Feb 23, 2024 NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience
NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience
A Sample Answer For the Assignment: NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience
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.
The agonist spectrum can be explained best as a scale from agonist to inverse agonist; with natural neurotransmitters being an agonist or drugs that stimulate the receptors for that action. Partial agonist follows the agonist because of drugs that stimulate the same receptors on a lower gradation of the spectrum (Stahl, 2021). The next level on the spectrum is the antagonist blocking the action of the agonist (Stahl, 2021). The final function is the inverse agonist has two behaviors: (1) block the agonist, and (2) lower the level of activity below the starting point in absence of an agonist (Stahl, 2021).
The best way to explain a partial agonist is to present a medication used in the treatment of depression. Vilazodone is a serotonin reuptake inhibitor, which causes a rise in serotonin at the synaptic cleft by preventing the re-uptake of serotonin at the presynaptic axon terminal (Comprodon & Roffman, 2016).
However, Vilazodone also signals the 5HT1A presynaptic receptors and causes a decrease in the production of serotonin acting as a partial agonist (Baumgartnera et al., 2020). The outcome of partial and inverse agonists can be a marked increase or decrease in the concentration of a drug from the inhibition or excitation of the drug’s receptors (Comprodon & Roffman, 2016).
2. Compare and contrast the actions of g couple proteins and ion gated channels.
Two of the four methods of signal transduction involve neurotransmitters rather than hormones or neurotrophins (Stahl, 2021). G-coupled proteins and ion-gated channels are similar because they are stimulated by drugs that cause neurotransmitters to activate genes inside of the cell when a phosphate is added to the cAMP protein (Stahl, 2021).
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Although they have similarities, the first, G-coupled proteins, cause a slow neuronal effect as a result of its action with cAMP and protein kinase A (Comprodon & Roffman, 2016). The second, ion-gated channels, cause a rapid neuronal effect on the membrane potential as a result of calcium and a kinase called CaMK (Comprodon & Roffman, 2016).
3. Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics describes the heritable action of DNA when gene function changes from one generation to the next because of the influence of the external milieu (Comprodon & Roffman, 2016). DNA can be affected by experiences triggering phenotype modifications rather than genotype changes medications (Quevedo et al., 2022). Stress, such as physical abuse in children, is positively correlated with the development of borderline personality disorder (Comprodon & Roffman, 2016; Quevedo et al., 2022).
The downstream effect of neuroplasticity can result in changes at the genetic level resulting in DNA sequencing variations (Quevedo et al., 2022). Once the chromatin’s structure is modified, the encoding of proteins may alter the original behavior of synaptic uptake of drugs causing changes of pharmacological action, such as enhanced or diminished responses to medications (Quevedo et al., 2022). The increased or decreased action at the receptor site may enhance or inhibit the action of a drug and cause an unexpected outcome.
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 medication’s action.
Epigenetic changes are crucial to understand when prescribing medications to patients who have suffered trauma (child abuse, substance misuse, malnutrition, etc.) resulting in DNA silencing or activation (Comprodon & Roffman, 2016). The stress response to physical, emotional, or sexual abuse can cause increased DNA methylation in various tissues in the body, namely blood, saliva, and brain tissue (Quevedo et al., 2022).
Therefore, the PMHNP should be well versed in the biomechanics of a medication for appropriate and effective prescribing. One example is the higher reactivity of the HPA axis to adverse childhood experiences stimulating Corticotropin Releasing Hormone (CRH), which triggers the release of adrenocorticotropin hormone from the pituitary gland (Quevedo et al., 2022).
A corticotropin releasing hormone antagonist may be ineffective if one’s mental health is severely affected by a history of abuse. Therefore, the PMHNP should consider an alternative medication to a CRH antagonist.
References
Baumgartnera, K., Doeringb, M., & Schwarz, E. (2020). Vilazodone poisoning: A systematic review. Clinical Toxicology, 58(5), 360–367. https://doi.org/10.1080/15563650.2019.1691221
Links to an external site.
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. 1–19). Elsevier.
Quevedo, Y., Booij, L., Herrera, L., Hernández, C., & Jiménez, J. P. (2022). Potential epigenetic mechanisms in psychotherapy: A pilot study on DNA methylation and mentalization change in borderline personality disorder. Frontiers in Human Neuroscience. https://doi.org/10.3389/fnhum.2022.955005
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.
NURS 6630 Discussion Reflect On Concepts Of Foundational Neuroscience
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.
