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NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience

NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience

NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience

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

Agonists are drugs that stimulate receptors similar to natural neurotransmitters, while antagonists are drugs that block the actions of a natural neurotransmitter at its receptor. True antagonists only apply their actions in the presence of an agonist since they have no intrinsic activity of their own in the absence of an agonist (Stahl & Stahl, 2013). Drugs acting at a receptor occur in a spectrum from full agonist to antagonist to an inverse agonist. Antagonists block the actions of everything in the agonist spectrum.

At one end of the agonist-to-antagonist spectrum, there is the full agonist, which produces the same degree of physiologic receptor-mediated response as the natural neurotransmitter agonist itself (Stahl & Stahl, 2013). At the other end of the spectrum is a full inverse agonist, which in concept does oppose the agonist. In the middle of the spectrum is the antagonist, which blocks the effects of all participants in the spectrum but has no properties of its own in altering the ion channel (Stahl & Stahl, 2013). Thus, the agonist-to-antagonist spectrum goes from full agonist to partial agonist to antagonist to partial inverse agonist to full inverse agonist.

Compare and Contrast the Actions of G Couple Proteins and Ion Gated Channels

Both G couple proteins and ion-gated channels are involved in the opening and closing of postsynaptic ion channels. However, the two accomplish this in different ways. Ion-gated channels are directly linked to ion channels and contain two functional domains. An extracellular site binds neurotransmitters and a membrane-spanning domain that forms an ion channel and thus combines transmitter-binding and channel functions into a single molecular entity (Wulff & Christophersen, 2015). On the other hand, G-protein-coupled receptors do not have ion channels as part of their structure. They thus affect channels by activating intermediate molecules called G-proteins (Johnson & Lovinger, 2016). G-protein-coupled receptors act by dissociating from the receptor and interacting directly with ion channels or bind to other effector proteins, such as enzymes, that form intracellular messengers that open or close ion channels.

I really enjoyed reading your article, it was very informative. However, in addition to your points about the agonist-antagonist spectrum, I will like to share additional insight I found interesting too.

NURS 6630 Discussion Reflect On Concepts Of Foundational NeuroscienceAccording to Berg and Clarke (2018), Agonists have intrinsic efficacy (the ability to increase the activity of a receptor), and inverse agonists are said to have negative intrinsic efficacy (the ability to decrease the activity of a receptor). Just as agonist intrinsic efficacy for a receptor varies with the structure of the agonist (resulting in strong agonists and weaker [partial] agonists), inverse agonists also have different degrees of negative intrinsic efficacy, resulting in strong and weak (partial) inverse agonists.

Inverse agonists are ligands that selectively bind to the inactive state of the receptor (Kenakin, 2017). If any receptor happens to be in an active state spontaneously, then an inverse agonist will reverse the resultant constitutive activity. However, the main pharmacological effect of inverse agonists is receptor antagonism, that is, inverse agonists will block the effect of agonists and the effect on constitutive activity is only relevant if the system is spontaneously active (Kenakin, 2017). There is a property of inverse agonists that may be therapeutically relevant in nonconstitutively active systems (Kenakin, 2017).

References

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse agonism and functional selectivity. The international journal of neuropsychopharmacology21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

Kenakin, T. P. (2017). Pharmacology in Drug Discovery and Development (Second Edition). ScienceDirect. Retrieved June 10, 2022, from https://doi.org/10.1016/B978-0-12-803752-2.00004-1

As a psychiatric mental health nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat clients, 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.

Required Readings

Note: All Stahl resources can be accessed through the Library using this link. This link will take you to a log-in page for the Library. Once you log into the library, the Stahl website will appear.

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press *Preface, pp. ix–x

Note: To access the following chapters, click on the Essential Psychopharmacology, 4th ed tab on the Stahl Online website and select the appropriate chapter. Be sure to read all sections on the left navigation bar for each chapter.

Chapter 1, “Chemical Neurotransmission”

Chapter 2, “Transporters, Receptors, and Enzymes as Targets of Psychopharmacologic Drug Action”

Chapter 3, “Ion Channels as Targets of Psychopharmacologic Drug Action”

Document: Midterm Exam Study Guide (PDF)

Document: Final Exam Study Guide (PDF)

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Required Media

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

Note: The approximate length of this media piece is 3 minutes.

Accessible player

Optional Resources

Laureate Education (Producer). (2009). Pathopharmacology: Disorders of the nervous system: Exploring the human brain [Video file]. Baltimore, MD: Author.

Note: The approximate length of this media piece is 15 minutes.

Dr. Myslinski reviews the structure and function of the human brain. Using human brains, he examines and illustrates the development of the brain and areas impacted by disorders associated with the brain.

Accessible player

Laureate Education (Producer). (2012). Introduction to advanced pharmacology [Video file]. Baltimore, MD: Author.

Note: The approximate length of this media piece is 8 minutes.

In this media presentation, Dr. Terry Buttaro, associate professor of practice at Simmons School of Nursing and Health Sciences, discusses the importance of pharmacology for the advanced practice nurse.

