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pre reg > Chapter 8: Immune system and malignant disease > Flashcards

Chapter 8: Immune system and malignant disease Flashcards

1
Q

What do immunosuppressants do?

A

Suppresses or prevents the immune response

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2
Q

Immunosuppressant uses?

A
  • transplant rejection

- inflammatory diseases e.g. rheumatoid arthritis, severe eczema or IBD

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3
Q

Antiproliferative immunosuppressants?

A
  • azathiopurine
  • mercaptopurine
  • mycophenolate mofetil
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4
Q

Other immunosuppressants?

A
  • ciclosporin
  • tacrolimus
  • corticosteroids
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5
Q

What should be avoided with immunosuppressants ?

A

Live vaccines! - high risk of infections when on immunosuppressants

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6
Q

Azathioprine/mercaptopurine MOA

A

Mercaptopurine inhibits purine metabolism therefore DNA, RNA and protein synthesis. Azathioprine is metabolised to mercaptopurine

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7
Q

Azathioprine/mercaptopurine side effects?

A
  • hypersensitivity reactions; STOP immediately!; rash, fever, myalgia, arthralgia, malaise, interstitial nephritis, nausea, vomiting and diarrhoea
  • bone marrow suppresion: pre-treatment screening for thiopurine methyl transferase. Low enzyme activity = high risk of myelosuppression
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8
Q

Azathioprine/mercaptopurine interactions?

A
  • reduce dose with allopurinol = toxicity

- allopurinol is a xanthine oxidase inhibitor; inhibits metabolism of purines

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9
Q

Mycophenolate mofetil MOA?

A

Metabolised to mycophenolic acid. A selective mode of action than purine synthesis inhibitors e.g. azathioprine

“Mycophenolate mofetil (MMF, CellCept) is a prodrug of mycophenolic acid (MPA), an inhibitor of inosine-5’-monophosphate dehydrogenase. MPA depletes guanosine nucleotides preferentially in T and B lymphocytes and inhibits their proliferation, thereby suppressing cell-mediated immune responses and antibody formation.”

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10
Q

Mycophenolate mofetil side effects?

A
  • hypogammaglobinaemia: recurrent infections = measure serum immunoglobulin
  • bronchiectasis: respiratory symptoms e.g. cough, dyspnoea
  • bone marrow suppression
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11
Q

Mycophenolate mofetil and pregnancy?

A

GENOTOXIC AND TERATOGENIC

  • women: two methods of effective contraception until 6 weeks after discontinuing
  • men: use condoms until 90 days after discontinuing OR female partners use effective contraception until 90 days after discontinuing
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12
Q

What is tacrolimus?

A

Calcineurin inhibitor

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13
Q

Tacrolimus side effects?

A
  • heart = cardiomyopathy e.g. arrhythmias
  • kidney = nephrotoxicity
  • liver = hepatotoxicity
  • bone marrow = blood dyscrasias
  • blood = hypertension, hyperglycaemia, hyperuricaemia
  • neurotoxicity = headaches and tremors
  • eye disorders = blurred vision, photophobia
  • skin = rashes, toxic epidermal necrolysis
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14
Q

Tacrolimus patient counselling?

A
  • avoid exposure to sunlight/UV light: use wide spectrum SPF
  • diet: avoid high potassium and grapefruit juice = high tacrolimus level
  • driving may be affected

MHRA reminder to maintain on the same brand (oral), reports of toxicity and transplant rejection when switching between products

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15
Q

Ciclosporin MOA?

A

Lowers activity of T cells and their immune responses

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16
Q

Ciclosporin side effects?

A
  • kidneys = nephrotoxicity
  • liver = hepatotoxicity
  • bone marrow = blood dyscrasias
  • blood = lipids (hyperlipidaemia), hypertension, hyperkalaemia and hypOmagnesaemia
  • visual disturbances = secondary to benign intracranial hypertension
  • gingival hyperplasia
  • neurotoxicity
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17
Q

Ciclosporin patient counselling?

A
  • avoid excess sun exposure/UV light: use wide spectrum SPF
  • diet: avoid high potassium and grapefruit jucie = high ciclosporin level

MHRA advice: oral ciclosporin, maintain on same brand - switching between can lead to clinically important changes in ciclosporin concentration

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18
Q

Cancer therapy aims?

