NURS 6630 Foundational Neuroscience Discussion

NURS 6630 Foundational Neuroscience Discussion

Foundational Neuroscience

Question 1

Agonists are drugs that imitate the endogenous molecule (hormone or neurotransmitter) molecule that causes the same neuronal response. Dopamine agonists are used to treat the motor systems of Parkinson’s disease (PD), such as Requip. The exogenous dopamine agonists have the same effect as the endogenous dopamine molecule itself and help correct the dopamine starved motor state of the patient with PD. There are other agonists that stimulate the serotonin system. Examples of serotonin agonists include 5-HT agonists like buspirone and sumatriptan (Kowalski et al., 2017) NURS 6630 Foundational Neuroscience Discussion.

Antagonists attach to a receptor so that an endogenous agonist like dopamine or serotonin cannot attach. This either blocks a biologic response or reduces the response of the neuron to the endogenous molecule. Medications that fall under this category include antipsychotics, anticholinergics, antihistaminergic, beta-blockers, calcium channel blockers, and neuromuscular blockers (Kowalski et al., 2017).

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Partial agonists elicit a response that is less than the response of an agonist. A partial agonist can increase endogenous activity in some areas of the brain and slow it down in another area. Aripiprazole increases neuronal activity in the underactive mesocortical dopaminergic tract while decreasing the neuronal activity in the overactive mesolimbic tract. Aripiprazole has a higher affinity for the dopamine receptor than dopamine itself (Kowalski et al., 2017).

Inverse agonists have an opposite effect to that of an agonist. An inverse agonist is dependent on the receptor having some level of basal activity. Many neurons continue to fire even in the absence of an agonist. If an agonist opens an ion channel, the inverse agonist will close the channel. Examples of some inverse agonists are naloxone and naltrexone (Kowalski et al., 2017).

Question 2

G protein-coupled receptors (GPCRs) are integral cell membrane proteins responsible for translating the molecular signals encoded in the chemical structure of hormones and neurotransmitters from outside to inside the cell. The binding of endogenous or synthetic agonists causes the activation of the receptor, which results in conformational changes that allow the allosteric coupling of accessory proteins such as G-protein at the intracellular part of the receptor. Activation of these accessory proteins triggers the series of steps that constitute the signal transduction mechanism which, eventually lead to the observed physiological responses (Cruz- Barbosa et al., 2018).

Ligand-gated ion channels are multimeric proteins constructed from large glycoprotein subunits. They are activated by a chemical (agonist) binding to a distinct site or sites within the channel complex. In most cases, neurotransmitters released from the presynaptic neurons serve as the primary agonists, acting as part of a complex integrated process required for rapid neuronal communication. Binding of the neurotransmitter to the protein induces a conformational change, resulting in the opening of the integral ion channel. The charge and the direction of ion flux through the activated channel determine its effect on cellular function (Weir, 2020).

In pharmacology, a receptor is a protein that recognizes an endogenous chemical mediator such as a neurotransmitter, hormone, or inflammatory mediator. When the mediator (agonist) binds to the receptor, a series of reactions takes place, ultimately leading to a change of function of the host cell (Weir, 2020). GPCRs are at the center of current drug discovery programs. As of November 2017, approximately 35% of approved drugs in the United States or European Union targets GPCRs (Cruz- Barbosa et al., 2018). There are different criteria for different drug designs. One is selectivity, as it seems appropriate that drugs act selectively through specific receptors. Another is the concept of receptor polypharmacology in which a drug exerts a combination of positive effects by binding to different receptors (Cruz- Barbosa et al., 2018).

The voltage-gated ion channel (VGIC) is a large number of membrane-bound proteins that are structurally similar. These proteins can be activated by a change in the transmembrane voltage. The proteins are divided into voltage-gated calcium, potassium, and sodium channels. VGICs can be opened according to the changes in the membrane potential, so the ion can flow down the electrochemical gradient across the cell membrane. Because of the importance of the VGICs, these proteins are the molecular targets for a variety of biological toxins from many organisms. These VGIC toxins provide valuable tools for exploring the function of ion channels. Moreover, these VGIC toxins can be used as pharmacological tools for exploring a variety of physiological processes and understanding potential therapeutic targets. Some VGIC toxins have been proved to have therapeutic value and are currently being investigated as drugs (Weir, 2020).

