A Patient Exhibits a Rapid Loss of Responsiveness to a Drug

A patient exhibits a rapid loss of responsiveness to a drug during the first several hours of drug administration. Which event is most likely responsible for this effect?

A) up-regulation of drug metabolizing enzymes
B) down-regulation of drug metabolizing enzymes
C) internalization of cell membrane receptors
D) formation of receptor antibodies
E) phosphorylation of G protein-coupled receptors