What are the subtypes of IBS?
-IBS w/ constipation (IBS-C): the presence of hard/lumpy stools with 25+% of BMs and loose or watery stools iwth less than 25% of BMs
IBS w/ diarrhea (IBS-D): opposite of above
MIxed IBS (IBS-M): the presence of hard/lumpy stools with 25+% of BMs and loose or watery stools also with 25+% of BMs
How is IBS initially managed?
lifestyle and diet modifications (low in fermentable -saccharides) for mild symptoms
-durgs for more severe
Describe serotonin in the GI
At rest, 5-HT is synthesized by enterochromaffin cells and upon mechanical or chemical stimulation is released into the interstitial space of the lamina popria where it binds to receptors or nearby nerve fibers for action
5-HT is transported by SERT into epithelial cells after acting where it is enzymatically degraded, or it enters the blood stream wehre it is transported into platelts and stored for future use.
T or F. Serotonin has mutliple receptors that modulate neuronal activity, both pre- and psotsynaptically, on all types of enteric neurons, on extrinsic affarent fibers, and on interstitial cells of Cajal/smooth muscle cells
T. AT least 6 subtypes of 5-HT recepotrs are expressed in teh wall of the gut and they can exert excitatory OR inhibitory influences depending on their location and cell type.
Dont forget how the mind can affect GI function as well. SSRIs and TCAs are sometimes used to modulate GI function in IBS pts.
What drugs are used for IBS-C?
-Psyllium Methylcellulose polycarbophil
How does PEG work?
It is an osmotic agent that binds water and causes it to be retained within the stool to stimualte stretch receptors to icnrease cholinergic activity in the ENS
How does PMCP work?
Absorb liquid in the GI tract, thereby altering intestinal fluid and electrolyte transport and causing stool expansion, and increased peristalsis and bowel motility
How does Linaclotide work?
It activates guanylate-cyclase C receptors to icnrease intracellular cGMP which stimulates secretion (by CFTR) of Cl- and HCO3- into the GI lumen to increase GI transit
How does Lubiprostone work?
It is a PGE1 derivative that activates plasma chloride channels (CIC-2) to increase GI fluid secretion and accelerate GI motility
What are some main channels on the apical membrane of enterocytes that are responsible for intestinal fluid secretion?
CFTR and CIC2. Whereas lubiprostone directly activates CLC, linaclotide indirectly activates CFTR channels by promoting increased cGMP
T or F. In general, laxatives are contraindicated in pts with known or suspected GI obstruction
What are the AEs of PEG?
flatulence, nausea, abdominal pain, bloating cramping
What are the AEs of Psyllium?
same as PEG mostly and vomiting
What are the AEs of Linaclotide?
diarrhea, usually within 2 weeks of starting
Linaclotide is contraindicated in which pts?
neonates, infants, and childen under 6 yo
What are the AEs of Lubiprostone?
dose-related nausea, HA, and diarrhea
What are the drugs for IBS-D?
-TCAs and SSRIs
How does alosetron work?
Its a selective antagonist at 5-HT3 receptors
How does loperamide work?
OTC that has direct action on the circular AND longitudinal muscles of the intestinal wall to slow motility. Does not exhibit analgesic or opiate-like effects, even at high doses
What are the AEs of alosetron?
Physicians must enroll in the prescribing progresion
BBW for pre-existing colitis and severe constipation
-constipation (complications include GI obstruction, perforation, impaction, toxic megacolon, secondary ischemic colitis, and death)
-s-TACH and arrhythmias
What are the AEs of loperamide?
What are the AEs of anti-cholingergics?
baldder, vision, and CNS dysfunction
What are the AEs of rifaximin?
flatulence, abdominal pain, N/V, fecal urgency, constipation
What is Eluxadoline?
PO 2x daily drug that acts as a G-coupled u-opiod receptor antagonist to improve motility, increase visceral sensation, and promote secretion
Effective for about 6 mos.
What are the AEs of Eluxadoline?
Substrate and inhibitor of OATP 1B1 and an inhibitor of BCRP (rosuvastatin affected- reduce dose)