Foundational Neuroscience? The foundations of neuroscience a

  Foundational Neuroscience 

The foundations of neuroscience are based on the ability to understand the pathophysiology of psychiatric disorders in relation to the central nervous system. Psychopharmacologic agents have two mechanisms of action which are agonist and antagonist. Agonists emulate and link to and stimulate a receptor, while antagonists fasten to a receptor but stop them from manufacturing a particular response. Psychoactive medications can reduce activity at the synapse (antagonist) or increase activity at the synapse (agonist) (Barron, 2021). A partial agonist maintains reasonable action and solely creates half impact of a complete agonist. An incomplete or partial agonist can represent an agonist and equally be an antagonist and have the power to block the receptors from the full agonist. The molecular impact can be down restrained by antagonist medications which can attach to a receptor without any inherent reaction (Rosenthal & Burchum, 2018).

According to Berg &Clarke (2018), agonists have affinity and efficacy; this means they have target receptors that they bid to and can change receptor functionality to produce the desired response. Alternatively, antagonists have an affinity but cannot make a response; therefore, the antagonist will reduce the receptor ability of an agonist hence reduction in receptor response. Where there is a full agonist, the essential functions of an antagonist can be blocked as a full agonist produces a maximum response.

The couple proteins and ion-gated channels are prominent dualistic families of the receptor proteins, and their significant role is the closing and opening of the postsynaptic channels. The receptor is the first family identified as an ionotropic disorder and has a direct link to the ion channel. A neurotransmitter is considered the second family and is the metabotropic receptor, and one or more metabolic steps determine the movement of ions. The receptors have no ion channels and are directly affected by the initiation of the intermediate molecules. Metabotropic receptors are comprised of monomeric proteins that have an extracellular domain. The inotropic receptors bring together the transmitter bidding and channel function hence developing a single molecular entity known as a ligand-gated ion channel. The receptors are comprised of four or five individual protein subunits. The metabolic receptors activate the g-proteins, thus disassociating from the receptor and developing a direct interaction with the ion channel or binding to other effective proteins (Badheka et al., 2017).

Epigenetics is the study of changes that influence the phenotype without influencing the variation in the genotype. It focuses on heritable but rescindable gene expression variations without altering the primary DNA sequence. Epigenetic regulation plays a significant role in upholding normal cell phenotypic activity and treating illnesses such as neurogenerative disorders like dementia (Feinberg, 2018).

Antipsychotics are commonly prescribed for the treatment of psychosis and behavioral and psychological symptoms of dementia in elderly patients. The treatment is often ineffective and causes side effects (McClarty et al., 2018). When prescribing medication, it is always essential to individualize the patient and understand their history to assess their genetic implications to treatment and diagnosis. Although aging can affect drug metabolism and clearance, other pharmacokinetic and pharmacodynamics changes due to age-induced epigenetic alterations also impact important processes for antipsychotic function. Mechanisms of epigenetics account for some of the altered efficacy and increased side effects seen in patients, especially elderly patients, that involve histone modifications that can adversely affect the efficacy of antipsychotics and increased side effects in elderly patients (McClarty et al., 2018). Individualizing patient treatment helps the Psychiatric Nurse Practitioner (PNP) understand how to treat the psychotic symptoms presented in each case and how to treat the side effects that follow antipsychotic medication. Understanding that neurogenerative illness starts slowly and worsen with time and it cannot be treated, but its symptoms can be controlled (Cox et al., 2018), will help the PNP when treating patients with illness such as Alzheimer's to know better whether the focus in on controlling the symptoms or reversing the disease process.

 References

Barron, S. (2021). Psychopharmacology. In R Biswas-Diener & E Diener (Eds), Noba textbooks series: Psychology. Champaign, IL: DEF publishers. https://noba.to/umx6f2t8Links to an external site.

Rosenthal, L. D., & Burchum, J. R. (2018). Lehne’s pharmacotherapeutics for advanced practice providers. St Louis, MO: Elservier

Badheka, D., Yudin, Y., Borbiro, I., Hartle, C. M., Yazici, A., Mirshashi, T., & Rohacs, T. (2017). Inhibition of transient receptor potential melastatin 3ion channels by G-proteins By subunits. Elife, 6, e26147.https://elifesciences.org/articles/26147Links to an external site.

Feinberg, A. p. (2018). The key role of epigenetics in human disease prevention and mitigation. New England Journal of Medicine, 378(14), 1323–1334.

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse agonism and functional selectivity. The International Journal of Neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071Links to an external site.

McClarty, B. M., Fisher, D. W., & Dong, H. (2018). Epigenetic alterations impact on antipsychotic treatment in elderly patients. Current treatment options in psychiatry, 5(1), 17-29

Coc, P. A., Kostrzewa, R. M., & Guillemin, G. J. (2018). BMAA and neurodegenerative illness. Neurotoxicity research. 33(1), 178–183. https://limks.springer.com/article/10.1007/s12640-017-9753

Types of Actions of Psychopharmacologic Agents

Psychopharmacologic agents can have different effects on the brain depending on their position on the agonist-to-antagonist spectrum of action. An agonist is a drug that binds to a receptor and activates it, leading to a physiological response. On the other hand, antagonists bind to the same receptor but do not activate it; instead, they block other molecules from binding to it. Agonists and antagonists are both used to treat psychiatric disorders, such as depression, which is often treated with selective serotonin reuptake inhibitors (SSRIs) (Lenci et al., 2021). The agonist-to-antagonist spectrum of action of psychopharmacologic agents is essential in understanding how drugs interact with the brain and how they can be used to treat mental health conditions. By understanding this spectrum, doctors can better choose the proper medication for a patient's individual needs.

