Immunomodulators

Question 1

Methotrexate

• Class/MOA?
• Indications? (2)
• Which of the following doses is the most appropriate for Crohn’s disease?
  a) 10mg once a week
  b) 10mg once a day
  c) 20mg once a week
  d) MTX is not used in Crohn’s disease

Answer 1

• Folic acid antagonist, inhibits conversion of folic acid to folinic acid (inhibiting DNA synthesis and cell replication). Cytotoxic, immunosuppressive and anti-inflammatory effects.
• Used in RA, Crohn’s disease, psoriasis, some cancers
• c) 20mg once a week (inducing remission = 25mg weekly, maintenance = 15-25mg weekly)

Question 2

Methotrexate cont’d

• Counselling points? (5)
• Monitoring? (5)

Answer 2

Counselling
- Take tablet(s) once a WEEK only, on the same day each week
- Use sun protection/wear protective clothing/avoid excessive sun exposure
- use contraception during treatment, and for at least 1 menstrual cycle after ceasing (can cause congenital defects)
- Can interact with many meds - refer to dr or pharmacist if starting new med(s)
- cytotoxic medication, ensure correct disposal/handling/keep out of reach of children
(others e.g. adverse effects, folic acid supplementation, missed doses)

Monitoring

• CBC
• Renal, hepatic
• sx of pulmonary toxicity (e.g. cough)
• efficacy eg dec. CRP in RA
• signs of infection
• hydration status of patient

Question 3

What is the MOA of anastrozole, and what is its’ primary indication?
What is the usual dose?
List three adverse effects?

Answer 3

Aromatase inhibitor (same class as exemestane, letrozole)
Inhibits aromatase enzymes eg in breast tissue, to inhibit the conversion from testosterone to estradiol (reducing oestrogen concentration).
Indicated for hormone receptor positive early breast cancer.
Usual dose is 1mg daily
Adverse effects = due to dec oestrogen therefore hot flushes, reduced BMD, vaginal dryness, fractures (also - carpal tunnel syndrome lol)

Question 4

Ciclosporin

• class and MOA
• 2x indications
• what medication is given in conjunction with ciclosporin to decrease the dosing requirements and why?
• is concentration monitoring recommended in transplant patients? what factors can influence concentration?
• list 2 counselling and 2 monitoring points

Answer 4

• Calcineurin inhibitor, forms a complex to inhibit calcineurin binding to t cells (prevents production of cytokines, preventing t cell proliferation).
• Indicated for transplant rejection, RA, psoriasis
• diltiazem given in combination, inhibits metabolism and increases concentration
• yes, conc monitoring recommended. depends on time since transplant, has rejection occurred, using other immunosuppressants
• Avoid sun exposure, wear protective clothing and use sunscreen, interacts with many meds, have regular blood tests
• monitor fbc, renal, concentration, BP (HTN AE), CBC, BGL, K+, lipids

Question 5

Azathioprine in Rheum Arthritis

• usual maintenance dose?
• what C&A labels to include (and therefore counselling points)
• monitoring points (3)
• list 3 drug interactions (which drug and what happens)

Answer 5

• dose = 50-150mg daily in 1-2 doses
• C&As = 8 (photosensitivity), 21 (handling and disposal, cytotoxic), A (swallow whole), B (take with food)
• monitor TPMT (lel), FBC, LFT, efficacy eg dec pain/stiffness
• Allopurinol (reduces metabolism of AZP, inc toxicity), 5-ASAs eg mesalazine (may inc bone marrow toxicity), warfarin (AZP may dec efficacy of warfarin)