Chapter 8: Immune system and malignant disease Flashcards
What are main side effects of azathioprine?
- Hypersensitivity reactions - fever, rash
- Neutropenia and thrombocytopenia
- Nausea
- Myelosuppression
What pre-treatment screening is needed with azathioprine?
Thiopurine S-methyltransferase (TPMT) deficiency = reduced activity of an enzyme that helps the body process drugs called thiopurines. These drugs, which include 6-thioguanine, 6-mercaptopurine, and azathioprine, inhibit (suppress) the body’s immune system. TPMT metabolises the drug, so with reduced levels, there is an increased risk of myelosuppression
What is the MHRA advice regarding ciclosporin prescribing?
Must be prescribed and dispensed by BRAND name
What is the MHRA advice surrounding tacrolimus prescribing? Calcineurin inhibitors (CNI) are a family of three drugs (cyclosporine, tacrolimus, and pimecrolimus) that clinicians can use to suppress the immune system
Prescribe and dispense by BRAND name only, to minimise risk of inadvertent switching between products => reports of toxicity and graft rejection
When monitoring tacrolimus, should peak or trough levels be taken?
Trough for Tacrolimus
Especially when there is diarrhoea, levels need to be closely monitored
What is the MHRA advice surrounding the use of mycophenolic acid/MMF?
Monitoring requirements?
MHRA
- exclude pregnancy in females before tx —2 preg tests 8–10 days apart are recommended.
- Women should use at least 1 method of effective contraception before and during treatment, and for 6 weeks after discontinuation - 2 are preferred.
- genotoxic
- contraindicated in women of childbearing potential without reliable contraception and in pregnant women unless no suitable alt to prevent transplat rejection
- Male patients or their female partner should use effective contraception during treatment and for 90 days after discontinuation.
Monitoring: Monitor FBC every week for 4 weeks then twice a month for 2 months then every month in the first year (consider interrupting tx if neutropenia develops).
Fingolimod, a drug used for MS, carry what MHRA warnings?
- Signal of rebound effect after stopping or switching therapy
- Not rec for patients at known risk of CVS events e.g. persistent bradycardia
- Has an immunosuppressive effect and can ^! skin cancers and lymphoma - refer pts with any skin lesions
What is the MHRA advice surrounding the use of bevacizumab?
Bevacizumab is a monoclonal antibody that inhibits vascular endothelial growth factor.
- Treatment with bevacizumab or sunitinib may be a risk factor for the development of osteonecrosis of the jaw.
- Systemically administered VEGF pathway inhibitors: risk of aneurysm and artery dissection
- at risk if pt on tx with bevacizumab or sunitinib also took/taking bisphosphonates; Dental examination and appropriate preventive dentistry considered before treatment.
- If possible, invasive dental procedures should be avoided in patients treated with bevacizumab or sunitinib who have previously received, or who are currently receiving, intravenous bisphosphonates
- The MHRA advises to monitor blood pressure regularly
What is the MHRA advice surrounding the use of EGFR inhibitors e.g. cetuximab?
Epidermal growth factor receptor (EGFR) inhibitors: serious cases of keratitis and ulcerative keratitis
In rare cases, this has resulted in corneal perforation and blindness
What is the MHRA advice surrounding the use of nivolumab?
Risk of organ transplant REJECTION
Which two cytotoxic drugs do not cause bone marrow suppression?
Vincristine
Bleomycin
Ciclosporin can cause what kinds of toxicity?
Neurotoxicity
Nephrotoxicity
What is the patient advice surrounding ciclosporin?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
Tacrolimus can cause what kinds of organ damage?
Nephrotoxicity Cardiomyopathy Neurotoxicity - headaches, tremors Hepatotoxicity Eye disorders- burred vision
Can also disturb glucose metabolism
What is the patient advice surrounding tacrolimus?
- Avoid live vaccines
- Avoid excess UV light
- Avoid high potassium diet and grapefruit juice
- Warning signs about immunsuppression
Maintain brand
What is a local reaction that can happen when IV cytotoxics are given?
Extravasation - severe local tissue necrosis
What are the main side effects of cytotoxics?
- Alopecia
- n+v
- Oral mucositis - imp. to maintain good oral hygiene
- Tumour lysis syndrome
- HyperUricaemia - this is associated with acute renal failure. Give allopurinol/rasburicase
- Bone marrow suppression apart from vincristine and bleomycin
- Thromboembolism - cancer itself increases this risk too
What are the features of tumour lysis syndrome?
HyperKalaemia, hyperUricaemia, hyperPHosphataemia with
hypocalcaemia; renal damage and arrhythmias
How is acute nausea and vomiting symptoms managed in low risk chemotherapy patients?
Dexamethasone or lorazepam
How is acute nausea and vomiting symptoms managed in high risk chemotherapy patients?
5HT3 antagonist e.g. ondansetron + dexamethasone + aprepritant
What is used for prevention of anticipatory nausea and vomiting in chemotherapy patients?
Symptomatic control
Lorazepam can help
Which cytotoxic drug class has a high risk of cardiotoxicity and how is this prevented?
Anthracyclines - doxorubicine, epirubicine
An iron chelate derazoxane is given
What is given to counteract the folate-antagonist action of methotrexate in chemotherapy?
Folinic acid (calcium folinate)
This is also used in overdose but does not work for antibiotics with anti-folate action e.g. trimethoprim
Mesna is given with what cytotoxic drugs and why?
Cyclophosphamide and ifosdamide
Prevents haemorhaegic cystitis as metabolites of the drugs cause a toxin (acrolein)
Cyclophosphamide and ifosfomide carry a risk of what?
What is done to prevent this?
Haemorrhaegic cystitis
MESNA is given to prevent urinary tract toxicity and increasing fluid intake for 24-48 hours after administration
What colour does doxorubicin turn your urine?
Red