antidiarrhoeals Flashcards
what are the major groups of drugs used to treat diarrhoea?
acute:
(1) opioid agonists
(2) colloidal bismuth compounds
(3) intestinal adsorbents
(4) products of lactobacillus acidophilus
chronic:
(5) bile salt-binding resins
(6) somatostatin-like peptides
what is the most important non-pharmacological treatment for diarrhoea?
oral rehydration therapy!! with water and oral rehydration salts in severe diarrhoea causing dehydration and loss of electrolytes
examples of opioid agonists?
LOPERAMIDE, diphenoxylate (+ atropine)
MOA of opioid agonists
- first line for rapid, symptomatic relief of diarrhoea
- acts on the enteric nervous system to increase colonic transit time
adverse effects of opioid agonists
- potential for CNS effects including addiction and abuse (if opioid crosses BBB)
- loperamide: does not cross BBB
- diphenoxylate: at higher doses, can have CNS effects and LT use can lead to dependence
- risk of cardiac abnormalities on OVERDOSE of loperamide
how is dependence on diphenoxylate dealt with?
preparations include atropine to discourage overdose
- leads to anticholinergic adverse effects - eg. dry mouth, hypothermia, flushing
- can contribute to anti-diarrhoeal action
examples of colloidal bismuth compounds
- bismuth subcitrate, bismuth subsalicylate
MOA of colloidal bismuth compounds
- precise MOA unknown
- has antimicrobial effect and binds enterotoxins which has benefit for treating traveller’s diarrhoea
- can also be used as mucosal protective agents in acid-peptic diseases
bismuth subsalicylate
- rapid dissociation in stomach allowing absorption of salicylate (NSAID)
- salicylate inhibits intestinal prostaglandin production and chloride secretion
- reduces stool frequency and liquidity in acute infectious diarrhoea
adverse effects of bismuth compounds
- 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 bismuth compounds generally have a good safety profile when used short-term
- harmless blackening of stool and reversible darkening of tongue
- salicylate toxicity with high dose of bismuth subsalicylate
examples of intestinal adsorbents
kaolin: naturally occurring hydrated magnesium aluminium silicate clay
DIOSMECTITE: a magnesium and aluminium silicate clay
MOA of intestinal adsorbents
- absorbents of bacteria, bacterial toxins and fluid
- decrease stool liquidity and number
- useful in acute diarrhoea but seldom used chronically
adverse effects of intestinal adsorbents
- not absorbed so little risk of significant adverse effects
- constipation is only likely adverse effect
- can bind to and inhibit absorption of other medications (should not be taken within 2 hours of other oral medications)
difference between intestinal adsorbents and bulk forming laxatives
bulk forming laxatives form a gel-like mass in the GIT while the diosmectide goes into the GIT and absorbs the water but forms a solid (not gel-like) mass
example of lyophilizate of killed Lactobacillus acidophilus
lacteol fort (oral capsule or powder mixed with water)
MOA of lyophilizate of killed Lactobacillus acidophilus
- preparation contains heat-inactivated Lactobacillus acidophilus
- adheres onto the surface of intestinal cells and normalises the intestinal flora by competitive exclusion
- by interfering with the intestinal adherence of other micro-organisms, over colonisation of these organisms is prevented
when is lyophilizate of killed Lactobacillus acidophilus indicated?
traveler’s diarrhoea or bacterial diarrhoea
adverse effects of lyophilizate of killed Lactobacillus acidophilus
- not systemically absorbed so little risk of adverse effects
- important to maintain hydration
- contraindicated in patients with lactose intolerance as formulation contains lactose monohydrate (can worsen diarrhoea)
examples of bile salt-binding resins
colestyramine
MOA of bile salt-binding resins
- bile salts are normally absorbed in the terminal ileum
- disease of the ileum (eg. Crohn’s disease) or surgical resection leads to malabsorption of bile salts resulting in colonic secretory diarrhoea (osmotic laxative-like effect of bile salt in colon)
- bile salt-binding resins bind to bile salts alleviating diarrhoea caused by excess fecal bile salts
adverse effects of bile salt-binding resins
- bloating, flatulence, constipation and fecal impaction
- exacerbation of malabsorption of fat if underlying deficiency is present
- bind to a number of drugs and should not be given within 2 hours of other oral drugs
examples of somatostatin-like peptides
octreotide (synthetic peptide similar to somatostatin hormone but has a longer half life), subcutaneous injection and IM depot formulations
MOA of somatostatin-like peptides
- mimics somatostatin hormone released in the GIT, pancreas and the hypothalamus in the brain
- in GIT: widespread physiological effect include
- inhibition of release of various
neurotransmitters and
hormones (eg. gastrin, VIP, 5-HT)
–> shuts down GIT motility and
secretions
- reduces intestinal and pancreatic
secretions
- slows GI motility and inhibits
gallbladder contraction
when are somatostatin-like peptides used?
use for secretory diarrhoea caused by GI and neuroendocrine tumours –> eg. carcinoid tumour and vasoactive intestinal peptide-secreting (VIP) tumour
adverse effects of somatostatin-like peptides
- impaired pancreatic secretion can cause steatorrhoea which can lead to fat-soluble vitamin deficiency (A, D, E, K)
- 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 (because it alters the hypothalamic pituitary thyroid axis)
- bradycardia
