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
any part of GI tract
transmural inflammation
cobblestone appearance of bowel wall
DEEP ulcerations
bleeding (less than UC) and nutritional deficiencies
crohn’s disease
why are 5-ASA prodrugs
very ulcergenic so formulated to prevent early release in the GI tract
which agent requires up to 17 weeks to produce any therapeutic effect
6 mercaptopurine
presents as diarrhea or constipation with abdominal pain
more common in women
Irritable bowel syndrome
blocking 5HT3 (antagonist)
blocking abdominal pain
good for diarrhea dominant
activation of 5HT4 (Agonists)
induces peristalsis (prokinetic) useful for constipation predominant form of IBS
what are chloride channel activators used for
constipation predominant IBS (women)
stimulates chloride type 2 channels , stimulates intestinal fluid secretion, decreases colonic transit time
acute CINV
Combination: 5-HT3 receptor antagonist NK1 receptor antagonist Glucocorticoid Prochlorperazine (D2 receptor antagonist) Metoclopramide (D2 receptor antagonist) Diphenhydramine Lorazepam
delayed CINV
prevent acute CINV
anticapatory CINV
lorazepam
alprazolam
diazepam
general antiemetic therapy
5HT3 receptor antagonist
phenothiazines
PONV
5-HT3 receptor antagonist Glucocorticoid Dimenhydrinate Prochlorperazine Metoclopramide
Motion sickness
Scopolamine
Dimenhydrinate
Promethazine
