Anti-cancer drugs Flashcards
What is cancer?
Uncontrolled multiplication and spread of cells
Explain the pathogenesis of cancer (what are the causes of cancer?)
- Mutations of DNA (normal cells turn cancerous or inherited or aquired)
- Environmental factors
- Ionizing radiation
- Exposure to viruses
- carcinogens - Genetic changes
- Activation of proto-oncogenes to oncogenes
- Inactivation of tumour suppressor genes (inhibit apoptosis)
Explain the different cancer treatment regimens (localized and metastatic)
- Localized
- Surgery
- Radiotherapy for solid tumors - Metastatic tumours
- Chemotherapy alone (early stages)
- Chemotherapy and radiotherapy =- surgery depending on the severity
- surgery can occur for both localized and advanced
Explain the three types of chemotherapy
Primary chemotherapy:
- Patients with advanced cancer where no alternative treatment exists
Neoadjuvant chemotherapy:
Chemotherapy is given to the patient before alternative therapies e.g. to shrink the tumor before surgery (localized tumor)
Adjuvant chemotherapy:
Chemotherapy given after surgery to reduce the incidence or reoccurrence of the cancer
Explain the stages of the cell cycle
G1= synthesis of cellular components needed for DNA synthesis (enzymes)
S= DNA synthesis
G2= Synthesis of cellular components for mitosis, enzymes and RNA
M= Mitosis
G0= resting phase
Explain what is meant by cycling cells, cell cycle-specific drugs, non-cycle specific drugs and the log-kill hypothesis
Cycling cells: More sensitive to cancer drugs. This is because many anticancer drugs target processes that are critical for cell division, such as DNA replication and mitosis.
Cell-cycle specific drugs (CCS)
Agents that act selectively on cycling cell. Target a specific process in cell division/ phase
Cell-cycle nonspecific drugs (CCNS)
Kill tumuor cells in both cycling and resting phases of cell cycle. Phase non-specific
The log-kill hypothesis
A given dose kills a constant proportion of cell population
List the classification of anticancer drugs
- Ankylating drugs
- Antimetabolites
- Natural products
- Anti-tumor antibiotics
- Miscellaneous
- Hormonal
Discuss alkylating agents
- examples
- MOA
- Mechanisms of resistance
- Adverse effetcs
cyclophosphamide, chlorambucil
CCNS (cell cycle non-specific)
Transfer alkyl groups to cellular components
Alkylation of DNA in the nucleus:
- cross-linking of bases
- Abnormal base pairing
- Strand breakage
Resistance mechanisms
- DNA repair
- Reduced cellular transport of drug
- Increased expression of glutathione which conjugates the alkylating agent
- Increased glutathione S transferase activity which catalyzes the conjugation
GIT distress- diarrhea, nausea and vomiting
Carcinogenic–> increases risk if secondary malignancies
myelosuppression
Potent vesicants
go CMP
Explain the MOA and examples of the anti-metabolites
- Cell cycle-specific drugs (target S phase)
- Have immunosuppressant actions
- Antifolate: Methotrexate
- inhibits dihydrofolate reductase
- Purines: thioguaine, mercaptoprine
- Inhibits purine metabolism
- Pyramidines: gemcitabine, fluorouracil
- inhibits thymidylate synthesis
Explain methotrexate in terms of pharmacokinetics, adverse effects and reduced effects
Elimination depends on renal function
◦ Adequate hydration needed to prevent renal crystallization in renal tubules
Bone marrow suppression= thrombocytopenia
GIT distress= mucositis
Hepatotoxicity and fibrosis, pulmonary infiltrates (long term)
be happy please fibrosis (meth addicts are happy)
- reduced with folinic acis= leucoverin= leucoverin rescue
list the different types and examples of the natural product anticancer drugs as well as MOA and adverse effects
- CCS
- Vinka alakoids (M cycle)
- Vinblastine- alopecia, GIT and bone marrow suppression
-Vincristine- neurotoxicity
Act in the M phase of the cancer cell cycle
Block the formation of mitotic spindles - Taxanes (M cycle)
Docetaxel
Interferes with mitotic spindle - Topoisomerase inhibitor ii
- Etoposide
- induces DNA breakage
(G1-S phase) - Topoisomerase i inhibitor/camptothecins
-irnotecan
(G2-M)
Discuss Antitumour antibiotics examples,
Anthracycline:
MOA
Adverse effects
Anthracyclines= doxorubicin, bleomycin, mitomycin
Anthracycline mechanism
-CCNS
-Intercalates between DNA base pairs
- Inhibits topoisomerase ii and generates free radicals
- Blocks the synthesis of RNA and DNA
- membrane disruption
Adverse effects (BAC)
- Bone marrow suppression
- Alopecia
- Cardiotoxicity- cardiomyopathy and heart failure
Discuss bleomycin characteristics
- MOA
-Adverse effects
- Mixture of glycopeptides
- SSC= G2 phase of cancer cell cycle
- Generates free radicals, which bind to DNA and cause strand breaks
- Inhibit DNA synthesis
Adverse effects:
Pulmonary dysfunction= fibrosis and pneumonitis
Hypersensitivity reactions fever, chills
Mucotaneous reactions: alopecia, blister, hyperkeratosis
Mitomycin
MOA
Adverse effects
- CCNS
- Metabolized by liver enzymes to form alkylating agents that cross-link DNA
Myelosuppression, hepatoxicity, cardiotoxicity, nephrotoxicity
Discuss platinum analogues
Examples
MOA
Adverse effects
Cisplatin, carboplatin
MOA:
Forms inter and intrastrand DNA cross-links binding to nuclear and cytoplasmic proteins
Adverse effects
- mild Haematological effects
- GIT
- Neurotoxicity
-Nepthrotoxic
** Carboplatin has less nephrotoxic effect but greater myelosuppression action
