Pharm of IBD and IBS - Segars Flashcards
what is the primary goal of IBD therapy?
achieve and maintain remission (few to no symptoms)
what is the secondary goal of IBD therapy?
- preserve intestinal function
- resolve presence of fistulizing disease (CD)
- decrease risk of surgery
- maintain steroid-free remission
what are the major class of drugs used for UC?
- 5ASA
- Corticosteroids
- TNF-a Inhibitors
- a-4 integrin inhibitors
what drugs have –sala- in the middle
5-ASA drugs used for UC
What are the TNF-a inhibitors used for UC
All end in mab
- Adalimumab
- golimumab
- infliximab
what is the a-4 integrin inhibitor used for UC
Vedolizumab
what catregories of drugs are used for Crohns disease?
- IL-12/23 inhibitors
- Corticosteroids
- TNF-a inhibitors
- a-4 integrin inhibitors
What is the IL-12/23 inhibitor used for Crohns
Ustekinumab
What TNF-a inhibitors are used for Crohns
- adalimumab
- certolizumab
- Infliximab
Adalimumab and infiximab are also used for (UC)
what a-4 integrin inhibitors are used for Crohns
Natalizumab and vedolizumab.
vedolizumab is also used for UC
what is the MOA of 5-ASA?
Inhibition of PG and LT (tx-A) production via arachidonic acid pathway (similar to aspirin)
- reduce PMN and macrophage chemotaxis (may also inhibit activatio of NF-kB )
what are the contraindications for 5-ASA as used in IBD
- contraindicated in ASA allergy
- Sulfasalazine contraindicated in sulfonamide-allergic pts
what is the indication of 5-ASA
mild to moderate active UC and Maintenance of remission of UC.
which 5-ASA agent is only used for maintenance of UC?
Olsalazine
which 5-ASA agent is used only for treatment of active disease?
Balsalazide
what is the MOA of TNF-a inhibitors?
- neutralize membrane-associated and soluble human TNF-a mediated proinflammatory cell signaling (inhibits TNF-a mediated actions)
- inhibit expression of pro-inflammatory genes
what is a serious potential side effect of TNF-a inhibitors?
- Infections (TB testing pre-therapy required)
what is the indication of TNF-a inhibitors?
- Adalimumab: UC and CD
- Infliximab: UC and CD- only one that’s given IV. all other are SQ
- Golimumab: UC only
- Certolizumab: CD only
what is the MOA for a-4 integrin inhibitors?
- limits integrin-associated cell adhesion, transendothelial migration, and immune cell activation within inflamed tissue
Side effect of a-4 integrin inhibitors
Infection: PML - 3 risk factors: treatment >2 yrs; prior immunosuppressant, and anti-JC virus antibodies
what are the indication for a-4-integrin inhibitors?
Natalizumab: Moderate to severe treatment resistant CD and maintenance therapy to prevent relapse
Vedolizumab: Both UC and CD - moderate to severe treatment resistant and maintenance
what is the MOA of interluekin (Il12/23) inhibitors?
bind to specific subunit of IL-12/23 reeptor located on surface of T cells and natural killer cells and inhibit signal transduction-related activities and production of pro-inflammatory TH1 and 17
Side effect of Interleukin (IL12/23) inhibitors:
Infection: TB testing pre therapy recommended
what is Interluekin (IL12/23) inhibitor used for?
treatment resistant CD both active and maintenance
In pts with IBS, what drugs are used for abd pain?
antimuscarinic agents such as hyoscyamine, dicyclomine, clidnium/chlordiazepoxide
what is the MOA for antimuscuarinics used for IBS
competitively inhibit autonomic, post-ganglionic cholinergic recetprs (multiple sites)
Side effects of antimuscularinics
class anticholingeric based effects: dry mouth, urinary retenion, constipation, drowsiness, confusion, blurred vision etc
what group of drugs are used for diarrhea in IBS?
- Anti-diarrheals
- opioids agonists/antagonists
- Serotonin antagonists
what are the anti diarrheal drugs used in IBS
loperamide
diphenoxylate
what is the opioids used for diarrhea in IBS
eluxadoline
what is the serotonin antagonist used in iBS for diarrhea
alosetron
what is the MOA of loperamide?
- interferes with peristalsis by a direction action on circular and longitudinal muscles of intestinal wall, slowing motility
- also may directly inhibit fluid and electrolyte secretion and/or increase water absorption
what is the MOA of alosetron
selectively blocks GI-based 5HT3 receptors
what is a concerning side effect of alosetron
Ischemic colitis
what is the indication for alosetron?
- women with chronic severe IBS-D, not responsible to other conventional therapies
what is the MOA of Eluxadoline?
- agonist at opioid mu and kappa receptors in GI tract
- antagonist at delta opioid receptors in GI tract
Side effects of eluxadoline
GI-related
- hepatic/pancreatic toxicity
- CNS-related
what group of drugs are used for constipation in IBS
- Guanylate cyclase agonist (linaclotide)
- selective chloride channel activators (lubiprostone)
what is the MOA of linaclotide
binds to guanylate cyclase-C on luminal surface and increase cGMP –> stimulates secretion of Cl/bicarb into intestinal lumen via CFTR ion channel –> increased intestinal fluid and accelerated transit
Side effect of Linaclotide
- diarrhea
- Other GI issues
Indication of linaclotide
IBS-C
- chronic idiopathic constipation (not supported under 17)
what is the MOA of lubiprostone
activates specific CIC-2 chloride channel in luminal cells of intestinal epithelium –> produce Cl rich intesinal fluid secretion w/o altering serum electrolyte concentration
side effects of lubiprostone
Nausea, dyspepsia, dizziness
Indication of lubiprostone
IBS-C
- chronic idiopathic constipation (CIC) in adults
