PharmGKB summary

Mazaleuskaya, Liudmila L.; Theken, Katherine N.; Gong, Li; Thorn, Caroline F.; FitzGerald, Garret A.; Altman, Russ B.; Klein, Teri E.

doi:10.1097/fpc.0000000000000113

Cited by 128 publications

(50 citation statements)

References 101 publications

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“…This would have been especially useful for the opioids. Another example is that CYP2C8 was not tested by phenotype or genotype, but has implications in the metabolism of several NSAIDs, in particular diclofenac and ibuprofen [35,36,41,42].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Rollason

Lloret‐Linares

Lorenzini

et al. 2020

JPM

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This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities. The relation between the event and the result of the genotype and/or phenotype was evaluated using a semi-quantitative scale. Our analysis included 243 individual genotypic and/or phenotypic explorations. Genotypes/phenotypes were mainly assessed because of an ADR (n = 145, 59.7%), and the majority of clinical situations were observed with prodrug opioids (n = 148, 60.9%). The probability of a link between an ADR or a non-response and the genotypic/phenotypic status of the patient was evaluated as intermediate to high in 40% and 28.2% of all cases, respectively. The drugs in which the probability of an association was the strongest were the prodrug opioids, with an intermediate to high link in 45.6% of the cases for occurrence of ADRs and 36.0% of the cases for non-response. This study shows that the genotypic and phenotypic approach is useful to understand ADRs or therapeutic resistance to a usual therapeutic dosage, and can be part of the evaluation of chronic pain patients.

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Section: Discussionmentioning

confidence: 99%

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Rollason

Lloret‐Linares

Lorenzini

et al. 2020

JPM

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“…Recently, several studies suggested that Ibuprofen, a non-steroidal anti-inflammatory drug, should not be used in suspected cases of SARS-CoV-2 infection [55]. Non-steroidal anti-inflammatory drugs act in the selective or non-selective inhibition of the COX-1 and COX-2 ( Fig.…”

Section: Anti-inflammatory Drugs In the Treatment Of Patients With Comentioning

confidence: 99%

“…Non-steroidal anti-inflammatory drugs act in the selective or non-selective inhibition of the COX-1 and COX-2 ( Fig. 1), blocking the cascade of ARA and the formation of prostaglandins [10,55]. The inhibition of prostaglandin expression induces vasoconstriction, altering blood flow and favoring the activation of the "reninangiotensin" system, which can lead to an increased expression of ACE2 in the lungs, kidneys and intestines.…”

Section: Anti-inflammatory Drugs In the Treatment Of Patients With Comentioning

confidence: 99%

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19

Rogero

Leão

Santana

et al. 2020

Free Radical Biology and Medicine

138

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Studies have shown that infection, excessive coagulation, cytokine storm, leukopenia, lymphopenia, hypoxemia and oxidative stress have also been observed in critically ill Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) patients in addition to the onset symptoms. There are still no approved drugs or vaccines. Dietary supplements could possibly improve the patient's recovery. Omega-3 fatty acids, specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), present an anti-inflammatory effect that could ameliorate some patients need for intensive care unit (ICU) admission. EPA and DHA replace arachidonic acid (ARA) in the phospholipid membranes. When oxidized by enzymes, EPA and DHA contribute to the synthesis of less inflammatory eicosanoids and specialized pro-resolving lipid mediators (SPMs), such as resolvins, maresins and protectins. This reduces inflammation. In contrast, some studies have reported that EPA and DHA can make cell membranes more susceptible to non-enzymatic oxidation mediated by reactive oxygen species, leading to the formation of potentially toxic oxidation products and increasing the oxidative stress. Although the inflammatory resolution improved by EPA and DHA could contribute to the recovery of patients infected with SARS-CoV-2, Omega-3 fatty acids supplementation cannot be recommended before randomized and controlled trials are carried out.

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“…The isobutyl group in ibuprofen contains three classes of carbon: two primary (C3, C3), one tertiary (C2), and one benzylic (C1) ( Figure 3). As depicted in Figure 4, phase I metabolic hydroxylation occurs at the three carbons to varying extents [17][18][19][20][21][22]. 3-Hydroxyibuprofen is further oxidized via the aldehyde intermediate to the carboxylic acid metabolite.…”

Section: Ibuprofenmentioning

confidence: 99%

Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity

El‐Haj

Ahmed

2020

Molecules

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Alkyl moieties—open chain or cyclic, linear, or branched—are common in drug molecules. The hydrophobicity of alkyl moieties in drug molecules is modified by metabolic hydroxy functionalization via free-radical intermediates to give primary, secondary, or tertiary alcohols depending on the class of the substrate carbon. The hydroxymethyl groups resulting from the functionalization of methyl groups are mostly oxidized further to carboxyl groups to give carboxy metabolites. As observed from the surveyed cases in this review, hydroxy functionalization leads to loss, attenuation, or retention of pharmacologic activity with respect to the parent drug. On the other hand, carboxy functionalization leads to a loss of activity with the exception of only a few cases in which activity is retained. The exceptions are those groups in which the carboxy functionalization occurs at a position distant from a well-defined primary pharmacophore. Some hydroxy metabolites, which are equiactive with their parent drugs, have been developed into ester prodrugs while carboxy metabolites, which are equiactive to their parent drugs, have been developed into drugs as per se. In this review, we present and discuss the above state of affairs for a variety of drug classes, using selected drug members to show the effect on pharmacologic activity as well as dependence of the metabolic change on drug molecular structure. The review provides a basis for informed predictions of (i) structural features required for metabolic hydroxy and carboxy functionalization of alkyl moieties in existing or planned small drug molecules, and (ii) pharmacologic activity of the metabolites resulting from hydroxy and/or carboxy functionalization of alkyl moieties.

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PharmGKB summary

Cited by 128 publications

References 101 publications

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study

Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19

Metabolic-Hydroxy and Carboxy Functionalization of Alkyl Moieties in Drug Molecules: Prediction of Structure Influence and Pharmacologic Activity

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