Anti-Diarrhoeals Flashcards
What is diarrhoea?
Passage of unformed stools more frequently than normal for an individual
Roughly >3 times per day
Often accompanied by faecal urgency, nausea, vomiting and abdominal pain
What are the three types of diarrhoea?
Acute <14 days
Persistent 14-28 days
Chronic >28 days
What does diarrhoea result in?
Increased motility
Reduced absorption
Increased secretion of fluids/ electrolytes
What are the causes of diarrhoea?
Existing chronic disease
Infectious agents
Drugs
Psychological factors
What are some chronic diseases that can cause diarrhoea?
IBD
Gut resections
Motor abnormalities of IBS
Celiac disease
Mal absorption
Endocrine disorders
(All lead to loss of functioning mucosa)
What are some of the infectious agents that can cause diarrhoea?
Viral gastroenteritis
Bacterial pathogens
Parasites / protozoa
How do the rotavirus and norovirus cause diarrhoea?
Damaging the small bowel villi
Causes a net secretion of substances
Mild watery stools
Describe how adhesive enterotoxigenic bacteria cause diarrhoea
E.G. V cholerae, E. coli
Adhere to brush borders of intestinal absorptive cells
Secrete enterotoxins
Alter fluid electrolyte transport
Increases PG activity
Increases enteric NS activity
Severe watery stools
Explain how invasive bacteria cause diarrhoea
E.G. C. difficile, salmonella
Invade endothelium
Secrete enterotoxins
Cause inflammation
Tissue destruction
Bloody and watery stools
What drugs can cause diarrhoea?
Propanolol
Parasympathomimetics
Levodopa
Indomethacin
Digoxin
Antacids
Metformin
Laxatives
Is there a relationship between antibiotic use and diarrhoea?
Antibiotics may cause diarrhoea in 5-35% of individuals
Depends on the antibiotic, pathogen and underlying host health
Antibiotics disrupt normal microbiota leading to metabolic imbalances.
What impact can severe diarrhoea have?
It interferes with the absorption of drugs such as the contraceptive pill, anti convulsants and warfarin
What should be the first concern when dealing with (severe) diarrhoea?
Rehydration therapy
Priority over reducing stool fluid output
Oral hydration first
If electrolyte imbalances are severe move to IV fluid
Food intake should be maintained
What does rehydration therapy do?
Corrects electrolyte imbalance, fluid imbalance and acidosis
Increases water absorption and electrolytes
Alkalinising agent included to counter acidosis
Hypo osmolar solutions to avoid osmotic diarrhoea
What are the components of the WHO oral rehydration therapy?
Sodium
Potassium
Chlorine
Citrate (Alkali)
Glucose
What do anti-motility agents do?
Stop the movement of substances along the intestine
Less frequent bowel movements
Not good for infectious diarrhoea
Relieves symptoms of acute uncomplicated diarrhoea in adults
When are anti-motility agents used?
Can be used in immediate cases to pause diarrhoea but won’t ‘stop’ it
Should not be used in children
List some examples of opiate like anti diarrhoeals
Diphenoxylate
Codeine
Loperamide (Imodium)
How do opiate like anti diarrhoeals work?
They act on mu opioid and serotonin receptors in the myenteric plexus
Decreases ACh release
Decreased peristaltic activity
Increased segmental activity / tone
Increased transit time
Increased time for fluid absorption
What are the side effects of opiate like anti diarrhoeals?
Constipation
Abdominal cramps
Bloating
What are the side effects of codeine and diphenoxylate?
Cross the blood brain barrier causing
Euphoria
Respiratory depression
Drowsiness
Tolerance and dependence
Restrict to severe cases only
What is cophenotrope?
A combination of diphenoxylate and atropine
Typical anti muscarinic side effects
Dry mouth, blurred vision
What can happen due to chronic use of opiate like agents?
Paralytic ileus and toxic mega colon
Paralyses peristaltic movement, bacteria can proliferate, colon can become distended
What are some other anti diarrhoeal agents?
Stool modifiers
Antibiotics
Vaccines
What are stool modifiers?
Absorbent clays
Recommended for chronic cases
What do stool modifiers do?
Bulking action
Increase stool consistency
Potentially absorb micro organisms or toxins
Could provide a protective coating to the mucosa to prevent bacteria and toxins adhering
What does bismuth salicylate do?
Pepto bismol
Promotes intestinal sodium and water reabsorption
Attenuates intestinal secretion
Binds to enterotoxins
Has direct anti bacterial effect
Prophylactic use in some countries
Discolours the tongue and teeth
What antibiotics are used to treat diarrhoea?
Rifaximin - benefit in combination with anti motility agent
Ciproflaxacin - campilobacter jejuni
Tetracyclin - severe cholera
When should vaccines be used to treat diarrhoea?
For typhoid and and cholera infections
Especially in developing countries where sanitation is poor
What is the dukoral oral vaccine?
A mixture of inactivated vibrio cholerae bacteria and non toxic component of the toxic bacteria being treated
What is the protective efficacy of the dukoral oral vaccine?
V cholera - 85%
Enterotoxigenic E. coli - 67%
Travellers diarrhoea - 43%
Name some of the novel anti disrrhoeal approaches
Racecadortil
Novel anti secretory angents
Probiotics
Zinc supplements
What does racecadotril do?
Destroys the bodies natural opioid peptides
Enkephalinase inhibitor - prevents metabolism of opioid peptides secreted by myenteric and submucosal plexus
Augments opioid effects on decreased fluid secretion, propulsive motility
Safe for acute diarrhoea in children
What are novel antisecretory agents?
Chloride channel blockers
Prostaglandin analogs
How do probiotics help?
Optimise mucosal immune responses to infections
Possible applications of acute childhood diarrhoea, antibiotic associated diarrhoea, prophylaxis of traveller diarrhoea and IBD
How do zinc supplements help?
Decreased duration and severity of of diarrhoea
Decreased mortality (especially children younger than five)
Unsure of mechanism
