Malignancy Flashcards by Inori D

Names of antiproliferative Immunosuporessants?

Azathioprine (metabolised to mercaptopurine)
Mycophenolate (more selective mode of action that azathioprine)
Cyclophosphamide (less commonly prescribed)

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Names of calcineurin inhibitors?

Ciclosporin

Tacrolimus

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Mode of action of azathioprine/mercaptopurine?

Inhibits purine metabolism therefore DNA, RNA and protein synthesis

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Side effects of azathioprine /mercaptopurine?

Hypersensitivity reactions (rash, fever, N&V, diarrhoea) = stop immediately

Bone marrow suppression (neutropenia and thrombocytopenia) neutropenia is dose dependent

Nausea

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How to manage nausea with azathioprine?

Common side effect early in the course and usually resolves after few weeks without dose alteration.

Can be managed by dividing daily dose, taking dose after food, using antiemetic or reducing dose temporarily

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Pre treatment screening for azathioprine ?

Thiopurine methyltransferase (TPMT)
Risk of myelosupression is increased in pts with reduced activity of TPMT

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Interaction between allopurinol and azathioprine?

Toxicity risk because allopurinol is a xanthine oxidase inhibitor which inhibits metabolism of purines
So reduce dose of azathioprine to 1/4 with concurrent use of allopurinol

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Side effects of Mycophenolate?

Hypogammaglobinaemia which causes recurrent infection

Bronchiectasis causes Respiratory symptoms like cough and dyspnoea

Bone marrow suppression

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Monitoring requirements for azathioprine?

FBC weekly for the first 4wks then at least every 3 months

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Pregnancy advice and Mycophenolate?

Gentoxic and teratogenic
Women need to use 2 methods of effective contraception until 6wks after discontinuing

Men need to use condoms 90 days after discontinuing or female partners of the male pt use effective contraception until 90 days after discontinuing

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Side effect of tacrolimus?

Heart = cardiomyopathy e. G. Arrhythmia

Kidney = Nephrotoxicity

Liver = hepatotoxicity

Bone marrow = blood dyscrasias

Blood = hypertention, hyperglycaemia, Hyperkalaemia, hyperuricaemia

Neurotoxicity = headaches and tremors

Eye disorders = blurred vision, photophobia

Skin = Rashes, toxic epidermal necrolysis

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Pt counselling on tacrolimus?

Avoid exposure to sunlight/UV light, use Wide spectrum SPF

Diet = avoid high potassium and grapefruit juice = leads to high tacrolimus level

Driving may be affected

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MHRA warning on tacrolimus?

Maintain on the same brand for oral tacrolimus

Different use of brads have reports of toxicity and graft rejection

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Mode of action of ciclosporin?

Lowers activity of T cells and their immune response

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Side effects of ciclosporin?

Similar to tacrolimus
Kidney = Nephrotoxicity

Liver = hepatotoxicty

Bone marrow = blood dyscrasias

Blood = hyperlipidaemia, hypertention, Hyperkalaemia, Hypomagnesium

Visual disturbances = secondary to benign intracranial Hypertension

Gingival hyperplasia

Neurotoxicity

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Patient counselling on ciclosporin?

Avoid excess sun exposure /UV light, use Wide spectrum SPF

Diet wise avoid high potassium and grapefruit juice

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MHRA warning on ciclosporin?

Maintain on the same brand

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Mycophenolate MHRA warning?

Male pts need contraception

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How are vinka alkaloid administered?

intravenous administration only. Inadvertent intrathecal administration can cause severe neurotoxicity, which is usually fatal.

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What’s neoadjunctive therapy?

Initial Chemotherapy aimed at shrinking the primary tumour delivered before the main treatment
This makes local therapy less destructive or more effective

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What’s adjuvant therapy?

Follows neoadjuvant to destroy remaining cancer cells

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Guidelines for handling cytotoxic drugs?

