

Prevalence of constipation

Answer 2

1% of population
More common in
Women, elderly, pregnancy

Question 3

Influencing factor for primary constipation

Answer 3

Social : low fibre diet, lack of exercise, restricted access to toilet

Physical: immobility, dehydration, postures when defecating

Psychological: anxiety, eating disorders

Question 4

Organic Causes for secondary constipation

Answer 4

Endocrine, metabolic disease: diabetic autonomic neuropathy, hypercalcaemia

Myopathy: myotonic muscular dystrophy type 1- trouble with bowel

Neurological disease : multiple sclerosis, Parkinson’s disease, spinal cord injury

Structural abnormalities: colonic obstruction due to colorectal cancer, rectal relapse, pelvic floor dysfunction

Question 5

Drug related causes:

Answer 5

Al antacids 
Iron supplements
Anti Muscarinics
Opioid
Tricyclic antidepressant (amitriptyline)
Certain antiepileptics (phenytoin)
Sedating antihistamine 
Ca channel blockers

Question 6

Untreated chronic constipation leads to …

Answer 6

Faecal impaction

Question 7

Types of laxatives

Answer 7

Bulk forming e.g. Ispaghula husk (fybogel)
Stool softening e.g. Docusate Na
Osmotic eg lactulose
Stimulant eg senna, bisacodyl (ducolax)

Question 8

What is Prucalopride?

Answer 8

A selective 5HT 4 receptor agonist

Question 9

What does Prucalopride do?

Answer 9

Promotes motility and mucosal secretion

Reduce transient time

Question 10

What’s the MOA of Prucalopride

Answer 10

Binds to 5HT 4 Rec on PREsynaptical cholingeneric neurons
Increase ACh release by interneurons in the myenteric, submucosal plexus
Stools easier to move as fluids around

Question 11

What is the name of Cl- channel

activator?

Answer 11

Lubiprostone: a selective chloride channel activator

Question 12

What’s lubiprostones MOA

Answer 12

Increase the luminal secretion of Cl-
Which links to movement of Na and water
Activates PGE2 rec 4 (EP4) in colonic epithelial cells
Increase expression of Cl- in the apical membrane

Question 13

What’s the NICE guidelines about lubiprostone and Prucalopride

Answer 13

At least 2 different classes of laxative has failed to provide relief
After 6 months
Second line treatment

Question 14

What’s the treatment for opioid induced constipation

Answer 14

Opioid miu rec antagonist
Naloxegol

PERIPHERAL - PEGylation limited access to BBB
Poorly absorbed by gut, rapid metab

Question 15

MOA of naloxegol

Answer 15

Binds to opioid Rec in myenteric and submucosal plexuses

Blocks adverse action of opioid on motility/ secretion (reduction) and reabsorption (increase)

Question 16

NICE recom on naloxegol

Answer 16

In opioid induced constipation patient (adult) not showing an adequate response to laxative treatment

Question 17

Definition for diarrhoea

Answer 17

The abnormal passage of loose or liquid stools more than 3 times daily

Question 18

Episodes of diarrhoea can be classified into 3 categorise…

Answer 18

Acute- last less than 14 days
Persistent- longer than. 14 days
Chronic- more than 4 weeks

Question 19

Pathophysiology of diarrhoea

Answer 19

Results from excessive secretion and impaired reabsorption of fluid and electrolytes cross the intestinal epithelium
NA CL HCO3 K, glucose

Question 20

What are the Cl- channels

Answer 20

CFTR

CLCA

Question 21

Channels involved in diarrhoea mechanism

Answer 21

CFTR CLCA. Increase CL- excretion
NHE3- reduce NA absorption
Tight junction- increase paracellular permeability
DRA- reduced CL- absorption
Aquaporins- reduced absorption
SGLT-1 - reduce Na and glucose (–>water) absorption