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Related Concept Videos

Pharmacogenetics and Pharmacogenomics: Overview01:29

Pharmacogenetics and Pharmacogenomics: Overview

Pharmacogenetics and pharmacogenomics examine how genetic factors influence an individual's response to drugs. While pharmacogenetics focuses on the impact of specific genetic variants on drug effects, pharmacogenomics takes a broader approach, studying how genetic variation across populations contributes to differences in drug responses. These fields aim to explain why individuals may experience varying levels of efficacy or adverse reactions to the same medication.Variability in drug...
Principles of Pharmacogenetics: Types of Genetic Variants01:27

Principles of Pharmacogenetics: Types of Genetic Variants

The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Metabolism: Overview01:27

Pharmacogenetics of Drug Metabolism: Overview

Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...

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Autonomic nervous system pharmacogenomics: a progress report.

Shelli L Kirstein1, Paul A Insel

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Area of Science:

  • Pharmacogenomics
  • Autonomic Nervous System Pharmacology
  • Molecular Genetics

Background:

  • Pharmacogenetics, the study of inherited drug response variations, has evolved into pharmacogenomics with advancements in molecular tools and genomics.
  • The autonomic nervous system (ANS) plays a crucial role in regulating physiological functions through neurotransmitters like acetylcholine (ACh) and norepinephrine.
  • Neuronal nicotinic acetylcholine receptors (nAChRs) and adrenergic receptors (ARs) are key ANS components with significant genetic variability.

Purpose of the Study:

  • To review current understanding of pharmacogenomics related to ANS components, focusing on nAChRs and ARs.
  • To examine the prevalence and impact of genetic variants in specific ANS receptor subtypes.
  • To identify challenges and limitations in current pharmacogenomic research for the ANS.

Main Methods:

  • Review of existing literature on pharmacogenomics of ANS receptor subtypes.
  • Analysis of genetic variants, including single nucleotide polymorphisms (SNPs), in muscarinic cholinergic receptors (mAChRs) and adrenergic receptors (ARs).
  • Evaluation of in vitro and in vivo study results associating genotypes with phenotypes like cardiovascular and metabolic responses.

Main Results:

  • Genetic variants are common in alpha(2)-AR and beta-AR subtypes, while less frequent in M(1-3) mAChRs and alpha(1)-ARs.
  • Studies attempting to link receptor genotypes (especially SNPs) to phenotypes have yielded inconsistent results.
  • Significant conceptual and methodological issues, including sample size, ethnicity, tissue specificity, and variant interactions, limit definitive conclusions.

Conclusions:

  • While progress has been made in identifying genetic variations affecting ANS drug response, the field is nascent.
  • Further research is needed to overcome methodological limitations and define critical genetic determinants.
  • Understanding these genetic factors is essential for advancing human physiology and pharmacology related to the ANS.