Anticancer drugs decreased accumulation

Correct answer = D. Elevated blood pressure would not be expected to markedly influence the type of antimicrobial treatment employed. Anticancer drugs often suppress the immune function, and these patients require additional antibiotics to eradicate infections. Impaired renal function may lead to accumulation of toxic levels of antimicrobial drugs. Renal and hepatic function are often decreased among the elderly. Impaired liver function may lead to the accumulation of toxic levels of antimicrobial drugs. 

The chemical structures of four commonly used anticancer drugs are shown in Fig. 15-17. Methotrexate was the first "true anticancer drug, synthesized in 1949, and has been in clinical use for treatment of a variety of cancers since the early 1950s. Methotrexate is a potent inhibitor of dihydrofolate reductase with an inhibition constant (Kt) for interaction with the enzyme of 10 9Af. Inhibition of this enzyme in a cell leads to major accumulation of DHF to concentrations of 2.5 fiM, and minor decreases in THF. Marked decreases in THF may not be seen due to the release of bound THF in methotrexate-treated cells. The high levels of DHF are toxic to the cell, inhibiting the reaction catalyzed by thymidylate synthase,... 

Metallothionein is also induced by a variety of nonmetals, and exposure to these agents often can cause tesistance to anticancer drugs such as cisplatin (Basu and Lazo 1991). Expression of v mos can attenuate the glucocorticoid-induced metallothionein expression and cisplatin resistance. Transcriptional activation of c-Ha-ras oncogene expression in murine NIH 3T3 cells with dexamethasone produces an increase in metallothionein content and a decrease in cisplatin accumulation (Isonishi et al. 1991). The ability of dexamethasone to affect the sensitivity of cells to electrophilic antineoplastic agents could be of some clinical interest because of its frequent usage as an antiemetic. 

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