Chapter 8: Immune system and malignant disease Flashcards
What is extravasation of IV drugs? What can chemo drugs cause?
Leakage of the drug into surrounding tissue
Extravasation of cytotoxics Can lead to permanent tissue damage
Chemotherapy can cause Neutropenic sepsis, a MEDICAL EMERGENCY. This is essentially neutropenia. What are the symptoms?
General Malaise/ high temp above 38 (due to infection)
Shivering/ flu-like symptoms
Uncontrolled gum/ nose bleeds (due to low platelets)
Bruising
Mouth ulcers (worse than usual)
Diarrhoea/ uncontrolled vomiting (dont forget- chemo can cause some vomiting itself)
Advise patient to go to A&E asap and not to take paracetamol
What are the Side effects of Chemotherapy?
Oral mucositis- inflammation of the mouth- ulcers and pain or difficulty swallowing.
Diarrhoea
Nausea and vomitting
Hyperuricaemia (high uric acid level)
Alopecia
dry mouth
Neutropenia
Which Chemo drugs can only be given by IV administration only?
VINCA ALKALOIDS
e.g. Vinblastine, Vincristine (all the Vin’s)
Which two immunosuppressant drugs used in chemo have a lot of interactions, plus must always maintain the same brand?
Ciclosporin
Tacrolimus
What is important to let patients know on therapy with Azathioprine?
Reporting- Blood disorders- sore throat, mouth ulcers, bleeding, fever- seek medical attention
Which chemo drugs have a lower emetogenic (vomitting) potential?
Methotrexate 5-FU Etoposide Vinka Alkolids
How much will a patient recieving treatment for unpleasant side effects they experienced from their last dose of chemotherapy, have to pay for their prescription of Folinic acid (used for methotrexate side effects)?
Nothing- free
Those on cancer meds and on meds for effects of cancer are medically exempt
Tamoxifen is usually used for breast cancer at a dose of 20mg daily. It can increase the risk of another cancer: ______ cancer. It can also result in thromboembolism and patients are required to report symptoms like?
Endometrial cancer
Symptoms such as SOB, pain in one leg
Which class of chemotherapy drug is Cardio toxic and associated with cardiomyopathy?
Anthracyclines eg
Doxorubicin
Epirubicin
Daunorubicin
What class of anti cancer drugs are useful for lung and breast cancers?
Vinca- alkaloids (vincristine, vinblastine)
Also for Leukaemias and Lymphomas
What drug is used as a protectorant from cytotoxic induced urothelial toxcitiy such as heamorrhagic cystitis/ blood in urine?
Mesna
What antiemetic is indicated for chemo-therapy induced nausea and vomiting?
Ondansetron
What would a high temperature following a dose of Chemo indicate?
Febrile Neutropenia
Remember neutropenia warning signs = fever- this is all it is
Which 2 anticancer drugs DO NOT cause bone marrow suppression?
Bleomycin (an anthracycline cytotoxic antibiotic)
Vincristine
When does bone marrow suppression, caused by most chemo drugs bar vincristine and bleomycin, usually occur?
7 -10 days after administration
What are some main side effects of azathioprine?
Hypersensitivity reactions Hypersensitivity reactions (including malaise, dizziness, vomiting, diarrhoea, fever, rigors, myalgia, arthralgia, rash, hypotension and renal dysfunction) call for immediate withdrawal. Neutropenia and thrombocytopenia Neutropenia is dose-dependent. Management of neutropenia and thrombocytopenia requires careful monitoring and dose adjustment. Bruising, bleeding, infection (Bone marrow suppression) Nausea Nausea is common early in the course of treatment and usually resolves after a few weeks without an alteration in dose. Moderate nausea can be managed by using divided daily doses, taking doses after food, prescribing concurrent antiemetics or temporarily reducing the dose.
What pre-treatment screening is needed with azathioprine?
TPMT levelsTPMT metabolises the drug, so if 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?
Prescribe and dispense by brand name only, to minimise the risk of inadvertent switching between products, which has been associated with reports of toxicity and graft rejection
When monitoring tacrolimus, should peak or trough levels be taken?
Trough Especially when there is diarrhoea, levels need to be closely monitored
What is the MHRA advice surrounding the use of mycophenolic acid/MMF?
The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy 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 preferredMycophenolate medicines remain contraindicated in women of childbearing potential who are not using reliable contraception and in pregnant women unless there are no suitable alternatives to prevent transplant rejectionMale patients or their female partner should use effective contraception during treatment and for 90 days after discontinuation.
