Agonist to Antagonist Spectrum of Action of Psychopharmacologic Agents
Receptors are either in the resting or active formation; a small amount of constitutive activity occurs even in the receptors resting state. Agonists added to a high concentration of resting receptors will bind to them and shift the resting receptor into a high number of active receptors, increasing the constitutive activity in those active receptors. The smaller number of receptors that were active now is shifted into the resting formation. When Antagonist binds to the same population of resting receptors in high concentration and a low number of active receptors, it does not change the resting or active population. Still, it decreases the constitutive activity in those receptors, and natural ligands cannot bind to those receptors (Khilnani & Khilnani, 2011).
Full agonist drugs bind to a receptor, have a strong ion bond, and causes proteins on the cellular membrane to open its channel fully. Partial agonists are larger than natural ligands and do not allow the protein channel to open fully. Antagonists do not have the strong ion bond that the agonist has to the protein, and the channel does not open up at all. Still, natural ligands cannot bind to the protein receptor due to the blocking of the antagonist, but constitutive activity continues. Inverse agonist blocks the natural ligand from binding to the protein receptor; like the antagonist, it inhibits the constitutive activity (Berg & Clarke, 2018). Psychopharmacological drugs will not be effective if the protein receptor is blocked by an antagonist or an inverse agonist, because of the psychopharmaceutic drug’s inability to bind to the blocked protein receptor (Berg & Clarke, 2018).
Compare and Contrast G protein-coupled receptor and Ion Gated Channels
In eukaryotes, the largest and most diverse group of membrane receptors are called G-protein-coupled receptors. The cell surface receptors can bind to light energy, peptides, lipids, sugars, and proteins. G-protein-coupled receptors mediate most human physiological responses such as physiological responses to hormones, neurotransmitters and environmental stimulants, vision, olfaction, and taste. Due to the considerable potential as therapeutic targets, G-protein-coupled receptor drugs help fight a broad spectrum of diseases. G-protein-coupled receptors are shaped the same at the primary level and have seven membrane-spanning α-helical segments separated by alternating intracellular and extracellular loop regions. Single GPCRs have one of its kind combinations of signal-transduction activities involving multiple G-protein subtypes, as well as G-protein-independent signaling pathways and complex regulatory processes (Rosenbaum et al., 2009).
Ligand-gated ion channels are one type of integral ionotropic protein channel-linked membrane receptor with a regulated flow through pores of selected ions across the plasma membrane. The electrochemical gradient directs the passive Ion flow through the permeant ions. Ligand-gated ion channels open or gated due to the binding of chemical messengers to a group of transmembrane ion channels, that triggers a conformational change that results in the conducting state. Endogenous or exogenous modulators bind to allosteric sites to modulate gating. The nervous system and somatic neuromuscular junction have Ligand-gated ion channels that mediate synaptic transmission in a millisecond. The communication involves releasing neurotransmitters from a pre-synaptic neuron and the subsequent activation of post-synoptically located receptors that mediate a fast, phasic, electrical signal. Ligand-gated ion channels mediate a tonic form of neuronal regulation, and the outcome is the activation of extra synaptic receptors by ambient levels of the neurotransmitter, along with phasic neurotransmission. Ligand-gated ion channels may have additional functions due to the non-excitable cells. The three types of gated ion channels are in most cells and are very important physiological. According to the stimulus to which they reply, ion channels are divided into three superfamilies: voltage-gated, ligand-gated, and mechano-sensitive ion channels (Alexander et al., 2011).
The Contribution of Epigenetics to Pharmacologic Action
Epigenetics is the study of how DNA interacts with many smaller molecules found with cells, which can activate or deactivate genes. Epigenetics changes can boost or interfere with the transcription of specific genes. The most common way interference happens is that DNA or the protein it’s wrapped around is labeled with a chemical tag that can inhibit gene expression or boost a gene’s transcription. Epigenetics changes can survive cell division and can affect an organism its entire life. Epigenetics changes are part of normal development; as an embryo grows, some expression genes are activated, and some genes are inhibited, normally. As the embryo continues to grow in the womb, its cells begin to form into the heart, while others develop into the liver. Other cells form organs that make up the body; all of these cells have almost the same genome but their own distinct epigenome. Epigenomes can be affected by the environment; the chemical tags that turn genes on or off can be affected by diet, chemical exposure, medication, and diseases. Environmental induced epigenetic changes can have long-term effects on how a person ages and their disease susceptibility. Social experiences can cause epigenetic changes that could be passed on to the offspring (Weinhold, 2006).
Epigenetics Impact on Prescribing Medications
The impact that epigenetics has on psychiatric diseases places a significant burden on affected individuals, their caregivers, and the health care system. There is a large amount of evidence that many psychiatric issues are inherited. Still, there is little effort to identify the DNA sequences of these disease processes, and the research that has been done was not productive. The lack of research in epigenetic dysregulation leaves a small number of treatment options available to stop these disease processes at the cellular level. Experimental technologies have made progress and have increased the number of epigenome studies, its role in the maintenance of normal genomic functions, and disease etiopathogenesis (Ptak & Petronis, 2010).
