Immune System and Malignancy Flashcards
What is azathioprine metabolised to?
Mercaptopurine
What two drugs when given together reduce the risk of organ rejection?
Azathioprine and mycophenolate mofetil
Which immunosuppressant is licensed for renal transplantation?
Sirolimus
When is multiple sclerosis considered as active?
When two clinically significant relapses occur within the last 2 years
What is thought to be a risk factor for multiple sclerosis?
Vitamin D deficiency
What increases the progression of dsiability in multiple sclerosis?
smoking
How do you treat MS relapses?
1st line: oral methylprednisolone
2nd line: IV methylprednisolone
What can be used for MS related fatigue?
Amantadine
SSRI
Modafinil
What is licensed for walking disability in MS?
Fampridine
How is spasticity managed in MS?
1st line: baclofen
2nd line: gabapentin
3rd line: combination of both
4th line: 4-week trial of cannabis extract for moderate-severe spasticity
How is oscillopsia treated in MS?
1st line: gabapetin
2nd line: memantine
How do you treat emotional reliability in MS?
Amitriptyline
What are some common side effects of cytotoxic drugs?
Extravasation of IV drugs
Oral mucositis
Tumour lysis syndrome
Hyperuricaemia
Bone marrow suppression - usually 7-10 days after administration
Alopecia
Thromboembolism
Which cytotoxic drugs are most associated with oral mucositis?
Fluorouracil, methotrexate and the anthracyclines
What are the predisposing factors of tumour lysis syndrome?
Non-hodgkins lymphoma
Burkitt’s lymphoma
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
Occasionally solid tumours
Pre-existing hyperuricaemia, dehydration, and renal imapirment
Who is most at risk of hyperuricaemia and how is it prevented?
High-grade lymphoma and leukaemia
Allopurinol should be started 24 hours before treatment and patients should be adequately hydrated (reduce doses of mercaptopurine and azathioprine is this is used in conjunction)
Febuxostat may be used and started 2 days before cytotoxic treatment
What drug is licensed for hyperuricaemia in patients with haematological malignancy?
Rasburicase
What are the only two cytotoxic drugs that do not cause bone marrow suppression?
Vincristine sulfate
Bleomycin
What drugs carry the risk of permanent male sterility?
Alkylating drug or procarbazine
What are the mildly emetogenic cytotoxic treatments?
Fluorouracil
Etoposide
Methotreaxte (less than 100mg/m2)
Vinica alkaloids
Abdominal radiotherapy
What are the moderately emetogenic cytotoxic treatments?
The taxanes
Doxorubicin
Intermediate and low doses of cyclophosphamide
Mitoxantrone
High doses of methotrexate (0.1-1.2g/m2)
What are the highly emetogenic cytotoxic treatments?
Cisplatin
Dacarbazine
High doses of cyclophosphamide
How do you prevent acute N/V for low-risk emesis patients?
Pre-treatment with dexamethasone or lorazepam
How do you prevent acute N/V for high-risk emesis patients?
5HT3-receptor antagonist (e.g. ondansetron) by mouth in combination with dexamethasone and aprepitant
How do you prevent delayed N/V?
Moderately emetogenic chemotherapy: dexamethasone and 5HT3-receptor antagonist
Highly emetogenic chemotherapy: dexamethasone and aprepitant
How do you prevent anticipatory N/V?
Lorazepam
What is used for methotrexate overdose?
Folinic acid
Does folinic acid interact with antibacterial activity?
No it does not counteract antibacterial activity of folate antagonists such as trimethoprim
How do you improve metastatic colorectal cancer response-rate?
Add folinic acid with fluorouracil
Are calcium folinate and calcium levofolinate bioequivalent?
No, the dose of calcium levofolinic is generally half that of calcium folinate
What is used to prevent haemorrhagic cystitis from urothelial toxicity with cyclophosphamide?
Mesna
What group of drugs should be avoided with radiotherapy?
Anthracyclines (e.g. doxorubicin)- act as radiomimetics = may increase toxicity
What is used in men and pre-menopausal women with oestrogen-receptor-positive invasive breast cancer?
Tamoxifen
What are the contraindications of methotreaxte?
Active infection
Ascites
Immunodeficiency syndromes
Significant pleural effusion
Avoid in active peptic ulcerations
What increases the risk of methotrexate toxicity?
Advanced age
Renal impairment
Concomitant use with other anti-folates e.g. trimethoprim
What blood test changes would you discontinue methotrexate immediately due to?
A drop it white blood cells
Drop in platelet count
What do you do if a patient develops stomatitis or diarrhoea while taking methotreaxte?
Withdraw as may be first sign of GI toxicity
What type of toxicities are associated with methotreaxte?
GI toxicity
Photosensitivity - skin ulcerations reported
Liver toxicity - liver cirrhosis reported (LFTs)
Pulmonary toxicity - may be a special problem in rheumatoid arthritis
What symptoms are suggestive of pulmonary toxicity with methotrexate?
