Drugs- Treatment of IBD (Kinder) Flashcards
5- aminosalicylic acid (5-ASA, melsalamine) agents
and MOA?
sulfasalazine (azo compound- prodrug)- works topically
various forms of mesalamine (formulated to reach specific areas of the GI tract)
MOA:
modulates inflammatory mediators derived from cyclooxygenase (prostaglandins) and lipoxygenase (leukotrienes)
Other mechanisms: Interferes with cytokine production Inhibits nuclear factor-KB Inhibits function of natural killer cells, mucosal lymphocytes, macrophages Scavenges reactive oxygen species
corticosteroids used in IBD
prednisone
budesonide
hydrocortisone
Infliximab (Remicade)
Anti- TNFalpha antibody
what is the therapeutic use of 5-ASA compounds
1st line for mild-to-moderate UC
Efficacy in CD unproven
Must reach site of action!
Added as an adjunct to glucocorticoids in severe colitis
Regardless of severity, plays a useful role in preventing UC relapses once remission has been achieved
what are the adverse drug reactions of 5-ASA compounds
High incidence with sulfapyridine- due to the sulfapyridine component of the pro-drug
Nausea, gastrointestinal upset, headache, arthralgias, bone marrow suppression, malaise
Other 5-ASA’s well tolerated
Rare: nephrotoxicity, lupus-like syndrome, pancreatitis, hepatotoxicity
MOA of corticosteroids
Inhibits production of inflammatory cytokines (TNF-α, IL-1) and chemokines (IL-8)
Reduces expression of inflammatory cell adhesion molecules
Inhibits gene transcription of nitric oxide synthase, phospholipase A2, cyclooxygenase-2, and NF-κβ
therapeutic use of corticosteroids in IBD
moderate to severe IBD
high doses for active disease
severe exacerbations–> IV dose
NOT useful in retaining remission in pt’s
prednisone dose
daily oral dose
budesonide dose and site of action
Budesonide – controlled-release, released in distal ileum and colon
hydrocrotisone
enemas, foams, suppositories
allow direct local action which provides less systemic toxicity
ADR’s of corticosteroids
Insomnia, behavioral changes, acute peptic ulcers
long-term
Fluid and electrolyte abnormalities, metabolic changes, hypertension, hyperglycemia, increased susceptibility to infections, osteoporosis
limit their use!! difficult to wean pt’s off
Infliximab MOA
-IgG1 monoclonal antibody
bind soluble and membrane bound TNF -alpha with high affinity, preventing the cytokine from binding its receptors
antibody binding to membrane bound TNF also causes reverse signaling which suppresses cytokine release
Therapeutic use of Anti-TNF antibodies (infliximab)
Acute and chronic use in moderate-to-severe CD in those with inadequate response to conventional therapies
median time to clinical response is 2 weeks
ADRs of infliximab
Serious infections – TB, bacterial sepsis, invasive fungal infections, opportunistic infections
Antibodies to the antibody, delayed serum sickness–> myalgia, arthralgia, jaw tightness, fever, rash, edema
very expensive
rectum and colon
superficial inflammation
fistula, perforation, or obstruction common
hemorrhoids , anal fissures, perirectal abSCESSS
ulcerative colitis
