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Pharamacology, theraputics and prescribing > Chemotherapy and immunosurpressants > Flashcards

Chemotherapy and immunosurpressants Flashcards

1
Q

Name 4 mode of actions of chemotherapy drugs

A
  • Antimetabolites
  • Alkylating agents
  • Intercalating agents
  • Spindle poisions
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2
Q

How does 5- flurouracil (eg capecitabine) and methotrexate work?

A

Inhibit folic acid cycle, so inhibit purine synthesis (antimetabolite)

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3
Q

How do taxoids work?

A

Promote assembly and prevent disassembly of spindle–> cell death (spindle poisions)

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4
Q

How do platinum compounds such as cisplatin work?

A

Cause inter and intra strand adducts, leads to single, then double strand breaks which trigger apoptosis (alkylating agent)

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5
Q

How do vinca alkaloids work?

A

inhibit spindle formation

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6
Q

Name 3 classes of anti- emesis drugs

A
  • Antihistamines (cyclizine)
  • Anti muscarinics (hyoscine)
  • Serotonin inhibitors (ondansetron)
  • Dopamine antagonists (domperidone)
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7
Q

Name 1 vinca alkaloid?

A

Vincristine or vinblatine

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8
Q

Name 1 taxoid/ taxanes chemo?

A

paclitaxel

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9
Q

How do methotrexate and 6- mercaptopurine work?

A

They’re both antimetabolites- inhibit folic acid, so DNA synthesis

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10
Q

Why is chemo given in many rounds?

A

Fractional kill hypothesis- chemo will destroy tumours cells and bone marrow cells, but bone marrow will regenerate faster. Therefor successive rounds of chem will destroy the cancerous cells, whilst only depleting bone marrow by little bits each time

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11
Q

Give 2 examples of cancers that are very sensitive to chemo?

A

lymphomas, germ cell tumours, Small cell lung cancer.

Breast, colorectal, bladder, ovary and cervix have mild- moderate sensitivity

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12
Q

Give 2 examples of cancers which are not very susceptible to chemo?

A

Prostate, renal cell, brain tumours, endometrial

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13
Q

Give 3 methods of resistance to chemotherapy

A
  • decreased entry/ increased expulsion of agent
  • inactivation of agent within the cell
  • enhanced repair of DNA lesions produced by alkylating
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14
Q

How can chemo be administered?

A
  • IV bolus, bag, continious pump, PICC or hickman line
  • oral
  • subcut
  • into body cavity (bladder, pleura)
  • intra lesional
  • intrathecal
  • topical
  • IM (rare)
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15
Q

Give 3 common side effects of chemo and how each can be minimised

A
  • Alopecia (can be prevented with scalp cooling, but v. uncomfortable)
  • Nausia and vomiting (acute, delayed or anticipatory, anti- emesis meds like hyoscine can help prevent this)
  • Mucositis (sore mouth, throat, bleeds, diarrhoea etc, hard to prevent)
  • myalgia (muscle pain)
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16
Q

Give a consequence of incorrect administration of chemo

A

A local reaction of local tissue destruction. For this reason the chemo is always administered by specialist nurse.

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17
Q

State rarer effects of chemo on 4 body systems

A
  • Heart- cardiotoxicity leading to myopathy or arrhythmias
  • lungs- fibrosis esp with bleomycin or cyclophosphamide
  • Repro- usually sterile
  • Renal- renal failure often due to tumour lysis releasing urate which precipitates in tubules, this risk can be minimised by giving drugs to reduce urate levels before giving chemo
  • Blood- decreased RBCs, WBCs and platelets
  • GI perforation at site of cancer (Esp w/ lymphoma)
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18
Q

What investigations should be done before starting chemo?

A
  • BMI
  • Body surface area
  • Liver function
  • Renal function
  • heart function
  • FBC
  • general well being
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19
Q

Which drugs need to be used cautiously with methotrexate?

A

protein bound drugs- NSAIDS, penicillins

20
Q

List 3 drugs used to treat rheumatoid arthiritis?

A

Methotrexate- gold standard, azathioprine (rarer use), rituximab and other biologics

21
Q

How does methotrexate work?

A

Inhibits dihydrofolate reductase, so inhibits folic acid and DNA synthesis.
Mechanism in non- malignant disease unclear, may be to do with T cell activation inhibition.

