Immune system and malignant disease Flashcards
Name two types of antiproliferative immunosuppressants
- Azathioprine
- mycophenolate mofetil
What should be considered when allopurinol is given concurrently with azathioprine?
Doses of azathioprine should be reduced when allopurinol is given concurrently
due to the risk of bone marrow suppression.
What side effect has been reported with azathioprine and mycophenolate mofetil?
Red cell aplasia
which may require dose reduction or discontinuation under specialist supervision
What are signs or symptoms of bone marrow suppression while taking azathioprine?
inexplicable bruising or bleeding, or infection
patient should report such symptoms immediately
How often should we monitor full blood count in patients taking azathioprine?
A full blood count should be performed for 4 weeks initially, and then every 3 months thereafter.
What should be monitored throughout treatment with azathioprine
Toxicity
(ncluding blood tests and signs of myelosuppression, especially in long-term treatment)
What enzyme metabolizes thiopurine drugs such as azathioprine and mercaptopurine?
Thiopurine methyltransferase (TPMT)
What should patients be warned to report immediately when taking mycophenolate?
any signs or symptoms of bone marrow suppression, such as infection or inexplicable bruising or bleeding.
What are the risks associated with using mycophenolate in combination with other immunosuppressants?
recurrent infections (hypogammaglobulinemia)
and respiratory symptoms such as cough and dyspnea (bronchiectasis)
What should be considered if red cell aplasia is reported in patients taking azathioprine or mycophenolate mofetil?
Dose reduction or discontinuation should be considered under specialist supervision
What precautions should be taken regarding pregnancy when using azathioprine or mycophenolate mofetil?
Pregnancy should be prevented
womenshould use two effective methods of contraception during treatmentwith azathioprine or mycophenolate mofetil and for 6 weeks after discontinuation
Men and their partners should both use contraception** during treatment** and for at least 90 days after discontinuation.
What is the main risk associated with ciclosporin?
nephrotoxic
What are some warning signs that should be reported immediately to a doctor when taking ciclosporin? (10)
- neurotoxicity (such as tremor, headache, or confusion)
- blood disorders (signs of infection or unexplained bruising or bleeding)
- liver toxicity (jaundice, nausea, vomiting, abdominal discomfort, dark urine)
- nephrotoxicity (elevated serum creatinine concentrations)
- vomiting
- drowsiness
- tachycardia
- hypertension
- benign intracranial hypertension (headache, visual disturbances
- gingival hyperplasia.
What action should be taken if benign intracranial hypertension occurs while taking ciclosporin?
discontinue ciclosporin
What are some components of monitoring when taking medications like ciclosporin? (7)
- full blood count
- liver function tests
- serum electrolytes (potassium and magnesium)
- blood lipids
- renal function (including creatinine and urea)
- blood pressure
- dermatological and physical examination.
How should ciclosporin be managed during pregnancy?
Ciclosporin should be continued under specialist supervision during pregnancy.
What precautions should patients taking ciclosporin follow regarding exposure to UV light? (2)
should avoid excessive exposure to UV light including sunlight
and use a wide spectrum sunscreen to reduce the risk of secondary skin malignancies.
What dietary adjustments should patients on ciclosporin follow?
avoid a high potassium diet and grapefruit juice
Why is it important to stabilize on a particular brand of ciclosporin?
Switching between formulations of ciclosporin without close monitoring may lead to changes in blood-ciclosporin concentration.
If the brand is switched then we must monitor:. blood-ciclosporin concentration, serum creatinine, blood pressure, and transplant function
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What are some medications or substances that can increase plasma concentration when taken with ciclosporin? (10)
- Clarithromycin
- erythromycin
- fluconazole
- grapefruit juice
- itraconazole
- ketoconazol
- miconazole
- metoclopramide
- verapamil
- tacrolimus
What is the increased risk associated with colchicine when taken with ciclosporin?
an increased risk of nephrotoxicity and myotoxicity
Name some medications or substances that can decrease plasma concentration when taken with ciclosporin (6)
- Carbamazepine
- orlistat
- phenobarbital
- phenytoin
- rifampicin
- St John’s wort
What is the risk of hyperkalemia when ciclosporin is given with certain medications?
an increased risk of hyperkalemia
when ciclosporin is given with ACE inhibitors or ARBs, or aldosterone antagonists.
What medication’s plasma concentration does ciclosporin increase, potentially leading to toxicity?
increases the plasma concentration of digoxin
What are some warning signs that should be reported immediately to a doctor when taking tacrolimus? (8)
- neurotoxicity (such as tremor, headache)
- elevated serum creatinine concentrations indicating nephrotoxicity
- eye disorders (blurred vision, photophobia)
- skin disorders (rash, toxic epidermal necrolysis)
- signs of infection
- hyperglycemia (increased thirst or excessive urination)
- cardiovascular disorders (cardiomyopathy, arrhythmias, hypertension)
- liver toxicity (jaundice, nausea, vomiting, abdominal discomfort, dark urine).
