146. Discussion: Foundational Neuroscience As a psychiatric nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat patients, you must not only understand the pathophysiology of psychiatric disorders but also how medications for these disorders impact the central nervous system. These concepts of foundational neuroscience can be challenging to understand. Therefore, this Discussion is designed to encourage you to think through these concepts, develop a rationale for your thinking, and deepen your understanding by interacting with your colleagues. Photo Credit: Getty Images/Cultura RF For this Discussion, review the Learning Resources and reflect on the concepts of foundational neuroscience as they might apply to your role as the psychiatric mental health nurse practitioner in prescribing medications for patients. By Day 3 of Week 2 Post a response to each of the following: Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments. Compare and contrast the actions of g couple proteins and ion gated channels. Explain how the role of epigenetics may contribute to pharmacologic action. Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medications action. Read a selection of your colleagues’ responses. By Day 6 of Week 2 Respond to at least two of your colleagues on two different days in one of the following ways: If your colleagues posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained. If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective. Discussion 1 R 1. Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact the efficacy of psychopharmacologic treatments. Psychopharmacologic agents can demonstrate their therapeutic effects by regulating the action of neurotransmitters at post-synaptic receptor sites. Agonists increase the effects of neurotransmitters by binding to and activating specific receptor sites (Kowalski et al., 2017). They can be used to treat disorders with low levels of a neurotransmitter. Antagonists decrease or block the effects of neurotransmitters by binding to specific receptor sites without activating them. They can be used to treat disorders characterized by too much of a neurotransmitter. Partial agonists produce partial or submaximal effects at receptor sites, which can be therapeutic when a reduced response is desired. Many receptors retain a baseline effect even when they are not bound with a neurotransmitter, which is known as constitutive activity. Inverse agonists can be therapeutic when bound to receptor sites by causing an opposite effect of the agonist and removing the constitutive activity at the receptor site (Kowalski et al., 2017). 2. Compare and contrast the actions of g couple proteins and ion gated channels. G protein-coupled receptors (GPCRs) and ion gated channels are both transmembrane signaling systems that have ligand receptor sites. GPCRs are the most numerous receptors in eukaryotes, having many diverse functions and being involved in many biological and pathological processes (Alexander et al., 2017). Consequently, they are the target of almost half of all pharmaceutical drugs. They are activated by numerous signaling molecules, or ligands, that allow it to activate a second messenger system or directly trigger a response inside the cell. Ion gated channels are present in the cellular membrane and allow ions (i.e. sodium and potassium) to pass in and out of the cell via a gated mechanism. Activation of its receptor site opens the channel, allowing ions to influence the cellular action potential (Alexander et al., 2017). 3. Explain how the role of epigenetics may contribute to pharmacologic action. Epigenetics refers to variations in gene expressionwithout changes to the DNA codethat typically form in response to environmental stimuli (Kular & Kular, 2018). The cellular alterations, including DNA methylation and histone acetylation, are perpetuated as they are retained following cell division. This subsequently leads to the alteration or silencing of specific genes that can disrupt various biological pathways and influence the development of disease. Research to identify biomarkers, such as DNA methylation on specific genes, aims to improve the diagnosis and treatment of disease by allowing pharmacologic therapy to target specific alterations for potential correction, as well as make predictions about treatment response (Kular & Kular, 2018). 4. Explain how this information may impact the way you prescribe medications to patients. Include a specific example of a situation or case with a patient in which the psychiatric mental health nurse practitioner must be aware of the medications action. Prescribers must consider the above-mentioned concepts in order to formulate a safe and effective treatment strategy. An understanding of neurotransmitters actions at receptor sites, as well as how they can be manipulated for therapeutic effect, can help prescribers choose more targeted drug therapy and better understand associated side effects of specific drug therapy (Camprodon & Roffman, 2016). For example, a psychiatric mental health nurse practitioner (PMHNP) has prescribed a Haldol, a first-generation antipsychotic drug to treat psychotic symptoms. Therapeutic outcome is achieved by producing an antagonistic effect on dopamine receptors in the mesolimbic pathway (Solmi et al., 2017). The PMHNP must understand and anticipate the potential for a wide range of side effects due to the blockage of dopaminergic activity at numerous receptor sites. Subsequently, the patient should be monitored for impaired cognitive function, exacerbated negative symptoms, and neuromotor dysfunction (Solmi et al., 2017). References Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Marrion, N. V., Peters, J. A., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators. (2017). THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: G protein-coupled receptors. British