microtubule inhibitors. microtubules inhibitors microtubules inhibitors these drugs disrupt...
TRANSCRIPT
Microtubule
inhibitors
Microtubules Microtubules InhibitorsInhibitors
These drugs disrupt These drugs disrupt microtubules, which are , which are structures that pull the cell structures that pull the cell apart when it dividesapart when it divides
are derived from natural are derived from natural substances such as plant substances such as plant alkaloids
ANTIMICROTUBULE AGENTSANTIMICROTUBULE AGENTS
Microtubules Microtubules InhibitorsInhibitors
CCS Vinca alkaloids
Vinblastine Vincristine
TaxanesPaclitaxelDocetaxel
Podophyllotoxine
Vinblastine and VincristineVinblastine and Vincristine
Both drugs are cell cycle-specific Both drugs are cell cycle-specific because they block mitosis in because they block mitosis in
metaphase metaphase They bind to the microtubular They bind to the microtubular
protein, tubulin and thus protein, tubulin and thus preventing the cell from making preventing the cell from making
the spindles the spindles This results in This results in arrest of mitosis
at metaphase
Therapeutic UsesTherapeutic Uses Vinblastine Vinblastine is used in testicular is used in testicular
carcinoma, Hodgkin’s disease carcinoma, Hodgkin’s disease VincristineVincristine is used in the treatment of is used in the treatment of
acute leukemia in children, Wilm’s tumor, acute leukemia in children, Wilm’s tumor, and Hodgkin’s and non-Hodgkin’s and Hodgkin’s and non-Hodgkin’s lymphomaslymphomas
Adverse Effects:Adverse Effects: Common adverse effects for both drugs Common adverse effects for both drugs
include include cellulitis or phlebitis cellulitis or phlebitis if the drugs if the drugs extra vasate during injectionextra vasate during injection
Nausea, vomiting, diarrhea, and alopeciaNausea, vomiting, diarrhea, and alopecia
Toxicity of Vinblastine & Toxicity of Vinblastine & Vincristine Vincristine
Vinblastine Myelo-supression
Vincristine
NOT myelosuppress
ant
Peripheral neuropathy:
Depressed deep tendon reflex,
paresthesia, foot drop
TaxanesTaxanes
Interferes with cell division by Interferes with cell division by keeping the spindles from being keeping the spindles from being broken down (freeze)broken down (freeze)
Paclitaxel (Taxol) Paclitaxel (Taxol) shows good shows good activity against activity against metastatic metastatic breast breast cancer cancer and advanced and advanced ovarian cancerovarian cancer
Side effects; Side effects; neutropenia ‼, neutropenia ‼, peripheral neuropathyperipheral neuropathy
Filgrastim ( granulocyte colony stimulating Filgrastim ( granulocyte colony stimulating factor)factor)
V. Miscellaneous
Anticancer Agents
V- Miscellaneous AgentsV- Miscellaneous Agents
L-AsparaginaseL-Asparaginase HydroxyureaHydroxyurea MitotaneMitotane Retenoic acid derivativesRetenoic acid derivatives InterferonInterferon
L- AsparaginaseL- Asparaginase Asparagine is amino acid required Asparagine is amino acid required
for protein synthesis) for protein synthesis) Neoplastic cells require an Neoplastic cells require an
external source of asparagine external source of asparagine (from the plasma) because of their (from the plasma) because of their limited capacity to make sufficient limited capacity to make sufficient
asparagine to support growthasparagine to support growth
L-Asparaginase L-Asparaginase
L-asparaginaseL-asparaginase
Asparagine Asparagine aspartic acid aspartic acid
+Ammonia+Ammonia L-asparaginase hydrolyzes serum L-asparaginase hydrolyzes serum
asparagine and thus deprives the tumor asparagine and thus deprives the tumor cells of this nutrient required for protein cells of this nutrient required for protein
synthesissynthesis Most normal cells can synthesize Most normal cells can synthesize
asparagine and thus are less susceptible to asparagine and thus are less susceptible to the action of asparaginasethe action of asparaginase
Theraputic uses:Theraputic uses: L-asparginase is used to treat L-asparginase is used to treat childhood childhood acute lymphocytic acute lymphocytic leukemialeukemia in combination with in combination with
vincristine and prednisonevincristine and prednisone AAdverse effects: dverse effects:
Hypersensitivity reactions, Hypersensitivity reactions, liver affection and pancreatitisliver affection and pancreatitis
HydroxyureaHydroxyurea
Hydroxyurea interferes with conversion Hydroxyurea interferes with conversion of ribonucleotides to of ribonucleotides to deoxyribonucleotides by inhibiting deoxyribonucleotides by inhibiting Ribonucleotide Diphosphate ReductaseRibonucleotide Diphosphate Reductase. . In addition, hydroxyurea blocks the In addition, hydroxyurea blocks the incorporation of the thymidine incorporation of the thymidine nucleotide into the DNA strand.nucleotide into the DNA strand.
Melanoma; recurrent metastatic or Melanoma; recurrent metastatic or inoperable carcinoma of the ovaryinoperable carcinoma of the ovary
MitotaneMitotane
Adrenal carcinomaAdrenal carcinomaReduces excessive steroid Reduces excessive steroid
secretionsecretion Retenoic acid derivativesRetenoic acid derivatives
Remissions -- acute leukemiaRemissions -- acute leukemia
Drug combinations
The administration of combinations of The administration of combinations of drugs in the treatment of cancer drugs in the treatment of cancer
produces produces better results than a single better results than a single drug drug
A combination of drugs with A combination of drugs with different different toxic effectstoxic effects and and affecting affecting
different biochemical pathwaysdifferent biochemical pathways has higher anti-tumour activity without has higher anti-tumour activity without
additive toxicityadditive toxicity Therapy is Therapy is given intermittentlygiven intermittently to to allow recovery of normal tissue i.e. bone allow recovery of normal tissue i.e. bone
marrow and immune system that has marrow and immune system that has been affected by the drugsbeen affected by the drugs
Examples of drug Examples of drug combinations combinations
Acute lymphocytic leukemia:Acute lymphocytic leukemia: vincristine, methotrexate and 6-vincristine, methotrexate and 6-mercaptopurinemercaptopurine
Hodgkin's disease:Hodgkin's disease: vinblastine, vinblastine, doxorubicin and bleomycindoxorubicin and bleomycin
Non-Hodgkin's lymphomas:Non-Hodgkin's lymphomas: cyclophosphamide, doxorubicin, cyclophosphamide, doxorubicin, vincristine vincristine
Thank Thank youyou