Patients diagnosed with anxiety disorders may be treated with habit-forming medications and are used and sold on the streets. Medications like Xanax and Valium are prevalent street drugs used to treat anxiety disorders in the clinical environment. The Psychiatric Mental Health Nurse Practitioner should be mindful about using these medications in the long-term setting (Mamat, 2015). Librium has been changed within the last ten years to a schedule IV-controlled substance due to increased street value (Ahwazi & Abdijadid, 2020). The list of habit-forming antianxiety medications continues with Ativan, Halcion, and Klonopin, which are not as valuable on the streets for sale but carry some street value. Some antianxiety medicines that come in pill form are crushed and snorted to amplify the potency, which increases the chances of an overdose, seizures, and coma (Mamat, 2015).
Ahwazi, H. H., & Abdijadid, S. (2020) Chlordiazepoxide. StatPearls Publishing.
Alexander, S. H., Mathie, A., & Peters, J. A. (2011). Ligand-gated ion channels. British Journal
of Pharmacology, 164(1), S115–S135.
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/pyy071
Khilnani, G., & Khilnani, A. K. (2011). Inverse agonism and its therapeutic significance. Indian
journal of pharmacology, 43(5), 492–501. https://doi.org/10.4103/0253-7613.84947
Mamat, C. F., Jamshed, S. Q., El Syed, T., Khan, T. M., Othman, N., Al-Shami, A. K., Zaini, S.
B., & Siddiqui, M. J. (2015). The use of psychotropic substances among students: The
prevalence, factor association, and abuse. Journal of pharmacy & bioallied sciences, 7(3), 181–187. https://doi.org/10.4103/0975-7406.160011
Ptak, C., & Petronis, A. (2010). Epigenetic approaches to psychiatric disorders. Dialogues in
clinical neuroscience, 12(1), 25–35. https://doi.org/10.31887/DCNS.2010.12.1/cptak
Rosenbaum, D. M., Rasmussen, S. G., & Kobilka, B. K. (2009). The structure and function of G-
protein-coupled receptors. Nature, 459(7245), 356–363. https://doi.org/10.1038/nature08144
Weinhold, B. (2006). Epigenetics: the science of change. Environmental health perspectives,
114(3), A160–A167. https://doi.org/10.1289/ehp.114-a160
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.
Post a response to each of the following:
Read a selection of your colleagues’ responses.
Respond to at least two of your colleagues on two different days in one of the following ways:
Note: For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the “Post to Discussion Question” link and then select “Create Thread” to complete your initial post. Remember, once you click on Submit, you cannot delete or edit your own posts, and you cannot post anonymously. Please check your post carefully before clicking on Submit!
Thank you for an informative post. Epigenetics needs further research to better understand the full affects of epigenetics in humans. Although the research is beginning, there has been some findings that correlates epigenetics and depression. ‘Levels of histone markers of increased gene expression were down regulated in people with a history of clinical depression’ (Weaver, 2020). It was found that giving antidepressants raised histone markers of increased gene expression and reversed the gene repression (Weaver, 2020). Continuing to study epigenetics will help identify the genes that have an impact on mental health disorders and ultimately proper treatment (Walsh, 2014).
Walsh, W. (2014 October 19). Methylation, Epigenetics, and Mental Health. [Power Point slides]. Walsh Research Institute. https://www.walshinstitute.org/uploads/1/7/9/9/17997321/methylation_epigenetic_and_mental_health_by_william_walsh.
Weaver, I. (2020). Epigenetics in psychology. In R. Biswas-Diener & E. Diener (Eds), Noba textbook series: Psychology. Champaign, IL: DEF publishers. Retrieved from http://noba.to/37p5cb8v
Thanks for you post!
I would like to add a bit to your comments on G protein-coupled receptors (GPCRs). GPCRs are the target of over 50% pharmaceuticals and involve almost all physiological and pathological processes of the body since they encode over 800 distinct genes (Zhao, Deng, Jiang, & Qing, 2016). In fact, GPCRs affect at least 200 genes responsible for work in the heart alone and play a vital role in diseases such as hypertension, coronary artery disease, and left heart failure (Wang, Gareri, & Rockman, 2018). What I find the most interesting is how the GPCRs work. They lay dormant on the cell membrane with attaches alpha, beta, and gamma subunits with a GDP (Wang, Gareri, & Rockman, 2018). When activated by a ligand, the GDP is exchanged for GTP with the alpha unit as it then signals second messengers,
Wang, J., Gareri, C., & Rockman, H. A. (2018. August 30). G protein-coupled receptors in heart disease. Circulation Research, 123(6), 716-735. https://doi.org/10.1161/CIRCRESAHA.118.311403
Zhao, J., Deng, Y., Jiang, Z., & Qing, H. (2016, March 24). G protein-coupled receptors (GPCRs) in Alzheimer’s disease: A focus on BACE1 related GPCRs.