Laxatives And Anti-diarrheals Flashcards
What are the 7 major groups of drugs used to treat constipation?
Physical:
- Bulk-forming laxatives
- Stool surfactant agents
- Osmotic laxatives
Physiological:
- Stimulant laxatives
- Opioid RA
- Serotonin 5-HT4 RA
- Chloride channel activators
What is a bulk-forming agent drug and what is the MOA?
- Psyllium drug
- Least invasive (1st line)
- As drug is hydrophilic, it absorbs water from the GIT to form bulk, emollient gel
~ Increases mass of stool to promote peristalsis
What are the main concerns of bulk-forming laxatives?
- Must be administered with plenty of water
- Need to avoid if there is a suspected obstruction
- Do not use within 2hrs before/after taking other drugs
~ May make stool more firm - Bacterial digestion of plant fibres within colon may lead to bloating, flatus and abdominal pain
What is an osmotic laxative and what is the MOA?
- Lactulose
- Macrogol
- 2nd line
- Osmotically-mediated water movement into bowel to increase stool liquidity and volume
- ^ vol stimulates peristalsis
- High doses can stimulate purging in 1-3 hours
What are the main concerns of osmotic laxatives?
- Requires adequate hydration
- Colonic bacteria will act on sugars in the drug, causing flatus and abdominal cramps
- Sodium phosphate in the drug can cause
~ ^ phosphate, sodium
~ Decreased sodium, potassium
~ Cardiac arrhythmias or acute renal failure (due to deposition of calcium phosphate)
What is an alternative to lactulose and what are its pros and cons?
- Macrogol
Pros:
- Artificial sugar so body does not break it down
~ Prevents flatus or cramps
- Balanced sugar and electrolytes to avoid significant electrolyte shifts
Cons:
- More costly
What is a stool surfactant agent/softener and what is its MOA?
- Glycerin + sodium chloride (enema)
- Lowers surface tension to allow water and lipids to penetrate
- Mineral oil lubricates and retards water absorption from stool, especially in the colon
What are the main concerns when taking stool surfactant agents?
- Mineral oil is not palatable but may be mixed with fruit juice
- Aspiration can lead to severe aspiration pneumonia
- Long-term use can impair absorption of fat-soluble vitamins (A,D,E,K)
What is a stimulant laxative/cathartic and what is its MOA?
- Bisacodyl (oral or enema)
- Used together with macrogol for colonic cleansing prior to colonoscopy
- Produce migrating colonic contractions/stimulates bowel movement
What are the main concerns for stimulant laxatives?
- Chronic use may lead to dependence (colonic atony and dilation)
- Long-term use needed in px who are neurologically impaired or bed-bound
- Chronic use can lead to melanosis coli/brown pigmentation of colon
- Milk products can cause the enteric coating of oral bisacodyl to break down too fast
~ ^ risk of gastric irritation and dyspepsia
~ Cannot be taken within 1 hour of each other
Compare the stool characteristics for drugs used in acute constipation
Soft stool in 1-3 days
- Bulk laxatives
- Lactulose (Osmotic laxative)
- Stool softeners/emollients
Soft/Semi-fluid stool in 6-8 hours
- Stimulant laxatives (oral)
Watery stool in 1-3 hours
- Osmotic laxatives
- PEG
- Bisacodyl (Stimulant laxative)
What are chloride channel activators and its MOA?
- Lubiprostone
- Stimulated type 2 chloride channels in small intestine
- Increases chloride-rich fluid secretions
- Stimulates motility and shortens intestinal transit time
What are the major concerns of chloride channel activators?
- Return of constipation after discontinuation
- Nausea due to delayed gastric emptying
What is an Opioid RA and what is its MOA?
- Methylnatrexone bromide
- Only for opioid-induced constipation
- Effects are mainly mediated through a blockade of intestinal opioid receptors
~ Shuts down sphincters, and movement of tract
~ Does not cross BBB so analgesic effect of opioid still works
What are the major concerns of Opioid RA?
- Abdominal pain, nausea, diarrhea, flatulence, sweating
- Gastrointestinal perforation
What are 5-HT4 RA and what is its MOA?
