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Pre-reg exam > Chemotherapy > Flashcards

Chemotherapy Flashcards

1
Q

Allopurinol

Common indications

A
  1. To prevent acute attacks of gout
  2. To prevent uric acid and calcium oxalate renal stones
  3. To prevent hyperuricaemia and tumour lysis syndrome associated with chemotherapy
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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
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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
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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
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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
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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
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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
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8
Q

MTX

Common indications

A
  1. As a disease-modifying treatment for RA
  2. As part of chemotherapy regimens for cancers including leukaemia, lymphoma and some solid tumours
  3. To treat severe psoriasis (including Psoriatic arthritis) that is resistant to other therapies
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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
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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
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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
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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
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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
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14
Q

Alkylating agents

Cisplatin, Oxaliplatin, Cyclophosphamide

Warnings

A
  • Peripheral neuropathy
  • Acute porphyrias
  • Secondary cancer due to chemotherapy
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15
Q

Alkylating agents

Cisplatin, Oxaliplatin, Cyclophosphamide

Interactions

A
  • Live vaccines- due to immunosuppression
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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
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17
Q

Pyrimidine antagonist (antimetabolite)

Capecitabine, Gemcitabine, Fluorouracil

MOA

A
  • Capcitabine and gemcitabine are pro-drugs of fluorouracil
  • They work in the S phase of the cell cycle
  • 5FU- Enters cells via a uracil transport mechanism, Anabolised to cytotoxic nucleotide forms, Incorporation into DNA, Inhibition of DNA synthesis and function (It does the same thing with RNA)
18
Q

Pyrimidine antagonist (antimetabolite)

Capecitabine, Gemcitabine, Fluorouracil

Adverse effects

A
  • Immunosuppression- neutropenia and thrombocytopenia the most common
  • Palmar-plantar erythema- reddening, pain and swelling of hands and feet. In severe cases, this can be debilitating as it can be difficult to use hands/walk
  • GI side effects
  • Mucositis and diarrhoea
  • Neurological toxicity
  • Cardiac toxicity – Due to vasospasm
  • Dermatological toxicity
  • Ocular toxicity
19
Q

Pyrimidine antagonists (antimetabolite)

Capcitabine, gemcitabine and flurouacill

Warnings

A
  • DPD testing- Patients with partial or complete dihydropyrimidine dehydrogenase (DPD) deficiency are at increased risk of severe and fatal toxicity during treatment with fluoropyrimidines
  • History of cardiac disease
20
Q

Pyrimidine antagonist (antimetabolite)

Capecitabine, Gemcitabine, Fluorouracil

Interactions

A
  • Live vaccines- Due to immunosuppression
  • Folic/folinic acid- this increases risk of toxicity
  • Metronidazole- increase risk of toxicity of 5-FU
  • Phenytoin- 5-FU increases concentration of phenytoin
  • 5-FU can increase the anticoagulant effect of warfarin
21
Q

Doxorubicin

Anthracyclines

Indications

A
  • Acute leukaemia,
  • Hodgkins lymphoma and Non-hodgkins lymphoma
  • Some solid tumours
  • Blader tumour
  • AIDS related kaposi sarcoma
22
Q

Doxorubicin

MOA

A
  • PEGylated liposomal doxorubicin HCL- a cytotoxic anthracycline antibiotic
  • The exact mechanism of the antitumour activity of doxorubicin
23
Q

Doxorubicin

Anthracyclines

Warnings

A
  • Serious harm and fatal overdoses have occured following confusion between liposomal, pegylated-liposomal, lipid-complex and conventional formulations of the same drug. They are not interchangable
  • Cautioned in
    • Cardiac disease
    • Elderly
    • HTN
    • Myelosuppression
    • Increased risk of malignancies
24
Q

Doxorubicin

Adverse effects

A
  • Neutropenia, leukopaenia, PPE (Palmar-Plantar Eythermea), anaemia, thrombocytopenia
  • Cardiac arrest, failure
  • PE
  • Thrombophlebitis
  • Increased risk of infection
  • Peripheral neuropathy
    *
25
Q

