Malignancy / Immunology

Question 1

Cyclophosphamide

Answer 1

• *Indications:** Malignancies (leukaemias, lymphomas, solid tumours) RA, SLE, systemic sclerosis, Wegener’s
• *MOA:** Alkylates DNA, affects B > T cells
• *SE’s:** BM suppression, haemorrhagic cystitis, alopecia, sterility esp in men
• *CI’s:** Haemorrhagic cystitis
• *Interactions:** Clozapine - increased risk of agranulocytosis
• *Other:** Give mesna to prevent haemorrhagic cystitis. Activated by P450

Question 2

Cisplatin

Answer 2

• *Indications:** Testicular, lung (SSLC), cervical, bladder, head/neck and ovarian cancers
• *MOA:** Alkylates DNA
• *SE’s: **BM suppression, severe N+V, nephrotoxic, ototoxic, peripheral neuropathy
• *CI’s:**
• *Interactions:** Methotrexate (increased risk of pulmonary toxicity), aminoglycosides, clozapine
• *Other:** Given IV. Carboplatin is associated with less severe SE’s. Requires pre-admin hydration

Question 3

Azathioprine

Answer 3

• *Indications:** Prevent transplant rejection, IBD, SLE RA (steroid sparing agent)
• *MOA:** Blocks de novo purine synthesis. Metabolised to active 6-mercaptopurine. Affects T > B cells
• *SE’s: **BM suppression, hepatotoxicity, N+V+D, arthralgia
• *CI’s:** Hypersensitivity - do TPMT assay before use
• *Interactions:** Allopurinol increases toxicity
• *Other:** 50% of patients intolerant of azathioprine will tolerate 6-MP

Question 4

Mycophenolate mofetil

Answer 4

Indications: Prophylaxis of acute rejection in renal, hepatic or cardiac transplants (in combination with ciclosporin + corticosteroids). Autoimmune disease
MOA: Metabolised to mycophenolic acid → blocks de novo nucleotide synthesis. Affects T > B cells
**SE’s: **BM suppression, skin malignancy, GI upset
CI’s: Monitor FBC
**Interactions:
Other: **

Question 5

Methotrexate

Answer 5

• *Indications:** Cancer, RA psoriasis, Crohn’s
• *MOA:** Dihydrofolate reductase inhibitor
• *SE’s: **BM suppression, pulmonary fibrosis, hepatotoxicity, mucositis
• *CI’s:** Renal + Liver impairment
• *Interactions:** Increased toxicity with NSAIDs, ciclosporin, steroids
• *Other:** Give with folinic acid to reduce risk of myelosuppression. Monitor U+Es, FBC, LFTs

If a pt has sepsis, methotrexate should be withheld - until neutropenic sepsis has been excluded. If in doubt, withhold.

Question 6

Chlorambucil

Answer 6

Indications: Some lymphomas and chronic leukaemias
MOA: Alkylates DNA
**SE’s: BM suppression, EM → SJS
CI’s:
Interactions:
Other: **

Question 7

Ciclosporin

Answer 7

Indications: Prevent transplant rejection, GvHD, UC RA, psoriasis
MOA: Calcineurin inhibitor → blocks IL-2 production
**SE’s: **Nephrotoxic, hepatic dysfunction, tremor, hypertrichosis, gingival hypertrophy, encephalopathy
CI’s:
Interactions:P450 metabolism
Other: Monitor LFTs

Question 8

Tacrolimus

Answer 8

Indications: Prevent transplant rejection
MOA: Calcineurin inhibitor → blocks IL-2 production
SE’s: Nephrotoxic, diabetogenic, neurotoxic
CI’s:
Interactions:P450 metabolism
**Other: **

Question 9

Sirolimus

Answer 9

Indications: Prevent transplant rejection
MOA: Blocks mTOR pathway
**SE’s: **Dyslipidaemia
**CI’s:
Interactions:
Other: **