Malignant disease and immunosupression

Question 1

Doxorubicin, Daunorubicin

Answer 1

Anthracycline antibiotics - inhibit DNA and RNA, damage DNA
Indications: acute leukaemias, lymphomas, paediatric malignancy, some solid tumours
ADRs: diarrhoea, dehydration, red urine, renal failure, SVT, heart failure
DDIs: radiotherapy - marked increase in toxicity

Question 2

6-Mercaptopurine

Answer 2

Antimetabolite - inhibits purine nucleotide synthesis
Indications: acute leukaemias, CML, IBD
ADRs: hepatotoxicity, anorexia, transient oligospermia, pancreatitis, intestinal ulceration, lymphoma

Question 3

5-Fluorouracil

Answer 3

Antimetabolite - inhibits synthesis of pyrimidine nucleotides by inhibiting thymidylate synthase.
Indications: GI cancers, breast cancer, skin lesions, with folinic acid in colorectal cancer
ADRs: Myelosuppression, mucositis, cerebellar syndrome, desquamative hand-foot syndrome

Question 4

Methotrexate

Answer 4

Antimetabolite - inhibits dihydrofolate reductase, prevents recycling of folate, inhibits synthesis od pyrimidine nucleotides
Indications: Crohn’s, malignancy, psoriasis, rheumatoid arthritis
GIVE WEEKLY
ADRs: blood disorders - bone marrow supression, liver toxicity, cirrhosis, pneumonitis
DDIs: NSAIDs

Question 5

Vincristine, Vinblastine

Answer 5

Vinca alkaloids - microtubule inhibitors (prevent formation of microtubule polymer and as such prevent cell division)
Indications: leukaemias, lymphomas, some solid tumours
ADRs: Peripheral or autonomic toxicity, ototoxicity, myelosuppression (vinblastine), extravasation, bronchospasm

Question 6

Paclitaxel

Answer 6

Taxane - microtubule inhibitors (Prevent depolymerisation of microtubule polymer and prevent cell division)
Indications: ovarian cancer, advanced breast cancer, usually second line
ADRs: hypersensitivity, myelosuppression, peripheral neuropathy, cardiac conduction defects with arrthymias, alopecia, muscle pain, nausea and vomiting.

Question 7

Cisplatin

Answer 7

Alkylating drug - covalent bonding between strands of DNA which impairs replication
Indications: testicular, lung, cervical, head and neck and ovarian cancer
ADRs: Nephrotoxicity, ototoxicity, peripheral neuropathy, hypomagnesaemia and myelosuppression, sever nausea and vomiting

Question 8

Azathioprine

Answer 8

Immunosuppressant - cleaved to 6-MP which is an antimetabolite, decreases DNA and RNA synthesis. Used as steroid sparing drugs.
Indications: SLE, vasculitis, RA, IBD
ADRs: myelosuppression, variable metabolism depending on genetics, increased risk of malignancy, increased risk of infection, hepatitis

Question 9

Cyclophosphamide

Answer 9

Immunosuppressant - alkylating agent which cross links DNA and prevents replication. Suppresses B and T cell activity.
Indications: lymphoma, leukaemia, lupus nephritis, Wegener’s granulomatosis, polyarteritis nodosum
ADRs: haemorrhagic cystitis, bladder cancer, lymphoma, leukaemia, infertility

Question 10

Mycophenolate Mofetil

Answer 10

Immunosuppressant - prodrug which inhibits the enzyme inosine monophosphate dehydrogenase which is needed for guanosine synthesis - impairs B and T cell proliferation. Spares other cells as they have guanosine salvage pathways.
Indications: transplantation, lupus nephritis,
ADRs: nausea, vomiting, diarrhoea, myelosuppression

Question 11

Ciclosporin, Tacrolimus

Answer 11

Calcineurin inhibitors - prevent the production of IL-2, prevent the action of helper T cells. Ciclosporin binds to cyclophilin, tacrolimus binds to tacrolimus-binding protein.
Uses: Post-transplant, atopic dermatitis, psoriasis, RA and SLE with cytopenias (no effect on bone marrow)
ADRs: Nephrotoxicity, hypertension, hyperlipidaemia, GI disturbance, hypertrichosis, gingival hyperplasia, hyperuricaemia