Journal of Pharmacology, 174, S17S129. https://doi-org.ezp.waldenulibrary.org/10.1111/bph.13878 Alexander, S. P., Peters, J. A., Kelly, E., Marrion, N. V., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators. (2017). THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Ligand-gated ion channels. British Journal of Pharmacology, 174, S130. Camprodon, J. A., & Roffman, J. L. (2016). Psychiatric neuroscience: Incorporating pathophysiology into clinical case formulation. In T. A. Stern, M. Favo, T. E. Wilens, & J. F. Rosenbaum. (Eds.), Massachusetts General Hospital psychopharmacology and neurotherapeutics (pp. 119). Elsevier. Kowalski, P. C., Dowben, J. S., & Keltner, N. L. (2017). My Dad Can Beat Your Dad: Agonists, Antagonists, Partial Agonists, and Inverse Agonists. Perspectives in Psychiatric Care, 53(2), 76. https://doi-org.ezp.waldenulibrary.org/10.1111/ppc.12208 Kular, L., & Kular, S. (2018). Epigenetics applied to psychiatry: Clinical opportunities and future challenges. Psychiatry & Clinical Neurosciences, 72(4), 195211. https://doi-org.ezp.waldenulibrary.org/10.1111/pcn.12634 Solmi, M., Murru, A., Pacchiarotti, I., Undurraga, J., veronese, N., Fornaro, M., Stubbs, B., Monaco, F., Vieta, E., Seeman, M. V., Correll, C. U., & Carvalho, A. F. (2017). Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Therapeutics & Clinical Risk Management, 13, 757777. https://doi-org.ezp.waldenulibrary.org/10.2147/TCRM.S117321 Response 2 S Agonist and antagonist play a key role in pharmacology and the human body by working against each other to establish a balance. When agonist is stimulating an action, the antagonist sits idle (Gordon, 2017). An agonist ties to the receptor site and causes the ion channel’s opening up to its full capacity and frequency, making the downstream signal transduction possible for utilization at the binding site. Compared to a full agonist, an additional receptor site allows the ion channel to open more frequently. Therefore, the agonist ties cause responses while the antagonist work against drugs by blocking the response (Staudt, et al., 2019). Agonist plays a role in binding and altering the receptors’ activity and functions while the antagonists help in biding receptors without altering its activities. The agonist, therefore, causes a response to the drug. Simultaneously, the antagonist works against the drug by blocking the response helping to cause stabilization in the receptor sites in resting phases, a mechanism similar to the lack of agonist at the receptor site (Staudt, et al., 2019). When comparing partial agonist to full agonist, both causes changes in receptors by opening ion channels; however, the frequency is different. Partial agonist opens ion channels with a frequency greater than a resting state but less frequent when compared to the effect of full agonist (Alexander, et al., 2017). Antagonists act similarly when it comes to reversing both full agonists and partial agonists by playing a reversing role that returns the receptor site to its resting state. The rate of iron flow and downstream signal transduction depends on agonist nature. Partial flow has an effect greater than agonist at its resting state but with a lesser effect than a full agonist. Partial agonist plays a key role in stabilizing neurotransmissions within the brain by causing an even reaction between extreme action potential to stabilize the receptor output (Alexander, et al., 2017). Psychotropic drugs majorly target a class of receptors linked to G proteins. The G couple proteins consist of seven transmembrane regions that span the membrane seven-folds. Each membrane region has a central core acting as the binding core of neurotransmitters where drugs interact within the receptor. The interaction and binding results in modifications of the receptor actions by fully or partially coping or even blocking neurotransmitter functions at a specific receptor site (Alexander, et al., 2017). Drug actions change the downstream molecular processes activating or deactivating phosphoproteins making the neurotransmitter modify receptors, enzymes, and ion channels differently. The alterations at the G-protein-linked receptor site caused by drugs is possible to cause actions on the psychiatric disorders or symptoms as the drug action changes gene expression, protein synthesis, and the downstream communication between neurons linked to G-protein-linked receptor (Alexander, et al., 2017). Ligand-gated ion channels are a type of receptor forming ion channels; they consist of long strings of amino acids forming subunits around ions channel; they act both as a ligand-gated ion channel as channel-linked receptors. Complex proteins contain sites that allow ions to pass through. This allows neurotransmitters, drugs, and other natural substances to bind to a site, either increasing or decreasing the channel opening’s sensitivity. The important ion channels in psychopharmacology include the channels controlling calcium, chloride, sodium, and potassium flow. The drug-induced modifications occurring with the inotropic receptors immediately changes the flow of ions, which in turn triggers clinical onset when medications are used, though other drugs acting at the G-protein-linked receptor sites may result in delayed response instigated by cellular functions activated by signal transduction cascade (Alexander, et al., 2017). References Alexander, S. P., Christopoulos, A., Davenport, A. P., Kelly, E., Marrion, N. V., Peters, J. A., … & CGTP Collaborators. (2017). The Concise Guide to PHARMACOLOGY 2017/18: G protein?coupled Gordon, M. (Ed.). (2017). Psychopharmacological agents (Vol. 4). Elsevier. Staudt, M. D., Herring, E. Z., Gao, K., Miller, J. P., & Sweet, J. A. (2019). Evolution in the treatment of psychiatric disorders: from psychosurgery to psychopharmacology to neuromodulation. Frontiers in neuroscience, 13, 108.