cancer pharmacology Flashcards
What are the anti-tumour antibiotics produced from streptomyces bacteria ?
Belyomycin, anthracyclines, Dactinomycin or actinomycin D the later two are cell cycle non-specific.
What happens in G1 phase of the cell cycle ( interphase) ?
cell grows and performs its function.
What happens in G1 check point ?
Screening for potential DNA damage and protein synthesis abnormalities. The cell will either progress to S phase or go to G0 phase where DNA repair or progression to apoptosis will happen.
What is the action of DNA helicase in S phase ?
It unwindes the DNA strands create replication fork.
What is the action of topoisomerase enzyme ?
In the S phase it helps to loosen up the DNA helix during the unwinding process mediated by the DNA helicase.
What is the action of RNA primase and DNA polymarase ?
they together create the new RNA template by adding base pairs to the unwound DNA strand.
What are the events in G2 phase and G2 check point ?
In G2 phase the cell grows again before entering mitosis and the G2 chekpoint does the final screening before mitosis for DNA damage.
Why are cytotoxic medications toxic to cancer cells and rapidly dividing normal cells?
These cells divide more rapidly and therefore they are more sensitive to DNA damage and errors in checkpoint functions. This makes them susceptible to cytotoxic drug mediated destruction.
What is the structure and action of Belomycin ?
It is a G2 phase of the cell cycle specific medication with an iron binding and DNA binding sites. In the presence of O2 it acts as an oxidase and generate ROS which oxidise DNA bases causing breaks in DNA strands.
What are the cancers treated using Belomycin ?
Hodgkin’s lymphoma, tetsticular cancer, and squamous cell carcinoma of the skin.
What is the mechanism of Belomycin toxicity ?
The enzyme hydrolase is essential for the inactivation of bleomycin. The lungs and skin lacks it. Therefore, Bleomycin causes pulmonary toxicity in the form of pneuomitis and fibrosis as well as skin rashes, exfoliation and hyper-pigmentation. It can also cause stomatitis and mucocytis in the mouth.
What is the unique feature of Bleomycin ?
Minimal myelosupression.
What is the action of Dactinomycin or actinomycin D ?
It is a peptide that intercalates into the DNA molecule. Which prevents the binding of RNA and DNA polymarase to the DNA leading to RNA and DNA synthesis inhibition. It also cause breaks in DNA strands through ROS generation in a cell cycle non-specific manner.
What is the indication for Dactinomycin ?
It is used to treat Wilm’s tumour, rhabdomyosarcoma and Ewing’s sarcoma. The main side effects are significant mylosupression and alopecia.
What are the drugs in the anthracyclin category ?
Doxorubcin, Daunorubicin, Idarubicin and Epirubicin.
What are the 3 MOAs of anthracyclins ?
- Inhibits RNA and DNA synthesis through intercalation into the DNA strand.
- Inhibits topoisomerase II.
- Damage DNA base pairs through ROS mediated oxidation.
What are the indications for Anthracyclins ?
treatment of solid tumours of the , thyroid, lungs, ovary, Lukemias and lymphomas.
What is the main side effect of anthracyclins ?
Dose dependent irreversible dilated cardiomyopathy.
What is the prophylaxis for Anthracyclins cardio toxicity ?
Iron chelating agent Dexrazoxane.
What is the general action of DNA alkylating medications?
They are anti-cancer agents which act all stages of cell cycle by adding an alkyl group at the number 7 nitrogen atom of the guanine leading to abnormal base pairing in the form of the T-G instead of T- cytosine leading to cell death.
What is the second MOA of DNA alkylating medications?
inter- and intra-strand cross linking which prevents DNA unwinding and replication.
What are the medications in the nitrogen mustard category ?
The nitrogen mustards comprise mechlorethamine, chlorambucil, melphalan, and the oxazaphosphorines cyclophosphamide, ifosfamide, and trofosfamide.
What are nitrogen Mustards ?
These are related to the mustard gas phosgene and are the first IV chemotherapy agents. these are pro-drugs which are converted to their active from by the CYP450 enzymes in the liver.
What are the cancers treated using cyclophosphamide and ifosfamide ?
leukemias, lymphomas, and solid ovarian and breast cancers.
What are the main non-oncological uses of cyclophosphamide ?
*Small vessel vascultiies such as granulomatosis with polyangitis ( Wegner’s ), microscopic polyangitis.
* Medium vessel vasculitis such as polyarteritis nodosa.
* refractory SLE and MS
What are the side effects of nitrogen mustards ?
- Aplastic anaemia
- Lukemia and other malignancies due to long term use.
