Pharmacogenetics of Opioid and Alcohol Addiction
Opiate and alcohol addiction are serious health and social problems, associated with high morbidity and mortality. The manifestation and development of these complex diseases involves genetic factors, environmental factors, and the pharmacokinetic and pharmacodynamic properties of the psychoactive substance.
Among the main therapeutic indications of opioids are substance abuse programs and treatment of pain. Classic welfare programs are aimed at drug abuse patient detoxification programs or opiate agonist maintenance, being the methadone maintenance program (MMP) the best known. However, for some of the most seriously affected drug users, these programs are ineffective, hence the existence of alternative therapies such as Heroin Prescription Program (HPP) in Switzerland and Holland. These programs are located within a therapeutic approach and integrated harm reduction in the public health network for drug abuse. In other countries, like Germany and Spain, several clinical trials with PPH have been successfully conducted.
The establishment of an individualized prescription of opioids safely and effectively is a difficult task for the physician, due to interindividual variability in the individual’s response to the substance and the individual risk of the administered dose which is within therapeutic range.
In recent years, numerous studies have described several genes involved in opioid and alcohol dependence. Among genetic variations that affect opioid receptors, the SNP that affects the mu receptor in position 118 seems to be one of the most clinically relevant in alcohol and opioid addiction. Current pharmacotherapy targeted to alcohol addiction also has been associated to gene polymorphisms in opioid receptors.
Polymorphisms in the different isoenzymes of CYP450 (CYP3A4, CYP2D6, CYP2B6, CYP1A2, CYP2C9, and CYP2C19) also significantly influence in the pharmacokinetics and the effects of opioids and concomitant treatment of patients.
Pharmacogenetic analysis, focused on the opioid system gene polymorphisms and interactions related to CYP450, together with the study of clinical parameters may be a useful tool for the physician to adjust the appropriate pharmacotherapeutic dose in each particular case.
This chapter will review the most relevant gene polymorphisms related to alcohol and opioid addiction in the opioid system and the CYP450 complex.
KeywordsGene Polymorphism Opioid Receptor Alcohol Dependence Opioid Dependence Sodium Oxybate
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