Anti cancer drugs (part 2/3) - lipincott review for preparation of test and interview

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ANTIBIOTICS

Anti biotics anti cancer review PharmaPhila PharmacoEasy pharmacology screening test and interview preparation


Cell non-specific

Dactinomycin

 called Actinomycin D…used with Vincristine in Wilms tumor…with MTX in Soft tissue carcinoma

MOA= form stable Dactinomycin-DNA compex b/w base pair of DN …interfere with DNA-depenndent RNA polymerase… single stand break by free radical or by action on Topoisomerase ll

S.E=Extravasation, Stomatitis,

Doxorubicin & Daunorubicin

 Anthracycline antibiotics…Idarubicin, Epirubicin are analogof Daunorubicin…

MOA=Doxorubicin induced free radical…memb. Lipid peroxidation…DNA strand scission…Direct oxidation of Purine, Pyrimidine, Thiol, Amine

S.E= Cardiotoxicity…Dark red color vein….Dexrazone (iron chelator) used to prevent cardiotoxicity….↑skin pigmentation

Bleomycin

G2 Phase specific…mix of Cu-chelating Glycopeptide….

MOA= DNA-Bleomycin Fe2+ undergo into Oxidation Bleomycin-Fe3+…Superoxide form attack on Phosphodiester bond…Scission of DNA strand

S.E= Pulmonary toxicity “Bleomycin lung”.

ALKYLATING AGENTS

Alkylating agent covalently binding with Nucleophilic group…Non-specific…not discriminate b/w divide & resting cell….Mutagenic & Carcinogenic

Mechlorethamine

Nitrogen mustard used in World war ll….cause Lymphocytoppenia

“Bifunctional agent” bind to 2 separate Nucleotide at position “7”on DNA

MOA= Alkylate N7Nitrogen of Guanine… lead to cross-linkage b/w DNA strand… Strand

breakage…G1 ,S Phase…Powerful Blistering agent..

Used in Hodgkin disease

S.E= Extravasation, Sodium Thiosulphate used to remove it…Herpes zoster infection due to Immunosuppression…

Cyclophosphamide & Ifosfamide=Mustard agent…..MESNA (sodium-2-MercaptoEthane sulfonate) used to ↓toxicity…

OH into Phosphoramide & Acrolein which alkylate DNA

S.E= Fibrosis of Bladder…Ifosfamide metabolize into ChlorAcetAldehyde cause Sec.Malignancies…Also cause Amenorrhea, Testicular atrophy,Aspermia

Carmustine & Lomustine

 Nitrosourea…Penetrate CNS…used in Brain tumor…

Alkylate DNA…also Carbamoylation of Amino acid

S.E= Hematopoietic depression, Pulmonary fibrosis,

Streptozocin

Nitrosourea…toxic to β-cells of Islet of Langharhan…used in Insulinoma…

 S.E; diabetogenic

Dacarbazine

used in Melanoma… metabolize into MTIC(MethylTriazenoImidazole Carboxamide) active & form Carbonium ion… alkylating agent…

Temozolamide

 metabolize into Active MTIC inhibit O6-guanine DNA –alkyltransferase .also cause methylation of DNA…

S.E; Neutropenia, Thrombocytopenia

Melphalan

 used in multiple Myeloma…

Buslfan= Leukemogenic

MICROTUBULE INHIBITOR

Mitotic Spindle= required for locomotion…larger part of Cytoskeleton…consist of Chromatin & Microtubules…also essential for Partitioning of DNA 

Vincristine & Vinblastine

 obtained from Vinca rosa(Periwinkle plant)….Vinca alkaloid… Vincristin (Oncovin) is “O” in POMP regimen

POMP for leukemia & MOPP for Hodgkin lymphoma 

MOA=”M”phase Specific….bind to Microtubule…block ability of Tubulin to Polymerize to 

form Microtubule…Paracrystalline aggregates formed…Dysfunctional Spindle

S.E= Hyperuricemia,Phelibitis, Cellulitis, Constipation with VX..Granulocytopenia with VBL(vinorelbine) 

Paclitaxel & Docetaxel

Taxol…from Needle of Pacific Yew plant…in Ovarian & 

Metastatic BREAST cancer 

MOA= G2/M phase non-specific…bind to β-tubulin…Promote Polymerization & Stabilize it…

Overly stable Microtubule nonfunctional

S.E= Neutropenia (Pt. with <1500 Neutrophil/mm3 not used) 

Filgrastim used to overcome… Hypersensitivity, overcome with H1-Blocker.

Paclitaxel cause Asymptomatic Bradycardia, Docetaxel cause Fluid retention


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