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2021 Pre-registration > Chapter 8: Immune and malignancy > Flashcards

Chapter 8: Immune and malignancy Flashcards

1
Q

Name 4 drugs that can be used in IBD?

A

Azathioprine, mercaptopurine, ciclosporin and methotrexate

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2
Q

Why is folic acid given alongside methotrexate? Is this licensed?

A

To reduce the risk of methotrexate toxicity and hence reduced MTX side-effects such as anaemia, hair loss, mouth sores (that could make a person not want to take methotrexate

Unlicensed

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3
Q

When should folic acid be administered after methotrexate?

A

Ideally 24hrs after to reduce the incidence of SE asap

But cannot be on the same day as methotrexate as it reduces folate levels and taking folic acid on same day would mean that the folate would be reduced further (ineffective)

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4
Q

Give two indications for immunosuppressant therapy?

A

1) Organ transplant rejection

2) Inflammatory diseases e.g. RA, Severe eczema, IBD

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5
Q

Solid organ transplant patients are maintained on drug regimens depending on the type of organ transplant. What are the drug choices?

A

1) Anti-proliferatives: Azathioprine, mycophenolate
2) Calcineurin inhibitors: Tacrolimus, ciclosporin
3) Corticosteroids

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6
Q

Immunosuppressant ________ the risk of infections

A

Increase

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7
Q

A patient is on azathioprine and arrives at your pharmacy to get a flu vaccine. What would you advise?

A

Due to the increase in risk of infections (eg sepsis/tb) that could be severe from your azathioprine, you cannot have a live vaccine. Therefore, I need to check what brands we have and check this (MMR is also live)

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8
Q

What is a key side-effect of immunosuppressants?

A

bone marrow suppression and hence, the increased risk of infections

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9
Q

When would you consider azathioprine as a treatment choice?

A

if corticosteroids are inadequate

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10
Q

What is azathioprine (prodrug) metabolised to?

A

mercaptopurine - which inhibits purine metabolism and DNA/RNA/protein synthesis not allowing that host response

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11
Q

With what drug does the dose of azathioprine need to be reduced?

A

Allopurinol (gout prophylaxis) - reduce dose to 1/4 of usual dose due to toxicity as allopurinol inhibits purine metabolism

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12
Q

Which drug has a more selective MOA? Azathioprine or mycophenolate?

A

Mycophenolate

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13
Q

Disadvantages of mycophenolate (used to prevent transplant rejection)?

A

Increased risk of infections and blood disorders such as leucopaenia

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14
Q

Advantages of mycophenolate?

A

Reduced risk of acute rejection

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15
Q

What drug class does ciclosporin belong to? Would you be worried if a patient was also on gentamicin?

A

Calcineurin inhibitors. Yes - ciclosporin and gentamicin are both nephrotoxic.

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16
Q

3 disadvantages of Tacrolimus?

A
  • Increased risk of neurotoxicity
  • cardiomyopathy
  • glucose metabolism impairment (hyperglycaemia)
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17
Q

What side-effect of azathioprine would prompt you to stop treatment?

A

Hypersensitivity reactions - malaise, n/v/d, dizzy, fever, rigors, myalgia, arthralgia, rash

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18
Q

Name two side-effects of azathioprine.

A

1) hypersensitivity
2) bone marrow suppression (pre-screen for enzyme thiopurine methyltransferase as low enzyme activity increases risk of myelosuppression) - report bleeding, bruising, infection, mouth ulcers, nasal bleed, blood in stools (unexplainable)

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19
Q

How often do you monitor FBC with azathioprine?

A

Weekly for 4 weeks then every 3 months

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20
Q

Ciclosporin MOA

A

Reduce T-cell activity and immune response

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21
Q

MHRA warning for ciclosporin?

A

Maintain the same brand

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22
Q

How does ciclosporin differ from tacrolimus?

A 
Ciclosporin = mainly nephrotoxicity
Tacrolimus =  mainly neurotoxicity
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23
Q

Ciclosporin common side-effects

A

1) eye inflammation
2) gingival hyperplasia
3) neurotoxicity
4) nephrotoxicity
5) hypertension
6) hyperlipidaemia
7) hyperglycaemia

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24
Q

Patient counselling for ciclosporin?

A

Use SPF and protect from sunlight
Avoid high potassium diet and grapefruit juice (inhibitor): increases levels

Pomelo juice is predicted to increase ciclosporin exposure, and purple grape juice is predicted to decrease ciclosporin exposure.

