drugs for constipation Flashcards
what are the 2 classes of drugs for constipation?
physical and physiological
what are the types of constipation drugs?
physical:
- bulk forming laxatives
- stool surfactant agents (softeners)
- osmotic laxatives
physiological
- stimulant laxatives
- chloride channel activators
- opioid receptor antagoinists
- serotonin 5-HT4-receptor agonists
examples of bulk forming agents
plant products/fibers: PSYLLIUM, sterculia, agar, bran
semi-synthetic: methylcellulose
synthetic: polycarbophil
MOA of bulk forming agents
- fibers work by forming an indigestible, hydrophilic colloids (fiber) which attracts water
- absorbs water forming bulk, emollient gel that distends colon (increases stool mass) –> promotes peristalsis
- fiber itself is not digested (it stays in the lumen and is entirely excreted from the lumen of the git)
adverse effects of bulk forming agents
- administer with plenty of water
- avoid if suspected obstruction!!
- interaction with absorption of other oral drugs –> do NOT use within 2 hours before or after
- bacterial digestion of plant fibers within the colon may lead to flatus, bloating and abdominal pain (due to distension caused by gas)
examples of stool surfactant agents (softeners)
GLYCERIN + SODIUM CHLORIDE (enema)
mineral oil (oral)
MOA of stool surfactant agents (softeners)
- lowers surface tension, allowing water and lipids to penetrate into the stool mass –> increases the stool mass and the softness of stool promoting peristalsis against the mass
- mineral oil lubricates + retards water absorption from the stool
adverse effects of stool surfactant agents (softeners)
- mineral oil is not palatable but may be mixed with fruit juice
- mineral oil aspiration can lead to severe lipid pneumonitis (aspiration pneumonia)
- LT use can impair absorption of vitamins A, D, E, K (fat-soluble vitamins)
osmotic laxatives examples
nonabsorbable sugars or salts
- sugars: sorbitol, LACTULOSE
- salts: magnesium hydroxide, magnesium citrate, sodium phosphate
MACROGOL
- balanced, isotonoic solution of osmotically active sugar (polyethylene glycol) and various salts
MOA of osmotic laxatives
- osmotically-mediated water movement into bowel increases stool liquidity and volume
- increased volume stimulates peristalsis
- high doses can produce bowel evacuation (purgation) within 1-3 hours
adverse effects of osmotic laxatives
- important to maintain adequate hydration by increasing oral fluid intake
- colonic bacteria act on sugars –> lead to severe flatus and abdominal cramps
adverse effects of sodium phosphate (osmotic laxative)
- hyperphosphataemia, hypernatraemia, hypocalcaemia and hypokalaemia
- may cause cardiac arrhythmias or acute renal failure due to tubular deposition of calcium phosphate (nephrocalcinosis)
- should not be used in patients who are frail, elderly, on diuretics, unable to maintain adequate hydration or have renal insufficiency or cardiac disease
which is the preferred osmotic laxative?
- balanced macrogol is a safer alternative
- contains macrogol (sugar) with electrolytes –> balanced to avoid significant electrolyte shifts
- macrogol although an osmotically active sugar does not produce significant cramps or flatus (less digested by GIT flora)
examples of stimulant laxatives (cathartics)
- most widely used physiologic agents
anthraquinone derivatives: aloe, senna, cascara (oral or per rectum)
- produce bowel movements in 6-12 hours (oral) or 2 hours (rectal)
diphenylmethane derivatives: BISACODYL (oral or per rectum)
- tablet or rectal suppository
- induces bowel movement in 6-10 hours (oral) or 30-60 minutes (rectal)
- used in conjuction with PEG (polyethylene glycol) for colonic cleansing prior to colonoscopy
MOA of stimulant laxatives (cathartics)
- produce migrating colonic contractions
- mechanisms poorly understood but may include: direct stimulation of enteric nervous system (innervating the smooth muscle of the GIT and increasing GIT motility), colonic electrolyte and fluid secretion
in what conditions are stimulant laxatives (cathartics) used
long-term use may be required in patients who are neurologically impaired
adverse effects of stimulant laxatives (cathartics)
- anthraquinone derivatives can lead to brown pigmentation of colon (chronic use)
- phenolphthalein withdrawn due to cardiac toxicity
- bisacodyl has no significant cardiac toxicity
- milk products can cause the enteric coating of oral bisacodyl tablets to break down too fast –> risk of gastric irritation/dyspepsia –> do NOT take within 1 hour of consuming milk products
how quickly are stools produced with these pharmacological agents?
soft stools in 1-3 days: bulk laxatives, lactulose (oral), stool softeners (oral)
soft/semi-fluid stool in 6-8 hours: stimulant laxatives (oral)
watery stool in 1-3 hours: osmotic laxatives, PEG, suppositories (bisacodyl)
chloride channel activators examples
lubiprostone
MOA of chloride channel activators
- stimualte type 2 chloride channels in small intestine
- increases chloride rich fluid secretions
- stimulates motility and shortens intestinal transit time
when are chloride channel activators used?
tends to be used not for more common cases of acute constipation but in situations when there is long-standing constipation in a patient that has not responded to other agents
(only about half of patients respond within 24 hours of a single dose)
adverse effects of chloride channel activators
- return of constipation after discontinuation
- avoid in pregnancy (still a rather new drug)
- nausea due to delayed gastric emptying
examples of opioid receptor antagonists
methylnaltrexone bromide (administered subcutaneously every 2 days)
when are opioid receptor antagonists used?
treatment of opioid-induced constipation in patients receiving palliative care (activating opioid receptors for the treatment of pain also results in the shutting down of motility + secretions along the GIT and closes down GIT sphincters)
