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Semester 5 - Farmocology > Session 10 - Chemotherapy > Flashcards

Session 10 - Chemotherapy Flashcards

1
Q

What are the two types of base in DNA?

A

Purine - Two ring structure (G&A)

Pyrimidines - One ring structure (C, T & U)

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2
Q

What do the base pairs form between?

A

G and C

A and T

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3
Q

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

A

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

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4
Q

What are the three steps of DNA replication?

A

Initiation
Elongation
Termination

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5
Q

What happens in initiation?

A

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)

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6
Q

What happens in elongation?

A

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.

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7
Q

What happens in termination?

A

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.

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8
Q

What are the four main types of chemotherapeutics?

A

Antimetabolites
Alkylating agents
Intercalating agents
Spindle poisons

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9
Q

Name three types of antimetabolites

A

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

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10
Q

How do anti-metabolites work in cancer?

A

Analogues of normal metabolites act by competition to inhibit DNA

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11
Q

Give two alkylatng agents

A

Cyclophosphamide

Melphalan

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12
Q

What do alkylating agents do?

A

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

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13
Q

Name three spindle poisons

A

Vincristine
Vinblastine
Vinca alkaloids

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14
Q

How do spindle poisons work?

A

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

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15
Q

Name an intercalating agent?

A

Dactinomycin

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16
Q

How does dactinomycin work?

A

Intercalates between base pairs of DNA and inhibits RNA synthesis

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17
Q

Give a few tumours which are highly sensitive to chemotherapy

A 
Lymphomas
Germ cell tumours
Small cell lung
Neuroblastoma
Wilm’s tumour
18
Q

Give a few tumours which are moderately sensitive to chemo

A 
Breast
Colorectal
Bladder
Ovary
Cervix
19
Q

Give a few tumours which are low sensitivity to chemotherapy

A

Prostate
Renal cell
Brain tumours
Endometrial

20
Q

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

A

Make sure treatments do not have overlapping toxicity

21
Q

Give 7 main ADRs of chemo

A 
Vomiting 
Alopecia
Skin toxicity 
Mucositis 
Cardiotoxicity 
Lung toxicity 
Haemtological toxicity
22
Q

How does vomiting occur in chemo?

A

Direct action of chemotherapy on central chemoreceptor trigger zone

23
Q

Give three different patterns of emesis in chemotherapy?

A

Acute phase
Delayed onset
Chronic phase

24
Q

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

A 
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
Q

What occurs if the cannula is messed up in chemo?

A

Local skin toxicity - irritation and thrombophlebitis of veins

26
Q

What drug causes general skin toxicity?

A

Bleomycin
Hyperkeratosis
Hyperpigmentation
Ulcerated pressure sores

27
Q

What is mucositis?

A

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
Q

What is cardio-toxicity?

A

o Cardio-myopathy

o Arrhythmias

29
Q

What occurs in chemo lung toxicity?

A

o Pulmonary fibrosis

30
Q

What is haematological toxicity in chemo?

A

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
Q

Give five things which can cause variability in chemotherapy pharmacokinetics?

A 
Absorption
Distribution
Metabolism 
Elimination
Protein binding abnormalities
32
Q

What can cause variabilities in absorption?

A

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

33
Q

What can cause variabilities in distribution?

A

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

34
Q

What can cause variabilities in metabolism

A

o Liver dysfunction, other medications

35
Q

What causes variabilities in elimination?

A

o Renal dysfunction

36
Q

What causes variability in protein binding?

A

Low albumin

Drug-drug interacion

37
Q

Give four important drug-drug interactions in cancer chemotherapy?

A

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
Q

How can you monitor the response of tumour to chemotherapy?

A

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

39
Q

How can you check chemo drug levels?

A

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

40
Q

How do you check for chemo organ damage?

A

o Creatinine clearance

o Echocardiogram

Semester 5 - Farmocology (27 decks)

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