PHARM: Drugs for IBS Flashcards
What is the first line treatment of a patient with IBS?
education, reassurance, dietary modification (exclusion of gas producing foods), and increased physical activity
When is drug treatment warranted with IBS?
for moderate to severe symptoms that are not relieved by lifestyle changes
What type of IBS is treated with: Linaclotide, Lubiprostone, PEG?
IBS-C
What type of IBS is treated with: Alostetron, Loperamide, Anti-spasmodics (Atropine, Dicyclomine, Glycopyrrolate)
IBS-D
What type of IBS has: Hard or lumpy stools with ≥25% of BMs and loose watery stools with ≥25% of BMs?
IBS-M
What type of IBS has: Presence of loose or watery stools with with ≥25% of BMs and hard or lumpy stools with <25% of BMs?
IBS-D
What type of IBS has: Presence of hard or lumpy stools with ≥25% of BMs and loose watery stools with <25% of BMs?
IBS-C
MOA: Osmotic agent; binds water and causes it to be retained within the stool AND stimulates stretch receptors to increase cholinergic activity in the ENS.
PEG
MOA: Absorb liquid in GI tract; thereby altering intestinal fluid and electrolyte transport and causing stool expansion, increased peristalsis and bowel motility
Polycarbophil
Methylcellulose
Psyllium
MOA: Activates guanylate cyclase-C receptor to increase intracellular cGMP→ sitmulates secretion of Cl- and CHO3- from CFTR ion channel into intestinal lumen and the increased GI fluid increases the GI transit (via stretch)
Linaclotide
MOA: PGE1 derivative that directly activates plasma Cl- channel (ClC-2) to increase GI fluid secretion and accelerate motility (via stretch)
Lubiprostone
What drug is STRONGLY recommended for IBS-C?
Linaclotide
What is a contraindication for all IBS-C drugs?
Contraindicated in known/suspected obstruction.
What IBS-C drug is contraindicated in children <6?
Linaclotide
TOXICITY: Infrequent flatulence, nausea, abdominal pain, bloating and cramping
PEG
TOXICITY: Rarely abdominal pain or cramps, diarrhea, increased flatulence, N/V
Polycarbophil
Methylcellulose
Psyllium
TOXICITY: Diarrhea (usually within 2 weeks of treatment start)
Linaclotide
TOXICITY: Dose related nausea, HA, and diarrhea
Lubiprostone
MOA: Selective antagonist at 5-HT3 receptors extensively distributed on enteric neurons in GI tract.
Alosetron
MOA: Competitive post-ganglionic muscarinic receptor antagonist. (modulate activity in the enteric nervous system)
Atropine
Dicyclomine
Glycopyrrolate
MOA: Direct action on the circular and longitudinal muscles of the intestinal wall to slow motility. (modulates activity in the enteric nervous system)
Loperamide
MOA: Selectively inhibits bacterial and mycobacterial DNA-dependent RNA polymerase. Reduces mucosal inflammation and barrier dysfunction induced by chronic stress by increasing population of lactobacillaceae.
Rifaximin
Which drug for IBS-D has a BBW: not for pt w/ pre-existing colitis or severe constipation?
Alosetron
What drug has severe constipation as an adverse effect (that can even lead to death)?
Alosetron
What drug can rarely cause V tach and arrhythmia?
Alosetron
Which drugs have systemic toxicity related to muscarinic antagonists: anhidrosis, flushing, bladder, vision and CNS dysfunction, s-TACH, impotence?
Atropine
Dicyclomine
Glycopyrrolate
Does loperamide show any opiate-like or analgesic effects?
NO!
What drug is a Oral rifampin analog?
rifaximin
What is commonly seen with rifaximin treatment?
Increase in Lactobacilli and reduced segmented filamentous bacteria after treatment
What types of adverse effects are seen with rifaximin?
GI symptoms: flatulence, N/V, fecal urgency, constipation, abdominal pain
What is the ultimate pathway of action for drugs that are used in IBS-C?
increase stimulation of endogenous stretch receptors which, in turn, increases cholinergic activity, stimulate peristalsis and promote evacuation of the stool
What is the ultimate pathway of action for drugs that are used in IBS-D?
by blocking neurotransmitter systems involved in gastric motility
What is the important distinction between Lubiprostone and Linaclotide
Lubiprostone is a DIRECT activator of ClC-2 and Linaclotide is an INDIRECT activator of the CFTR (via increase in cGMP)*** Important
What is the function of CIC-2 and CFTR?
channels are on apical surface of enterocytes that allow Cl- flow into the lumen
What type of cells synthesize serotonin in the GI?
Enterochromaffin Cells
List the function of intrinsic circuits of serotonin activity.
epithelial secretion/vasodilation OR for propulsive motility
What are extrinsic circuits serotonin acts on?
vagal and spinal afferent fibers
When does serotonin signaling end?
recovery phase
What happens in the recovery phase?
5-HT is transported by SERT into epithelial cells where it is enzymatically degraded, or it enters the blood where it is transported into platelets and stored for further use
What type of factors can also influence activity of the sympathetic and parasympathetic nervous systems and their effect upon modulating smooth muscle function in the intestinal wall?
psychosocial factors
What is the MOA of tri-cyclic antidepressants?
reduce reuptake of NE and serotonin in CNS and some have strong anticholinergic activity
What is the role of SSRIs?
enhance actions of 5-HT in CNS
True or False: American Gastroenterological Association recommends using tricyclic antidepressants in the treatment of IBS
FALSE: they do NOT
What can be used instead of TCAs to treat mood-related aspects of IBS?
SSRIs
True or false: • Patients with both psychologic and drug treatment respond better than patients who have drug therapy alone
TRUE
What may contribute to the increased activity of the enteric nervous system in IBS?
activation of inflammatory process
What may signal the inflammatory process to begin in IBS?
dietary components or from the microflora in the intestinal lumen
What substance is used by around 50% of IBS patients to self-medicate before seeking attention by a physician?
probiotics
True or false: probiotics help with abdominal symptoms.
TRUE (in some studies)
Are probiotics recommended in the treatment of IBS?
NO
