Session 10 - Chemotherapy Flashcards Preview

Semester 5 - Farmocology > Session 10 - Chemotherapy > Flashcards

Flashcards in Session 10 - Chemotherapy Deck (40)
1

What are the two types of base in DNA?

Purine - Two ring structure (G&A)
Pyrimidines - One ring structure (C, T & U)

2

What do the base pairs form between?

G and C
A and T

3

In which direction do the strands of the DNA double helix run?

Complimentary and anti-parallel to each (top strand 5' -> 3', bottom 3' -> 5')

4

What are the three steps of DNA replication?

Initiation
Elongation
Termination

5

What happens in initiation?

Helicase unravels the DNA double helix. Requires specific proteins to interact with DNA and recruit DNA polymerase (because DNA polymerase can only extend from 3’ ends of pre-existing chains to 5’, a special enzyme primase is required to initiate each strand)

6

What happens in elongation?

leading strand is replicated from 5’  3’ as normal. However the lagging strand is replicated discontinuously in Okazaki fragments. These fragments are then joined by DNA ligase from OH group to Phosphate group covalently.

7

What happens in termination?

Replication forms move from the ends of the DNA strands towards each other. Lead strands move towards lagging strands and vice versa. The terms ‘leading’ and ‘lagging’ have no bearing once ligase has joined up all the fragments.

8

What are the four main types of chemotherapeutics?

Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons

9

Name three types of antimetabolites

Methotrexate (folic acid anatgonist)
Fluorouracil (antipyrimidine)
Mercatopurine (antipurine)

10

How do anti-metabolites work in cancer?

Analogues of normal metabolites act by competition to inhibit DNA

11

Give two alkylatng agents

Cyclophosphamide
Melphalan

12

What do alkylating agents do?

Alkyl groups react to form bonds with nucleic acids. This causes cross linking of DNA strands, preventing replication

13

Name three spindle poisons

Vincristine
Vinblastine
Vinca alkaloids

14

How do spindle poisons work?

Bind tubulin and inhibit the polymerisation of microtubules that is necessary to form the mitotic spindle. Prevents mitosis, arrests cells at metaphase

15

Name an intercalating agent?

Dactinomycin

16

How does dactinomycin work?

Intercalates between base pairs of DNA and inhibits RNA synthesis

17

Give a few tumours which are highly sensitive to chemotherapy

Lymphomas
Germ cell tumours
Small cell lung
Neuroblastoma
Wilm’s tumour

18

Give a few tumours which are moderately sensitive to chemo

Breast
Colorectal
Bladder
Ovary
Cervix

19

Give a few tumours which are low sensitivity to chemotherapy

Prostate
Renal cell
Brain tumours
Endometrial

20

What is one thing you must make sure when prescribing chemo?

Make sure treatments do not have overlapping toxicity

21

Give 7 main ADRs of chemo

Vomiting
Alopecia
Skin toxicity
Mucositis
Cardiotoxicity
Lung toxicity
Haemtological toxicity

22

How does vomiting occur in chemo?

Direct action of chemotherapy on central chemoreceptor trigger zone

23

Give three different patterns of emesis in chemotherapy?

Acute phase
Delayed onset
Chronic phase

24

What is alopecia? What chemodrugs cause it? How can it be corrected?

o Hair thins at 2-3 weeks
o May be total
o May regrow during therapy
o Marked with Doxorubicin, Vinca Alkaloids, Cylophosphamide
o Minimal with Platinums
o Scalp cooling may help

25

What occurs if the cannula is messed up in chemo?

Local skin toxicity - irritation and thrombophlebitis of veins

26

What drug causes general skin toxicity?

Bleomycin
Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores

27

What is mucositis?

o GI tract epithelial damage
o May be profound and involve the whole tract
o Most commonly worst in Oropharynx
o Presents as sore mouth/throat, diarrhea, GI bleed

28

What is cardio-toxicity?

o Cardio-myopathy
o Arrhythmias

29

What occurs in chemo lung toxicity?

o Pulmonary fibrosis

30

What is haematological toxicity in chemo?

o Most frequent dose limiting toxicity
o Most frequent cause of death from toxicity
o Different agents cause variable effects on degree and lineages
 Neutrophils
 Platelets

31

Give five things which can cause variability in chemotherapy pharmacokinetics?

Absorption
Distribution
Metabolism
Elimination
Protein binding abnormalities

32

What can cause variabilities in absorption?

o Nausea and vomiting – May vomit drugs back up
o Compliance
o Gut problems – E.g. mucositis

33

What can cause variabilities in distribution?

o Nausea and vomiting – May vomit drugs back up
o Compliance
o Gut problems – E.g. mucositis

34

What can cause variabilities in metabolism

o Liver dysfunction, other medications

35

What causes variabilities in elimination?

o Renal dysfunction

36

What causes variability in protein binding?

Low albumin
Drug-drug interacion

37

Give four important drug-drug interactions in cancer chemotherapy?

o Vincristine and Itraconazole (commonly used antifugngal)
 Neuropathy
o Capecitabine (oral 5FU) and Warfarin
 Very important interaction!! Increases bleeding risk
o Capecitabine (oral 5FU) and CYP450 enzyme inhibitors
 AO-DEVICES
 Grapefruit Juice, Omeprazole, Disulfiram, Erythromicin, Valporate, Isoniazid, Cimetidine & Ciprofloxacin, Ethanol (acutely), Sulphonamides
o Methotrexate and penicillin, NSAIDs

38

How can you monitor the response of tumour to chemotherapy?

o Radiological imaging
o Tumour marker blood tests
o Bone marrow/cytogenics

39

How can you check chemo drug levels?

o Methotrexate drug assays taken on serial days to ensure clearance from blood after folinic acid rescue

40

How do you check for chemo organ damage?

o Creatinine clearance
o Echocardiogram