Metabolism genetic factors

Various factors affect the activities of the enzymes metabolizing xenobiotics. The activities of these enzymes may differ substantially among species. Thus, for example, the possible toxicity or carcinogenicity of xenobiotics cannot be extrapolated freely from one species to another. There are significant differences in enzyme activities among individuals, many of which appear to be due to genetic factors. The activities of some of these enzymes vary according to age and sex. 

Genetics and metabolic risk factors mediate other less common causes of cirrhosis. These diseases vary widely in prevalence, disease progression, and treatment options. 

Bosron WF, Ehrig T, Li T-K. Genetic factors in alcohol metabolism and alcoholism. Semin Liver Dis 1993 13 126-135. 

A broad variety of diseases may cause neuropathic pain. The majority of diseases associated with neuropathic pain involve the peripheral nervous system. These diseases include traumatic injuries hereditary, metabolic, inflammatory or paraneoplastic neuropathies and infections. However, neuropathic pain can also be caused by injuries or disorders affecting the spinal cord or the brain (central neuropathic pain) tumors stroke epilepsy and neurodegenerative disorders [20]. Genetic factors appear to contribute to inter-individual differences in the susceptibility to neuropathic pain. 

Nebert, D.W. and Felton, J.S. Importance of genetic factors influencing the metabolism of foreign compounds. Fed. Proc. (1976) 35 1133-1141. 

The metabolic and clinical condition of the patient also plays a role The individual with good kidney and liver function will respond quite differently to a drug than the patient who is not able to detoxify or excrete the compound. The user of laboratory data must be aware of the possible occurrence of drug-mediated enzyme induction, biological variations in the rate of clearance and storage in depot areas (B24), and the genetic factors that play a role in the toxicity of a drug (L2). 

There is no other genetic factor, which has a greater effect on drug kinetics than genetically-determined drug metabolism. 

The dose and frequency of administration required to achieve effective therapeutic blood and tissue levels vary in different patients because of individual differences in drug distribution and rates of drug metabolism and elimination. These differences are determined by genetic factors and nongenetic variables, such as age, sex, liver size, liver function, circadian rhythm, body temperature, and nutritional and environmental factors such as concomitant exposure to inducers or inhibitors of drug metabolism. The discussion that follows summarizes the most important of these variables. 

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