22
Q

Give 3 ADRs of methotrexate?

A
  • mucositis and bone marrow surpression (both respond well to folic acid supplementation)
  • hepatitis and cirrhosis
  • pneumonitis
  • infection risk
  • highly teratogenic
23
Q

How is methotrexate administered?

A
  • poor oral bioavailablity

- so given IM once per week- long half life and 50% protein bound

24
Q

Name one drug used to treat inflammatory bowl disease and why it is used for this

A

Mesalazine (a sulphasalazine) as poorly absorbed with great activity in the intestine.
Influximab (and other biologicals), azathioprine (rarer) also used.

25
Q

How do sulphasalazines work?

A

Inhibit T cell proliferation, Il-2 production and also induced apoptosis of WBCs. Also reduced chemotaxis and neutrophil degranulation. Over reduced inflammatory response

26
Q

Give 3 side effects of sulphasalazines?

A

Myelosurpression (dont need long term monitoring, as will arise in first few weeks if ever do), hepatitis, rash, N+ V, abdo pain.

27
Q

Are suphasalazines safe in pregnancy?

A

Yes

28
Q

How does azathioprine work?

A

It is cleaved to 6MP which is an antimetabolite which decreases DNA and RNA synthesis

29
Q

What is azathioprine used for (3)?

A

SLE and vasculitis as maintainance therapy. Also used less commonly in RA and IBD. It has other uses as a steroid sparing immunosurpressant.

30
Q

What is significant about the pharamacokinetics of azathioprine?

A

It is metabolised to 6MP by TPMT, which is highly polymorphic, so you need to monitor response to treatment and TPMT levels prior to treatment.

31
Q

Give 3 ADRs of azathioprine?

A
  • myelosupression-> needs FBC monitoring
  • malignancy risk
  • infection risk
  • hepatitis
32
Q

How does mycophenolate mofetil work?

A

Inhibits guanosine synthesis which inhibits B and T cell proliferation. It is selective to B and T cells because they have different guanosine salvage pathways to most cells.

33
Q

When is mycophenolate mofetil used?

A

Mostly used for immunosurpression around transplants but also maintenance in SLE

34
Q

Give 3 ADRs of mycophenolate mofetil?

A

Mucositis, N+V, diarrhoea, myelosurpression, infection risk

35
Q

how does cylcophosphamide work?

A

Alkylating agent- cross links DNA, suppressing B and T cell activity

36
Q

When is cyclophosphamide used?

A

Lymphoma, leukaemia and solid cancers.

Also lupus nephritis (2nd treatment to mycophenolate mfetil), ANCA vasculitis

37
Q

Give 3 ADRs of cyclophosphamide?

A
  • acrolein (a side product) is toxic to bladder epithelium, leading to haemorrhagic cystitis-> prevent w/ aggressive hydration and mesna (binds acrolein)
  • bladder cancer, lymphoma, leukaemia, infertility, renal failure, infections
  • Can only have 20 cycles to reduce infertility risk
38
Q

What is significant about the metabolism of cyclophosphamide?

A
  • metabolised by CYP450 and excreted by kindey

- susceptible to renal failure, liver failure and CYP inducers and inhibitors

39
Q

Name 2 calcineurin inhibitors

A

ciclosporin, tracolimus

40
Q

How do calcineurin inhibitors work?

A

Prevent Il-2 production, via inhibiting calcineurin enzyme.

41
Q

When are calcineurin inhibitors used?

A

Often in transplants, also psoriasis and in severe atopic dermatitis

42
Q

Give 3 ADRs of calcineruin inhibitors?

A
  • Nephotoxic (check BP and GFR regularly)

- headache, N+V, Acne, GI upset, infections

43
Q

How does infliximab work?

A

monoclonal antibody which binds TNFa to decrease inflammation, angiogenesis, joint destruction via MMPs

44
Q

What test needs to be conducted before starting anyone on a biological agent which blocks TNFa?

A

Screen for TB.

This is because TNFa is released by macrophages to support and maintain the granuloma.

45
Q

How does rituximab work?

A

Binds to CD20 on B cells, causing B cell apoptosis- very effective in RA.

46
Q

Give 3 drugs used to SLE?

A

Infliximab, mycophenolate mofetil, cyclophosphamide (rarer, as more ADRs)

Pharamacology, theraputics and prescribing (15 decks)

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