Fingolimod, a drug used for MS, carry what MHRA warnings?
1) Not recommended for patients at known risk of cardiovascular events - known to cause bradycardia and heart block after first dose - can cause arrhythmias 2) Rebound MS after stopping or switching Tx 3) Skin cancer and lymphoma 4) Risk of congenital malformations (contraception during and 2 months after stopping) 5) Serious liver injury and herpes meningocephalitis
What is the MHRA advice surrounding the use of bevacizumab?
Risk of osteonecrosis of the jaw Aneurysm and aortic dissection
What is the MHRA advice surrounding the use of EGFR inhibitors e.g. cetuximab?
Keratitis and ulcerative keratitisIn 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 Reports of cytomegalovirus (CMV) gastrointestinal infection or reactivation (October 2019)
Which two cytotoxic drugs do not cause bone marrow suppression?
Vincristine Bleomycin
Ciclosporin can cause what kinds of toxicity?
Neurotoxicity Nephrotoxicity Hepatoxicity
What is the patient advice surrounding ciclosporin?
Manufacturer advises avoid excessive exposure to UV light, including sunlight. In psoriasis and atopic dermatitis, avoid use of UVB or PUVA. Avoid grapefruit juice
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 excessive exposure to UV light including sunlight. May affect performance of skilled tasks (e.g. driving). Pomelo and pomegranate juices might greatly increase the concentration of tacrolimus.
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?
Oral mucositis N+V Alopecia Bone marrow suppression Hyperuricaemia Thromboembolism Extravasation
What are the features of tumour lysis syndrome?
Hyperkalaemia, hyperuricaemia, hyperphosphataemia withhypocalcaemia; 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 controlLorazepam can help
Which cytotoxic drug class has a high risk of cardiotoxicity and how is this prevented?
Anthracyclines - doxorubicine, epirubicineAn 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 methotrexate 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 ifsfomide 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
Do normal or liposomal formulations of doxorubicin carry a higher risk of cardiotoxicity?
Normal formulations carry a higher risk
What monitoring needs to be done before starting doxorubicin?
ECG due to the cardiotoxicityMonitor during treatment too
What are the main side effects of bleomycin?
Progressive pulmonary fibrosis Progressive pulmonary fibrosis is dose-related, and may occur at lower doses in the elderly. Suspicious chest X-ray changes are an indication to stop therapy with this drug. Pulmonary toxicity Patients who have received bleomycin may be at risk of developing pulmonary toxicity if exposed to high inspired oxygen concentrations, for example peri-operatively, or during lung function testing.
Should vinca alkaloids e.g. vincristine, vinblastine, be given IV or intrathecally?
Only ever IVIntrathecal administration isassociated with severe neurotoxicity
What is the patient advice surrounding methotrexate?
- Weekly dose not daily- The patient must report any signs of blood disorders i.e. sore throat, bruising, mouth ulcers), liver toxicity (i.e. nausea, vomiting, abdominal pain and dark urine) and respiratory effects (SOB).
What are the serious side effects of methotrexate?
Blood count Bone marrow suppression can occur abruptly; factors likely to increase toxicity include advanced age, renal impairment, and concomitant use with another anti-folate drug (e.g. trimethoprim). Manufacturer advises a clinically significant drop in white cell count or platelet count calls for immediate withdrawal of methotrexate and introduction of supportive therapy. Gastro-intestinal toxicity Manufacturer advises withdraw treatment if stomatitis or diarrhoea develops—may be first sign of gastro-intestinal toxicity. Liver toxicity Liver cirrhosis reported. Manufacturer advises treatment should not be started or should be discontinued if any abnormality of liver function or liver biopsy is present or develops during therapy. Abnormalities can return to normal within 2 weeks after which treatment may be recommenced if judged appropriate. Persistent increases in liver transaminases may necessitate dose reduction or discontinuation. Pulmonary toxicity Pulmonary toxicity may be a special problem in rheumatoid arthritis. Manufacturer advises patients to seek medical attention if dyspnoea, cough or fever develops; monitor for symptoms at each visit—discontinue if pneumonitis suspected.
How is it recommended that methotrexate tablets are dispensed?
Single strength tablets only to avoid confusion, usually 2.5mg tablets
What is the MHRA warning regarding the use of imatinib?
Can cause reactivation of Hepatitis B
What is the first sign of methotrexate GI toxicity?
Stomatitis - Inflammation of mouth and lips OR diarrhoea
What are the pre-treatment screening requirements for methotrexate?