- Prucalopride
- Stimulation of receptors in GIT ^ neurotransmitter release and smooth muscle motor activity
- ^ SM activity causes prokinetic effect to ^ GI motility
- Do not use if there is complete intestinal obstruction
What are the adverse effects of using 5-HT4 RA?
- Abdominal pain, nausea, dizziness, headache, diarrhea
- Cisapride has adverse CVS events but not prucalopride
What are the 6 major groups of drugs used to treat diarrhoea?
Acute diarrhoea:
- Opioid agonists
- Colloidal Bismuth compounds
- Intestinal adsorbents
- Lyophilizate of Lactobacillus acidophilus
Chronic diarrhoea:
- Bile salt-binding resins
- Somatostatin-like peptides
What are opioid agonists and what is its MOA?
- Loperamide
- First-line for rapid, symptomatic relief
- Actions in the enteric nervous system increase colonic transit time and reduce GIT motility
What are the major concerns for opioid agonists?
- Potential for CNS effects including addiction if diphenoxylate is used
~ Not so much for loperamide (does not cross BBB) - Atropine can be used to discourage overdose but leads to dry mouth
- Risk of cardiac abnormalities on overdose of loperamide
What are colloidal Bismuth compounds and what is its MOA?
- Bismuth subcitrate
- Has antimicrobial effect and binds enterotoxins
~ Treats traveller’s diarrhoea - Mucosal protective agents in acid-peptic diseases
- Reduces stool frequency and liquidity in acute infectious diarrhoea
What are the major concerns of using colloidal bismuth compounds?
- Small % of bismuth may be absorbed and stored in tissues
~ Those on long-term use may have bismuth accumulation (encelopathy, headaches, confusion, seizures)
~ Slow renal excretion - Harmless blackening of stool which may be confused for melena
- Harmless darkening of tongue
- Not to be used in px with renal insufficiency
- Salicylate toxicity with high doses of bismuth subsalicylate
What are intestinal adsorbents and what is its MOA?
- Diosmectite
- (Kaolin)
- Absorbents of bacteria, bacterial toxins and fluid
- Decreases stool liquidity
- Rarely used for chronic diarrhoea
What are the major concerns for intestinal adsorbents?
- Can bind to and inhibit absorption of other medications
~ Should not be taken within 2 hours of other medications - Constipation rarely
What is lyophilizate of killed Lactobacillus acidophilus?
- Lacteol fort
- For bacterial/traveller’s diarrhoea
- Contained heat-inactivated Lactobacillus acidophilus
- Adheres on the surface of intestinal cells and normalizes the intestinal flora
~ By interfering with the intestinal adherence of other micro-organisms, over-colonization of these organisms is prevented
What are the major concerns of the lyophiliizate of killed Lactobacillus acidophilus?
- Requires adequate hydration
- Contraindicated in px with lactose intolerance
~ Formulation contains lactose monohydrate
What are bile salt-binding resins and what is its MOA?
- Colestyramine
- For chronic and severe diarrhea
- Due to certain diseases, bile salts are not absorbed in the ileum
~ TF drug binds to bile salts and prevent colonic secretory/osmotic laxative-like effect of bile salt
What are the major concerns of bile salt-binding resins?
- Binds to a number of drugs and should not be given within 2 hours of other oral drugs
- Bloating, flatulence, constipation and fecal impaction
- Exacerbation of malabsorption of fat if underlying deficiency is present
What are somatostatin-like peptides and what is their MOA?
- Octreotide
- Mimics somatostatin hormone released in the GIT, pancreas and hypothalamus
- Slows GI motility and inhibits gallbladder contraction
What are the main concerns of somatstatin-like peptides?
- Impaired pancreatic secretion can lead to steatorrhea and fat-soluble vitamin deficiency
- Nausea, abdominal pain, flatulence and diarrhoea
- Formation of gallstones
- Hypothyroidism if treatment is prolonged
- Bradycardia
When and how is activated charcoal used in treating diarrhoea?
- Used in emergency treatment of certain types of poisoning (prevent absorption of poison)
What are the adverse effects of activated charcoal?
- N&V
- Respiratory side effects if aspiration of charcoal or emesis occurs
- Cannot be used for long-term as it interferes with nutrient and drug absorption