Question 3

Epigenetics studies heritable changes in gene expression that are not caused by alteration in DNA sequences. Epigenetic regulation may lead to relatively stable changes that are affected by other factors such as age, diet, lifestyle, disease, and environment. Some mechanisms of epigenetics that have been studied extensively include DNA methylation, histone modifications, and non-coding RNAs. Each of these can change gene expression without altering the underlying DNA sequences (Boks et al., n.d.). Evidence suggests that epigenetic regulation of brain functions is important in the etiology of psychiatric disorders. The recent interest in the role of epigenetics in the brain has led researchers to explore the possibility that drugs can modify epigenetic processes involved in psychiatric disorders. So far, several psychiatric drugs have been found to influence epigenetic mechanisms, suggesting that this may partially explain their mechanism of action (Boks et al., n.d.).

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With recent improvements in understanding of the actual function of the entire genome, there needs to be some modification in pharmacology to tackle disease not only in the drug-receptor sense but in a more global-response sense. Drugs may have to act broadly over a range of epigenetic events. The regulatory mechanisms of these events may regulate a large group of genes. The advantage of this approach is that epigenetic variations can often be the underlying cause of a particular disease, and simply targeting one protein of the multiple pathways involved may be futile (Stefanska & MacEwan, 2015).

Question 4

As providers, nurse practitioners (NPs) should be cautious about the epigenetic properties of drugs which may affect drug-metabolizing gene expression and drug disposition. Some clinically used drugs may also have the property to alter epigenetic signatures of drug-metabolizing genes, and lead to unexpected changes in drug metabolism and toxicity (Boks et al., n.d.). Evidence shows that valproic acid has been discovered as a histone deacetylase inhibitor with potent antitumor activity. When this kind of epigenetic drug is administered, the prescriber needs to consider potential changes in drug-metabolizing genes under epigenetic regulation (Boks et al., n.d.). Also, risperidone, an atypical antipsychotic antagonizes D2 receptors and binds to 5HT2 receptors. This induces global phosphor-acetylation of H3 in the striatum, mediated by the NMDA receptor, suggesting that dopamine, serotonin, and glutamate act in synchrony to influence chromatin regulation (Boks et al., n.d.).

References

Boks, M. P., de Jong, N. M., Kas, M. J. H., Vinkers, C. H., Fernandes, C., Kahn, R. S., Mill, J., & Ophoff, R. A. (n.d.). Current status and future prospects for epigenetic psychopharmacology. EPIGENETICS, 7(1), 20–28. https://doi-org.ezp.waldenulibrary.org/10.4161/epi.7.1.18688

Cruz-Barbosa, R., Ramos-Pérez, E.-G., & Giraldo, J. (2018). Representation Learning for Class C G Protein-Coupled Receptors Classification. Molecules, 23(3), 690. https://doi-org.ezp.waldenulibrary.org/10.3390/molecules23030690

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), 76–79. https://doi-org.ezp.waldenulibrary.org/10.1111/ppc.12208

Stefanska, B., & MacEwan, D. J. (2015) Epigenetics and pharmacology. Br J Pharmacol,

172(11):2701-4. doi:10.1111/bph.13136. PMID: 25966315; PMCID: PMC4439868.

Weir, C. J. (2020). Ion channels, receptors, agonists and antagonists. Anaesthesia & Intensive Care Medicine, 21(1), 62–68. https://doi-org.ezp.waldenulibrary.org/10.1016/j.mpaic.2019.10.022

 

Week 2: Neurotransmitters and Receptor Theory

Receptors and neurotransmitters are like a lock-and-key system. Just as it takes the right key to open a specific lock, it takes the right neurotransmitter to bind to a specific receptor. Not surprisingly, as it concerns psychopharmacology, the pharmacotherapeutics that are prescribed must trigger the release of certain neurotransmitters that bind to the correct receptors in order to elicit a favorable response for the patient. The mechanism of this binding and the response that follows reflects receptor theory and lies at the foundation of pharmacology.

This week, you will continue your examination of neuroanatomy and neuroscience as you engage with you colleagues in a Discussion. You will also explore the potential impacts of foundational neuroscience on the prescription of pharmacotherapeutics.

