smooth endoplasmic reticulum induction
The smooth ER is involved in the metabolism of various chemicals, and cells exposed to these chemicals show hypertrophy of the ER as an adaptive response that may have important functional consequences.
Protracted use of barbiturates leads to a state of tolerance, with a decrease in the effects of the drug and the need to use increasing doses. Patients are said to have "adapted" to the medication.
This adaptation is due to increased volume (hypertrophy) of the smooth ER of hepatocytes, which metabolizes the drug.
Barbiturates are modified in the liver by oxidative demethylation, which involves the P-450 mixed function oxidase system found in the smooth ER.
The role of these enzyme modifications is to increase the solubility of a variety of compounds (e.g., alcohol, steroids, eicosanoids, and carcinogens as well as insecticides and other environmental pollutants) and thereby facilitate their secretion.
Although this is often thought of as "detoxification," many compounds are rendered more injurious by P-450 modification. In addition, the products formed by this oxidative metabolism include reactive oxygen species, which can cause injury of the cell.
With prolonged use, the barbiturates (and many other agents) stimulate the synthesis of more enzymes, as well as more smooth ER. In this manner, the cell is better able to modify the drugs and adapt to its altered environment.
Cells adapted to one drug have increased capacity to metabolize other compounds handled by the system. Thus, if patients taking phenobarbital for epilepsy increase their alcohol intake they may have subtherapeutic levels of the antiseizure medication because of induction of smooth ER in response to the alcohol.
References
Robbins