A

Curative intent OR prolong life OR palliate symptoms

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19
Q

What is neoadjuvant cancer therapy?

A
  • initial chemotherapy aimed at shrinking the primary tumour

- this makes local therapy less destructive or more effective

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20
Q

What is adjuvant cancer therapy?

A
  • this follows a definitive treatment of the primary disease when there is a high risk of sub-clinical metastatic disease
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21
Q

What are the guidelines for handling cytotoxic drugs?

A
  • trained personnel should reconstitute cytotoxic drugs
  • designated pharmacy area for reconstituting cytotoxic drugs
  • wear protective clothing and cover eyes
  • first aid should be specified
  • pregnant staff should avoid exposure to cytotoxic.
  • females of child bearing age should be informed of reproductive hazard
  • local procedures for spillages and safe waste disposal
  • monitor staff exposure
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22
Q

Safe system requirements for cytotoxics?

A

Chemotherapy is given as a part of a wider pathway of coordinated care by a multidisciplinary team:

  • cytotoxic medicines should be prescribed, dispensed and administered according to written protocol or treatment plan
  • injectable cytotoxic drugs should only be dispensed if they are prepared for administration
  • oral cytotoxic medicines should be dispensed with clear directions for use
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23
Q

Non-specialists and cytotoxic drugs ?

A
  • have access to written protocols or treatment plan when prescribing/administering ongoing oral cytotoxic medicines
  • protocols include guidance on monitoring and treatment of toxicity
24
Q

Dispensing cytotoxic drugs ?

A
  • confirm dose is appropriate
  • prescriptions should not be repeated unless specialist instructs
  • patient must have written information on their oral anti-cancer regimen which includes treatment plan and monitoring arrangements taken from the original hospital protocol
  • pharmacists must have access to this information and to advise from experienced cancer pharmacist in the initiating hospital
25
Q

Cytotoxic side effects?

A
  • extravasation of IV drugs
  • pregnancy and reproductive function
  • oral mucositis
  • urothelial toxicity
  • bone marrow suppression
  • nausea and vomiting
  • alopecia
  • hyperuricaemia
  • thromboembolism
26
Q

Cytoxic drugs and pregnancy and reproductive function?

A

Most cytotoxic drugs are teratogenic
- exlude pregnancy before treatment
- offer contraceptive advice to men and women
Alkylating drugs and procarbazine:
- permanent male sterility, counsel patient on sperm storage
- women are less affected; early menopause may occur

27
Q

What side effect does procarbazine have on reproductive function?

A
  • permanent male sterility - counsel on sperm storage

- women less affected - may enter early menopause

28
Q

What is tumour lysis syndrome?

A
  • caused by rapid destruction of malignant cells (high risk in lymphomas or leukaemias)
  • clinical features: hyper K, hyper urea, hyper PO4 and hypo Ca2+
  • followed by renal failure and arrthythmias
  • at risk patients: renal impairment, dehydration and hyperuricaemia
29
Q

Thromboembolism cytotoxic side effect?

A
  • malignant disease is a risk factor for venous thromboembolism but cytotoxic drugs also increase this risk
  • tamoxifen (also causes endometrial cancer)
  • thalidomide/linadamide
30
Q

Cytotoxic side effect oral mucositis and how to avoid?

A
  • good oral hygiene prevents a sore mouth
  • rinse mouth frequently
  • use a soft toothbrush 2-3 times daily, suck on ice cubes
  • saline mouthwashes
  • folinic acid in MTX-induced adverse effects
  • anthracyclines
  • antimetabolites (methotrexate, fluorouracil, capecitabine)
31
Q

What is urothelial toxicity?

A

Urothelial toxicity = haemorrhagic cystitis
- treatment = MESNA

  • Cyclophosphamide
32
Q

Cytotoxic side effect bone marrow suppression?

A
  • all cytotoxic drugs except vincristine and bleomycin
  • take FBC before each treatment
  • c/i: infections, avoid live vaccines
  • treatment: withdraw or reduce dose until bone marrow recovers
  • fever with neutropoenia: broad spec antibiotic (filgrastrim) - avoid paracetamol, delays starting antibiotic
  • symptomatic iron-deficiency anaemia: erythpoietin or rbc transfusions
33
Q

Hyperuricaemia cytotoxic side effect?

