Immunology bits and pieces! Flashcards
Azathioprine - antimetabolite that breaks down into mercaptopurine which inhibits repairment and making of DNA
Azathioprine is broken down by TPMT (thiopurine methyltransferase) => pre-screening TPMT levels is advisable as having reduced activity on the enzyme means an increase in myelosuppression
SE:
- hypersensitivity => malaise, dizzines, D/V, fever, rash, hypotension, myalgia
- Neutropenia & thrombocytopenia => report a sore throat, bruising, bleeding
- N => more common at start of dose but resolves over time
- Teratogenic => avoid in pregnancy
Monitoring:
- TPMT
- Regular LFT, FBC in severe liver or renal impairment
- FBC OW for first 4 wks, then at least every 3 months
Interactions:
- Azathioprine + Allopurinol => increased risk of haematological toxicity => reduce dose of azathioprine
- azathioprine + ACEi => increased risk of anaemia / leucopenia => avoid concomitant use!
Ciclosporin - calcineurin inhibitor inhibiting lympokines which suppresses cell-mediated response
BRAND!
Avoid exposure to UV light / sunlight
Avoid in pregnancy and breast-feeding!
SE:
- HYPER: glycaemia, lipidaemia, tension, uricaemia, kalaemia
- HYPO: Mg
- Renal / liver impairment
- skin reactions
- gingival hyperplasia
- hair changes - hirsutism
- eye inflammation and visual disturbances in eye drops! => Eye drops can affect driving / performing skilled tasks
Pre-screening:
- exclude malignancies b4 systemic use
Interactions:
- Grapefruit + Pomelo juice => increases ciclosporin exposure
- Purple grape juice => decreases ciclosporin exposure
Monitor:
- LFT, Mg, K, lipids, CrCl, BP
- Trough levels need to be monitored (range depends on indication)
Tacrolimus - calcineurin inhibitor inhibiting lymphokines which suppress cell-mediated response (Prograf)
BRAND!
Avoid exposure to UV light / sunlight
May affect diving / performing skilled tasks
Avoid in pregnancy and breastfeeding
SE:
- HYPER: glycaemia, uricaemia, kalaemia
- HYPER/HYPO tension
- renal / liver impairment
- skin reactions
- visual disturbances
- blood dyscrasia
- CVD - QT prolongation, cardiomyopathy in kids
- NS disorder, peripheral neuropathy
Interactions:
- Grapefruit + promegranate + pomelo juice => increases tacrolimus exposure
- Avoid HIGH K+
- DON’T USE IF PT HAS HYPERSENSITIVITY TO MACROLIDES
Monitor:
- BP, ECG, blood glucose, LFT, electrolytes, CrCl
Mycophenolate mofetil - Inhibits purine synthesis (CellCept)
Bone marrow suppression = report infection or bruising or bleeding
Pure red cell aplasia = reduce dose or discontinue
Hypogammaglobulinaemia = measure immunoglobulin levels in recurrent infections
Bronchiectasis = consider if persistent cough and SoB develops
MHRA contraceptive advice (teratogenic)
- Women => 1 effective contraception during and 6 wks after (2 methods preferred)
- men => effective contraception during and 90 days after (for partner as well)
MHRA - PO products: 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
Multiple Sclerosis = a chronic autoimmune disease demyelinating the CNS. 3 different types: Relapsing, Progressive, or Both
Active = 2 relapses in the past 2 years despite treatment with INTERFERON BETA
Managing symptoms:
- SPASTICITY = baclofen = Must increase dose slowly to avoid major SEs such as sedation and hypotonia; diazepam, tizanidine and dantrolene
- RELAPSES = methylprednisolone
- OSCILLOPSIA (objects appear to vibrate) = gabapentin
- MOOD ALTERATION = Amitriptyline
- FATIGUE = Amantadine (DA receptor agonists) or Fampridine
Cytotoxic Drug Classes
Alkylating agents = Cyclophosphamide, Ifosfamide, Melphalan
Anthracyclines = Daunorubicin, Doxorubicin, Epirubicin, Idarubicin
Antimetabolites = Cytarabine, Fluorouracil, Methotrexate, Mercaptopurine
Cytotoxic Abx = Bleomycin, Mitomycin
Platinum compounds = Carboplatin, Cisplatin, Oxaliplatin
Taxanes = Cabazitaxel, Docetaxel, Paclitaxel
Vinca Alkaloids = Vincristine, Vinblastine, Vindesine
Cytotoxin SE - Extravasation of IV drugs
Severe local tissue necrosis due to leakage of the cytotoxin
Vinca alkaloids
Anthracyclines
Cytotoxin SE - Oral mucositis
- Sore mouth associated with 5-FU, methotrexate, anthracyclines (-rubicins)
- Advise good oral hygeine, and sucking ice chips with 5-FU
- Treating less effective than preventing => treat with saline mouthwashes
- If caused by methotrexate => use folinic acid (levofolinic acid)
Cytotoxin SE - Tumour Lysis Syndrome
- Occurs due to rapid destruction of malignant cells
- Risk is higher in non-Hogkin’s lymphoma, Burkitt’s lymphoma, acute lymphoblastic leukaemia and acute myeloid leukaemia
- Higher risk in pre-existing hyperuricaemia, dehydration and renal impairment
- Causes HYPER: K, Ph, and uricaemia and HYPO: Ca => renal damage and arrhythmias
Cytotoxin SE - Hyperuricaemia
- More present in high-grade Lymphoma and Leukaemia
- ALLopurinol started 24h b4 treating those tumours - HYDRATE PT
- Alternative: FEBUXOSTAT given 2 days b4 treatment
- Rasburicase: hyperuricemia associated with blood cancer
Cytotoxin SE - Bone Marrow Suppression
- ALL DRUGS apart from Vincristine and Bleomycin
- Happens 7 - 10 days AFTER administration
- check blood count b4 treatments - reduce dose if bone marrow hasn’t recovered
- Avoid treatment during acute infection - or seek medical attention if currently taking
- Neutropenic fever immediate => broad-spec Abx! FILGRASTIM, avoid paracetamol as it delays starting Abx
- Symptomatic iron-deficiency anaemia => Erythpoietin or Red Blood Cell Transfusions
- AVOID LIVE VACCINES
Cytotoxin SE - Alopecia
Common
Reversible hair loss
Cytotoxin SE - Thromboembolism
Chemo increases risk
Tamoxifen (also causes endometrial cancer)
Thalidomide/Linadamide
Cytotoxin SE - Urothelial toxicity
- causes haemorrhage in urinary tract
- common in CYCLOPHOSPHAMIDE and IFOSFAMIDE
- treated with MESNA
Cytotoxin SE - Myelosuppression
Methotrexate = folinic acid to treat if toxicity!
