Impacts of Epigenetics in Pharmacologic and Examples of Psychiatric Mental Health Cases

Impacts of Epigenetics in Pharmacologic and Examples of Psychiatric Mental Health Cases

The Agonist-to-Antagonist Spectrum of Action of Psychopharmacologic Agents

The agonist-to-antagonist spectrum is made up of two words that are important to be understood singly. An agonist is a chemical that binds to a receptor thereby activating it to trigger a biological response.  Antagonist, on the other hand, blocks the response mediated by the agonist. Antagonist causes an action opposite to that of the agonist, which reaction is called reverse agonist, to occur (Stahl, 2013). Once an agonist binds to a receptor, a full/conventional or partial agonist reaction may occur. As the concentration of the agonist increases, the occupancy of receptors also increases, consequently increasing the response (Stahl, 2013). The antagonist effect of a drug occurs when the antagonist increases in concentration thereby surmounting the activation effect of the agonist and inhibiting their response. A full agonist produces the maximal response system while a partial agonist produces a submaximal one.

The Actions of G-Couple Proteins and Ion-Gated Channels

There are two broad families of protein receptors involved in the opening and closing of the postsynaptic ion channels, namely g-couple proteins and ion-gated channels (Laureate Education Producer, 2016i). G protein-coupled receptors/seven transmembrane (7-TM) receptors form the largest protein family (about 600 – 1000 members) and are involved in many normal biological and pathological conditions (Inanobe & Kurachi, 2014). They have a diverse function and recognize many ligands including proteins, small molecules, and photons (Stahl, 2013). They specifically maintain the electrochemical gradient across the cell.

Ligand-gated ion channels (LGICs), on the other hand, are transmembrane ion channels found in the cellular membrane. They help in the opening and closing of the membrane to allow for the passage of ions such as Na+, K+, Ca2+, and/or Cl−. The human genome has over 400 genes for ion channels. Their opening and closing are dependent on the attachment of a chemical messenger, a ligand, such as a neurotransmitter (Inanobe & Kurachi, 2014).

The Role of Epigenetics in Pharmacologic Action

Different patients respond differently to various medications due to the genetic alterations that occur at an individual level. Epigenetic allows the understanding of these modifications in gene expressions that occurs in the DNA sequence of a gene for some patients. These genetic modifications are called epigenetic alterations. They include methylation, phosphorylation, acetylation, and ubiquitylation of DNA (Swathy & Banerjee, 2017). These alterations make many patients not to respond to standard therapies. The alterations not only regulate gene expression but also other cellular and biological functions related to allostasis, homeostasis, and disease (Rasool et al., 2015). These processes generally influence pharmacogenetics activities such as the contribution of receptors, drug transporters, and drug-metabolizing enzymes.

Impacts of Epigenetics in Pharmacologic and Examples of Psychiatric Mental Health Cases

The epigenetic alterations that occur at individual levels require doctors to provide personalized treatments to patients. Since epigenetic alterations differ from one patient to the other, physicians should do genetic screenings of patients to guide disease prediction and prevention and decision making on the medical recommendations and lifestyle and disease management practices that are best at an individual level (Rasool et al., 2015). For instance, in the case of Schizophrenia, the genetic modifications occur in the histones or DNA such as DNA methylation. For histone modification, HDAC (histone deacetylase) inhibitors drugs are recommended because they up-regulate the levels of reelin and GAD67. HMT (histone demethylase) inhibitors also prevent the demethylation of the H3K4 histone protein. As for DNA methylation, DNMT (DNA Methyltransferases) inhibitors are recommended because they raise the reeling levels of proteins and protein and GAD67 (Swathy & Banerjee, 2017). This requires physicians to make an individual genetic screening of a patient to determine the particular epigenetic alteration they experience before recommending drug prescriptions that are best and specific to them.

References

Inanobe, A., & Kurachi, Y. (2014). Membrane channels as integrators of G-protein-mediated signaling. Biochimica Et Biophysica Acta (BBA)-Biomembranes, 1838(2), 521-531.

Laureate Education (Producer). (2016i). Introduction to psychopharmacology [Video file]. Baltimore, MD: Author.

Rasool, M., Malik, A., Naseer, M. I., Manan, A., Ansari, S. A., Begum, I., & Kamal, M. A. (2015).