Dyspnoea
Cough
Fever
What are common side effects of methotrexate?
Anaemia
Appetite decreased
Diarrhoea
Drowsiness
Fatigue
GI discomfort
Headache
Increased risk of infection
Leucopenia
N/V
Oral disorders
Respiratory disorders
Skin reactions
Throat ulcers
Thrombocytopenia
What side effects of methotrexate does folic acid reduce?
Mucosal and GI side effects and may prevent hepatotoxicity
What is the contraception advise given with methotrexate?
During and 6 months after
- teratogenic and fertility may be reduced during treatment but this may be reversible
What counselling is required for methotrexate?
Report any signs of infection:
- sore throat, bruising and mouth ulcers
Report signs of liver toxicity:
- N/V, abdominal discomfort and dark urine
Report respiratory effects:
- SOB
Avoid exposure to UV light
Avoid OTC aspirin and ibuprofen
What can ciclosporin be mixed with to improve taste?
Mix solution with apple juice, orange juice or other soft drinks immediately before taking
DO NOT MIX WITH GRAPEFRUIT JUICE
What is a specific side effect of IV tacrolimus?
Anaphylactoid reaction - due to excipient
What is the contraindication for tacrolimus?
Contraindicated in history of hypersensitivity to macrolides
What is the counselling for tacrolimus and ciclosporin?
Avoid exposure to UV
Take on an empty stomach
What are the cytotoxic drug handling guidelines?
➢ Trained personnel should reconstitute cytotoxics
➢ Reconstitution should be carried out in designated pharmacy areas
➢ Protective clothing (including gloves, gowns, and masks) should be worn
➢ The eyes should be protected and means of first aid should be specified
➢ Pregnant staff should avoid exposure to cytotoxic drugs (all females of child-bearing age should be informed of the reproductive hazard)
➢ Use local procedures for dealing with spillages and safe disposal of waste material, including syringes, containers, and absorbent material
➢ Staff exposure to cytotoxic drugs should be monitored
Which cytotoxic drugs have less on affect on ferility?
Regimens that do not contain an alkylating drug or procarbazine may have less effect on fertility, but those with an alkylating drug (cyclophosphamide, cisplatin) or procarbazine carry the risk of causing
permanent male sterility (there is no effect on potency)
What is used as the scoring system for recording toxicity associated with cytotoxic drugs?
Common Toxicity Criteria for Adverse Events
Who is more susceptible to N/V with cytotoxic drugs?
➢ Women
➢ Patients under 50 years of age
➢ Anxious patients
➢ Those who experience motion sickness
➢ Concurrent use of opioids
➢ Susceptibility also increases with repeated exposure to the cytotoxic drug
What cytotoxic drugs are most associated with oral mucositis?
fluorouracil, methotrexate, and the anthracyclines (‘-rubicin’)
How is tumour lysis syndrome treated?
Allopurinol or rasburicase
What are the features of tumour lysis syndrome?
➢ Hyperkalaemia
➢ Hyperuricaemia
➢ Hyperphosphataemia
➢ Hypocalcaemia
➢ Renal damage
➢ Arrhythmias
Which cytotoxics are most associated with cardiotoxicity?
Anthracyclines (‘-rubicin’)
What is the impact of administering vincristine intrathecally?
This is a never event and can cause neurotoxicity
Vincristine injections are for IV ONLY!
What kind of contraception should be used for Buserelin when used in women with endometriosis?
Barrier methods - do not use hormonal contraception
When should the first injection of Buserelin be given for endometriosis?
During menstruation or straight after or use barrier contraception method one month beforehand
How much space do you need to leave between Buserelin and nasal decongestnats?
Avoid before and for 30 minutes after
What is the contraception advice for Trastuzumab (Herceptin)?
Effective contraception during and for 7 months after treatment
What are the glucocorticoid side effects?
- Diabetes
- Osteoporosis - danger because it can result in fractures in elderly
- High doses associated with avascular necrosis of the femoral head
- Muscle wasting (proximal myopathy)
- Peptic ulceration and perforation
- Psychiatric reactions
- Cushing’s syndrome
What are the mineralcorticoids side effects?
- Hypertension
- Sodium retention
- Water retention
- Potassium loss
- Calcium loss
Name two alkylating drug
Chlorambucil
Cyclophosphamide
Name 4 antimetabolite drugs
Mercaptopurine
Fluorouracil
Methotrexate
Cytarabine
What are the adverse effects of cyclophosphamide?
Haemorrhagic cystitis - prevented by increasing fluid intake for 24-48 hours after IV injection
–> mesna can also help prevent this
Myelosuppresion
Secondary neoplasms - transitional cell carcinoma
What is the contraception advice regarding cyclophosphamide?
Effective contraception during and for three months after in men and women
What are the adverse effects of methotrexate?
