Immune System and Malignant Disease Flashcards
Azathioprine MoA
- antimetabolite that breaks down into mercaptopurine, which inhibits the repairment and making of DNA
- broken down by thiopurine methyltransferase (TPMT) - pre-screen as underachieve TPMT = myelosuppression
Azathioprine side effects
- hypersensitivity = malaise, dizziness, DNV, fever, rash, hypotension
- neutropenia and thrombocytopenia = sore throat, bruising, bleeding
- nausea = more common at start but resolves over time
- teratogenic = avoid in pregnancy
Azathioprine monitoring
- TPMT
- LFT/FBC in severe liver/renal impairment - weekly for first 4 weeks then every 3 months
Azathioprine interactions
- allopurinol = increased risk of haematological toxicity = reduce azathioprine dose
- ACEi = increased risk of anaemia/leucopenia - avoid concomitant use
Ciclosporin MoA
- calcineurin inhibitor = inhibits lymphokines = suppress cell-mediated response
- prescribed and dispensed by brand name
Ciclosporin side effects
- HYPER - glycaemia, lipidaemia, tension, uricaemia, kalaemia
- HYPO - magnesaemia - monitor
- renal/liver impairment
- skin reactions
- gingival hyperplasia
- hair changes
- eye inflammation & visual disturbance (in topical use with eyes)
Ciclosporin interactions
- grapefruit and pomelo juice = increases ciclosporin exposure
- purple grape juice = reduced ciclosporin exposure
Ciclosporin monitoring
- pre-screening: exclude malignancies before systemic use
- LFTs, Mg, K+, lipids, CrCl, BP, trough levels (range depends on indication)
- avoid exposure to UV light/sunlight
- topical (eye) may affect driving/performed skilled tasks
Tacrolimus MoA
- calcineurin inhibitor = inhibits lymphokines = suppress cell-mediated response
- prescribed and dispensed by brand name
Tacrolimus side effects
- HYPER - glycaemia, uricaemia, kalaemia
- HYPO/HYPER - tension
- renal/liver impairment
- skin reactions, visual disturbances, blood dyscrasia
- CVD (QT prolongation, cardiomyopathy in children)
- nervous system disorder, peripheral neuropathy
Tacrolimus interactions
- grapefruit, pomegranate and pomelo juice = increases exposure to tacrolimus
- DON’T use if sensitive/allergy to macrolides
Tacrolimus monitoring
- BP, ECG, blood glucose, LFT, electrolytes, CrCl
- avoid exposure to UV light/sunlight
- may affect driving/performing skilled tasks
Mycophenolate mofetil MoA
inhibits purine synthesis
Mycophenolate mofetil side effects
- bone marrow suppression = report infection, bruising, bleeding
- pure red cell aplasia = reduce dose or discontinue
- hypogammaglobulinaemia = measure immunoglobulin levels in recurrent infections
- bronchiostasis = persistent cough and SOB
Mycophenolate mofetil MHRA Alerts
- contraception advice (teratogenic):
- women = 1 effective contraception during and 6 weeks after (2 methods preferred)
- men = effective contraception during and 90 days after (for partner aswell)
What is multiple sclerosis
autoimmune disease demyelinating the CNS - relapsing, progressive or both
Define active MS
2 relapses in the past 2 years despite tx with interferon beta
Managing MS symptoms
- spasticity = baclofen, diazepam, tizanidine, dantrolene
- relapses = methylprednisolone
- oscillopsia (objects appear to vibrate) = gabapentin
- mood alteration = amitriptyline
- fatigue = amantadine or fampridine
- titrate baclofen dose slowly to avoid major side effects (sedation and hypotonia)
Drug handling of Cytotoxics
- trained personnel in designates pharmacy areas (aseptics)
- protective clothing (gloves, gowns, masks, eye protection)
- avoid by pregnant - childbearing age informed of hazard
- local procedure for spillage and safe disposal
- monitor staff exposure to cytotoxics
Name alkylating agents
cyclophosphamide, ifofosfamide, melphalan
Name anthracyclines
daunorubicin, doxorubicin, epirubicin, idarubicin