What parameters should be monitored in patients taking medications like tacrolimus?
Blood pressure
ECG for cardiomyopathy (discontinue if it occurs)
fasting blood glucose concentration
renal function
liver function
serum electrolytes (particularly potassium)
and haematological, neurological (including visual), and coagulation parameters
Why should we avoid tacrolimus in pregnancy and breastfeeding?
due to the risk of premature delivery
What precautions should patients on tacrolimus follow regarding exposure to UV light?
Patients on tacrolimus should avoid excessive exposure to UV light, including sunlight
and should use a wide-spectrum sunscreen to reduce the risk of secondary skin malignancies.
Why is it important for patients to understand the importance of taking immunosuppressants regularly?
to maintain the effectiveness of the treatment and prevent rejection of transplanted organs.
What caution should be taken regarding oral tacrolimus products?
Switching between oral tacrolimus products has been associated with toxicity and graft rejection.
Therefore, oral tacrolimus should be prescribed and dispensed by brand name only.
Can tacrolimus affect the performance of skilled tasks such as driving?
Yes
due to its potential neurotoxic effects
Which medications or substances can increase plasma concentration when taken with tacrolimus? (9)
- Clarithromycin
- diltiazem
- erythromycin
- fluconazole
- grapefruit juice
- itraconazole
- nifedipine
- omeprazole
- ranolazine
What effect does phenobarbital and St. John’s Wort have on tacrolimus plasma concentration?
can reduce tacrolimus plasma concentration
What medications or substances can increase the risk of nephrotoxicity when taken with tacrolimus? (4)
- Aminoglycosides
- amphotericin
- NSAIDs (especially ibuprofen)
- certain antivirals (e.g., aciclovir, ganciclovir)
What interaction occurs between tacrolimus and ciclosporin?
Tacrolimus increases the plasma concentration of ciclosporin.
What is the increased risk associated with taking tacrolimus with potassium-sparing diuretics, potassium salts and ARBS?
Increased risk of hyperkalaemia
What is the nature of cytotoxic drugs in terms of their effects and potential risks?
Cytotoxic drugs possess both anti-cancer activity and the potential to harm normal tissue
and most are teratogenic.
What guidelines are recommended for handling cytotoxic drugs? (7)
Trained personnel should reconstitute cytotoxics in designated pharmacy areas
while wearing protective clothing (including gloves, gowns, and masks).
Eye protection should be utilized
first aid measures should be specifie
Pregnant staff should avoid exposure
local procedures for spillages and waste disposal should be followed.
Staff exposure to cytotoxic drugs should be monitored.
What are the requirements for a safe system regarding the administration of cytotoxic drugs?
They should only be prescribed, dispensed, and administered according to a written protocol or treatment plan.
Injectable cytotoxic drugs should only be dispensed when prepared for administration
and oral cytotoxic medicines should come with clear usage instructions.
What standards should be followed to prevent incorrect oral dosing of cytotoxic drugs? (3)
providing non-specialists access to written protocols and treatment plans,
ensuring staff dispensing oral cytotoxic drugs confirm the prescribed dose’s appropriateness
providing patients with written information detailing the treatment plan and arrangements for monitoring.
How are doses of cytotoxic drugs often determined?
using body surface area or body weight.
- Adjustment may occur based on the patient’s neutrophil count
- renal and hepatic function
- history of previous adverse effects
- whether the drug is used alone or in combination.
When do many side effects of cytotoxic drugs typically occur?
Many side effects of cytotoxic drugs often do not occur at the time of administration
but may manifest days or weeks later.
What is thromboembolism, and how is it related to chemotherapy?
Thromboembolism refers to the formation of blood clots within blood vessels.
While venous thromboembolism can be a complication of cancer itself, chemotherapy increases the risk.
What is tumor lysis syndrome, and what are its features?
Tumor lysis syndrome occurs when large amounts of tumor cells
are killed off by treatment releasing their contents into the bloodstream.
Features include hyperkalemia, hyperuricemia, and hyperphosphatemia with hypocalcemia
which can lead to renal damage and arrhythmias.
How can hyperuricemia associated with chemotherapy be managed?
medications such as allopurinol, febuxostat, and rasburicase for treatment and prophylaxis.
If allopurinol needs to be given, the dose of mercaptopurine or azathioprine should be reduced due to the risk of bone marrow suppression.
Which drugs are used for the prevention of nausea and vomiting associated with cytotoxic drugs?