- Bone marrow suppression - monitor blood count every 1-2 weeks until stable then every 2-3 months
- Liver toxicity - same as above
- Pulmonary toxicity - baseline x-ray
- Nephrotoxicity
- GI toxicity
- Mucositis
Which cytotoxic is indicated for HER2 positive breast cancer?
trastuzumab (Herceptin)
Which cytotoxic is indicated for oestrogen-receptor-positive invasive breast cancer?
Tamoxifen
What is the contraindication for letrazole?
pre-menopausal women
What is the contraception advice for letrazole?
Use effective contraception until post menopausal status fully established
What is a risk associated with letrazole?
Increased risk of osteoporosis - assess bone mineral density before treatment and at regular intervals
What risk is associated with taking rituximab
Hepatitis B infection and reactivation
Other infection associations:
- TB
- Septicaemia
What is the contraception advise regarding rituximab?
Effective contraception during and for 12 months after
Which cytotoxic drug is associated with Progressive multifocal leucoencephalopathy?
Rituximab
Monitor for cognitive, neurological, or psychiatric signs ans symptoms
What are the side effects of myclophenilate?
Hepatotoxicity
Bone marrow suppression
Hypogammaglobulinaemia
Respiratory disorders
Red cell aplasia
What is the pregnancy prevention process for myclophenilate?
Negative pregnancy test before initiating - 2 tests 8-10 days apart
Effective contraception male and female during treatment and for 6 weeks after discontinuation (90 days)
How is neutropenic sepsis treated?
Filgratism - granulocyte-colony stimulating factor
What are the side effects of azathioprine?
Blood disorders - screen for TMTP before treatment
Pancreatitis
Hypersensitivity
Nausea - take after food
What is the interaction between azathioprine and allopurinol?
Toxicity with allopurinol - reduce dose (1/4 of normal dose)
Can mycophenilate be taken while pregnant?
Myophenilate is genotoxic - damages genetic information in a cell and major teratogen
- can cause miscarriages and serious birth defects
Part of PPP - must take 2 pregnancy tests before treatment to exclude pregnancy and use at least 1 method of effective contraception during treatment and for 6 weeks after stopping
What is the contraception advise for mycophenilate in men?
Male patients or their partners must use effective contraception during treatment and for 90 day after stopping
What are the side effects of tacrolimus?
Blood disorders
Hyperkalaemia
Hyperglycaemia
Cardiomyopathy
Nephrotoxicity
Photosensitivity
What is the MHRA warning for tacrolimus and ciclosporin?
Prescribe and dispense by brand name
What drugs increase tacrolimus and ciclosporin concentrations and lead to toxicity?
Amiodarone
Azoles
Macrolides
Rate-limiting CCB
Pomelo, pomegranate and grapefruit
(just pomelo and grapefruit juice in ciclosporin)
What drugs decrease tacrolimus and ciclosporin concentrations?
Carbamazepine
Phenobarbital
Phenytoin
Rifampicin
(purple grapefruit jucie in ciclosporin)
What drugs increase the risk of nephrotoxicity when given with tacrolimus or ciclosporin?
Aminoglycosides
Cephlosporins
Ciclosporin
Glycopeptide
Methotrexate
NSAIDs
What drugs increase the risk of hyperkalaemia when given with tacrolimus or ciclosporin?
ACEi/ARB
Aldosterone antagonsis
Potassium sparing diuretics
NSAIDs
Trimethoprim
Heparin
What are the side effects of ciclosporin?
Blood disorders
Hyperkalaemia
Hyperglycaemia
Hypertension
Hypomagnesaemia
Gingival hyperplasia
Nephrotoxicity
How do you treat symptomatic iron-deficiency anaemia as a side effect of cytotoxic drugs?
Red blood cell transfusion
OR
Erythropoietin which stimulates the production of more RBC - but MHRA has warned that is can cause death and has an increased risk of tumour progression
Which cytotoxic drug is associated with causing endometrial cancer?
Tamoxifen
What drugs are most associated with urothelial toxicity?
Cyclophosphamaide
Ifosfamide
How are vinca alkaloids administered?
Intravenously
Never intrathercally - can cause severe neurotoxicity which is fatal and is irreversible
(vinca alkaloids can also cause severe bronchospams)
What are the side effects of anthracyclines?
‘-rubicin’
Cardiotoxicity
Extravasion injury
Red urine
What is the antidote for and reduces side effects of anthracyclines?
Dexrazoxane
- giving a liposomal formulation of this can also reduce risk of cardiotoxicity and extravasion injury
HOWEVER, these formulations cause hand and foot syndrome - prevented by cooling hands and feet and avoiding wearing socks and gloves for 4-7 days
Which cytotoxic drug does not have venous thromboembolism as a side effect?
Doxorubicin
What is given to speed-up recovering related to adverse drug reactions of methotrexate?
Calcium folinate
What are the side effects of bleomycin?
Pulmonary fibrosis
Hypersensitivity
Dermatological toxicity
