Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The field of pharmacogenomics seeks to understand how an individual's unique gene sequence can affect their response to certain drugs. It is particularly relevant in anesthesia when the interindividual response to pain medication is essential. Codeine and tramadol are prodrugs metabolized by CYP2D6, polymorphisms of which can cause dangerous or even fatal levels of their metabolites, or decrease the level of metabolites to decrease their analgesic effect. Many other opioids are metabolized by CYP2D6 or CYP3A5, of which loss-of-function variants can cause dangerous levels of these drugs. The OCT1 transporter facilitates the movement of drugs into hepatocytes for metabolism, and variants of this transporter can increase serum levels of morphine and O-desmethyltramadol. Many NSAIDs are metabolized by CYP2C9, and there is concern that variants of this enzyme may lead to high serum levels of these drugs, causing gastrointestinal bleeding, however the data does not strongly support this. The ABCB1 gene encodes for P-glycoprotein which facilitates efflux of opioids away from their target receptors. The C3435T SNP may increase the concentration of opioids at target receptors, although the data is not conclusive. Catechol-O-Methyltransferase (COMT) is shown to indirectly upregulate opioid receptors. Certain haplotypes of COMT have been demonstrated to have an effect on opioid requirements. The OPRM1 gene codes for the mu-opioid receptor, and there is conflicting data regarding its effect on analgesia and opioid requirements. Overall, there is a fair amount of conflicting data in the above topics, suggesting that there is still a lot of research to be done on these topics, and that pain perception is multifactorial, likely including many common genetic variants.
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PMID:Pharmacogenomics of analgesics in anesthesia practice: A current update of literature. 3010 20

Several over-the-counter (OTC) drugs are known to be misused. Among them are opioids such as codeine, dihydrocodeine, and loperamide. This work elucidates their pharmacology, interactions, safety profiles, and how pharmacology is being manipulated to misuse these common medications, with the aim to expand on the subject outlined by the authors focusing on abuse prevention and prevalence rates. The reviewed literature was identified in several online databases through searches conducted with phrases created by combining the international non-proprietary names of the drugs with terms related to drug misuse. The results show that OTC opioids are misused as an alternative for illicit narcotics, or prescription-only opioids. The potency of codeine and loperamide is strongly dependent on the individual enzymatic activity of CYP2D6 and CYP3A4, as well as P-glycoprotein function. Codeine can also be utilized as a substrate for clandestine syntheses of more potent drugs of abuse, namely desomorphine ("Krokodil"), and morphine. The dangerous methods used to prepare these substances can result in poisoning from toxic chemicals and impurities originating from the synthesis procedure. OTC opioids are generally safe when consumed in accordance with medical guidelines. However, the intake of supratherapeutic amounts of these substances may reveal surprising traits of common medications.
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PMID:Pharmacological Aspects of Over-the-Counter Opioid Drugs Misuse. 3286 17