Smoking drug metabolism affected

The apparent variable effect of age on drug metabolism is probably due to the fact that age is only one of many factors that affect drug metabolism. For example, cigarette smoking, alcohol intake, dietary modification, drugs, viral illness, caffeine intake, and other unknown factors also affect the rate of drug metabolism. 

Often a single drug will have many metabolites including some which have effects similar to the parent (cyclosporin, chlorpromazine). Microsomal drug metabolism can be stimulated by medications such as the barbiturate phenobarbital or by cigarette smoke. Metabolism may be slowed by medications such as the monoamine oxidase inhibitors which are used in treatment of psychiatric disease. There are genetic and sex-related differences as well as age-related effects which may affect an individual patient s metabolism. 

In general, a poor nutritional state and a diseased state can be expected to influence the sensitivity to chemicals. This is of special concern when the target organ of the toxic effect is affected by the disease, or when the metabolism and elimination are disturbed. Also lifestyle factors such as alcohol, tobacco smoke, and drugs may modify the toxic responses of chemicals. 

Increasing evidence indicates that diet/nutrition plays an important role in modulating the action and/or metabolism of a number of chemicals, drugs and environmental pollutants. Nutrients are essential for all fundamental cellular processes. The nutritional status of the affected subject may, therefore, influence cellular susceptibility to the effect of xenobiotics, including those from cigarette smoke. While the precise role of vitamin E in cellular metabolism is not yet clear, the vitamin may protect essential cellular components from the adverse effects of xenobiotics either via a free radical scavenging mechanism or as a component of the cell membrane (10-11). Administration of vitamin E has been shown to lessen the toxicity of a variety of compounds (12-16). 

The development of easy-to-use assays for determining theophylline blood levels afforded a handle on maintenance of effective but nontoxic levels. The relatively good availability of such assays in the United States probably contributed to the historical preference for theophylline treatment by U.S. physicians. Carefiil titration of the dose must be done on a patient-by-patient basis because individual rates of metabolism vary widely. Most ( 85%) of an oral dose of theophj line is metabolized by liver microsomal enzymes. As a result many drugs, eg, cimetidine [51481-61-9], anticonvulsants, or conditions, eg, fever, cigarette smoking, liver disease, which affect liver function alter theophylline blood levels. 

The metabolism of erlotinib is markedly affected by other drugs that are potent inhibitors (e.g. ketoconazole) or inducers (e.g. ri-fampicin) of the cytochrome P450 isoenzyme CYP3A4. Alternatives to these drugs should be used where possible if not, alteration of the dose of erlotinib is required. The concurrent use of temozolomide may either reduce or increase erlotinib levels, depending on the dose of erlotinib. Smoking increases the metabolism of erlotinib. 

The rates and routes of metabolism can vary with age and the lower rates and reduced routes of metabolism usually seen in the yoimg and the old can make them more susceptible to drug action. Differences in hormonal levels, in particular, can lead to differences in metabolism between sexes. Dietary and environmental factors such as the presence of alcohol and cigarette smoke can affect metabolism, as can certain disease conditions, e.g., liver disorders, diabetes. Such conditions can lead to decreased enzyme activity, altered hepatic blood flow, and changes in plasma protein levels which, in turn, can affect circulating active drug levels. 

A calorimetric study [18] was done to estimate whether propranolol and terbutaline affected human erythrocyte metabolism after short treatment with therapeutic doses of the drugs. The study had a double blind, cross-over design. Propranolol and terbutaline slow-release 7.5 mg were randomly administered twice daily for 1 week to 15 healthy non-smoking males. Placebo tablets of similar shape and colour were employed. Blood samples were taken after seven days on each drug. A "wash-out" period of at least two weeks separated each study period. Neither of the drugs was found to influence overall erythrocyte metabolism or the energy expenditure connected with the Na+ K pump. 

---