Caution as SE can be: HYPERURICAEMIA (caution gout), HYPERLIPIDAEMIA (caution with uncontrolled cholesterol) AND HYPERTENSION (caution in BP)

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25
Ciclosporin rarely causes bone marrow suppression, true or false?
True
26
Which calcineurin inhibitors have to be prescribed and dispensed by brand? (MHRA warnings)
tacrolimus | ciclosporin
27
Mycophenolate MHRA warning?
genotoxic: effective contraception required
28
Cancer therapy aims?
- curative intent - prolong life - palliate symptoms
29
Define neoadjuvant therapy in cancer.
Aims to shrink the primary tumour making local therapy less destructive/more effective e.g. pre surgical meds to shrink tumour before surgery
30
Define adjuvant therapy in cancer.
Administered after surgery for tx of cancer to help prevent recurrence
31
Guidelines for handling cytotoxic drugs
- trained personell - desginated area to prepare - PPE: hats, gloves, aprons, goggles - specify first aid - pregnant staff should avoid exposure to cytotoxics - spillage + waste disposal - local procedure - monitor staff exposure
32
Why do cytotoxics have to be administered by specialist trained staff?
Risk of extravasation = local tissue necrosis (cell death) and can lead to amputation
33
What specific side-effect is associated with vinca alkaloids?
neurotoxicity
34
Cytotoxics cause various side-effects, give examples.
1) Oral mucositis 2) preg and reproductive function: exclude pregnancy + effective contraception (as kills fast dividing cells such as sex cells) 3) extravasation with IV drugs 4) thromboembolism 5) hyperuricaemia 6) alopecia 7) nausea/vomiting 8) bone marrow suppression 9) urotherlial toxicity
35
Which drugs often cause oral mucositis/mouth ulcers?
Anthracyclines Methotrexate 5-FU - Recommend good oral hygiene, saline washes
36
Fertility normally returns once chemotherapy is complete. What are the exceptions?
Alkylating drugs and procarbazine: permanent male sterility so advise on sperm storage
37
Rapid destruction of tumour cells can cause...
tumour lysis syndrome
38
what are the clinical features of tumour lysis syndrome?
Hyperuricaemia, hyperkalaemia, hyperphosphotaemia and hypocalcaemia.. leads to renal failure and arrhythmias
39
What groups of patients are at risk of tumour lysis syndrome?
renal impairment dehydration hyperuricaemia
40
the risk of VTE increases with...
the cancer itself and cancer chemotherapy
41
What anti-cancer therapies particularly increase risk of VTE
Tamoxifen | Thalidomide
42
Treatment options for hyperuricaemia
1) allopurinol: start 24hrs before - reduce dose of azathioprine/mercaptopurine by 1/4 2) febuxostat: 2 days before 3) rasburicase - v effective and quick but expensive so only if ass with blood cancer/severe -G6PD def risk
43
All cytotoxics except _____ and _____ cause bone marrow suppression.
Vincristine and bleomycin | FBC before each tx
44
Cytotoxics are contra-indicated in:
``` ACUTE infections (treat infection first) and Avoid live vaccines ```
45
What is defined as neutropenia?
<1.06 x 10^9/litre: give broad spec AB stat if fever + neutropaenia - avoid paracetamol as masks fever.
46
How would you treat symptomatic iron-deficiency anaemia?
- erythropoietin | - RBC transfusion
47
What can be used to inc WBC count?
Filgrastim
48
Chemotherapy-induced nausea/vomiting can cause significant distress. Give some risk factors for this.
Women aged 50+ anxiety Motion sickness
49
A patient asks how long after chemo will they feel nauseous/vomit. What do you advise?
Acute: within 24hrs Delayed: after 24hrs
50
What drug can be given as anticipatory (before treatment) to prevent n/v?
lorazepam
51
Give examples of some mild emetogenics
Methotrexate fluorouracil vinca alkaloids
52
Give examples of some moderate emetogenics
taxanes doxorubicin cyclophosphomide high dose methotrexate
53
Give examples of somehigh emetogenics
cisplatin | high dose cyclophosphomide
54
For acute symtpoms of low risk nv (within 24hrs) what anti emetics can you use?
dexamethasone/lorazepam
55
For acute symtpoms of high risk nv (within 24hrs) what anti emetics can you use?
5ht3 antagonists aprepitant dexamethasone
56
For delayed symptoms, and moderate emetogenic chemo, what can you use?
Dexamethasone | + 5ht3 receptor antagonist
57
For delayed symptoms, and highly emetogenic chemo, what can you use?
Dexamethasone | + aprepitant
58
A patient is concerned about alopecia with their chemotherapy. What would you advise?
Reversible hair loss but unfortunately no treatment. Can use wigs/caps
