Chemotherapy Flashcards
1
Q
Allopurinol
Common indications
A
- To prevent acute attacks of gout
- To prevent uric acid and calcium oxalate renal stones
- To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy
2
Q
Allopurinol
MOA
A
- Allopurinol is a xanthine oxidase inhibitor
- Xanthine oxidase metabolised xanthine (produced from purines) to uric acid.
- Inhibition of xanthine oxidase lowers plasma uric acid concentrations and reduces precipitation of uric acid in the joints or kidneys
3
Q
Allopurinol
Adverse effects
A
- Allopurinol is generally well tolerated
- The most common side effect is a skin rash, which may be mild or may indicate a more serious hypersensitivity reaction such as stevens-johnson syndrome or toxic necrolysis
- Drug hypersensitivity syndrome is a rare life-threatening reaction to allopurinol that can induce fever, eosinophilia, lymphadenopathy and involvement of other organs, such as the liver and skin
- Starting allopurinol can trigger or worsen an acute attack of gout
4
Q
Allopurinol
Warnings
A
- Allopurinol should not be started during acute attacks of gout, but can be continued if a patient is already established on it, to avoid sudden fluctuations in serum uric acid levels
- Recurrent skin rash or signs of more severe hypersensitivity to allopurinol are contraindications to therapy
- Allopurinol is metabolised in the liver and excreted by the kidney
- The dose should therefore be reduced in patients with severe renal impairment or hepatic impairment
5
Q
Allopurinol
Interactions
A
- The cytotoxic drugs mercaptopurine and its pro-drug azathioprine require xanthine oxidase for metabolism
- When allopurinol is prescribed with these drugs, it inhibits their metabolism and increases the risk of toxicity
- Co-prescription of allopurinol with amoxicillin increases the risk of skin rash and with ACEI or Thiazide increases the risk of hypersensitivity reactions
6
Q
Allopurinol
Communication
A
- Advise patients that the purpose of treatment is to reduce attacks of gout (formation of kidney stones)
- Warn patients to seek medical advise if they develop a rash
- Explain that this is usually mild and goes away on stopping the drug, but it can be a sign of a serious allergy
- Advise patients not to stop allopurinol if they get an acute attack of gout, as this could make the attack worse
7
Q
Allopurinol
Monitoring
A
- Serum uric acid concentrations should be checked 4 weeks after initiating allopurinol or after a change in dose
- You should aim to lower uric acids concentrations to less than 300 umol/L where possible, by increasing the dose of allopurinol as needed
- Allopurinol treatment should be stopped if a rash develops
- For mild skin rashes, treatment can be reintroduced cautiously once the rash resolves
- Recurrence of the rash or signs of more severe hypersensitivity to allopurinol are contraindications to further therapy
8
Q
MTX
Common indications
A
- As a disease-modifying treatment for RA
- As part of chemotherapy regimens for cancers including leukaemia, lymphoma and some solid tumours
- To treat severe psoriasis (including Psoriatic arthritis) that is resistant to other therapies
9
Q
MTX
MOA
A
- MTX inhibits dihydrofolate reductase, which converts dietary folic acid to tetrahydrofolate (FH4)
- FH4 is required for DNA and protein synthesis, so lack of FH4 prevents cellular replication
- Actively dividing cells are particularly sensitive to the effects of MTX, accounting for its efficacy in cancer
- MTX also has anti-inflammatory and immunosuppressive effects
- These are mediated in part by inhibition of inflammatory mediators such as IL-8,6 and TNF-a, although the underlying mechanisms are not fully understood
10
Q
MTX
Adverse effects
A
- Dose-related adverse effects of MTX include mucosal damage (sore mouth, GI upset) and bone marrow suppression (resulting most significantly in neutropenia and an increased risk of infection
- Rarely, hypersensitivity reactions including cutaneous reactions, hepatitis or pneumonitis may occur
- Long-term use can cause hepatic cirrhosis or pulmonary fibrosis
- As MTX is usually administered once weekly, there is a risk of accidental overdose if patients take treatment daily
- Overdose causes severe dose-related adverse effects with renal impairment
11
Q
Alkylating agents
Cisplatin, Oxaliplatin, Cyclophosphamide
Common indications
A
- Cisplatin- treatment of testicular, lung, cervical, bladder, head and neck, and ovarian cancer (alone or in combination)
- Oxaliplatin- Colorectal cancer
- Cyclophosphamide- RA, connective tissue disorders, Leukaemia, lymphoma
12
Q
Alkylating agents
Cisplatin, Oxaliplatin, Cyclophosphamide
MOA
A
- Alkylating agents probably work in any section of the cell cycle (G1, S, G2, M)
- Alkylating agents cross-link with DNA preventing transcription and are generally cytostatic
13
Q
Alkylating agents
Cisplatin, Oxaliplatin, Cyclophosphamide
Adverse effects
A
- GI side effect
- Myelosuppression- reduced bone marrow activity which results in lower concentrations of platelets, RBC and WC
- Mucositis- Inflammation of GI membranes
- Interstitial pneumonitis,lung injury and fibrosis- if lung side effects occur they should be discontinued
14
Q
Alkylating agents
Cisplatin, Oxaliplatin, Cyclophosphamide
Warnings
A
- Peripheral neuropathy
- Acute porphyrias
- Secondary cancer due to chemotherapy
15
Q
Alkylating agents
Cisplatin, Oxaliplatin, Cyclophosphamide
Interactions
A
- Live vaccines- due to immunosuppression
16
Q
Pyrimidine antagonists (Antimetabolites)
Capcitabine, Gemcitabine, Flurouracil
Common indication
A
- Gemcitabine- Metastatic breast, pancreatic, bladder, ovarian, non-small cell lung cancer
- Capcitabine- Colon, colorectal, breast and gastric
- Flurouracil- Solid tumours (e.g. breast and GI), colorectal cancer recombination with folinic acid and superficial malignant and pre-malignant skin lesions
