Diarrhea Flashcards
What is the first-line drug class for symptomatic control of diarrhoea of unidentified cause?
Peripherally acting, opioid receptor agonist e.g., loperamide
Name TWO examples of opioid agonist antidiarrhoeals.
Loperamide
Diphenoxylate
Briefly explain the mechanisms of action of opioid agonist antidiarrhoeals.
Opioid agonists activate mu or mu and delta opioid receptors in the gastrointestinal system to inhibit motility, inhibit secretions, and shuts down sphincters.
Inhibition of acetylcholine release from enteric interneurons and motor neurons and inhibition of purine/nitric oxide release from inhibitory motor neurons causes inhibition of propulsive motility patterns. Reduction of prostaglandin release has been implicated in reducing secretions.
Describe the major differences between loperamide and diphenoxylate.
Loperamide is a mu opioid receptor agonist that does not cross the blood-brain barrier.
Diphenoxylate is a mu and delta opioid receptor agonist with limited blood-brain barrier penetration.
Explain why diphenoxylate is formulated together with atropine.
At higher doses, diphenoxylate can cross the blood-brain barrier to and therefore its use is associated with a risk of dependence.
Atropine is formulated together with diphenoxylate to:
Cause adverse effects on overdose to discourage abuse.
Adverse effects are anticholinergic parasympatholytic adverse effects such as dry mouth, flushing, etc.
Anticholinergic effects reducing GIT motility and secretions further add to antidiarrhoeal actions
Name an example of a colloidal bismuth compound used for the treatment of diarrhoea.
Bismuth subsalicylate
Bismuth subcitrate e.g., bismuth subcitrate potassium
Briefly describe the mechanisms of action of colloidal bismuth compounds in the treatment of diarrhoea.
Precise mechanisms of action not known
Bismuth has an antimicrobial effect and binds enterotoxins, which has benefit for treating traveller’s diarrhoea
Specifically for bismuth subsalicylate:
Rapid dissociation in stomach allowing absorption of salicylate
Salicylate inhibits intestinal prostaglandin production and chloride secretion
Reduces stool frequency and liquidity in acute infectious diarrhoea
Describe the adverse effects and concerns with the use of bismuth compounds for the treatment of diarrhoea.
Although > 99% of bismuth is eliminated in stool <1% is absorbed and stored in many tissues, elimination is by slow renal excretion
Prolonged use may rarely produce bismuth toxicity resulting in encephalopathy (ataxia, headaches, confusion, seizures)
Use only for short periods
Avoid in patients with renal insufficiency
But generally, the safety profile of bismuth formulations is good
Harmless blackening of the stool, which may be confused for gastrointestinal bleeding
Harmless darkening of tongue (liquid formulations)
Specifically for bismuth subsalicylate: Salicylate toxicity with high doses
Name an example of a bile salt-binding resin used to treat chronic diarrhoea.
Colestyramine (also known as cholestyramine in the USA), colestipol, or colesevelam
Briefly explain the mechanisms of action of bile salt-binding resins in the treatment of diarrhoea
Diseases of the ileum (e.g., Crohn’s disease) or surgical resection lead to malabsorption of bile salts resulting in colonic secretory diarrhoea
Bile salt-binding resins bind to bile sales alleviating diarrhoea caused by excess faecal bile salts
To what class of antidiarrhoeals does octreotide belong?
Somatostatin-like peptides
What is the route of administration and duration of action of octreotide?
Octreotide is a synthetic octapeptide similar to somatostatin but with a half-life of about 1.5 hrs in serum.
To extend the duration of action to 6 to 12 hours it is administered by subcutaneous injection.
It can also be administered as a monthly intramuscular depot formulation.
List examples of indications for use of octreotide as an antidiarrhoeal.
Use for secretory diarrhoea caused by gastrointestinal neuroendocrine tumours (carcinoid and VIP-oma)
Can also treat diarrhoea due to chemotherapy, vagotomy, gastric dumping syndrome, short bowel syndrome and AIDS
What are the adverse effects of somatostatin-like peptides?
Adverse effects of somatostatin-like peptides are numerous as they mimic the endogenous somatostatin hormone.
Major concerns / adverse effects:
Impaired pancreatic secretion can cause steatorrhoea, which can lead to fat-soluble vitamin deficiency
Nausea, abdominal pain, flatulence, and diarrhoea
Formation of gall sludge or gallstones in 50% of patients, rarely leading to acute cholecystitis
Prolonged treatment can result in hypothyroidism
Bradycardia
Are probiotics effective in the treatment of diarrhoea?
Although frequently taken for bacterial and traveller’s diarrhoea, the use of probiotics is not an evidence-based medical treatment for infectious or bacterial diarrhoea.