According 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 neuropsychopharmacology, 21(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)
Also Read: NURS 6053 Review of current Healthcare Issues
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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.
Accessible player
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.
Thank you Ruth for this informational post. I enjoyed learning the concept through reading your post. I will add to that an agonist tend to bind to the receptor to produce a response. The opposite is said of an antagonist, which tend to stop the receptor from producing its response.
Agonist perform different function in the body when it comes to medication response such as in a patient with diabetes. glucagon-like peptide-1 (GLP-1) agonists, which improve insulin secretion, decrease glucagon secretion, increase satiety (and therefore decrease food intake), and may have beneficial effects on [beta]-cell function, represent an important addition to treatment options.
I agree with your statement on the action of G couple proteins and the ion-gated channels, they both help in their own ways. GPCRs represent the largest family of integral membrane proteins and were first identified as receptor proteins that couple via heterotrimeric G-proteins to regulate a vast variety of effector proteins to modulate cellular function.
It is now recognized that GPCRs interact with a myriad of proteins that not only function to attenuate their signaling but also function to couple these receptors to heterotrimeric G-protein-independent signaling pathways (Magalhaes et al., 2012).
In my future practice as a mental health practitioner, l will state that understanding neurobiology will help in understanding the science first, before prescribing a medication for my patient. You are right that it will help a professional with making diagnosis. Inappropriate prescribing of drugs is associated with unnecessary healthcare costs and risk of side effects for patients.[1]
These side effects can lead to harmful consequences such as falls, hospitalization and an increased one-year mortality rate.[2] The prevalence of inappropriate prescribing of drugs is high (Danielle et al., 2021).
References:
Spellman CW. (2011). Pharmacology of GLP-1 agonists: describing the therapeutic potential to patents. JAOA: Journal of the American Osteopathic Association, 111 (2 Suppl 1), eS10-4.
Magalhaes AC, Dunn H, Ferguson SS, Magalhaes, A.C., Dunn, H., Ferguson, S.S. G., & Ferguson, S. S. (2012). Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. British Journal of Pharmacology, 165 (6),1717-1736.
Daniëlle Kroon, Nina F Steutel, Hester Vermeulen, Merit M Tabbers, Marc A Benninga, Miranda W Langendam, Simone A van Dulmen, Effectiveness of interventions aiming to reduce inappropriate drug prescribing: an overview of interventions, Journal of Pharmaceutical Health Services Research, Volume 12, Issue 3, September 2021, Pages 423–433.
An agonist-to-antagonist spectrum of action of psycho pharmacologic agents, -is explained as when a chemical binds or connect to a receptor, the receptor activates, and a biological response is produced. When agonists activate receptors, like hormones, neurotransmitters, and other endogenous regulators that activate the receptors to which they bind (Golier, J. A., & Yehuda, R. (2018).
Antagonists have no effects on the receptor function, but it can block effectiveness and prevent receptor activation by endogenous molecules and drugs(Golier, J. A., & Yehuda, R. (2018).The antagonist can be a drug with an affinity to bind to a receptor but does not have any intrinsic activity. The process is considered an example of a full agonist (Golier, J. A., & Yehuda, R. (2018). A partial agonist means that the molecules do not elicit a full response therefore does not obtain the maximum response from system even when they bind to the same number of receptors as an agonist (Golier, J. A., & Yehuda, R. (2018).
When there is an agonist and a partial agonist working at the same time the partial agonist becomes an antagonist because they are both fighting for space on the same receptors (Frånberg, O et al).. An antagonist refers to molecules that block agonist mediated responses. Inverse agonists are molecules that want to attach to the same receptors as agonists, but they produce an opposite response than the agonist on the target cell (Golier, J. A., & Yehuda, R. (2018).
Compare and contrast the actions of g couple proteins and ion gated channels.
G protein-coupled receptors (GPCRs) are a large family of cell surface receptors on the plasma membrane that transmit signals inside the cell through a type of protein called a G protein (Sunamita de Carvalho et al 2018). G protein-coupled receptors serve many purposes in the body, and the disorder of GPCR signaling can cause disease. G proteins bind with nucleotide guanosinetriphosphate (GTP) (Sunamita de Carvalho et al 2018).
G protein divides into two portions (one called the α subunit, the other consisting of the β and γ subunits), which are released from the GPCR (Sunamita de Carvalho et al 2018). The subunits can interact with other proteins, triggering other signaling pathways that lead to different responses.
