Gastroenterology: Pharmacology - Laxatives Flashcards
7 classes of laxatives with example(s)
- Bulk-forming: psyllium, methylcellulose, polycarbophil
- Stool softeners: docusate, glycerin suppository, mineral oil
- Osmotic: magnesium hydroxide (milk of magnesia), sorbitol, lactulose, combination purgatives, PEG
- Stimulant: senna, aloe, cascara, bisacodyl
- Chloride secretion activators: lubiprostone, linaclotide, plecanatide
- Opioid receptor antagonists: methylnaltrexone, alvimopan
- 5HT-4 agonists: cisapride, prucalopride, tegaserod
Mechanism of action of bulk-forming laxatives
Indigestible hydrophilic colloids that absorb water and distend the colon to promote peristalsis
Adverse effect of bulk-forming laxatives
Increased bloating and flatus
Mechanism of action of stool softeners
Soften stool material to allow water and lipids to penetrate
May also impair water and lipid absorption from stool
Adverse effects of mineral oil as stool softener
- Aspiration causes severe lipid pneumonitis
- Long-term use inhibits fat-soluble vitamin absorption
Mechanism of action of osmotic laxatives
Soluble but nonabsorbable compounds which increase faecal fluid
Adverse effect of milk of magnesia
Hypermagnesaemia in patients with renal insufficiency
Adverse effects of sorbitol and lactulose
Sugars are metabolised by colonic bacteria -> flatus, cramps
Adverse effect of sodium phosphate (used as osmotic laxative)
Electrolyte derangement (hyperphosphataemia, hypocalcaemia, hypernatraemia, hypokalaemia) leading to increased risk of cardiac arrhythmias or nephrocalcinosis-induced AKI
Adverse effects of anthraquinone derivatives (aloe, senna, cascara)
Brown pigmentation of the colon (“melanosis coli”)
Mechanism of action of lubiprostone, linaclotide, plecanatide
Stimulates type 2 chloride channel CIC-2 in small intestine, increasing intestinal motility
Mechanism of action of methylnaltrexone, alvimopan
Selective mu-opioid receptor antagonists
Which opioid receptors are responsible opioid-induced constipation?
Mu receptors
Mechanism of action of tegaserod, cisapride, prucalopride
5HT-4 receptor agonists
How do 5HT-4 agonists exert their laxative effects?
Stimulation of 5HT-4 receptors results in activation of enteric neurons promoting peristalsis
Mechanism of action of loperamide, diphenoxylate, eluxadoline. What is special about eluxadoline?
Opioid agonists
Eluxadoline has high affinity for mu-opioid receptor
Contraindications to eluxadoline
Can induce sphincter of Oddi spasm: should not be used in patients with a history of pancreatitis, alcoholism, or known sphincter of Oddi disease (and with caution in patients with prior cholecystectomy)
How does bismuth salicylate exert its antidiarrhoeal effects?
Inhibits intestinal prostaglandin and chloride secretion
What medications can be used to treat colonic secretory diarrhoea secondary to bile salt malabsorption?
Bile salt-binding resins (cholestyramine, colestipol, colesevelam)
Five physiologic effects of somatostatin
- Inhibits numerous GI hormones and transmitters (gastrin, CCK, glucagon, GH, insulin, secretin, VIP, 5HT)
- Reduces intestinal and pancreatic secretions
- Slows GI motility and inhibits gall bladder contraction
- Reduces portal and splanchnic blood flow
- Inhibits secretion of some anterior pituitary hormones
What is octreotide?
Synthetic octapeptide with actions similar to endogenous somatostatin
Four clinical uses of octreotide
- Inhibition of neuroendocrine tumour effects (carcinoid, VIPoma)
- Antidiarrhoeal
- Treatment of pituitary tumours (e.g. treatment of acromegaly)
- UGIB in setting of portal HTN (reduce portal blood flow and variceal pressures)
