Antineoplastic therapy - Alkylating agents 19-32 Flashcards
Name the nitrosureas
Carmustine
Lomustine
Streptozocin
How is Carmustine administered?
IV, also transdermal wafer in brain after brain tumor removal
How is Lomustine administered?
Oral
How is Carmustine activated?
Non-enzymatically
How is Lomustine activated?
Non-enzymatically
How does Carmustine work?
Alkylates DNA and carbamoylate proteins
How does Lomustine work?
Alkylates DNA and carbamoylate proteins
What is Carmustine used for?
Brain tumors, melanoma, non-Hodgkin’s lymphoma
What is Lomustine used for?
Brain tumors, melanoma, non-Hodgkin’s lymphoma
Toxicity associated with Carmustine?
Nausea, vomiting, fibrosis, myelosuppression, RENAL TOXICITY, secondary leukemia
Toxicity associated with Lomustine?
Nausea, vomiting, fibrosis, myelosuppression, RENAL TOXICITY, secondary leukemia
How is Dacarbazine activated?
P-450 system to Diazomethne, a cytotoxic agent
How is Procarbazine activated?
P-450 system to Diazomethne, a cytotoxic agent
Procarbazine also has several active metabolites including H2O2 and formaldehyde
Which drug has active metabolites H2O2 and formaldehyde?
Procarbazine
What is Dacarbazine used for?
Hodgkin’s disease, malignant melanoma
ABVD regimen
What is Procarbazine used for?
Hodgkin’s disease, malignant melanoma
MOPP regimen
Toxicities associated with Dacarbazine
Severe N/V Myelosuppression Alopecia Flu-like syndrome Renal/hepatotoxicity
Toxicities associated with Procarbazine?
Myelosuppression Alopecia Flu-like syndrome CNS depression Renal/hepato toxicity Leukogenic Immunosuppressant Infertility
How is Temozolamide administered?
IV, oral
What drug is the DOC for malignant gliomas and astrocytoma together with radiation?
Temozolamide
TEAMzolamide - TEAM UP with radiation for malignant gliomas and astrocytoma
What is the MOA of temozolamide?
Similar to dacarbazine - prodrug to MTIC which is a cytotoxic agent
How is Altretamine administered?
Oral
How is Altrematine activated?
Activated to alkylating agent
What is Altrematine used for?
It is 2nd line for ovarian cancer
Toxicities of Altrematine?
Myelosuppression
Nausea/vomiting
Neurotoxicity - ataxia, depression, confusion, hallucinations
How is Thiotepa activated?
Converted to TEPA
Multiple metabolites, many of which are active
How does Thiotepa work?
Cross links DNA
What is Thiotepa used for?
Bladder, breast, Hodgkin’s, ablation of bone marrow
Toxicity of Thiotepa?
Allopecia, hematological, immunological, coma, seizures
How is Busulfan administered?
Oral
How does Busulfan work?
Alkyl sulfonate acts like mustards
What is Busulfan used for?
Chronic myelogenous leukemia (CML)
Used with cyclophosphamide to ablate marrow before transplant
Toxicities associated with Busulfan?
Diarrhea, mild nausea, vomiting, myelosuppression, pulmonary fibrosis, secondary malignancies, infertility, teratogenic, HIGH DOSE SEIZURES must use antiepileptics, can cause busulfan lung which is fatal after 3 years
Which drug must be taken with epileptics if given in high doses?
Busulfan
How is Cisplatin activated?
Water activated
How does Cisplatin work?
Doesn’t formally alkylate DNA
Cross-link 7-nitrogen on guanine or adenine within same strand, blocks reading by enzymes
What is Cisplatin used for?
Bladder, cervical, ovarian, testicular, melanoma, esophageal, head and neck, non-small cell lung tumors, colorectal cancer
Which drug reacts with sulfhydryl groups?
Cisplatin