A
  • present in high grade lymphoma and leukaemia: markedly worsened by chemotherapy and associated with renal failure
    TREATMENT
  • allopurinol 24 hours before treating such tumours. reduce dose of concomitant mercaptopurine/azathioprine
  • febuxostat 2 days before if allopurinol contraindicated
  • rasburicase for hyperuricaemia associated with blood cancer
34
Q

Mild emetogenics ? (cytotoxic drugs)

A
  • methotrexate
  • flurouracil
  • vinca alkaloids
35
Q

Moderate emetogenics?

A
  • taxanes
  • doxorubicin
  • cyclophosphamide
  • high dose MTX
36
Q

High emetogenics?

A
  • cisplatin

- high dose cyclophosphamide

37
Q

Treatment of nausea and vomiting cytotoxic side effect?

A
  • before treatment: lorazepam

Acute symptoms <24 hrs after chemotherapy

  • low risk of emesis = dexamethasone or lorazepam
  • high risk of emesis = 5-HT3 antagonist

Delayed symtpoms > 24 hours after chemotherapy
- moderately emetgenic drugs = dexamethasone + aprepitant

38
Q

Alopecia cytotoxic side effect?

A
  • reversible hair loss is a common complication of chemotherapy
  • there are no treatments available to prevent it
39
Q

Extravasation of IV drugs cytotoxic side effect?

A
  • severe local tissue necrosis if they leak from the veins into the surrounding subcutaenous or subdermal tissue
  • in worse cases it can lead to amputation
  • vinca alkaloids
  • anthracyclines
40
Q

Cytotoxic antibiotics?

A
  • cytotoxic antibiotics are radiomimetics, avoid concomitant radiotherapy = toxicity
  1. anthracyclines
  2. antineoplastic antibiotics
41
Q
  1. anthacyclines “rubicin”?
A
  • doxorubicin (excreted in bile - reduce dose if high bilirubin)
  • epirubicin
  • idarubicin
  • daunorubicin
42
Q

Anthracyclines side effects?

A
  • cardiotoxicity (dose related; higher risk if given with herceptin)
  • red urine

Liposomal formulations of doxorubicin reduce incidence of cardiotoxicity and extravasation BUT cause:

  • hand and foot synfrome: macular, red skin eruptions
  • prevention: cool hands and feet and avoid socks and gloves for 4-7 days after treatment
43
Q

What is given to treat anthracycline-indiced side effects?

A

DEXRAZOXANE

44
Q

Antineoplastic antibiotics?

A
  • bleomycin
45
Q

Antineoplastic antibiotics side effects?

A
  • pulmonary fibrosis = basal lung crepitations
  • respiratory failure in anaesthesia
  • hypersensitivity = chills and fever (prevention: IV hydrocortisone)
  • dermatological toxicity = hyperpigmentation, sclerotic plaques
46
Q

What are vinca alkaloids?

A
  • vincristine
  • vinblastine
  • vindesine
  • vinflunine
  • vinorelbine
47
Q

Vinca alkaloids route of administration?

A

IV ONLY - never give intrathecally = fatal neurotoxicity

NPSA alert: aduilt and teenagers unit recieve doses in 50ml mini bag
- childrens unit recieve doses by syringe

48
Q

Vinca alkaloids side effects?

A
  • CNS toxicity (peripheral/autonomic neuropathy)
49
Q

Antimetabolites ?

A
  • methotrexate (MTX)
  • capicitabine (pro drug of 5-FU)
  • fluorouracil (5-FU)
50
Q

Antimetabolites side effects?

A
  • oral mucositis
  • myelosuppression
  • folinic acid speeds up recovery in MTX side effects and overdose
51
Q

Alkylating drugs ?

A
  • cyclophosphamide (causes urothelial toxicity)
  • carmustine
  • lomustine
  • mephalan
  • chlorambucil
  • ifosfamide
52
Q

Alkylating drugs side effects?

A
  • permanent male sterility

- non-lymphocytic leukaemia

53
Q

Aromatase inhibitors?

A
  • anastrazole
  • letrozole

Not for premenopausal women
- aromatase inhibitors are “anti-oestrogens”

54
Q

Taxanes?

A

Paclitaxel

55
Q

Taxanes side effects?

A
  • cardiac disease
  • pneumonitis
  • sepsis

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