Exclude pregnancy before treatmentFBC, renal function and LFTs
What needs to be monitored in a patient on methotrexate and how often?
Have full blood count and renal and liver function tests repeated every 1–2 weeks until therapy stabilised, thereafter patients should be monitored every 2–3 months
What OTC medicines should a patient on methotrexate not have?
NSAIDs - aspirin, ibuprofenPatients should be counselled on the use of NSAIDs
True or false:Penicillins increase toxicity risk of methotrexate
TRUE
How does allopurinol and azathioprine/mercaptopurine interact?
Azathioprine/mercaptopurine inhibits purine metabolism Allopurinol also does this Reduced dose by 1/4 needed if given with allopurinol to reduce risk of toxicity
What are the main side effects of MMF to look out for?
Hypogammaglobulinaemia or bronchiectasis - Measure serum immunoglobulin levels if recurrent infections develop, and consider bronchiectasis or pulmonary fibrosis if persistent respiratory symptoms such as cough and dyspnoea develop Bone marrow suppression Patients should be warned to report immediately any signs or symptoms of bone marrow suppression e.g. infection or inexplicable bruising or bleeding.
What does the MHRA suggest for excluding pregnancy when starting MMF?
The MHRA advises to exclude pregnancy in females of child-bearing potential before treatment—2 pregnancy tests 8–10 days apart are recommended.Pregnancy prevention programme
What kind of juice should be avoided if on tacrolimus?
Grapefruit juice, pomegranate and pomelo - increase conc of tacrolimus
What is neoadjuvant chemotherapy?
Delivered before the main treatment e.g. to shrink the tumour
What role does febuxostat play in chemotherapy patients?
Prophylaxis and treatment of acute hyperuricaemiaStarted 2 days before chemo
Rasburicase is used for the treatment of acute hyperuricaemia in what kind of cancer?
Blood cancers
What is a common side effect of doxurubicin (more common with liposomal formulations)?
Hand-foot syndromeMay be prevented by cooling hands and feet and avoiding socks, gloves, or tight-fitting footwear
What biomarker can you measure to see if you need to reduce the dose of doxorubicin?
Doxorubicin is largely excreted in the bile and an elevated bilirubin concentration is an indication for reducing the dose.
What bags should vincristine and vinblastine go in for adults and teenagers to prevent it from being administered intrathecally?
50mL mini bagShould also have a sticker on to say “For IV use only”
What is the contraception advice for men and women on methotrexate?
Use effective contraception for at least 6 months after treatment
What is the advice surrounding the use of ciclosporin and malignancies?
Like other immunosuppressants, ciclosporin increases the risk of developing lymphomas and other malignancies, particularly those of the skin.In psoriasis, exclude malignancies (including those of skin and cervix) before startingIt is contraindicated in malignancy for non-transplant indications (can be used in UC, RA, psoriasis)
Can chemotherapy prescriptions be on repeat?
No unless indicated by a specialistDose is dependent each time on a lot of factors e.g. blood count
How is delayed nausea and vomiting symptoms managed in moderate risk chemotherapy patients?
Ondansetron and dexamethasone
How is delayed nausea and vomiting symptoms managed in high risk chemotherapy patients?
Dexamethasone + aprepitant Metoclopramide and rolapitant also licensed
Is cyclizine used for nausea and vomiting in chemo patients?
No - it is not licensedThis is mainly used for post op and palliative care N+V
Can metoclopramide be used in acute N+V in chemo patients?
No, only licensed in the delayed phase
Is it recommended to have a chest X Ray before methotrexate treatment?
Not usually indicated
What are the 3 UK cancer screening programmes?
BreastBowelCervicalThere is no screening programme for prostate cancer because the PSA test is not reliable enough, but men over 50 can ask their doctor about it.
Is there a screening programme for prostate cancer?
There is no screening programme for prostate cancer because the PSA test is not reliable enough, but men over 50 can ask their doctor about it.
What is the bowel cancer screening programme e.g. age, what does the patient need to do, how often, what gender?
In England, people between the ages of 60 and 74 years take part. Both male and femaleEvery 2 yearsSend off a stool sample You need to be registered with a GP to receive screening invitations
What is the breast cancer screening programme e.g. age, how often, what does the patient need to do,?
50-70 yearsIn some areas this extends from 47 to 73 yearsEvery 3 yearsMammogram You need to be registered with a GP to receive screening invitations
What is the cervical cancer screening programme e.g. age, how often?
25-49 years every 3 years49-64 years every 5 yearsNeed to be registered with GP