Further, Partial agonists bind to the same receptor as an agonist but activate it to a lesser degree. In contrast, inverse agonists bind to the same receptor and cause it to become inactive. Therefore, the different ways that drugs can interact with receptors can significantly impact the efficacy of psychopharmacologic treatment (Deluigi et al., 2021). For instance, partial agonists can be beneficial in cases where a milder effect is desired, such as in opioid addiction treatment, where buprenorphine produces a lower opioid effect than an agonist. Inverse agonists can be beneficial in cases where a receptor's products need to be reduced, such as in the treatment of schizophrenia, where clozapine is used to reduce the effects of a receptor.

Comparing the Actions of G Protein Coupled Receptors and Ion Gated Channels

The primary action of G-coupled proteins is to act as a signaling pathway for neurons in the brain. When a ligand binds to the protein, it triggers a signal transduction pathway that leads to the production of a secondary messenger, such as cyclic AMP, which then triggers a cascade of events in the cell (Duncan et al., 2020). These events can include the activation of specific genes or the release of neurotransmitters. G-coupled proteins are essential for various neurological functions, including memory formation, learning, and the control of hormone release. In contrast, the direct action of ion-gated channels is to regulate the flow of ions across the cell membrane. These channels can be selectively opened or closed in response to various stimuli, allowing specific ions to pass through the membrane (Wang et al., 2020). Ion-gated channels play an essential role in neuronal signaling. They allow ions such as sodium and potassium to enter and exit the cell, creating a wave of electrical activity essential for the brain to function correctly. Also, Ion-gated channels regulate ion concentrations within the cell, which can affect the activity of enzymes, the metabolism of the cell, and other processes.

The Role of Epigenetics in Pharmacologic Action

The term "epigenetics" describes heritable modifications to gene expression that take place without a change in the DNA sequence. These alterations are brought about by the DNA molecule receiving additional or fewer chemical markers, such as methyl groups. These epigenetic marks can affect how a gene is expressed, which can contribute to pharmacologic action (Hogg et al., 2020). For example, drugs that target enzymes involved in epigenetic modifications, such as histone deacetylases, could alter gene expression and, consequently, the pharmacologic action of a drug. By understanding the role of epigenetics in gene expression, it can be possible to develop drugs that are more effective and have fewer side effects.

Impact of Medication Action on Prescribing Medications to Patients

Understanding the agonist-to-antagonist spectrum of action of psychopharmacologic drugs and the impact of epigenetics in gene expression is crucial for psychiatric mental health nurse practitioners. This knowledge can help us as practitioners to better understand how drugs interact with receptors in the brain and how these interactions can be used to treat mental health disorders (Morrow et al., 2016). By considering this information when prescribing medications, practitioners can tailor their treatments to the individual needs of their patients. For example, when prescribing an antidepressant to a patient, the practitioner can consider the patient’s history and medical conditions, as well as the agonist-to-antagonist spectrum of action of the drug. Suppose the patient has a history of anxiety. In that case, the practitioner can opt for a selective serotonin reuptake inhibitor (SSRI), which is an agonist of the 5-HT receptor, as this type of drug is effective for this condition (Hogg et al., 2020). Alternatively, suppose the patient has a history of depression. In that case, the practitioner can opt for a partial agonist, such as bupropion, as this type of drug has been shown to have fewer side effects than a full agonist.

References

Deluigi, M., Klipp, A., Klenk, C., Merklinger, L., Eberle, S. A., Morstein, L., Heine, P., Mittl, P. R. E., Ernst, P., Kamenecka, T. M., He, Y., Vacca, S., Egloff, P., Honegger, A., & Plückthun, A. (2021). Complexes of the neurotensin receptor 1 with small-molecule ligands reveal structural determinants of full, partial, and inverse agonism. Science Advances, 7(5). https://doi.org/10.1126/sciadv.abe5504

Duncan, A. L., Song, W., & Sansom, M. S. P. (2020). Lipid-Dependent Regulation of Ion Channels and G Protein–Coupled Receptors: Insights from Structures and Simulations. Annual Review of Pharmacology and Toxicology, 60(1), 31–50. https://doi.org/10.1146/annurev-pharmtox-010919-023411

Hogg, S. J., Beavis, P. A., Dawson, M. A., & Johnstone, R. W. (2020). Targeting the epigenetic regulation of antitumour immunity. Nature Reviews Drug Discovery, 19(11), 776–800. https://doi.org/10.1038/s41573-020-0077-5

Lenci, E., Calugi, L., & Trabocchi, A. (2021). Occurrence of Morpholine in Central Nervous System Drug Discovery. ACS Chemical Neuroscience, 12(3), 378–390. https://doi.org/10.1021/acschemneuro.0c00729

Morrow, E. M., Roffman, J. L., Wolf, D. H., & Coyle, J. T. (2016). Psychiatric Neuroscience: Incorporating Pathophysiology into Clinical Case Formulation. Massachusetts General Hospital Comprehensive Clinical Psychiatry, 543–564. https://doi.org/10.1016/b978-0-323-04743-2.50042-1

Wang, Y., Yutuc, E., & Griffiths, W. J. (2020). Neuro‐oxysterols and neuro‐sterols as ligands to nuclear receptors, GPCRs, ligand‐gated ion channels and other protein receptors. British Journal of Pharmacology. https://doi.org/10.1111/bph.15191