Trained person should reconstitute cytotoxic drugs
Designated pharmacy area for reconstitution drugs
Wear protective clothing and cover eyes
First aid should be specified
Pregnant staff should avoid exposure to cytotoxic. Females should be informed of reproductive hazard
Local procedures for spillages and safe waste disposal
Monitor staff exposure

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Safe system requirements for cytotoxics?

Chemotherapy is given as a part of a wider pathway of coordinated care by multidisciplinary team
So 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 meds should be dispensed with clear directions for use

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Non specials protocol on handling cytotoxic drugs?

The standards for prescribing and using parenteral cytotoxics should also be the same for oral cytotoxics

Have access to written protocol or treatment plan when prescribing or administering

Protocol include guidance on monitoring and treatment of toxicity

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Dispensing cytotoxics protocol?

Confirm dose prescribed is appropriate Prescriptions should not be repeated unless specialist instructs Pts must have written information on their regimen which includes treatment plan and monitoring arrangements taken from the original hospital protocol Pharmacist's must have access to experienced cancer pharmacist

Cytotoxic side effects?

``` Extravasatoon of IV drugs Tumour lysis syndrome Thromboembolism Hyperuricaemia Alopecia N&V Bone marrow suppression Urothelial toxicity Oral mucositis Pregnancy and reproductive dysfunction ```

Pregnancy and cytotoxic drugs?

Most cytotoxic drugs are teratogenic So exclude pregnancy before treatment And offer contraceptive advice to men and women

Which cytotoxic drugs cause permanent male sterility?

Alkylating drugs and procarbazine - counsel pts on sperm storage - women are less affected but early Menopause may occur

What is tumour lysis syndrome?

A condition that occurs when a large number of cancer cells die within a short period, releasing their contents into the blood

Symptoms of tumour lysis syndrome?

``` N&V Diarrhoea Muscle cramps and twitches Weakness Fatigur Numbness or tingling Decreased urination ```

Clinical features of tumour lysis syndrome?

``` Hyperkalaemua Hyperuricaemia Hyperphosphataemia Hypocalcaemia Renal damage Arrhythmia ```

At risk pts of tumour lysis syndrome?

Renal imapirment Dehydration Hyperuricaemia

Anti cancer drugs that especially increase the risk of thromboembolism?

Tamoxifen which can also cause endometrial cancer | Thalidomide /Linadamide

How to prevent oral mucositis?

``` Good oral hygiene prevents a sore mouth Rinse mouth frequently Use a soft toothbrush 2-3times/daily Suck in ice cubes (for fluorouracil, sucking ice chips during short infusions of the drug also help) Saline mouthwash ```

What cytotoxic drugs commonly cause oral mucositis?

Anthracyclines | Anti metabolites like methotrexate, fluorouracil, capecitabine

How to prevent oral mucositis caused by antimetabolites?

Good hygiene And Folinic acid

What's Urothelial toxicity?

Causes Haorrhagic cystitis = an inflammation of the Bladder

How to treat Urothelial toxicity?

Mesna

What cytotoxic drug commonly cause Urothelial toxicity?

Cyclophosphamide

All cytotoxic drugs cause bone marrow suppression except which drugs?

Vincristine | Bleomycin

FBC should be measured how often when using cytotoxic drugs for cancer?

Before each treatment | Doses should be reduced or therapy delayed if bone marrow has not recovered

Treatment of fever with neutropenia caused by bone marrow suppression caused by cytotoxic drugs

Broad spectrum antibiotics if signs of infection (avoid paracetamol as can delay starting an antibiotic) Filgtastrim can reduce the duration and severity of neutropenia

Treatment of symptomatic iron deficient anaemia caused by cytotoxic bone marrow suppression

Erythropoietin Or RBC transfusions

Hyperuricaemia tends to be present in what kind of condition?

High grade lymphoma and leukaemia | Markedly worsened by Chemotherapy and associated with renal failure

Treatment if Hyperuricaemia caused by cytotoxics?

