Relaxatives Laxative Agents

1.3 – “Relaxatives”: Laxative agents (lactulose, magnesium, polyethylene glycol, docusate, Senna, psyllium, lopera loperamide, mide, diphenoxylate) & antidiarrhea antidiarrheals ls Laxatives • Alternatively, eat enough fiber, exercise, and stay hydrated; that’ll be enough for most folks, and has far fewer adverse effects! • Note that laxatives ≠ prokinetics (those would be the muscarinic agonists, metoclopramide, erythromycin). Laxatives work on the stuff that comes out, and may indirectly stimulate peristalsis by increasing stool volume → luminal distension. Osmotic laxatives • Nonabsorbable substances draw water into the intestinal lumen(bubbling spa water). Serves to loosen stool, as well as distending the lumen → stimulating peristalsis. Can cause rapid movement of water and rapid action (rapid relaxation by hanging out in the water filled tub). Can result in dehydration d/t water loss (water spilling down drain). OTC availability leads to potential for abuse, as in eating disorders. • magnesium hydroxide & magnesium citrate (magnets) act rapidly, resulting in large volumes of water and consequent high volume of stool. Can result in hypermagnesemia, especially in patients with kidney disease • Polyethylene glycol (PEG) is used for endoscopy prep (peg used as a drain plug). Usually combined with electrolytes to keep balanced • Sodium polystyrene sulfonate (Kayexalate) used occasionally as a laxative. Used as well to manage hyperkalemia. • Lactulose o Non-absorbable sugar (“relaxulose” tub additive). Used occasionally as laxative, but causes severe gas and cramps (bubbling tub). o More often used in cases of hepatic encephalopathy (liver and brain-shaped corals in fish tank). Gut flora degrade lactulose into lactic acid & acetic acid, driving down the pH of the intestinal lumen (fish gobbling up lactulose; acid meter on side of tank). This in turn favors NH4+ (non-absorbable) over NH3 (absorbed form), favoring excretion of the excess ammonia (tank cleaner guy has ammonia cleaner is his belt, and is drawing NH4 out of tank). o May be combined with rifaximin to eradicate ammonia-producing gut bacteria in the case of hyperammonemia (fisherman is removing fish altogether) Bulk forming laxatives • Psyllium, methylcellulose (bulky seaweed). Works as a hydrophilic colloid, absorbing water in the lumen → distention & peristalsis. Cause bloating & gas in some patients. • Surfactants (stool softeners, emollients) • Docusate & glycerin, given PO or as enema. Work by allowing water & lipids to penetrate stool (canoe on the dock is filling with water). Not known for being especially effective. • Stimulant laxatives, a.k.a. cathartics • Senna and others. Work by direct stimulation of enteric nervous system → electrolyte & fluid secretion. MOA is not entirely understood. (Guy tanning in sun, with masseuse rubbing oil into skin, stimulating stomach). Chronic use of Senna may cause benign brown pigmentation of the colon called melanosis coli (brown stomach) Antidiarrhea Antidiarrheals ls (muddy slipper slippers) s) • ONLY use in cases where there is neither infection nor hemorrhage (red stool outside of the massage parlor). In either of those situations, need to treat the underlying cause. • Most of these are opioid agonists which act on μ-receptors, present in high density in the GI tract (“Utopia μ-ssage”). Like all opioids, these are notorious for causing constipation (clogged bathroom) o Loperamide increases colonic transit time by increasing colonic phasic segmenting activity, pushing colonic juju back and forth more (lop-eared rabbits hopping back and forth across person’s back). Does not cross BBB, so has no analgesic or addiction potential. o Diphenoxylate increases colonic transit time by the same mechanism (two dolphins). At high doses, typically higher than prescribed, can cross BBB. To prevent abuse, typically combined with atropine such that doses high enough to cross BBB will cause miserable atropine adverse effects. • VIPomas & carcinoid tumors cause secretory diarrhea along with other systemic symptoms (“VIP customers” crab sign). If unable to fully resect, can use octreotide to limit (octagonal stop sign). Can also use octreotide for other causes of secretory diarrhea (e.g. Chemo)