- GI disturbance and infertility.
- Hair loss
- Teratogenicity.
What is the specific side effect of nitrogen mustards ?
SIADH
What are the common side effects of cyclophosphamide ?
Transitional cell carcinoma of the bladder and hemorrhagic cystitis.
What are the prophylactic measures for cyclophosphamide induced hemorrhagic cystitis ?
High Fluid intake + Mensa or sodium 2 mercaptoethane sulfonate.
What is the action and indication, and side effects of Busalfan ?
It is a drug that is highly myelotoxic and is a drug of choice for myeloablative Tx of CML before transplant. It decreases the formation of ganulocytes and platelets at low dosage and RBC at high dosage. The main side effects are pancytopenia and less commonly pulmonary fibrosis.
What are the drugs in the alkylating drug category nitrosoureas ?
Carmustine and Lomustine.
What is the MOA and side effects of nitrosoureas ?
They are lipid soluble drugs that can cross the blood brain barrier and are primarly used to treat CNS tumours. The side effects are neutroxicity induced convulsions and ataxia
Carmustine is an alkylating chemotherapy agent that ———– which prevents gene expression.
crosslinks DNA
What type of alkylating antineoplastic agent is Streptozocin?
Nitrosourea
The mechanism of action of cyclophosphamide is?
formation of carbonium ions with guanine-N7 which inhibit the duplication of DNA and the creation of RNA.
What are the major teratogenic effect of alkylating agents?
Skeletal abnormalities including syndactyly, digital aplasia.
What is the MOA of platins ?
Platins are cell cycle non-specific agents which act by attaching to the number 7 nitrogen atom of the two adjacent guanines and creates intra- strand cross-bridges. This leads to inhibition of DNA repair and replication leading to cell death.
What are the commonly used platinum containing agents ?
Cisplatin, carboplatin, and oxaloplatin. which are administered IV and renaly eliminated.
What are the indications for cisplatin and carboplatin ?
For the treatment of solid tumours and osteosarcoma.
What are the indications for oxaloplatin?
It is indicated for the Tx of advanced colon cancer, hepato-billiary, pancreatic, ovarian cancer, and lymphomas.
What are the side effects of platins ?
*GI disturbances
* Nephrotoxicity
* Neuotoxic peripheral neuropathy
* Ototoxicity causing tinitus.
* Allergic reactions and mild bone marrow suppression.
what is the prophylaxis for Platin induced nausea and emesis ?
5-HT3R antagonist Odansterone.
What is the prophylaxis for platin induced nephrotoxicity ?
- Hydration and osmotic diuresis using manitol.
- ROS scavenger Amifostin can also be used to prevent renal damage.
Which is the platin that causes most severe nephrotoxic and neurotoxic side effects ?
Cisplatin
What is the main side effect of Carboplatin ?
Bone marrow suppression.
Which is the platin with minimal side effects ?
Oxaloplatin.
What are the classes of drugs in the Microtubule inhibitors category ?
Vinka alkaloids and taxens which inhibit mitosis.
What is the structure and function of the cytoskeleton of the cell ?
It is a network consisting of actin filaments, intermediate filaments, and microtubules. It gives the cells their shape and anchors organells in place and responsible for conformational changes.
What is the structure of microtubules ?
It is a cluster of 13 protofilaments each containing alternating chain of alpha and beta tubulin.
what are the steps of mitosis ?
- Prophase- nuclear membrane disintegration and chromosome condensation occurs.
- Metaphase- Formation of metaphase plate.
- Anaphase- centrosome mediated separation of cistocromatides occurs resulting in the formation of mitotic spindle.
- Telophase- Formation of new nuclear membrane around the each pairs of 46 chromosomes. leading to cytokinesis.
All Microtubule inhibitors are given ______
IV
What are the drugs in the vinka alkaloid class of medications ?
vinCRIStine, vinBLAStine, vindesine, vinORELBbine and vinflunine
What is the MOA of vinka alkaloids ?
They are metaphase specific drugs that bind to beta tubulin and block its polymarization into proto- filaments leading to mitotic arrest at metaphase.
What are the indications for vinka alkaloids ?
They are indicated for the Tx of breast cancer, rhabdomyosarcoma, nephroblastoma and leukaemias.
Vincristine and Vinblastine are both indicated for the treatment of both ——– and ————lymphoma.
Hodgkins and non-hodgkins.
What are the side effects of vinka alkaloids ?
Alopecia, GI symptoms and bone marrow supression. Vincrestine is myelotoxic whereas vinblastine is more neurotoxic.