Laxatives: drugs used in constipation Flashcards
List out PHYSICAL drugs for constipation
- bulk-forming laxatives
- stool surfactant agents (softeners)
- osmotic laxatives
List out PHYSIOLOGICAL drugs for constipation
- stimulant laxatives
- chloride channel activators
- opioid receptor antagonists
- serotonin 5-HT4- receptor agonists
Examples of bulk-forming laxatives
- Plant products/fibers:
- Synthetic fibers:
- Plant products/fibers:
- psyllium (ispaghula husk), sterculia, agar, bran
- methylcellulose (semi-synthetic) - Synthetic fibers: polycarbophil
Mechanism of bulk-forming laxatives
- Bulk-forming laxatives are not digested but absorb liquid in the intestines and swell to form a soft, bulky stool.
- The bowel is then stimulated normally by the presence of the bulky mass. (promotes peristalsis)
Main concerns of bulk-forming laxatives
- bacterial digestion of plant fibers within colon may lead to flatus, bloating & abdominal pain
- interference with absorption of other drugs
What drugs are the safest & most natural way for patients with occasional constipation?
bulk-forming agents
Examples of stool surfactant agents (softeners)
- docusate (oral or enema)
- glycerin (rectal suppository)
- mineral oil (oral)
Mechanism of stool surfactant agents
- lowers surface tension, allowing water & lipids to penetrate
- mineral oil lubricates + retards water absorption from stool
- soften stool mass, promote peristalsis
Main concerns of stool surfactant agents:
- if drug accidentally gets into lungs:
- long-term use:
Mineral oil:
- if drug accidentally gets into lungs: aspiration can result in severe lipid pneumonitis (aspiration pneumonia)
- long-term use: impairs absorption of fat-soluble vitamins (A,D,E & K)
Examples of osmotic laxatives
1. Non-absorbable sugars or salts:
2.
- Non-absorbable sugars or salts:
- sugars: sorbitol, lactulose
- salts: magnesium hydroxide; Mg citrate; sodium phosphate - Balanced Polyethene Glycol (PEG)
Mechanism of osmotic laxatives
- osmotically-mediated water movement into the bowel increases ________________
- increased vol. stimulates _________
- high doses can produce ___________ within _______
- osmotically-mediated water movement into the bowel increases stool liquidity & volume
- increased vol. stimulates peristalsis
- high doses can produce bowel evacuation (purgation) within 1-3hrs
Main concerns of osmotic laxatives
- colonic bacteria act on _____, causing ___________
- sodium phosphate:
- colonic bacteria act on sugars — causing severe flatus & abdominal pain
- sodium phosphate: can cause overabsorption of phosphate, sodium and under absorption of calcium, potassium
- Na phosphate can also cause cardiac arrythmias or acute renal failure (nephrocalcinosis)
In osmotic laxatives,
- it is important to maintain ________ by increasing ______
- should not be used in patients who are _________, unable to ________ or who have ________ or ______
- maintain adequate hydration by increasing oral fluid intake
- should not be used in patients who are frail, elderly, on diuretics, unable to maintain adequate hydration or who have renal insufficiency or cardiac disease
- Non-absorbable sugars or salts:
vs - Balanced Polyethene Glycol (PEG)
which is safer?
why?
Balanced Polyethene Glycol (PEG)
- avoid significant electrolyte shifts
- PEG altho an osmotically active sugar, does not produce sig. cramps or flatus
Examples of stimulant laxatives
- Anthraquinone derivatives
- Diphenylmethane derivatives
- Anthraquinone derivatives:
- aloe, senna or cascara (oral or rectum) - Diphenylmethane derivatives
- bisacodyl (oral or rectum)
- Anthraquinone derivatives
- Diphenylmethane derivatives
produce bowel movements in:
_____ (oral)
_____ (rectal)
1. Anthraquinone derivatives 6-12 hrs (oral) 2 hrs (rectal)
- Diphenylmethane derivatives
6-10 hrs (oral)
30-60 mins (rectal)
______ is used in conjunction with PEG for colonic cleansing prior to colonoscopy
Bisacodyl (stimulant laxative)
Mechanisms of stimulant laxatives
- produce ______________
- ______________ of enteric nervous system
- ______________ secretion
- produce migrating colonic contractions
- direct stimulation of enteric nervous system
- colonic electrolyte & fluid secretion
Main concerns of stimulant laxatives
- long-term use: may lead to ________ and ________of myenteric plexus → colonic atony & dilation
- anthraquinone derivatives: chronic use leads to __________
- diphenylmethane derivatives: phenolphthalein withdrawn due to __________
- long-term use: (may be needed in pts who are bed bound) may lead to dependence and destruction of myenteric plexus → colonic atony & dilation
- anthraquinone derivatives: chronic use leads to brown pigmentation of colon
- diphenylmethane derivatives: phenolphthalein withdrawn due to cardiac toxicity
Examples of chloride channel activators
lubiprostone
Mechanisms of chloride channel activators
- stimulate
- increases
- stimulates _____ & shortens __________
- stimulate type 2 chloride channels in small intestine
- increases chloride-rich fluid secretions
- stimulates motility & shortens intestinal transit time
Main concerns of chloride channel activators
- return of constipation after discontinuation
- nausea due to delayed gastric emptying
Avoid chloride channel activators in ______ patients
pregnant
Example of opioid receptor antagonists
methylnaltrexone bromide
Opioid receptor antagonists are administered _________ every ____
subcutaneously every 2 days
Opioid receptor antagonists are used to treat opioid-induced constipation in ________ patients
palliative care
Mechanisms of opioid receptor antagonists
- they block ______________
- do not ______________ thus they do not ______________
- they block intestinal mu opioid receptors
- do not readily cross blood-brain barrier so do not block CNS analgesics effects
Side effects of opioid receptor antagonists
- Common:
- Rare but severe:
- Common: abdominal pain, nausea, diarrhoea, flatulence, sweating
- Rare but severe: GI perforation
Examples of serotonin 5-HT4- receptor agonists
cisapride, prucalopride
Mechanisms of serotonin 5-HT4- receptor agonists
- stimulate 5-HT4 receptors on __________ in the GI walls → increases ____________ & ____________ → ____________ → promotes ____________
- stimulate 5-HT4 receptors on nerve terminals in the GI walls → increases neurotransmitter release & smooth muscle motor activity → prokinetic effect → promotes GI motility
Do NOT use serotonin 5-HT4- receptor agonists in the event of _________
intestinal obstruction
Side effects of serotonin 5-HT4- receptor agonists
1. Common:
- Severe–
- cisapride:
- Common: abdominal pain, nausea, diarrhoea, dizziness, headache
- Severe–
- cisapride: is a 5-HT4 partial agonist → adverse cardio events due to actions at hERG K+ channel
Are there any side effects of prucalopride? Why?
prucalopride: high affinity 5-HT4 agonist → does not appear to have sig. cardio affects
