Chapter 8- Immune System & Malignant Disease Flashcards
What’s given with methotrexate (cancer and non cancer treatments) and why
Folic acid - non cancer
Folinic acid - cancer
Reduce the possibility of methotrexate toxicity and methotrexate induced myelosuppression
How are chronic inflammatory, autoimmune diseases and organ transplant patients managed on drug regime
Antiproliferative drugs (azathioprine, mychophenolate)
Calcineurin inhibitors (ciclosporin or tacrolimus)
Corticosteroids
Sirolimus
What is azathioprine used for
Transplant recipients and auto immune conditions
Why should dose of azathioprine be reduced when given with allopurinol
Risk of bone marrow suppression
Side effects of azathioprine
Red cell aplasia Hypersensitivity reactions (stop immediately)
Monitoring requirements for azathioprine
Thiopurine methyltransferace (TPMT) enzyme that metabolises azathioprine
Full blood count for 4 weeks then 3 monthly
What is mychophenolate licensed for
The prophylaxis of acute rejection in renal hepatic or cardiac transplantation
(More selective MOA than azathioprine)
Side effects of mycophenolate
Bone marrow suppression
Respiratory symptoms
Red cell aplasia
Congenital malformation (so pregnancy prevention)
Warning signs for ciclosporin
Neurotoxicity Blood disorders (hyperlipidaemia) Liver toxicity Nephrotoxicity Hypertension Visual disturbances Bone marrow Gingival hyperplasia (gum overgrowth)
Counselling point for ciclosporin and tacrolimus
Avoid UV exposure
Avoid high potassium diet and grapefruit juice
Must not receive immunisation with love vaccines
Stabilise in particular brand
Driving may be impaired (tacrolimus)
Daily dose divided in 2 doses (cislosporin)
What’s the greater disadvantage of tacrolimus over ciclosporin
Neurotoxicity is greater
Cardiomyopathy has been reported
Disturbance in glucose metabolism significant
Warning signs for tacrolimus
Neurotoxicity (headache and tremors)
Nephrotoxicity
Eye disorder (blurred vision)
Skin disorder (rash)
Blood disorder (BP, hyperglycaemia, hyperkalaemia, hyperuricaemia) Bone marrow
Cardiovascular disorder (arrhythmia)
Liver toxicity
Monitoring parameters for tacrolimus
BP ECG Fasting blood glucose Renal function Liver function Serum electrolytes
What is azathioprine metabolised to?
Mercaptopurine
What activity does cytotoxics have?
Anti cancer activity and the potential to damage normal tissue
Most are teratogenic
What contributes to determining the cytotoxic drug dose
BSA and weight
Dose adjustment is common after considering patients neutrophil count, renal and hepatic function and history of previous adverse effect
Also if the drug is being used alone or in combination
Commonn side effects of cytotoxic drugs
Alopecia Thromboembolism Tumour lysis syndrome Huperuricaemia Nausea and vomiting Bone marrow suppression Oral mucositis Cardiotoxicity Urothelial toxicity Myelosupression Pregnancy and reproductive function Extravasion of IV drugs
Warning signs for methotrexate
GI toxicity Liver toxicity Blood disorders Pulmonary toxicity Pregnancy and breastfeeding
Avoid in significant renal impairment
Monitoring parameters for methotrexate
Full blood count
Renal function
Liver function
Counselling points for methotrexate
Same day each week (oral) Folic acid / folinic acid as prescribed Importance of effective contraception Avoid preparations containing NSAIDs/ aspirin Methotrexate book issued
What’s a good prevention for oral mucositis from cytotoxics
Good oral hygiene
Sucking on ice during chemo
What can be used for cytotoxic associated nausea and vomitting
Dexamethasone
Lorazepam
Ondansetron
Metoclopramide
What is cisplatin and Side effects of cisplatin
Platinum compound
Nausea and vomiting Nephrotoxicity Ototoxicity Peripheral neuropathy Myelosuppression
The different routes for methotrexate
Mouth
IV
IM
Intrathecally
Adverse effects of vinca alkaloids
Neurotoxicity
Myelosuppression
Side effect of tamoxifen
Endometrial changes
Risk of thromboembolism
How should vinca alkaloids be administered
IV only
IM can be fatal
What’s extravasation?
