Wk4 antidiarrheals/laxatives/IBS drugs Flashcards
Cisapride
Prokinetic –> increased motility
5HT4 agonist (and 5H3 ANtagonist)
Tx: diabetic gastroparesis
**restricted use dt cardiac toxicity
Domperidone
D2 receptor antagonist
increase GI motility throughout the entire GI tract
Macrolides (erythromycin)
stimulate motilin receptors directly on GI smooth muscle → initiation of migrating motor complex
Metoclopramide
D2 receptor antagonist
increase GI motility throughout the entire GI tract
Diphenoxylate
Opiate
most effective antidiarrheal
Crosses BBB so abuse potential and needs Rx
mixed with atropine to discourage abuse
Loperamide
opiate
most effective antidiarrheal
doesn’t cross BBB so available OTC
Cholestyramine
Binds bile salts
Colestipol
Binds bile salts
Kaolin/Pectin
Absorbant
Bismuth Subsalicylate
MOA as antidiarrheal?
inhibits prostaglandin and chloride secretion in the large intestine
Crofelmer use?
MOA?
HIV diarrhea
blocks CFTR –> decreases Cl- secretion
Octreotide MOA?
Effects at different doses?
Somatostatin analogue
low dose stimulates motility
high dose inhibits motility
overall decrease in secretion
Docusate class?
MOA?
Stool softener
surfactant –> softens stool by allowing mixing of aqueous and fatty substances
Mineral Oil Class?
MOA?
Stool softener
lubricates feces –> decreased water absorption from stool
Dietary fiber
increase mass of stool → distension → enteric reflexes → increased GI motility → decreased transit time through the colon
“stool stabilizers” – also less diarrhea
Anthraquinone
Contact cathartic
Stimulates peristalsis
large intestine
less potent
Bisacodyl
Contact cathartic
Stimulates peristalsis
large intestine
less potent
is given as a prodrug → 6 hour latency
Castor oil
Contact cathartic
Stimulates peristalsis
large AND small intestine
VERY potent
**uterine contractions
dehydration
Linaclotide
activates guanylyl cyclase-C on the luminal surface of intestinal epithelial cells
increased intra- and extra-cellular cGMP activates (CFTR) → increased Cl- secretion
Tx: constipation IBS
not in pregnancy or for peds
Lubiprostone
activation of chloride channel ClC-2 → more Cl- secretion → increased water content in stool
constipation IBS
NOT in PREGNANCY
Alvimopan
selective μ receptor antagonists that do not cross the BBB (won’t antagonize central analgesic effects of opiate medications)
used to shorten period of postoperative ileus following small or large bowel resection (short term)
**cardiotoxicity
Methylnaltrexone
selective μ receptor antagonists that do not cross the BBB (won’t antagonize central analgesic effects of opiate medications)
patients receiving palliative care for advanced illness (long term)
Lactulose
Osmotic cathartic (purgative)
reduces plasma NH4 conc; tx for hepatic encephalopathy
Magnesium hydroxide
Osmotic cathartic (purgative)
MOA???
Sodium Phosphate
Osmotic cathartic (purgative)
MOA: increased electrolytes in colon
Polyethylene glycol
Osmotic cathartic (purgative)
used for whole bowel irrigation prior to colonoscopy/endoscopy
TCA’s
Amitriptyline, Desipramine
blocking NE reptake into postganglionic sympathetic neurons results in increased NE concentrations in the synapse → increased NE actions on the α2 receptor → decreased ACh release
blocking DA reuptake into enteric interneurons → increased DA concentrations in the synapse → increased D2-mediated inhibition of cholinergic smooth muscle motoneurons
Diarrhea IBS tx
SSRIs
Fluoxetine, Paroxetine, Sertraline
Increased peristalsis
more 5HT in synapse –> afferent activation
Tx: constipation IBS
Alosterone
Antidiarrheal
5HT3 antagonist
Tx: diarrheal IBD
**last resort, bad constipation
Tegaserod
Prokinetic
selective 5HT4 agonist
Tx: constipation IBS
**last resort, big Cardiac side fx
cause a characteristic, harmless, brown pigmentation of the colonic mucosa
anthraquinones
D2 receptor antagonist
does not cross BBB
compassionate use only
not available in USA
Domperidone
D2 receptor antagonist
crosses BBB
parkisonism
pituitary effects (impotence, galactorhea, menstruation disorders)
Metaclopramide
Secondary MOA or tegaserod and cisapride:
activate cAMP-dependent chloride secretion form the colon
