2.7 Drugs used in malignancy Flashcards
What drugs are used in the treatment of malignancy?
- Control of disease progression
* Cytotoxics - Immunosuppressants
* Immunoglobins,
anti-lymphocytes such as
cyclosporine and tacrolimus - Control of symptoms
* Analgesics
* Antiemetics
* Anxiolytics
* Antisialogogues - Prevent/treat metastasis
* Bone-modifying drugs (e.g., Alendronic acid)
classify cytotoxic drugs.
- Alkylating agents
- Anti-metabolites
- Plant alkaloids
- Topoisomerase inhibitors
- Antitumour antibiotics
- Hormones
- Monoclonal Antibodies
Alkylating agents
Act by chemically altering DNA by adding alkyl groups to the
electronegative groups of cancer cells. (e.g. Cisplatin, Carboplatin,
Chlorambucil, Cyclophosphamide)
Anti-metabolites
The anti-metabolites function as the building blocks of DNA by imitating
the role of purine or pyrimidine and stop cell division. (e.g. Methotrexate,
cytarabine)
Plant alkaloids
They block cell division by inhibiting microtubule function. (e.g. vinca
alkaloids)
Topoisomerase inhibitors
Topoisomerases are enzymes that are essential to maintain the topology
of the DNA. Interfering with these enzymes prevents the normal functions
of the DNA, such as transcription, replication, and repair. (e.g. amasacrine
and etoposide)
- Antitumour antibiotics
(e.g. Dactinomycin, daunorubicin, doxorubicin)
- Hormones
Prednisone and dexamethasone in high doses can damage lymphoma cells.
Tamoxifen is a selective oestrogen receptor modulator.
Finasteride is a 5 alpha reductase inhibitor
- Monoclonal antibodies
Monoclonal antibodies attach themselves to tumour-specific antigens,
thereby increasing immune response to tumour cell. (e.g. rituximab,
cetuximab, trastuzumab)
What are the common side effects of chemotherapy drugs?
- Pulmonary toxicity
- Cardiac toxicity
- Renal toxicity
- Hepatotoxicity
- Neurotoxicity
- Haematological toxicity
What are the common side effects of chemotherapy drugs?
- Pulmonary toxicity
- Pulmonary toxicity
- Infection due to neutropenic myelosuppression
- Pneumonitis: methotrexate and cyclophosphamide
- Pulmonary fibrosis: bleomycin
- Cardiac toxicity
- Arrhythmias,
myocardial infarction,
congestive cardiac failure,
cardiomyopathy, myocarditis,
and pericarditis: cyclophosphamide
- Torsades de Pointes:
cisplatin and anthracyclines
- Renal toxicity
- Acute and chronic renal failure: cisplatin and carboplatin
- Hepatotoxicity
- Fatty change,
cholestasis,
and hepatocellular necrosis:
methotrexate and
cyclophosphamide
- Neurotoxicity
- Peripheral and cranial neuropathy,
autonomic dysfunction, and seizures:
Vinca alkaloids and methotrexate
- Haematological toxicity
- Myelodepression and neutropenic sepsis:
most agents
What specific problems arise with the use of steroids?
- Water and sodium retention,
- hypokalaemia
- hypertension
- hyperglycaemia
- diabetes
- osteoporosis
- proximal myopathy
- dyspepsia
- peptic ulcer
- euphoria
- depression
- infection,
- Poor wound healing
- Cushing’s
What are the problems in methotrexate?
- Increased infection
- abnormal LFTs
- thrombocytopenia
- photosensitivity
What is tumour lysis syndrome (TLS)?
It is a group of metabolic complications
that can occur after treatment of cancer,
usually lymphomas and leukaemias.
Precipitating medication includes
combination chemotherapy or steroids,
and it sometimes occurs without any treatment
and is known as ‘spontaneous tumour lysis syndrome’.
What are the pathophysiological changes in tLs?
- Hyperkalaemia
High turnover of tumour cells leads to spill of potassium into the blood.
* Cardiac conduction abnormalities (can be fatal)
* Severe muscle weakness or paralysis - Hyperphosphatemia
Causes acute renal failure because of deposition
of calcium phosphate crystals in the renal parenchyma - Hypocalcaemia
Calcium precipitates with phosphate to form calcium phosphate,
leading to hypocalcaemia.
* Tetany
* Seizures
* Emotional instability/agitation/anxiety
* Myopathy - Hyperuricaemia
Acute uric acid nephropathy (AUAN)
What are the pathophysiological changes in tLs?
- Hyperkalaemia
High turnover of tumour cells leads to spill of potassium into the blood.
* Cardiac conduction abnormalities (can be fatal)
* Severe muscle weakness or paralysis - Hyperphosphatemia
Causes acute renal failure because of deposition
of calcium phosphate crystals in the renal parenchyma - Hypocalcaemia
Calcium precipitates with phosphate to form calcium phosphate,
leading to hypocalcaemia.
* Tetany
* Seizures
* Emotional instability/agitation/anxiety
* Myopathy - Hyperuricaemia
Acute uric acid nephropathy (AUAN)
How can tLs be prevented?
- Adequate IV hydration
- Alkalinisation of urine
- Prophylactic oral or IV allopurinol
- Rasburicase as an alternative to allopurinol
Describe the analgesia in cancer patients.
Simple analgesics:
Paracetamol and nonsteroidal agents
Weak opioids:
tramadol and codeine
Strong opioids:
morphine, diamorphine in oral, parenteral, transdermal and
neuraxial routes
Special drugs:
gabapentin, pregabalin
Nerve blocks
What is breakthrough pain?
Breakthrough pain is defined as pain of
moderate or severe intensity occurring
against a background of controlled chronic pain.
It could be spontaneous, incidental, or procedural.
As with any cancer pain,
treatment relies on detailed assessment and
formulation of a multidisciplinary therapy plan.
Rapid acting opioids have been successfully used to treat breakthrough pain, but it remains a difficult therapeutic problem.
