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Enzymes of the smooth ER help detoxify drugs and poisons, especially in liver cells. Detoxification usually involves adding hydroxyl groups to drugs, making them more soluble and easier to flush from the body. The sedative phenobarbital and other barbiturates are examples of drugs metabolized in the manner by smooth ER in liver cells. In fact, barbiturates, alcohol, and many other drugs induce the proliferation of the smooth ER and its associated detoxification enzymes. This, in turn, increases tolerance to the drugs, meaning that higher doses are required to achieve a particular affect, such as sedation. Also, because some other the detoxification enzymes have relatively broad action, the proliferation of the smooth ER in response to one drug can increase tolerance to other drugs as well. Barbiturate abuse, for example, may decrease the effectiveness of certain antibiotics and other useful drugs.

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