Chapter 8: Immune and malignancy Flashcards
Name 4 drugs that can be used in IBD?
Azathioprine, mercaptopurine, ciclosporin and methotrexate
Why is folic acid given alongside methotrexate? Is this licensed?
To reduce the risk of methotrexate toxicity and hence reduced MTX side-effects such as anaemia, hair loss, mouth sores (that could make a person not want to take methotrexate
Unlicensed
When should folic acid be administered after methotrexate?
Ideally 24hrs after to reduce the incidence of SE asap
But cannot be on the same day as methotrexate as it reduces folate levels and taking folic acid on same day would mean that the folate would be reduced further (ineffective)
Give two indications for immunosuppressant therapy?
1) Organ transplant rejection
2) Inflammatory diseases e.g. RA, Severe eczema, IBD
Solid organ transplant patients are maintained on drug regimens depending on the type of organ transplant. What are the drug choices?
1) Anti-proliferatives: Azathioprine, mycophenolate
2) Calcineurin inhibitors: Tacrolimus, ciclosporin
3) Corticosteroids
Immunosuppressant ________ the risk of infections
Increase
A patient is on azathioprine and arrives at your pharmacy to get a flu vaccine. What would you advise?
Due to the increase in risk of infections (eg sepsis/tb) that could be severe from your azathioprine, you cannot have a live vaccine. Therefore, I need to check what brands we have and check this (MMR is also live)
What is a key side-effect of immunosuppressants?
bone marrow suppression and hence, the increased risk of infections
When would you consider azathioprine as a treatment choice?
if corticosteroids are inadequate
What is azathioprine (prodrug) metabolised to?
mercaptopurine - which inhibits purine metabolism and DNA/RNA/protein synthesis not allowing that host response
With what drug does the dose of azathioprine need to be reduced?
Allopurinol (gout prophylaxis) - reduce dose to 1/4 of usual dose due to toxicity as allopurinol inhibits purine metabolism
Which drug has a more selective MOA? Azathioprine or mycophenolate?
Mycophenolate
Disadvantages of mycophenolate (used to prevent transplant rejection)?
Increased risk of infections and blood disorders such as leucopaenia
Advantages of mycophenolate?
Reduced risk of acute rejection
What drug class does ciclosporin belong to? Would you be worried if a patient was also on gentamicin?
Calcineurin inhibitors. Yes - ciclosporin and gentamicin are both nephrotoxic.
3 disadvantages of Tacrolimus?
- Increased risk of neurotoxicity
- cardiomyopathy
- glucose metabolism impairment (hyperglycaemia)
What side-effect of azathioprine would prompt you to stop treatment?
Hypersensitivity reactions - malaise, n/v/d, dizzy, fever, rigors, myalgia, arthralgia, rash
Name two side-effects of azathioprine.
1) hypersensitivity
2) bone marrow suppression (pre-screen for enzyme thiopurine methyltransferase as low enzyme activity increases risk of myelosuppression) - report bleeding, bruising, infection, mouth ulcers, nasal bleed, blood in stools (unexplainable)
How often do you monitor FBC with azathioprine?
Weekly for 4 weeks then every 3 months
Ciclosporin MOA
Reduce T-cell activity and immune response
MHRA warning for ciclosporin?
Maintain the same brand
How does ciclosporin differ from tacrolimus?
Ciclosporin = mainly nephrotoxicity Tacrolimus = mainly neurotoxicity
Ciclosporin common side-effects
1) eye inflammation
2) gingival hyperplasia
3) neurotoxicity
4) nephrotoxicity
5) hypertension
6) hyperlipidaemia
7) hyperglycaemia
Patient counselling for ciclosporin?
Use SPF and protect from sunlight
Avoid high potassium diet and grapefruit juice (inhibitor): increases levels
Pomelo juice is predicted to increase ciclosporin exposure, and purple grape juice is predicted to decrease ciclosporin exposure.
Caution as SE can be: HYPERURICAEMIA (caution gout), HYPERLIPIDAEMIA (caution with uncontrolled cholesterol) AND HYPERTENSION (caution in BP)
Ciclosporin rarely causes bone marrow suppression, true or false?
True
Which calcineurin inhibitors have to be prescribed and dispensed by brand? (MHRA warnings)
tacrolimus
ciclosporin
Mycophenolate MHRA warning?
genotoxic: effective contraception required
Cancer therapy aims?
- curative intent
- prolong life
- palliate symptoms
Define neoadjuvant therapy in cancer.
Aims to shrink the primary tumour making local therapy less destructive/more effective e.g. pre surgical meds to shrink tumour before surgery
Define adjuvant therapy in cancer.
Administered after surgery for tx of cancer to help prevent recurrence
Guidelines for handling cytotoxic drugs
- trained personell
- desginated area to prepare
- PPE: hats, gloves, aprons, goggles
- specify first aid
- pregnant staff should avoid exposure to cytotoxics
- spillage + waste disposal - local procedure
- monitor staff exposure
Why do cytotoxics have to be administered by specialist trained staff?
Risk of extravasation = local tissue necrosis (cell death) and can lead to amputation
What specific side-effect is associated with vinca alkaloids?
neurotoxicity
Cytotoxics cause various side-effects, give examples.
1) Oral mucositis
2) preg and reproductive function: exclude pregnancy + effective contraception (as kills fast dividing cells such as sex cells)
3) extravasation with IV drugs
4) thromboembolism
5) hyperuricaemia
6) alopecia
7) nausea/vomiting
8) bone marrow suppression
9) urotherlial toxicity
Which drugs often cause oral mucositis/mouth ulcers?
Anthracyclines
Methotrexate
5-FU
- Recommend good oral hygiene, saline washes
Fertility normally returns once chemotherapy is complete. What are the exceptions?
Alkylating drugs and procarbazine: permanent male sterility so advise on sperm storage
Rapid destruction of tumour cells can cause…
tumour lysis syndrome
