Pharm 2 Flashcards
1
Q
Irritable Bowel Syndrome (IBS)
A
- Very common problem
- accounts for 3% of doctor visits
- Can’t make up its mind:
- associated with constipation
- IBS-C
- associated with diarrhea
- IBC-D
- Associated with both:
- alternating courses
- complicates treatment
- associated with constipation
2
Q
IBS is characterized by:
A
- Abdominal pain
- Disordered bowel habits
- constipation or diarrhea
- Often relieved by defecation
- implicating colonic involvement
3
Q
IBS is treated with
A
- Changes in diet
- Drugs
4
Q
Serotonin Signaling for IBS-C
A
- 5HT4 and 5-HT1 Receptors
-
intrinsic serotonin signaling
- activation=contraction and secretion
- selective 5-HT4 agonists are no longer available
- tegaserod
- Nonselective 5HT4 agonist=metaclopramide=only one readily available
-
intrinsic serotonin signaling
- 5HT3 receptors:
-
extrinsic signaling via visceral afferents
- responsible for GI pain and reflex contraction
-
extrinsic signaling via visceral afferents
5
Q
Linaclotide: uses
A
- used for:
- IBS-C and CIC
- CIC=chronic idiopathic consitaption
- Constipation feels like bricks piling up
- Belly pain and constipation feel like a giant knot
- CIC=chronic idiopathic consitaption
- IBS-C
- IBS-C and CIC
6
Q
Linaclotide: General info
A
- Peptide, 14 amino acids
- PO capsule administration
- Contraindicated in children <6 y.o.
- young mice: 1-3 weeks old were very sensitive
- dehydration caused by diarrhea=death
- Not yet elvaluated for 6-17 y.o.
- young mice: 1-3 weeks old were very sensitive
- Most common Side effect=Diarrhea
- Guanylate cyclase agonist increases cGMP
- Decreases pain transmission
- Stimulates secretion of intestinal fluid
- accelerates GI transit
7
Q
Linaclotide Mechanism in IBS-C
A
- Guanyl Cyclase Agonist
- Increases [cGMP] in intestinal epithelial cells
- cGMP activates chloride channels
- Intestinal chloride attracts sodium
- creates osmotic gradient
- Water enters intestine
- cGMP also inhibits extrinsic pain signaling
8
Q
IBS-D: 5HT3 antagonists
A
- Alosetron
- FDA approved IBS-D
- indication: only women
- Phase II trials:
- significant efficacy in women not men
- High Affinity Ligand
- long duration of action
- Adverse events limit usefulness
- serious constipation may occur
- fatal ischemic colitis has occured
- FDA approved IBS-D
- Ondansetron, granisetron, dolasetron
- are under investigation
9
Q
IBS-D: Mixed Opioid Agonists/Antagonist
A
- Eluxadoline
- u- and k-opioid agonist, S-antagonists
- mu opioid receptor:
- reduces pain, gastric propulsion
- Delta opiod receptor
- restores G-protein signaling
- removes mu agonist-related desensitization
- mu opioid receptor:
- u- and k-opioid agonist, S-antagonists
10
Q
IBS-D: Eluxadoline mechanism
A
- initial u agonist therappy
- u opioid receptor signals G-proteins
- produces analgesic effect
- Chronic u agonist therapy=Putative mechanism
- u/S heterodimer signal via B-arrestin
- instead of G-protein
- u/S heterodimer signal via B-arrestin
- Eluxadoline binds both u and S receptors
- restores G-protein signaling and analgesic activyt
11
Q
IBS-D: Eluxadoline DDI
A
-
other constipating agents
- other opiods
- -setrons
- anticholinergics
-
OAT inhibitors
- involved in eluxadoline elimination
- -statins, promote rhabdomyolysis
- rifampin
- cyclosporine
- gemfibrozil
12
Q
IBS-D: Eluxadoline side effects
A
- Constipation, N&V
- non-serious side effect
- low disconinuation rates
- 5 cases of mild pancreatitis
13
Q
IBS-D: Rifaximin
A
- FDA approved in 2015
- Tx of Travelers diarrhea and hepatic encephalopathy
- Targets E. Coli
- Reduces bloating, pain
14
Q
IBS-D: Rifaximin Side Effects
A
- WELL TOLERATED
- N/V
- Constipation
- Bloating
- Stomach pain
15
Q
IBS-D: Anticholinergics
A
- aka antispasmodics
- -mine
- Dicyclomine and hyoscyamine
- not used for IBS-D anymore
- used for severe spasms
- anti-muscarinic side effects limit usefulness
- not used for IBS-D anymore