Dexamethasone, Lorazepam, and Metoclopramide
What is the significance of bone marrow suppression in patients undergoing cytotoxic drug therapy?
All cytotoxic drugs except vincristine and bleomycin cause bone marrow suppression
typically occurring 7-10 days after administration
Blood counts must be checked before each treatment, and doses should be reduced or therapy delayed if bone marrow has not recovered.
What are the symptoms of neutropenic sepsis, and how should patients experiencing them respond?
Symptoms of neutropenic sepsis include:
* fever
* flu-like symptoms
* uncontrolled bleeding or bruising
* diarrhea
* uncontrolled vomiting
* severe mouth ulcers.
Patients experiencing these symptoms should attend the nearest A&E department
and should not take paracetamol without seeking advice.
What is the licensed medication for preventing anthracycline-induced cardiotoxicity?
Dexrazoxane
(an iron chelator)
What is a common manifestation of urothelial toxicity associated with cytotoxic drugs?
Haemorrhagic cystitis
How can methotrexate-induced mucositis and myelosuppression be counteracted?
folinic acid therapy
What advice should be given to men and women regarding contraception before and after cytotoxic therapy?
Men and women should receive advice for contraception before and after cytotoxic therapy.
consideration of sperm storage may be appropriate
Women are less severely affected, though the span of reproductive life may be shortened by the onset of a premature menopause.
What are the dose-limiting side-effects of all vinca alkaloids?
Neurotoxicity and myelosuppression
What route of administration is used for vinca alkaloid injections, and why is it important to administer them correctly?
intravenous administration only.
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Inadvertent intrathecal administration can cause severe neurotoxicity, which is usually fatal
What are the warning signs of gastro-intestinal toxicity associated with methotrexate?
an inflamed mouth or throat, which may be the first sign.
What are the warning signs of liver toxicity related to methotrexate?
jaundice, nausea, vomiting, abdominal discomfort, and dark urine.
What should patients do if they experience symptoms of bone marrow suppression while taking methotrexate?
Patients should report symptoms of bone marrow suppression, such as sore throat, bruising, mouth ulcers, fever, or rash, to a doctor immediately.
What parameters should be monitored while a patient is on methotrexate therapy? (3)
- Full blood count
- renal function
- liver function
Full blood count, renal function, and liver function
- Increased plasma concentration and risk of hepatotoxicity with acitretin (avoid).
- Excretion reduced by NSAIDs and penicillins, leading to increased risk of toxicity.
- Also, increased risk of toxicity with ciprofloxacin, doxycycline, tetracycline, ciclosporin, PPIs, and leflunomide.
- Increased risk of haematological toxicity when given with trimethoprim or co-trimoxazole.
How should methotrexate tablets be taken to minimize dosing errors?
Methotrexate tablets are to be taken once a week, on the same day each week
with folic acid as prescribed.
To avoid dosing errors, only one strength, usually 2.5mg, should be prescribed.
What precautionary advice should be given to patients taking methotrexate?
should be counseled on the importance of effective contraception during treatment
and how preparations containing NSAIDs/aspirin should be avoided
Methotrexate treatment booklets should be issued where appropriate.
What are the risks associated with tamoxifen therapy?
- endometrial changes such as increased risk of hyperplasia, polyps, cancer, and uterine tumors.
- There is also an increased risk of thromboembolism, particularly during and immediately after major surgery or periods of immobility. Patients should report sudden breathlessness and any pain in the calf of one leg.
What are side efefcts of cytotoxic drugs? (7)
- oral mucositis
- nausea and vomiting
- bone- marrow suppression
- alopecia
- tumour lysis syndrome
- hyperuricaemia
- venous thromboembolism
How is nausea commonly managed during the early stages of Azathioprine treatment? (4)
- by using divided daily doses
- taking doses after food
- prescribing antiemetics
- temporarily reducing the dose
What precaution should be taken regarding repeating prescriptions of cytotoxic drugs?
Prescriptions of cytotoxic drugs should not be repeated unless instructed by a specialist.
Why should pregnant staff members avoid exposure to cytotoxic drugs?
due to the reproductive hazards associated with these medications
and all females of child-bearing age should be informed about these risks
: What is the risk associated with reduced TPMT activity in patients starting azathioprine or mercaptopurine?
the enzyme that metabolizes thipurine drugs
Patients with reduced TPMT activity
have an increased risk of myelosuppression
when starting azathioprine or mercaptopurine
What symptoms indicate a hypersensitivity reaction to azathioprine? (11)
- malaise
- dizziness
- vomiting
- diarrhea
- fever
- rigors
- myalgia
- arthralgia
- rash
- hypotension,
- interstitial nephritis
requiring immediate withdrawal of the drug.
