Vinca Alkaloids as Mitotic Inhibitors Flashcards

Study Notes

Vinca Alkaloids Overview

Vinca alkaloids serve as inhibitors of microtubule polymerization, playing a critical role in cancer treatment.
Two primary drugs: Vinblastine and Vincristine, both antineoplastic and antimitotic agents.

Vinblastine

Known as Velban (Eli Lilly), with a classification as an Antineoplastic Antimitotic Agent.
Targets the M-phase of the cell cycle, preventing cancer cell division.
Mechanism of Action (MOA):
- Binds to tubulin during the G2 phase.
- Prevents mitotic spindle formation, causing cellular arrest in M-phase.
- Also inhibits RNA synthesis due to effects on DNA-dependent RNA polymerase.
Indications include testicular cancer, Hodgkin's disease, non-Hodgkin's lymphoma, breast carcinoma, and choriocarcinoma.
Dosage: 6 mg/m² IV weekly; or 0.3-0.4 mg/kg IV every 3 weeks for testicular cancer.
Pharmacokinetics (PK):
- Erratic oral absorption; biphasic plasma clearance with t1/2 of 4.5 min.
- Elimination half-life is 23 hours with 80% bound to plasma proteins.
- Primarily metabolized in the liver; small amount excreted unchanged in urine.
Toxicities include gastrointestinal disturbances, leukopenia, occasional thrombocytopenia and anemia, and mild neurological issues.

Vincristine

Known as Oncovin (Eli Lilly), with a similar classification as an Antineoplastic Antimitotic Agent.
Also specific to M-phase but can affect S-phase at high concentrations.
Mechanism of Action (MOA): Similar to Vinblastine, inhibiting spindle formation.
Indications involve acute lymphoblastic leukemia (especially in children), Wilms' tumor, neuroblastoma, rhabdomyosarcoma, non-Hodgkin's lymphoma, and Hodgkin's disease.
Dosage: 1.4-1.5 mg/m² IV weekly; maximum of 2 mg for individual patients.
Pharmacokinetics (PK):
- Poor oral absorption; biphasic plasma clearance with t1/2 of 5 min.
- Elimination half-life is 20 hours; primarily excreted in feces.
Notable toxicities include mild sensory neuropathy, severe peripheral nervous system damage, and constipation, amongst others.

4-Deacetyl Vinblastine

Identified as a major human metabolite of Vinblastine with clinical relevance.

Vindesine

Known as Eldisine and is a semisynthetic derivative of Vinblastine with modified functional groups.
Classified similarly as an Antineoplastic Antimitotic Agent.
Uses include management of malignant melanomas, breast carcinoma, and acute lymphoblastic leukemia.
Dosage: 3 mg/m² IV weekly, exhibiting a serum half-life of 24 hours.
Toxicities mirror those of Vinblastine and Vincristine but are generally less severe, including gastrointestinal and hematologic effects.

Description

Test your knowledge of Vinca alkaloids, their structures, classifications, and mechanisms of action as mitotic inhibitors. These flashcards cover essential definitions and terms related to this important class of antineoplastic agents. Perfect for students studying pharmacology or oncology.