DNA alkylating medications Flashcards
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 has 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. They side effects are neutroxicity idnuced 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