Severe tissue necrosis due to leakage occurring
What drugs can cause oral mucositis
Fluorouracil
Methotrexate
Anthracyclines
What worsens hyperuricaemia
Chemotherapy and renal failure
Which cytotoxics are highly emetogenic
Cisplatin
Dacarbazine
High does Cyclophophsamide
Which cytotoxics are moderately emetogenic
Doxorubicin
High dose methotrexate
Low does Cyclophophsamide
Which cytotoxics are mildly emetogenic
Fluorouracil
Low dose methotrexate
Radiation therapy
Vinca alkaloids
Which cytotoxics don’t cause bone marrow suppression
Vincristine (vinca alkaloids)
Bleomycin
How does cancer effect the risk of VTE
Both cancer and chemotherapy increase the risk of VTE
What is multiple sclerosis
Chronic immune mediated demyelinating inflammatory condition of the CNS which effects the brain, optic nerves and spinal cord leading to progressive severe disability
How should cytotoxic drugs be handled
Trained personnel
Reconstitution carried out in a designated area
Protective clothing should be worn
Eyes should be protected
Pregnant people should avoid exposure
Use local procedures to deal with spillage and safe disposal
Staff exposure to cytotoxic should be monitored
What does tamoxifen treat
Breast cancer
Risk of tamoxifen
Embolism Endometrial cancer (notice any changes to menstrual cycle)
Risk of doxorubicin
Low RBC (anaemia) Low WBC (infection) Low platelet (bleeding risk)
Risk of tamoxifen
Embolism Endometrial cancer (notice any changes to menstrual cycle)
How does azathioprine and mercaptopurine work
Azathioprine is metabolised to mercaptopurine
Mercaptopurine inhibits purine metabolism therefore dna and rna and protein synthesis
How does allopurinol and azathioprine and mercaptopurine interact
Allopurinol is a Xanthines oxidase inhibitor so inhibits metabolism of purine
Increasing risk of bone marrow suppression
How long should males and females use contraception for after mycophenalate
Men: use condoms until 90 days after discontinuing
Women: two methods of effective contraception until 6 weeks after discontinuing
Which cytotoxic affect male fertility
Alkylating drugs and procarbazine
Counsel patients on sperm storage
What clinical features can occur from tumour lysis syndrome
Hyperkalaemia Hyper urea Hypocalceamia Renal failure Arrhythmia
Which group of patients are at risk of tumour lysis syndrome
Renal impairment
Dehydration
Hyperuricaemia
Treatment for urothelial toxicity
MESNA
Which cytotoxics lead to extravasation of IV drugs
Vinca alkaloids
Anthracyclines
Side effects of cytotoxics
Tumour lysis syndrome Thromboembolism Urothelial toxicity Pregnancy and reproductive function Hyperuricaemia Nausea and vomiting Alopecia Extravasation of IV drugs Bone marrow suppression
Name the cytotoxic drug classes and examples
Cytotoxic antibiotics (Anthracyclines ‘rubicin’ and Antineoplasric antibiotics ‘bleomycin’
Vinca alkaloids (vincristine)
Antimetabolites (methotrexate)
Alkylating drugs (cyclophosphamide)
Aromatase inhibitors (anastrazole)
Taxanes (paclitaxel)
Side effects of anthracyclines
Cardio toxicity
Red urine
Hand and foot syndrome
(Doxorubicin excreted in bile so reduce dose if high bilirubin)
Treatment fo anthracyclines induced side effects
Dexrazoxane
Side effects of antineoplastic antibiotics
Pulmonary fibrosis
Respiratory failure
Hypersensitivity
Dermatology toxicity
Route of administration for vinca alkaloids
Intravenous only
Side effect of vinca alkaloids
CNS toxicity
Antimetabolites side effects
Oral mucositis
Myelosuppression
How can you speed up the recovery of methotrexate use for chemo
Folinic acid
Which cytotoxics causes urothelial toxicity
Cyclophosphamide
Which cytotoxics are not for premenopausal women and why
Aromatase inhibitors
They are anti-oestrogen
Side effect of taxanes
Cardiac disease
Pneumonitis
Sepsis
What can you give before chemo for nausea and vomiting
Lorazepam
What can you give for acute symptoms of nausea and vomiting associated with chemo
Low risk: dexamethasone or lorazepam
High risk: serotonin antagonist, aprepitent + dexamethasone
What can you give for delayed symptoms of nausea and vomiting associated with chemo
Moderately emotogenic drugs:
Dexamethasone and serotonin antagonist
Highly emotogenic drugs:
Dexamethasone + aprepitant
Treatment for hyperuricaemia associated with chemotherapy
Allopurinol (24hrs before treating tumour)
Of febuxostat (2 days before)
Rasburicase (hyperuricaemia associated with blood cancer)
What is extravasation of IV drugs
What can chemo drugs cause
Leakage of drugs 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 37.5 (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
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
Which chemo drugs have a lower emetogenic (vomitting) potential?
Methotrexate
Vinca alkaloids- vinblastine, vincristine
Highly emetogenic: Cisplatin, dacarbazine
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?
MENSA
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 pre-treatment screening is needed with azathioprine?
TPMT levels TPMT metabolises the drug, so if reduced levels, there is an increased risk of myelosuppression
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 bevacizumab?
Risk of osteonecrosis of the jaw
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
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 colour does doxorubicin turn your urine?
red
What monitoring needs to be done before starting doxorubicin?
ECG due to the cardiotoxicity
Monitor during treatment too
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
What OTC medicines should a patient on methotrexate not have?
NSAIDs - aspirin, ibuprofen
Patients should be counselled on the use of NSAIDs
True or false: Penicillins increase toxicity risk of methotrexate
TRUE
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 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”
Can chemotherapy prescriptions be on repeat?
No unless indicated by a specialist
Dose is dependent each time on a lot of factors e.g. blood count
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 female
Every 2 years
Send 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 years
In some areas this extends from 47 to 73 years Every 3 years Mammogram 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 years Need to be registered with GP
What would you give for a fever with neutropenia following bone marrow suppression due to cytotoxic drugs
Broad spec antibiotic
Filgrastrim- stimulate more wbc
Avoid paracetamol as it delays starting antibiotic