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To prepare for this Discussion:

Review this week’s Learning Resources.

Reflect on concepts of foundational neuroscience.

By using a combination of psychotherapy and medication therapy, psychiatric mental health nurse practitioners are positioned to provide a very unique type of care to clients with psychiatric disorders. To be successful in this role, you must have a strong theoretical foundation in pathophysiology, psychopharmacology, and neuroscience. This foundation will help you assess, diagnose, and treat clients as you relate presenting symptoms to theoretical neuronal functioning.

This week, as you begin to study psychopharmacology, you explore foundational neuroscience. You examine the agonist-to-antagonist spectrum of action of psychopharmacologic agents, compare the actions of g couple proteins to ion gated channels, and consider the role of epigenetics in pharmacologic action.

Note: In previous courses, the term “patient” was used to describe the person receiving medical care. In traditional medicine and nursing, this term is used to describe the person you do something to, and it often refers to a passive recipient of care and services. As you move into the realm of psychiatric mental health, a transition will occur. You will work with individuals who are active participants in their care, and these individuals are generally referred to as “clients” as opposed to “patients.” It is important to note that the term “client” is also favored in other mental health disciplines, such as psychiatry, psychology, and social work.

Neuroscience is the scientific study of the human central nervous system to understand the brain’s dysfunction that can lead to disease, mental disorders, and physical impairment (Karmarkar & Plassmann, 2019). The complex design of a neuron is the basic understanding of communication by sending impulses to other body organs. The brain controls human behavior and the functions of body organs. The anatomy and physiology of the brain help understand the part of the brain affected by mental illness. For example, poor concentration and cognitive skills dysfunction is the forebrain pathology. Additionally, one can understand the mode of action of psychopharmacology. For example, antidepressants may function by inhibiting the serotonin or epinephrine receptors.

An Agonist-To-Antagonist Spectrum of Action and How Partial and Inverse Agonists Influence Psychopharmacologic

An antagonist binds at the receptors by blocking any event of an agonist, hence, blocking the biological response. For example, naloxone is a competitive opioid antagonist and has no effects with opioid co-administration (Gicquelais, et al, 2019). An agonist binds to a receptor causing activation of the receptor, hence, the biological response. A partial agonist activates the receptors partially with lesser effect on the brain. For example, buprenorphine is a partial agonist, and therefore, an antagonist may block its opioid function without activating its receptors. An inverse receptor binds with constitutively active receptors and inhibits receptor activity by exerting opposite pharmacological effects that suppress spontaneous receptor signaling.

Comparison between Actions of G Couple Proteins and Ion Gated Channels

G coupled proteins GPCRs are integral membrane proteins that convert extracellular responses to hormones, neurotransmitters, olfaction, and taste signals. The GPCRs work by binding to the hormones, neurotransmitters, and growth factors to initiate a cellular response. The three types of G-couple receptors are alpha, beta, and gamma, in which the ligands bind and activate (Yudin & Rohacs 2019). Ion gated channels are integral membrane proteins of excitable cells that allow a flux of ions to pass only under defined circumstances. These channels are voltage-gated sodium channel neurons and ligand-dated acetylcholine receptors of the cholinergic synapses. The ion gated channel pull and bonds to the agonist changing the protein while g coupled proteins are used by the cells to convert intracellular signals into responses.

The Role of Epigenetics In the Pharmacologic Action

Epigenetics regulate gene activity by switching off the gene activity or activating the gene activity. Epigenetics plays a role in the phenotypic activity of the cell in diseases such as cancer and neurodegenerative disorders such as Alzheimer’s disease. Epigenetics modify gene expressions after drug administration to counteract the disease states in humans. Epigenetics proves its effectiveness in treating psychiatric and neurodegenerative disorders to its ability to modify gene expressions.

The Significance of the Information to Psychiatric Mental Health Nurse Practitioner

A psychiatric mental health nurse practitioner should have basic knowledge of the concepts of foundational neuroscience. Understanding the function of agonists, inverse and partial agonists, and antagonists prevent co-administration of drugs that agonize and antagonize the same receptors. For example, in treating a patient with a depressive mood disorder, prescribing antipsychotics such as fluphenazine worsens the depressive mood because it antagonizes the dopaminergic D1 and D2 receptors depressing the release of the hypothalamic hormone.

References

Gicquelais, R. E., Bohnert, A. S., Thomas, L., & Foxman, B. (2020). Opioid agonist and antagonist use and the gut microbiota: associations among people in addiction treatment. Scientific reports10(1), 1-11. https://doi.org/10.1038/s41598-020-76570-9

Karmarkar, U. R., & Plassmann, H. (2019). Consumer neuroscience: Past, present, and future. Organizational Research Methods22(1), 174-195.

https://doi.org/10.1177%2F1094428117730598

Yudin, Y., & Rohacs, T. (2019). The G‐protein‐biased agents PZM21 and TRV130 are partial agonists of μ‐opioid receptor‐mediated signalling to ion channels. British journal of pharmacology176(17), 3110-3125. https://doi.org/10.1111/bph.14702

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