Learning Objectives

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Students will:
  • Analyze the agonist-to-antagonist spectrum of action of psychopharmacologic agents
  • Compare the actions of g couple proteins to ion gated channels
  • Analyze the role of epigenetics in pharmacologic action
  • Analyze the impact of foundational neuroscience on the prescription of medications

Learning Resources

Required Readings (click to expand/reduce)
Required Media (click to expand/reduce)
Optional Resources (click to expand/reduce)

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:

  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.
  2. Compare and contrast the actions of g couple proteins and ion gated channels.
  3. Explain how the role of epigenetics may contribute to pharmacologic action.
  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.

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.

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!

 

NURS_6630_Week2_Discussion_Rubric

Excellent

Point range: 90–100

Good

Point range: 80–89

Fair

Point range: 70–79

Poor

Point range: 0–69

Main Posting:

Response to the Discussion question is reflective with critical analysis and synthesis representative of knowledge gained from the course readings for the module and current credible sources.

Points Range: 40 (40%) – 44 (44%)

Thoroughly responds to the Discussion question(s).

Is reflective with critical analysis and synthesis representative of knowledge gained from the course readings for the module and current credible sources.

No less than 75% of post has exceptional depth and breadth.

Supported by at least three current credible sources.

Points Range: 35 (35%) – 39 (39%)

Responds to most of the Discussion question(s).

Is somewhat reflective with critical analysis and synthesis representative of knowledge gained from the course readings for the module.

50% of the post has exceptional depth and breadth.

Supported by at least three credible references. NURS 6630 Foundational Neuroscience Discussion

Points Range: 31 (31%) – 34 (34%)

Responds to some of the Discussion question(s).

One to two criteria are not addressed or are superficially addressed.

Is somewhat lacking reflection and critical analysis and synthesis.

Somewhat represents knowledge gained from the course readings for the module.

Post is cited with fewer than two credible references.

Points Range: 0 (0%) – 30 (30%)

Does not respond to the Discussion question(s).

Lacks depth or superficially addresses criteria.

Lacks reflection and critical analysis and synthesis.

Does not represent knowledge gained from the course readings for the module.

Contains only one or no credible references.

Main Posting:

Writing

Points Range: 6 (6%) – 6 (6%)

Written clearly and concisely.

Contains no grammatical or spelling errors.

Adheres to current APA manual writing rules and style.

Points Range: 5 (5%) – 5 (5%)

Written concisely.

May contain one to two grammatical or spelling errors.

Adheres to current APA manual writing rules and style.

Points Range: 4 (4%) – 4 (4%)

Written somewhat concisely.

May contain more than two spelling or grammatical errors.

Contains some APA formatting errors.

Points Range: 0 (0%) – 3 (3%)

Not written clearly or concisely.

Contains more than two spelling or grammatical errors.

Does not adhere to current APA manual writing rules and style.

Main Posting:

Timely and full participation

Points Range: 9 (9%) – 10 (10%)

Meets requirements for timely, full, and active participation.

Posts main Discussion by due date.

Points Range: 8 (8%) – 8 (8%)

Posts main Discussion by due date.

Meets requirements for full participation.

Points Range: 7 (7%) – 7 (7%)
Posts main Discussion by due date.
Points Range: 0 (0%) – 6 (6%)

Does not meet requirements for full participation.

Does not post main Discussion by due date.

First Response:

Post to colleague’s main post that is reflective and justified with credible sources.

Points Range: 9 (9%) – 9 (9%)

Response exhibits critical thinking and application to practice settings.

Responds to questions posed by faculty.

The use of scholarly sources to support ideas demonstrates synthesis and understanding of learning objectives.

Points Range: 8 (8%) – 8 (8%)
Response has some depth and may exhibit critical thinking or application to practice setting.
Points Range: 7 (7%) – 7 (7%)
Response is on topic, may have some depth.
Points Range: 0 (0%) – 6 (6%)
Response may not be on topic, lacks depth. NURS 6630 Foundational Neuroscience Discussion
First Response:
Writing
Points Range: 6 (6%) – 6 (6%)

Communication is professional and respectful to colleagues.

Response to faculty questions are fully answered, if posed.