Paclitaxel

Indications

A
  • Ovarian cancer
  • Breast cancer
  • Non-small cell lung cancer
  • AIDs related Kaposi sarcoma
  • Metastatic adenocarcinoma of the pancreas
26
Q

Paclitaxel

MOA

A
  • Paclitaxel is an antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilises microtubules by preventing depolymerization
  • This stability results in the inhibition of the normal dynamic re-organisation of the microtubule network that is essential for vital interphase and mitotic cellular function
  • In addition, paclitaxel induces abnormal arrays or bundles of microtubules throughout the cell cycle during mitosis
    *
27
Q

Paclitaxel

Warnings

A
  • Cautioned in
    • Acute porphyrias
    • Patient aged over 75 with metastatic adenocarcinoma of the pancreas
28
Q

Paclitaxel

Adverse effects

A
  • Increased risk of infection- including sepsis
  • Bone marrow suppression- neutropenia, thrombocytopenia, leukopenia
  • Metabolism- anorexia, hypokalaemia
  • NB- All chemotherapy agents carry a risk of tumour lysis syndrome
  • Peripheral neuropathy
  • Visual disturbances
  • Cardiotoxicity- CHF, LV dysfunction
29
Q

Paclitaxel

Interactions

A
  • Paclitaxel is in part metabolised by CYP enzymes therefore inducers and inhibitors should be used with caution
30
Q

Paclitaxel

Monitoring

A
  • Cardiac monitoring (BP, HR, BNP, ECG)
  • Monitoring for signs of infection- sore throat, mouth ulcers, high temp
31
Q

Anastrazole

Indications

A
  • Adjuvant in the treatment of oestrogen-receptor-positive breast cancer
32
Q

Anastrozole

MOA

A
  • Anastrozole is a potent and highly selective non-steroidal aromatase inhibitor
  • Oestradiol is produced by aromatase enzyme complex in peripheral tissues from oestrone, this reduces circulating estradiol levels which is beneficial in breast cancer
  • NB- this does not have any effect on cortisol or aldosterone seceretion.
33
Q

Anastrazole

Contraindications

A
  • Contraindicated in pre-menopausal women
  • Cautioned in patients susceptible to oesteoporosis
34
Q

Anastrozole

Adverse effects

A
  • Effect on bone mineral density- increased risk of fracture
  • Haptic impairment- Increased LFTs
  • Hot flushes
  • Headahces
  • Anorexia
35
Q

Tamoxifen

Indications

A
  • Pre- and perimenopausal women with oesetrogen-receptor-positive breast cancer not previously treated with tamoxifen
  • Anovulatory infertility
  • Gynaecomastia
  • Breast cancer
36
Q

Tamoxifen

MOA

A
  • Tamoxifen displays a complex spectrum oestrogen antagonist and oestrogen agonist-like pharmacological effect
  • In breast cancer, at tumour level, tamoxifen acts primarily as an anti-oestrogen, preventing oestrogen binding to the oestrogen receptor
  • In the clinical situation, it is recognised that tamoxifen leads to reductions in levels of blood ChE and LDLs (NB- does not reduce bone mineral density)
    *
37
Q

Tamoxifen

Warnings

A
  • Trreatment in infertility is contraindicated in patients with a history of idiopathic VTE
  • Cautioned in acute porphyrias
38
Q

Tamoxifen

Adverse effects

A
  • Increased VTE risk- particularly after surgery/periods of immobility
  • Endometrial changes- including polyps, cancer, sarcoma. investigations must be made in patients with vaginal bleeding/discharge and pelvic pain
  • Blood- anaemia
  • Metabolism- fluid retention
  • Increased risk of ischaemic cerebrovascular events
  • Changes in liver enzymes
39
Q

Tamoxifen

Interactions

A
  • Tamoxifen can increases anticoagulant effect of warfarin
  • When used in combo with chemotherapy, this can increase the risk of VTE therefore prophylaxis should be considered
  • Tamoxifen is metabolised by CYP 3A4 therefore caution in inducers and inhibitors
    *
40
Q

Patient and carer advice

Tamoxifen

A
  • Endometrial changes
  • VTE
  • Unless used for female infertility effective contraception must be used during and 2 months after treatment.

Pre-reg exam (113 decks)

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