When communication is allow to occur from one cell to the next cell through a lipid membrane, charged molecules need assistance in the form of ion channels (Sunamita de Carvalho et al 2018). Ion channels control cellular excitability by using membrane-bound glycol proteins that contain pores filled with water (ion channels) which allows for the charged molecules to move from an extracellular to intracellular (Sunamita de Carvalho et al 2018).
Charged molecules can go into the cell while allowing for uncharged molecules to move out of the cell in an organized, efficient manner. This movement of ions is important in the role of cell excitation, muscle contraction and intracellular signaling (Weir, 2020). G-protein-coupled receptors (GPCRs) are the largest category of receptors allowing for the bodies physiological function (Sunamita de Carvalho et al 2018).
Most medications are made to target GPCRs due to their large distribution throughout the body. They are necessary membrane proteins used by cells to convert extracellular signals into intracellular responses by using hormones (Sunamita de Carvalho et al 2018).
Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics is when the expression of a gene can be controlled, promoting or repressing the expression of the gene without changing the code or genome’s sequence (Kumsta, R. 2019).Epigenetics is gene function is changed by an adaptation in the code. The role of epigenetics may contribute to pharmacologic action by changing a DNA molecule, resulting in amended gene expression.
When a DNA molecule is amended, then pharmacologic action is then modified. Gene articulation can be modified because of the variation of the DNA molecule chromatin. Long-term effects of cognition and behavior can be a result of the alteration of development brought on by abuse or mistreatment in childhood (Kumsta, R. 2019). Heritability is an effect of gene expression changes in the long-term
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 medication’s action.
As a provider, when prescribing medication, it is necessary to treat each patient as individual patient with his or her own familiar history. The assessment should include genetic questing that will be use for the implementation of diagnosing implementation for treatment. Will also access for allergy since most antipsychotics’ medication are commonly cause allergy reaction. Closely monitor medications prescribed for the treatment of psychosis and behavioral and psychological symptoms of dementia in elderly patients for any adverse reaction (Kumsta, R. 2019)
Monitoring should always continue; it should not only be at the beginning of the therapy because patient can develop tolerance to medication and eventually medication or doses that use to work might not work. Doses should be monitor and adjusted appropriately. Also, since aging can affect drug metabolism and clearance, additional pharmacokinetic and pharmacodynamic changes require additional attention (Kumsta, R. 2019).
References:
Sunamita de Carvalho Lima, Lucas de Carvalho Porta, Álvaro da Costa Lima, Joana D’Arc Campeiro, Ywlliane Meurer, Nathália Bernardes Teixeira, Thiago Duarte, Eduardo Brandt Oliveira, Gisele Picolo, Rosely Oliveira Godinho, Regina Helena Silva, & Mirian Akemi Furuie Hayashi. (2018). Pharmacological characterization of crotamine effects on mice hind limb paralysis employing both ex vivo and in vivo assays: Insights into the involvement of voltage-gated ion channels in the crotamine action on skeletal muscles. PLoS Neglected Tropical Diseases, 12(8), e0006700. https://doi.org/10.1371/journal.pntd.0006700
Frånberg, O., Wiker, C., Marcus, M., Konradsson, Å., Jardemark, K., Schilström, B., Shahid, M., Wong, E., & Svensson, T. (2008). Asenapine, a novel psychopharmacologic agent: preclinical evidence for clinical effects in schizophrenia. Psychopharmacology, 196(3), 417–429. https://doi.org/10.1007/s00213-007-0973-y
Kumsta, R. (2019). The role of epigenetics for understanding mental health difficulties and its implications for psychotherapy research. Psychology and Psychotherapy: Theory, Research and Practice, 92(2), 190–207. https://doi.org/10.1111/papt.12227
Golier, J. A., & Yehuda, R. (2018). Mifepristone as a Psychopharmacologic Agent: Consideration of Efficacy, Plasma Levels, and Mechanism of Action. Biological Psychiatry, 84(1), 5–
Thank you for your informative post. Epigenetics refer to heritable changes in gene expression which do not involve alterations to the DNA sequence itself (Stahl, 2021). These changes can be influenced by environmental factors and can impact the pharmacologic action of drugs. Epigenetic modifications, such as DNA methylation and histone modifications, can alter gene expression patterns, affecting the response to pharmacologic interventions (Cavalli & Heard, 2019).
Epigenetic techniques are capable of detecting chromatin states at multiple dimensions from locus-specific analysis to gen
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