Provides clear, concise opinions and ideas that are supported by two or more credible sources.

Response is effectively written in Standard, Edited English.

Points Range: 5 (5%) – 5 (5%)

Communication is mostly professional and respectful to colleagues.

Response to faculty questions are mostly answered, if posed.

Provides opinions and ideas that are supported by few credible sources.

Response is written in Standard, Edited English.

Points Range: 4 (4%) – 4 (4%)

Response posed in the Discussion may lack effective professional communication.

Response to faculty questions are somewhat answered, if posed.

Few or no credible sources are cited.

Points Range: 0 (0%) – 3 (3%)

Responses posted in the Discussion lack effective communication.

Response to faculty questions are missing.

No credible sources are cited.

First Response:
Timely and full participation
Points Range: 5 (5%) – 5 (5%)

Meets requirements for timely, full, and active participation.

Posts by due date.

Points Range: 4 (4%) – 4 (4%)

Meets requirements for full participation.

Posts by due date.

Points Range: 3 (3%) – 3 (3%)
Posts by due date.
Points Range: 0 (0%) – 2 (2%)

Does not meet requirements for full participation.

Does not post by due date.

Second Response:
Post to colleague’s main post that is reflective and justified with credible sources.
Points Range: 9 (9%) – 9 (9%)

Response exhibits critical thinking and application to practice settings.

Responds to questions posed by faculty.

The use of scholarly sources to support ideas demonstrates synthesis and understanding of learning objectives.

Points Range: 8 (8%) – 8 (8%)
Response has some depth and may exhibit critical thinking or application to practice setting.
Points Range: 7 (7%) – 7 (7%)
Response is on topic, may have some depth.
Points Range: 0 (0%) – 6 (6%)
Response may not be on topic, lacks depth.
Second Response:
Writing
Points Range: 6 (6%) – 6 (6%)

Communication is professional and respectful to colleagues.

Response to faculty questions are fully answered, if posed.

Provides clear, concise opinions and ideas that are supported by two or more credible sources.

Response is effectively written in Standard, Edited English.

Points Range: 5 (5%) – 5 (5%)

Communication is mostly professional and respectful to colleagues.

Response to faculty questions are mostly answered, if posed.

Provides opinions and ideas that are supported by few credible sources.

Response is written in Standard, Edited English.

Points Range: 4 (4%) – 4 (4%)

Response posed in the Discussion may lack effective professional communication.

Response to faculty questions are somewhat answered, if posed.

Few or no credible sources are cited.

Points Range: 0 (0%) – 3 (3%)

Responses posted in the Discussion lack effective communication.

Response to faculty questions are missing.

No credible sources are cited.

Second Response:
Timely and full participation
Points Range: 5 (5%) – 5 (5%)

Meets requirements for timely, full, and active participation.

Posts by due date.

Points Range: 4 (4%) – 4 (4%)

Meets requirements for full participation.

Posts by due date.

Points Range: 3 (3%) – 3 (3%)
Posts by due date. NURS 6630 Foundational Neuroscience Discussion
Points Range: 0 (0%) – 2 (2%)

Does not meet requirements for full participation.

Does not post by due date.

Total Points: 100

An agonist generates a structural change in the G-protein-linked receptor that activates the synthesis of the second messenger to the fullest extent possible (Stahl, 2013). At times, the action of full agonists can cause too much stimulation of neurotransmitters; in this situation, impeding the activity of the natural neurotransmitter may be advantageous (Stahl, 2013). The antagonists’ role is to simply hinder the activity of the agonist, but produces no result itself (Stahl, 2013). Partial agonists are often referred to as “stabilizers” because they create stability between the conditions of extreme agonist action and the absence of agonist action (Stahl, 2013). Since partial agonists are considered “stabilizers”, if a patient is experiencing the extreme action of a full agonist, a partial agonist would be appropriate to downgrade, or stabilize, the signals. The role of the inverse agonist is to generate a structural change in the G-linked-protein receptor that changes it to a completely inactive state; they bind to the receptor and create an opposite effect from the agonist, decreasing the signal transmission level to below baseline (Stahl, 2013). NURS 6630 Foundational Neuroscience Discussion