Allopurinol = start 24hrs before treating high grade lymphoma and leukaemia =reduce dose if Co administering purines Febuxostat = start 2 days before if allopurinol is contraindicated Rasburicase = for Hyperuricaemia associated with blood cancer

Mild emetogenic cytotoxic drugs?

``` Methotrexate Fluorouracil Vinca alkaloids Etoposide Abdominal radiotherapy ```

Moderately emetogenic cytotoxic drugs?

``` Taxanes Doxorubicin Cyclophosphamide High dose methotrexate Mitoxantrone ```

Highly emetogenic cytotoxic drugs?

Cisplatin Decarbazine High dose Cyclophosphamide

Anticipatory N&V treatment?

Lorazepam

Treatment of acute symptoms of N&V within 24hrs after low risk of emesis Chemotherapy

Dexamethasone or lorazepam

Treatment of acute symptoms of N&V within 24hrs after high risk of emesis Chemotherapy

Seratonin antagonist | Aprepitant + dexamethasone

Delayed N&V symptoms 24hrs after moderately emetogenic Chemotherapy?

Dexamethasone + seratonin antagonist

Delayed N&V symptoms 24hrs after highly emetogenic Chemotherapy?

Dexamethasone + Aprepitant

What is extravasation of IV drugs and what happens?

Severe local tissue necrosis if they leak from the veins into the surrounding subcutaneous of sub dermal tissue In worst cases, it can lead to amputation

Which cytotoxic drugs are likely to cause extravasation?

Vinca alkaloids | anthracyclines

What are cytotoxic antibiotics?

They are radiomimetics | So avoid concomitant radiotherapy as can lead to toxicity

Drugs of cytotoxic antibiotics?

Anthracyclines | Anti neoplastic antibiotics

Drugs of anthracyclines?

``` RUBICINS doxorubicin Epirubicin Idarubicin Daunorubicin ```

Side effects of anthracyclines?

Cardio toxicity = dose related, higher risk if given with herceptin Red urine

What formation go doxorubicin can reduce the incidence of cardio toxicity and extravasation?

Liposomal formulation of doxorubicin But! Cause hand and foot syndrome Which is macula, red skin eruptions

How to prevent hand and foot syndrome caused by liposomal formulations of doxorubicin?

Cool hands and feet | Avoid socks and gloves for 4-7days after treatment

What can be given to treat anthracyclines induced side effects such as extravasation and overdose?

Dexrazoxane

Drugs of Anti neoplastic antibiotics?

Bleomycin

Side effects of Anti neoplastic antibiotics?

``` Pulmonary fibrosis Respiratory failure in anaesthesia Hypersensitivity = chills and fever Dermatological toxicity = hyperpigmentation, sclerotic plagues ```

How to prevent hypersensitivity reaction with Anti neoplastic antibiotics?

IV hydrocortisone

Drugs of Vinca alkaloids?

``` Vincristine Vinblastine Vindesine Vinflunine Vinirelbine ```

What happens when you give Vinca alkaloids intrathecally?

Fatal neurotoxicity

NPSA alert of Vinca alkaloids?

Adult and teenagers unit receive doses in 50ml mini bag | Children's unit receive doses by syringe

Side effects of Vinca alkaloids?

CNS toxicity (peripheral / autonomic neuropathy)

Drugs of antimetabolites?

Methotrexate Capecitabine Fluorouracil

Side effect of antimetabolites?

Oral mucosutus | Myelosupression

Drugs of alkylating drugs?

``` Cyclophosphamide Carmustine Konustine Mephalan Chlorambucil Ifosfamide ```

Side effects of alkylating drugs?

Permanent male sterility | Non lymphocytic leukaemia

Drugs of aromatase inhibitors?

Anastrazole | Letrozole

Aromatase inhibitors are contra indicated in?

Pre menopausal women as they are anti oestrogen

Drugs of taxanes?

Paclitaxel

Side effects of paclitaxel?

Cardiac disease Pneumonitis Sepsis

Side effects of paclitaxel?

Cardiac disease Pneumonitis Sepsis