Pharm 20: Inflammatory Bowel Disease Flashcards
What are the 2 major forms of IBD?
- Ulcerative colitis (UC)
- Crohn’s disease (CD)
+ in terminate colities (10%)
what are environmental risk factors of IBD?
- diet
- smoking
- microbiome
- medication
- sleep
- stress
UC + CD = AI disease
- complex interaction btw host + microbes
- disrupts innate immunity + impaired clearance
- pro-inflammatory compensatory response occurs
- physical damage+ chronic inflammation occurs
compare between difference between crohn’s disease and ulcerative colitis /
CD = - TNF - A - th 1meidated affects all layers - affects any part of GI - get fissures - surgery = not curative
UC =
- IL-13
- th2 mediated
- affects mucosa/submucosa
- affects rectum –> spreading proximally
- surgery = curative
What are some supportive therapies for acutely sick IBD patients?
- Fluid/electrolyte replacement
- Blood transfusion/oral iron
- Nutritional support (malnutrition common)
Symptomatic treatments: MAINSTAY of treatment
When active disease + prevention of relapse
- -> Aminosalicylates e.g. Mesalazine
- -> GCs e.g. Prednisolone
- -> Immunosuppressives e.g. Azathioprine
How can Aminosalicylates be used as a method of therapy for IBD? (MOA)
What are the 2 types of Aminosalicylates?
Aminosalicylates deals with symptomatic treatment of IBD
–> active disease + Prevents remission
2 types:
a) Mesalazine or 5-aminosalicylic acid (5-ASA)
b) Olsalazine (2 linked 5-ASA molecules) = needs to be activated by colonic gut flora
MOA: - down regulates NFkB / MAPK pathway \+ also down regulates COX 2 \+ oxygen scavenger --> anti inflammatory agent
aminosalicylates (5-ASA molecules)
more/less effective in CD
more/ less effective in UC
aminosalicylates (5-ASA molecules):
less effective in CD
more effective in UC
How effect can glucocorticoids have on IBD?
- Anti-inflammatory + immunosuppressive drugs; derived from cortisol
MOA
- Activates intracellular GC Receptors, which can act as positive / negative transcription factors
- GCs act at multiple points in inflammation e.g. inhibit DCs
- BUT MANY SIDE EFFECTS when given chronically
note:
- UC: aminosalicylates superior –> avoid GCs
- CD: remain drugs of choice for inducing remission
- -> Budesonide preferred if mild - less SEs
What are some ways to reduce unwanted side effects of drugs?
- Administer topically - fluid or foam enemas or suppositories
- Use low dose in combination w/ another drug
- Use oral or topically given drug w/ high hepatic first pass metabolism e.g. Budesonide so little escapes into systemic circulation –> less SEs
new therapies:
a) increase packing –> so that drug is only released at specific point
b) give prodrugs
c) gut = more aqueous –> more fluid flows in through packaging –> pushes drug out
What is Azathioprine? and what effects can it have on IBD ?
- Azathioprine = pro-drug activated by gut flora to 6-mercaptopurin
- purine agonist
- -> interferes w dna dynthesis + replication
- immunosuppressive
- slow onset ( takes 3/4 months to take effect)
- End products can act as false-purines –> then incorporated into DNA OR can inhibit purine synthesis itself
CD = weak benefit in inducing remission unless in combination UC = effective
immunosuppressive effects of Azathioprine is because =
What are some unwanted side effects of immunosuppressive?
o Impairs: - Cell- and antibody-mediated immune responses - Lymphocyte proliferation - Mononuclear cell infiltration - Antibody production o Enhances: T cell apoptosis
unwanted side effects of immunosuppressive effect:
o Pancreatitis
o Bone marrow suppression
o Hepatotoxicity (due to 6-MeMP metabolite)
o Increased risk of lymphoma + skin cancer
What are some potentially curative therapies for IBD?
- Manipulation of microbiome
2. biologic therapies
In IBD, budesonide causes fewer unwanted systemic effects than prednisolone because:
- It can be administered topically
- It can be co-administered with another drug
- It has a higher potency at therapeutic doses
- It has a lower potency at therapeutic doses
- It is metabolised and inactivated locally
In IBD, budesonide causes fewer unwanted systemic effects than prednisolone because:
It is metabolised and inactivated locally
what are the 3 methods to deal with symptomatic active disease of IBD?
Glucocorticoids
Aminosalicylates
Immunosuppressives
The mechanism of action of Azathioprine in IBD:
- Interferes with purine biosynthesis
- Is a direct reduction of protein synthesis in the GI tract
- Is blocked by co-administration with allopurinol
- Means that it increases side-effects caused by infliximab
- Needs activation of the drug by metabolism to 5-ASA
The mechanism of action of Azathioprine in IBD:
Interferes with purine biosynthesis
