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Pharmacology /Pharm Y2S2 - Cancer

Pharm Y2S2 - Cancer

Pharmacology31 CardsCreated about 2 months ago

This deck covers key questions and answers related to cancer pharmacology, focusing on chemotherapy, alkylating agents, intercalating agents, and other cancer treatments.

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What is the purpose of chemotherapy?

Prevent cell growth
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Key Terms

Term
Definition
What is the purpose of chemotherapy?
Prevent cell growth
How does chemotherapy target DNA?
Indirect interaction with DNA - prevention of nucleic acid synthesis by inhibiting one or more enzymes involved
Give examples of alkylating agents
Melphalan Chlorambucil Cyclophosphamide Decarbazine Bulsulfan Temozolamide
How do mustards work?
Attack guanine in DNA, this causes cross linking of DAN strand - they can’t open and be copied for cell division. Linkage inhibits DNA synthesis - has...
Which other cells are also affected by mustards?
Those that divide frequently - GIT, bone marrow, testicles and ovaries
What is the state of the nitrogen on chlorambucil?
Nitrogen lone pair is delocalised
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Pharm Y2S2 - Cancer
TermDefinition
What is the purpose of chemotherapy?
Prevent cell growth
How does chemotherapy target DNA?
Indirect interaction with DNA - prevention of nucleic acid synthesis by inhibiting one or more enzymes involved
Give examples of alkylating agents
Melphalan Chlorambucil Cyclophosphamide Decarbazine Bulsulfan Temozolamide
How do mustards work?
Attack guanine in DNA, this causes cross linking of DAN strand - they can’t open and be copied for cell division. Linkage inhibits DNA synthesis - has a cytotoxic effect
Which other cells are also affected by mustards?
Those that divide frequently - GIT, bone marrow, testicles and ovaries
What is the state of the nitrogen on chlorambucil?
Nitrogen lone pair is delocalised
What does melphalan mimic?
An amino acid - drug enters by phenylalanine amino acid transporter
What is mitomycin C?
A pro-drug that requires reductive activation.
What do alkylating agents contain?
Highly electrophilic groups
How do alkylating agents work?
They form covalent bonds to nucleophilic groups in DNA. They prevent replication and transcription
What can alkylation of nucleic acid bases lead to?
Mutations which are carcinogenic
What is platinum covalently linked to in cis-platen?
Chloro-substituents
Where are chemotherapeutic metal complexes activated?
In cells with low Cl- ion conc
How does cisplatin work?
Binds to DNA regions rich with guanine units forming intra-strand links
What are the toxic side effects of cisplatin?
Severe nausea and vomiting nephrotoxicity ototoxicity bone marrow suppression
What do hydration procedures do?
Reduce side effects making it harder for drugs to activated in non-cancer cells
What is given as anti-sickness medication?
Metoclopramide
Give an example of an intercalating agent.
Doxorubicin
How do intercalating agents work?
Slide between stacked bases inserted between adjacent pairs - they are stabilised by electrostatic interactions between DNA phosphate groups and positively charged amino group of sugar moiety. This leads to inhibition of topo II and also generates O2 free radicals
What are the side effects of intercalating agents?
Nausea & vomiting myelosuppresion alopecia cardiotoxicity
How do DNA topoisomerases work?
They modify the topological state of DNA by inducing transient single strand or double strand - this leads to DNA breakage. This is essential for uncoiling of DNA for replication, transcription or recombination
What do inhibitors of DNA topoisomerases do?
Block the action of topoisomerase leading to permanent single strand or double strand break
How does Etopside work?
It forms a tertiary complex with DNA and topoisomerase II, this prevents DNA re-ligation so the double strand breaks. It is effective in chemo-sensitive tumours.
How do antimetabolites work?
They interfere with production of nucleic acids. Inhibit production of deoxyribonucleoside triphosphate, precursors of DNA synthesis inhibit formation of normal precursors by completing for metabolic enzymes
Give examples of antimetabolites.
5-FU Methotrexate Gemcitabine
What are vincristine and vinblastine used to treat?
Leukaemia and Hodgkins lymphoma
How do vincristine and vinblastine work?
They prevent polymerisation of microtubules
What is taxol used to treat?
Lung, ovarian and breast cancer | Karposi's sarcoma
How does taxol work?
Binds and stabilises microtubules
What are the advantages of antisense therapy?
Same effect as enzyme inhibitor or receptor antagonist highly specific where oligonucleotide is 17 nucleotides or more smaller dose levels required compared to inhibitors or antagonists potentially less side effects
What are the disadvantages of antisense therapy?
Exposed sections of mRNA must be targeted instability and polarity of oligonucleotides short life time of oligonucleotides and poor absorption across cell membranes.