#pharmacogenetics — Public Fediverse posts

another old, but interesting item - abstract only:

Involvement of human cytochrome P450 2D6 in the bioactivation of acetaminophen [2000]

Abstract

Acetaminophen (APAP), a widely used analgesic and antipyretic agent, can cause acute hepatic necrosis in both humans and experimental animals when consumed in large doses. It is generally accepted that N-acetyl-p-benzoquinone imine (NAPQI) is the toxic, reactive intermediate whose formation from APAP is mediated by cytochrome P450. Several forms of P450 in humans, including 2E1, 1A2, 2A6, 3A4, have been shown to catalyze the oxidation of APAP to NAPQI. We now present evidence which demonstrates that human cytochrome P450 2D6 (CYP2D6) is also involved in the bioactivation of APAP. The formation of NAPQI from APAP by cDNA-expressed CYP2D6 was examined. K(m) and V(max) values were 1.76 mM and 3.02 nmol/min/nmol of P450, respectively, such that the efficiency of CYP2D6 in the conversion of APAP to NAPQI is approximately one-third of that of CYP2E1. The contribution of CYP2D6 to the total formation of NAPQI from APAP (1 mM) in human liver was investigated using quinidine (1 microm) as a CYP2D6-specific inhibitor, and varied from 4.5 to 22.4% among 10 livers, with an average at 12.6%. The correlation between the contribution of CYP2D6 to NAPQI formation in human liver microsomes and the CYP2D6 activity probed by the O-demethylation of dextromethorphan was studied, and found to be strong (r(2) = 0.85), and significant (P <.0001). Our findings indicate that CYP2D6, one of the major P450 isoforms in humans and also one of the pharmacogenetically important isoforms, may contribute significantly to the formation of the cytotoxic metabolite NAPQI, especially in CYP2D6 ultra-rapid and extensive metabolizers and at toxic doses of APAP when plasma APAP concentrations reach 2 mM or more.

https://pubmed.ncbi.nlm.nih.gov/11095574/

#CYP2D6 #pharmacogenetics

Case report: metoclopramide induced acute dystonic reaction in adolescent CYP2D6 poor metabolizers [2023]

https://pmc.ncbi.nlm.nih.gov/articles/PMC10366597/

#metoclopramide #Reglan
#CYP2D6 #pharmacogenetics #pharamcogenomics #DrugMetabolism #pharmacology #gastroenterology #dopamine
#AdverseReactions #SideEffects

VIPs: Very Important Pharmacogenes
https://www.pharmgkb.org/vips

"The PharmGKB is a pharmacogenomics knowledge resource that encompasses clinical information including clinical guidelines and drug labels, potentially clinically actionable gene-drug associations and genotype-phenotype relationships."
https://www.pharmgkb.org/about

#pharmacogenomics #pharmacogenetics #pharmacy #pharmacology #genetics #genomics #DrugMetabolism
#medicine

Pharmacogenetics Applied to the Treatment of Psychiatric Illness |
Fralin Biomedical Research Institute

Presentation by David Oslin, M.D., U Penn.

To: All prescribers of any type of Rx drug

Please watch. This is important.

-- signed, mother of a child who had neuroleptic malignant syndrome from Reglan / metoclopramide

https://www.youtube.com/live/nl4v2IDSHp8?si=C2PxyUS-S9wHbw4k

#medicine #MedMastodon #tootRx #pharmacology #Pharmacogenetics #pharmacy