Module 4.1.1 (Pharmacology of Inflammatory Bowel Disease drugs) Flashcards
What are the drugs used in CD and UC? List FIVE types.
- Corticosteroids (glucocorticoids)
- Aminosalicylates (5-ASA)
- Possible immunosuppressants (chronic)
- Possible antimicrobials –> metronidazole or ciprofloxacin
- TNFα blockers eg. Infliximab
What are the examples of corticosteroids used in IBD? What is their MOA? When are they not suitable?
Budesonide, Hydrocortisone, and Prednisolone
MOA
- Antiinflammatory effect (1 of many effects)
- Increase annexin-1 production –> reduced production of mediators (prostaglandins such as phospholipase A2 and leukotrines)
- Reduces circulating neutrophils/macrophages
- Decreased activity of chronic stage macrophages/fibroblasts
Not for obstructions or perforations
Why are corticosteroids used? What are the benefits? What are the dosage forms?
- Treats acute stages (acute attacks)
- Decreases fever and diarrhoea
- Relieving abdominal pain and tenderness
- Improves appetite
- Increase sense of well being
Dosage forms: oral, rectal, parental
Why can’t corticosteroids be used long term?
Serious side effects preclude them from long-term maintenance treatment
- Must withdraw drugs over an extended time period (to avoid acute adrenal insufficiency crisis)
For budesonide
A) Is it as effective as hydrocortisone or prednisolone? Why not?
B) Can pregnant women use it? What is still a slight risk?
C) Only glucocorticoid that does what?
D) Dosage forms?
A)
- No, due to rapid liver metabolism –> little systemic action –> 100% absorbed
B)
- No
- Cushing syndrome slight risk
C)
- Delay in relapse during maintenance therapy
D)
- Oral or enema
For prednisolone;
A) Is it used for CD or UC?
B) Dosage forms?
A)
- Ulcerative Colitis (main indication)
B)
- Enema and suppository (local action)
Potent
For Hydrocortisone;
A) Is it used or CD or UC?
B) Dosage form?
A)
- Both CD and UC
B)
- Apply locally as rectal foam
Less potent
What are FOUR examples of 5-aminosalicylic acids (5-ASA)? Give a unique property for each one. What is the active form of all these 5-ASA drugs?
- Mesalazine –> not orally effective unless coated
- Olsalazine –> two 5-aminosalicylates linked by azo bond
- Sulfasalazine –> 5-aminosalicylate bound to sulfapyridine
- Balsalazide –> 5-aminosalicylate bound to inert carrier (also azo bond)
active form/agent: 5-aminosalicylate
What is the mode of action of 5-aminosalicylic acids (5-ASA)? What is the dosage form?
Local anti-inflammatory
- Decreased prostaglandin synthesis
- Decreased migration of inflammatory cells
- Decreased leukotrine synthesis
- Metabolite binds to PPAR γ – reduces nuclear movement of NF-κB – reducing pro-inflammatory gene expression
> Orally administered
> except known localised rectal ulcerative colitis - suppository
What are some examples of cautions for 5-ASA? Include specific cautions for sulfasalazine
- Salicylate hypersensitivity
- Hepatic impairment (all)
- Renal impairment and minor myelosuppression –> sulfasalazine
- Reduce TPMT activity –> azathioprine linked issue
What are examples of the adverse effects of 5-ASA? include specific ones for sulfasalazine.
AE
- Nausea, rash, headache & diarrhoea
Sulfasalazine only
- Male infertility, haemolysis, folic acid loss –> bind to folic acid and inactivates it
For immunomodulators;
A) Why are they used?
B) For UC or CD?
C) Example of one to get the patient into a remission state?
D) What to use after using the answer to C? (when in remission)? Why to use this?
TNF a drugs and a-B intregin drugs are also examples of immunomodulators.
A)
- Long term treatment (years)
B)
- Particularly CD
C)
- Cyclosporin IV for UC
D)
- Azathioprine or 6-mercaptopurine –> methotrexate if these dont work
> decrease requirement of glucocorticoids
> overall clinical improvement –> can be 3 months before effects noticed
What are examples of TNF-a monoclonals? What is the MOA? What is contraindicated?
- Infliximab –> Chimeric (75% human, 25% murine)
- Adalimumab –> 100% humanised -SC
MOA
- Decrease Gelatinase B & Tenascin [in mucosa]
Contraindications
Infections: tuberculosis and abscesses
other TNF-a drugs = certolizumab –> pegylated humanised TNF antibody
What is an example of a-b integrin drug? What is the MOA? What are some adverse effects?
Vedolizumab –> humanised monoclonal antibody
- α4-β7 integrins – attaches to MAdCAM-1 (endothelial receptor in gut)
- Inhibits adhesion, migration and activation of immune cells by working on cell surface glycoproteins
- Works better in UC than CD
AE
- headache, cough, upper respiratory tract infections, joint pain
What is another example of a monoclonal antibody used in IBD?
Ustekinumab
- Anti-IL23 and IL-12 monoclonal antibody
