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Pharmacology Anti-Neoplastic Agents 11a6ee3b

Resistance to Methotrexate develops due to?

A
Rapid Cancer cell multiplication
B
Deficiency of thymidylate kinase
C
Deficiency of thymidylate synthetase
D
Increased production of dihydrofolate reductase
High-Yield Explanation
Ans. is 'd' i.e., Increased production of dihydrofolate reductase Methotrexate resistanceo Methotrexate resistance may be due to any of the following mechanismDefective transport into cellsProduction of altered form ofDHFR that have decreased affinity for methotrexateIncreased concentrations of intracellular DHFR through gene amplification or altered gene regulationDecreased ability to synthesize methotrexate polyglutamatesIncreased expression o f a drug efflux transporter of the MRP (multidrug resistance protein) classDrugMost common mechanism of resistanceo Beta lactamsInactivating enzyme (Beta lactamase)o TetracyclinesEfflux pump (decreased concentration in the cell)o ChloramphenicolInactivating enzyme (acetyl transferase)o MacralidesDecreased permeability or efflux pumpo FluoroquinolonesAltered DNA gyrase with reduced affinityo AminoglycosidesInactivating enzyme

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