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Cells and cancer > Chemotherapy drug > Flashcards

Chemotherapy drug Flashcards

1
Q

What different types of alkylating agents and examples of each group?

A

Nitrogen mustards - cyclophosphamide, chlorambucil
Nitrosoureas - camustine, lomustine
other - bulsufan, dacarbazine, hydroxycarbamide

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2
Q

Why do alkylating agents commonly cause hair loss and GIT disturbance (nausea and vomiting)?

A

Alkylating agents are toxic to healthy cells, and it is the rapidly dividing cells that are the most sensitive because they are rapidly dividing

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3
Q

What is the mechanism of action of alkylating agents?

A

Attaches alkyl groups to nucleotide bases. These covalent bonding to bases stops the tumour growing because the strands can’t uncoil and therefore cannot undergo DNA replication

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4
Q

What is the difference between SN1 and SN2 alkylating agents?

A

SN1: these react directly with biological molecules - modify ring of nitrogen atoms and extra cyclic oxygen groups
SN2: these form intermediates which react with biological molecules mainly targeting the ring of nitrogen atoms

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5
Q

What are the aims of chemotherapy?

A

1) cure
2) prolong survival
3) palliation
4) radiosensitive (cisplatin with radiotherapy)

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6
Q

What are some specific side effects for nitrogen mustards?

A

cyclophosphamide/isofamide is metabolised to acrolein metabolite which is excreted into the bladder causing haemoorrhagic cystitis

isofamide causes neurotoxicity because its metabolite crosses the BBB and can cause encephalopathy

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7
Q

What are some specific side effects of nitrosureas?

A

Cause severe cumulative depression of bone marrow

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8
Q

What are some specific side effects of bulsufan (used to treat CML)?

A

depresses formation of granulocytes and platelets at low doses and red blood cells at high doses

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9
Q

What are platinum compounds and some examples?

A

Metal complex with central atom or ion (usually metallic) called coordination centre. Around the centre are an array of molecules/ions as ligands =coordination complex of platinum
Examples: cisplatin, oxalaplatin, carboplatin

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10
Q

What are the mechanism of actions for platinum compounds?

A

Cross-linking of DNA as mono adduct, inter strand crosslinks or DNA protein crosslinks
The cross linking inhibits DNA repair and / or DNA synthesis

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11
Q

What are some of the specific side effects associated with platinum based compounds?

A

Carboplatin has lower nephrotoxicity compared to cisplatin.
Cisplatin enters the renal epithelium, causing DNA and mitochondrial damage activating many cell death and survival pathways and inflammatory response. Causes PCT lesions causing loss of potassium and magnesium ions

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12
Q

What different types of antimetabolites (cytotoxic drugs) and examples of each group?

A

Folate antagonsits - methotrexate
Pyrimidine pathway - fluorouracil, capectibane, tegafur
Purine pathway - clofarabine, mercaptopuri, pentostatin, fludarabine

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13
Q

What is the mechanism of action of methotrexate?

A

Inhibits dihydrofolate reductase reducing tetrahydrofolate which is vital for purine and thymidylate synthesis inhibiting DNA synthesis

  • Folates are crucial for purine synthesis and thymidylate synthesis therefore inhibition leads to increased DNA damage - inhibition causes blockage or destabilisation of one or more metabolic pathways in DNA synthesis, preventing cell division and subsequent tumour growth
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14
Q

What are the side effects of methotrexate?

A

damage to GIT and depression of bone marrow
Pneumonitis can occur
high doses can lead to nephrotoxicity due to the drug precipitating in the renal tubules

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15
Q

How do the pyrimidine pathway antimetabolites work?

A

Fluorouracil works by producing fraudulent nucleotides (FDUMP_ which inhibits thymidylate synthase activity and/or incorporation into DNA and RNA preventing DNA synthesis

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16
Q

What are the side effects of pyrimidine and purine pathway antimetabolites?

A

stomatitis
hand-foot syndrome (acral erytherma) - reddening, swelling, desquamation and numbness
ocular toxicity
hyperbilirybinemia

17
Q

How do the purine pathway antimetabolites work?

A

Metacaptopurine is converted to a fradualent nucleotide.
pentostatin inhibits adenosine deaminase, cirtical for purine metabolism
Fludarabine inhibits DNA polymerase

18
Q

What are the different types of plant alkaloids?

A

Taxanes - cabazitaxel, docetaxel (breast and lung cancer)
Vinca Alkaloids - vinblastine, vincristine
Campothecins- irinotecan, toptecan
other - etoposide

19
Q

Mitotic inhibitors are a form of plant alkaloids. What do they do?

A

Inhibit mitosis/cell division

  • disrupt microtubule polymerization, preventing spindle formation
  • disruption during the M phase
20
Q

What are the side effects of plank alkaloids / mitotic inhibitors?

A

Taxanes- cumulative neurotoxicity
neurotoxic effects such as parathesias
campothecins= diarrhoea

21
Q

What is vincristine used to treat and what are its specific side effects?

A

active in leukaemia

- neurotoxic - disrupts axonal transport tubules

22
Q

What is vinblastine used to treat and what are its specific side effects?

A

active in lymphomas and testicular cancer

- myelosuppressive

23
Q

What is vinorelbine used to treat and what are its specific side effects?

A

active in lung cancer

- neurotoxic and mylesuppressive

24
Q

What are topoisomerase inhibitors ?

A

inhibit topoisomerase enzymes, which regulate DNA overwinding or underwinding - breaks the ligation step of the cell cycle and therefore causes single or double strand breaks, affecting the integrity of the genome and causing apoptosis

25
Q

What are examples of topoisomerase I and II inhibitors ?

A 
I = Irinotecan, topotecan
II = etoposide
26
Q

What are the anti-tumour antibiotics?

A

anthracyclines - doxorubicin, idarubicin, epirubicin

other- mitomycin, trabectedin

27
Q

How doe anthracyclines work?

A

intercalate with DNA strands forming a complex that inhibits DNA and RNA synthesis

28
Q

What are the side effects of anthracyclines?

A

binding to cell membranes and plasma proteins may induce cytotoxic effects - generates free radicals that cause cell and DNA damage = myocardial damage
epirubicin is prefered to doxorubicin due to fewer side effects

29
Q

How do mitomycins work?

A

natural products from streptomyces caespitosus or streptomycin lavendulare

it is one of the bi- or tri-functional alkylating agents causing cross linking of DNA preventing DNA synthesis

30
Q

What are the side effects of mitomycin?

A

can induce liver enzymes causing abnormalities

rare complications: haemolytic uremic syndrom, renal failure, haemolysis, interstitial pneumontitis

Cells and cancer (1 decks)

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