G coupled protein receptors (GPCR) stimulate various pathways in the cell, and specific GCPR ligands have the ability to preferably activate specific pathways (Wingler & Lefkowitz, 2020). Ion-gated channels are trans membrane proteins that contain an opening to allow the flow of particular ions through the plasma membrane (Alexander et al., 2017). Once open, ions such as potassium and sodium can move through the channel, changing the electrical signal in the cell. GPCRs and ion channels are similar in that they conclusively result in alterations in neuronal activity, often linked to variations in gene expression (Stern et al., 2016). GPCRs and ion-gated channels are structurally different. GPCRs have seven helices and possess the ability to change shape after binding occurs to alter the protein (Latorraca et al., 2017). In contrast, ion-gated channels are direct trans membrane pathways. Additionally, the movement of ions through the ion channels rapidly transform the membrane potential and neuronal action; GPCRs operate slower in the second messenger systems (Stern et al., 2016).

Lockwood and Youssef (2017) describes epigenetics as the examination of any possibly stable and inborn changes in gene expression or cell phenotype that takes place without changes in DNA sequence. Epigenetic modifications are the primary mechanism underlying numerous diseases, particularly growth and developmental conditions (Furtado et al., 2019). Understanding the epigenetics of different diseases and conditions can aid healthcare providers in developing individualized pharmacologic treatment plans that will lead to improved responses to drug therapy (Wachman & Farrer, 2019).

Studies show there is an association between abnormal epigenetic mechanisms of gene expression and schizophrenia, bipolar disorder, and major depressive disorder (Peedicayil & Grayson, 2018). Furthermore, evidence suggests that abnormalities in the DNA methylation throughout the genomes are present in patients with schizophrenia (Peedicayil & Grayson, 2018).  A patient with this particular epigenetic abnormality may benefit from a DNA methyltransferase (DNMT) inhibitor that acts on DNA methylation, such as 5-azacytidine (Kular & Kular, 2018). Understanding what the abnormality is in the gene will help the provider chose the appropriate pharmacotherapy for the best patient outcomes.

References

Alexander, S., Peters, J. A., Kelly, E., Marrion, N. V., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., & Davies, J. A. (2017). The concise guide to pharmacology 2017/18: Ligand-gated ion channels. British Journal of Pharmacology, 174, S130–S159. https://doi.org/10.1111/bph.13879 NURS 6630 Foundational Neuroscience Discussion

Kular, L., & Kular, S. (2018). Epigenetics applied to psychiatry: Clinical opportunities and future challenges. Psychiatry and Clinical Neurosciences, 72(4), 195–211. https://doi.org/10.1111/pcn.12634

Latorraca, N. R., Venkatakrishnan, A. J., & Dror, R. O. (2016). Gpcr dynamics: Structures in motion. Chemical Reviews, 117(1), 139–155. https://doi.org/10.1021/acs.chemrev.6b00177

Lockwood, L., & Youssef, N. (2017). Systematic review of epigenetic effects of pharmacological agents for bipolar disorders. Brain Sciences, 7(12), 154. https://doi.org/10.3390/brainsci7110154

Miranda Furtado, C., Dos Santos Luciano, M., Silva Santos, R., Furtado, G., Moraes, M., & Pessoa, C. (2019). Epidrugs: Targeting epigenetic marks in cancer treatment. Epigenetics, 14(12), 1164–1176. https://doi.org/10.1080/15592294.2019.1640546

Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology (4th ed.). Cambridge University Press.

Stern MD, Theodore A., Maurizio, F. M., Wilens MD, Timothy E., & Rosenbaum MD, Jerrold F. (2016). Massachusetts General Hospital psychopharmacology and neurotherapeutics (1st ed.). Elsevier.

Wachman, E. M., & Farrer, L. A. (2019). The genetics and epigenetics of neonatal abstinence syndrome. Seminars in Fetal and Neonatal Medicine, 24(2), 105–110. https://doi.org/10.1016/j.siny.2019.01.002

Wingler, L. M., & Lefkowitz, R. J. (2020). Conformational basis of g protein-coupled receptor signaling versatility. Trends in Cell Biology, 30(9), 736–747. https://doi.org/10.1016/j.tcb.2020.06.002 NURS 6630 Foundational Neuroscience Discussion

 

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