59
What cytotoxic drugs given IV can cause severe tissue necrosis?
vincal alkaloids | anthracyclines
60
Give examples of vinca alkaloids?
Vincristine | Vinblastine
61
What route should vinca alkaloids NOT be given by?
intrathecally as it can cause irreversible fatal neurotoxicity that leads to death (signs = pins and needles, abd pain, constipation)
62
What route should vinca alkaloids be given by?
IV
63
Give examples of anthracycline antibiotics.
Rubicins | - doxorubicin
64
Side-effects of anthracyclines (rubicins).
Cardiotoxicity | Red urine
65
What formulation of anthracyclines can reduce the risk of cardiotoxicity and extravasation. What do they instead increase the risk of?
Liposomal | Increased risk of hand and foot syndrome (ensure cool extremities, no socks/gloves for 4-7days after tx)
66
Describe hand and foot syndrome
Macular, red skin eruptions
67
How would you treat anthracycline-induced SE?
Dexrazoxane
68
What cytotoxic antibiotic drug class does bleomycin fall under?
Antineoplastics
69
Side-effects of antineoplastic antibiotics (bleomycin)?
- pulmonary fibrosis - respiratory failure - hypersensitivity: chills/fever (prevent with IV hydrocortisone) - dermatological toxicity (inc pigmentation and plaques)
70
Give an indication for vincal alkaloids.
Leukaemia
71
The dose of doxorubicin should be ______________ if there is __________
Reduced if there is high bilirubin
72
Common side-effects of cytotoxic therapy?
Extravasation and tissue necrosis: have trained staff Oral mucositis: good oral hygiene + saline mouthwash Alopecia: wigs/caps Bone marrow suppression Tumour lysis syndrome (hyper kal/uri/phos and hypocalcaemia): use allopurinol, febuxostat, rasburicase Thromboembolism
73
How would you treat urothelial toxicity caused by cyclophosphamides, oxazaphosphorines, ifosfamide?
Mesna - decreases risk of bleeding from bladder
74
Give examples of anti-metabolites.
Methotrexate Capecitabine Fluorouracil
75
Side-effects of antimetabolites?
Oral mucositis Myelopsuppression Folinic acid (MTX overdose + speeds up recovery in SE)
76
Key example of alkylating drugs.
Cyclophosphamide
77
Characteristic SE of alkylating drugs (cyclophosphamide).
- urothelial toxicity (treat with mesna) - permanent male sterility - leukaemia
78
Contraception advise for those on doxorubicin.
Contraception during and 6 months after.
79
What drug is metabolised to fluorouracil.
Capecitabine. | Monitor for eye disorders and severe skin rx e.g. SJS and hand-foot syndrome
80
Use of aromitase inhibitors and who should you not give them to?
They are anti-oestrogens and used to treat breast cancer. Do not give in pre-menopausal women (as cant stop ovaries making oestrogen)
81
Give examples of aromatase inhibitors.
Letrozole | Anastrazole
82
Give examples of taxanes
Docetaxel | Paclitaxel
83
Side-effects of taxanes.
Cardiac disease Pneumonitis Sepsis
84
What would you use as pre-medication for taxanes and why
Corticosteroid e.g. IV hydrocortisone to prevent severe hypersensitivity
85
contra-indication for rasburicase (used for hyperuricaemia) - Hint: enzyme
G6PD deficiency
86
1st line tx for breast cancer in ER +ve premenpausal women?
Tamoxifen + no hx of thromboembolic disease/endometrial cancer
87
1st line tx for breast cancer in ER -ve postmenpausal women?
Aromatase inhibitor such as letrozole anastrazole only if no hx of osteoporosis (otherwise give tamoxifen)
88
How long should chemoprevention be continued for?
5 years
89
Give an example of a drug used in prostate cancer to restore sexual function?
Bicalutamide - CAL: photosensitivity
90
Appropriate advise for oral mucositis caused by 5FU, Anthracyclines/methotrexate?
- Brush 2/3x weekly with a soft brush - generally self-limiting - after sore mouth; treatment could be less effective therefore prevent - suck icechips during infusions of FU - common complication of chemo
91
Ciclosporin levels are affected by several juices, what are they?
1) grapefruit juice - inhibitor - increases levels 2) pomelo juice - increase levels 3) purple grape juice - decrease levels 4) mix with orange or apple juic to improve taste
92
Tacrolimus can be used in severe, refractory eczema and and to prevent transplant rejection. What juices can increase its concentration?
Pomelo and pomegranate
93
Tacrolimus can be used in severe, refractory eczema and and to prevent transplant rejection. Which hypersensitivity is it contra-indicated in?
Macrolide

2021 Pre-registration (15 decks)

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