Immune System and Malignant Disease Flashcards
(39 cards)
How does Azathioprine work?
Antimetabolite which is broken down by thiopurine methyltransferase (TPMT) to produce the active metabolite mercaptopurine which inhibits repair and production of DNA.
Pre-screening test for Azathioprine
TPMT levels - low levels reduce metabolism which increases risk of myelosuppression.
Azathioprine adverse effects
- Hypersensivity - malaise, dizziness, fever, rash, D &V
- Myelosuppression leading to neutropenia and thrombocytopenia - report sore throat, bruising, bleeding
- Nausea - common at start of treatment but resolves over time
- Teratogenicity - avoid in pregnancy
Key Azathioprine interactions
- Allopurinol - increased risk of haemtological toxicity. REDUCE Azathioprine dose.
- ACE inhibitors - increased risk of anaemia/leucopenia. AVOID concomitant use.
How does ciclosporin work?
Calcineurin inhibitor - inhibits lymphokines to suppress cell-mediated immune response.
How does tacrolimus work?
Calcineurin inhibitor - inhibits lymphokines to suppress cell-mediated immune response.
Which immunosuppressants should be prescribed by brand name?
- Ciclosporin
- Tacrolimus
Ciclosporin adverse effects
- Skin reactions and photosensitivity (avoid UV)
- Eye inflammation and visual disturbances with topcial eye use (avoid driving)
- Hair changes - growth and repigmentation
- Renal/hepatic impairment
- Gingival hyperplasia
- Avoid in pregnancy and breastfeeding
- HYPO-magnasaemia (monitor)
- HYPER-glycaemia, lipidaemia, tension, uricaemia, kalaemia
Cutaneous reactions
I - eyes
Changes to hair
Liver and kidney damage
Oral changeS
Pregnancy & breastfeeding
hypOmagnaseamia
Raised uric acid, glucose, BP, lipids
Key food/drink interactions with ciclosporin
- Grapefruit and Pomelo juice - increased exposure
- Purple grape juice - decreased exposure
Tacrolimus adverse effects
- HYPER-glycaemia, uricaemia, kalaemia
- Hyper/hypo-tension
- Renal/hepatic impairment
- Skin reactions and photosensitivity (avoid UV)
- Blood dyscrasias
- CVD - QT prolongation, cardiomyopathy in children
- Visual disturbances (avoid driving)
- Nervous system disorders, peripheral neuropathy
- Avoid in pregnancy and breastfeeding
Key food/drink interactions with tacrolimus
- Grapefruit, Pomegranate & Pomelo juice - increased exposure
Ciclosporin monitoring
- Pre-screening for malignancy
- TDM: trough levels
- LFTs
- Mg
- K
- Lipids
- CrCl
- BP
When should Tacrolimus be avoided?
If patient has hypersenitivity to Macrolides
Mycophenolate Mofetil MOA
Inhibits purine synthesis
Mycophenolate Mofetil adverse effects (and how to respond)
- Bone marrow suppression - report infection, bruising, bleeding
- Pure red cell aplasia - reduce dose or discontinue
- Hypogammaglobulinaemia - measure immunoglobulin levels in recurrent infections
- Bronchiectasis - report persistent cough and SOB
- Teratogenic (men and women): Female patients must have 1 effective contraception (2 preferred) during and for 6 weeks after treatment. Male patients and their partner must use effective contraception during treatment and for 90 days after.
Rules for handling cytotoxic drugs
- Reconstituted by trained personel in designated parmacy areas
- Wear gloves, gown, masks, eye protection
- Monitor staff exposure for cytotoxins
- Avoided by pregnancy staff and inform women of child-bearing age of risk
- Use local procedures for spillages and safe disposal
Name the 7 cytotoxic drug classes and some examples
- Alkylating agents - cyclophosphamide, ifofsamide
- Anthracyclines - doxorubicin, epirubicin, idarubicin
- Antimetabolites - fluorouracil, MTX, mercapopurine
- Platinum compounds - carboplatin, cisplatin
- Taxanes - Paclitaxel, Docetaxel
- Vinca Alkaloids - Vinblastine, Vincristine, Vindesine
- Cytotoxic abx - bleomycin, mitomycin
Common adverse effects of cytotoxic drugs
- Local tissue necrosis due to extravasation of IV drug
- Oral mucositis
- Tumour lysis syndrome
- Hyperuricaemia
- Myelosuppression (all except Vibcristine & Bleomycin)
- Alopecia
- Thromboembolism (due to inflammation of blood vessels and immbolisation due to fatigue)
- Urothelial toxicity - causes haemorrhage in urinary tract.
- Teratogenicity
Oral mucositis recommendations
- Associated with fluorouracil, MTX, and anthracyclines
- Good oral hygeine to prevent
- Use saline mouthwash to treat
- Fluorouracil - suck ice chips to soothe mouth and prevent
- MTX - use folinic acid
What is tumour lysis syndrome?
Condition which occurs with use of cytotoxins due to rapid destruction of malignant cells which leads to release of their contents into the blood stream. Can result in low Ca and high K+, Ph, and uricaemia leading to renal damage and arrythmias.
Risk is higher in:
* Lymphoma (non-Hodgkins and Burkitts) and leukaemia (lymphoblastic and myeloid)
* Pre-existing hyperuricaemia, dehydration, or renal impairment.
Prevention of cytotoxin induced hyperuricaemia?
More present in high-grade Lymphoma and Leukaemia, so 24hrs before starting treatment:
* Allopurinol
* Hydration
Use febuxostat for 48h before if allopurinol not appropriate.
Recommendations for cytotoxic-induced myelosuppression
- Highest risk if 7-10 days after administration
- Check FBC before each treatment and reduce dose if bone marrow has not recovered.
- Avoid treatment during acute infection - if during/soon after, seek urgent medical attention.
- Occurrence of neutropenic fever requires immediate broad spectrum antibiotics
What is urothelial toxicity and how is it treated?
Damage and inflammation of cells in urinary tract leading to haemorrhagic cystitis caused by treatment with high-dose ifofsamide or cyclophosphamide.
Prevented with coadministration of Mesna with these drugs - a detoxifying agent which concentrated in the bladder and conjugates with urotoxic metabolites to inactivate them.
Effects of cytotoxics on reproductive system
- Alkylating agents & procarbazine: Increased risk of permanent male sterility - consider sperm storage. May also cause premature menopause in women.
- Most cytotoxics are teratogenic - pregnancy should be excluded before treatment and prevented during and sometime after (depends on drug).