Name antimetabolites
cytarabine, florouracil, mercaptopurine
Name cytotoxic antibiotics
bleomycin, mytomycin
Name platinum compounds
carboplatin, cisplatin, oxaliplatin
Name taxanes
cabazitaxel, docetaxel, paclitaxel
Name vinca alkaloids
vinblastine, vincristine, vindesine
Side effects of IV cytotoxics
extraversion of IV drugs - local tissue necrosis due to leakage
Which cytotoxics cause oral mucositis (sore mouth) & advice
- fluorouracil, methotrexate, anthracyclines
- good oral hygiene
- suck ice chips with fluorouracil
- tx with saline mouthwashes
What is tumour lysis syndrome
- from rapid destruction of malignant cells
- increased risk in NHL, Burkitts lymphoma, ALL, AML, hyperuricaemia, dehydration, renal impairment
- causes HYPER - K, Phos, Ca, uricaemia = renal damage & arrhythmias
- tx = allopurinol and rasburicase
Hyperuricaemia
- in high grade lymphoma and leukaemia
- allopurinol started 24 hours before tx - hydrate pt
- alternative = febuxostat 2 days before treatment
Which cytotoxics cause bone-marrow suppression
- all cytotoxics except vincristine and bleomycin
- happens 7-10 days post tx
- FBC before tx - reduce dose if bone marrow not recovered
- avoid tx during acute infection - neutropenic fever = broad spec abx
A common side effect of cytotoxics
alopecia
thromboembolism with cytotoxics
chemo increases risk of thromboembolism
Which drugs cause urothelial toxicity (haemorrhage in urinary tract)
- cyclophosphamide, ifophosphamide
- tx = mesna
Which drugs cause myelosuppression
- caused by methotrexate
- use folinic acid to treat toxicity
Cytotoxics and reproductive system
- most chemo = teratogenic - avoid in preg, exclude pregnancy before use
- contraception before tx begins - during and after
- alkylating drug or procarbazine = increase risk of permanent male sterility, consider sperm storage - affects women less but may cause onset of premature menopause
Chemo induce N&V types
- acute, delayed or anticipatory
- acute is easier to control
- more common in women, < 50 years, anxiety, repeated exposure
Cytotoxics with mild risk of N&V
fluorouracil, etoposide, methotrexate, vinka alkaloids
Cytotoxics with moderate risk of N&V
taxanes, doxorubicin, low dose cyclophosphamide, mitoxantrone, high doses methotrexate
Cytotoxics with high risk of N&V
cisplatin, dacarbazine, high dose cyclophosphamide
Prevention of acute N&V (within 24 hours of tx)
- low risk pts = dexamethasone or lorazepam
- high risk pts = ondansetron + dexamethasone + aprepitant
Prevention of delayed N&V (after 24 hours of tx)
- moderately emetogenic drugs = dexamethasone + ondansetron
- highly emetogenic drugs = dexamethasone + aprepitant
Prevention of anticipatory N&V (before tx)
lorazepam
Alkylating agents key points
- cyclophosphamide, ifosfamide, melphalan
- urothelial toxicity - tx = mesna
- increased risk of permanent male sterility
Anthracyclines key points
- daunorubicin, doxorubicin, epirubicin, idarubicin
- ‘rubi-red’ urine
- formulations not interchangeable (conventional, liposomal, pegylated liposomal)
- cardio toxic side effects
- liposomal = reduced cardio toxicity but causes painful macular skin eruptions - prevent by cooling hands/feet, avoid gloves/socks
Antimetabolites key points
- cytarabine, fluorouracil, MTX, mercaptopurine
- mucositis
- myelosuppression
Cytotoxic Abx key points
- bleomycin, mitomycin
- progressive pulmonary fibrosis
- pulmonary toxicity
Taxanes key points
- cabazitaxel, docetaxel, paclitaxel
- hypersensitivity reactions = premedicate with corticosteroids and antihistamines
- monitor cardiac output
- monitor for signs and symptoms of pneumonitis and sepsis
Vinka alkaloids key points
- vinblastine, vincristine, vindesine
- IV only, intrathecal = FATAL
- bronchospasms
- neurotoxicity - neuropathy, motor weakness, myalgia
