Feb 23, 2024 NUR 6630 Week 1 Discussion: Foundational Neuroscience
NUR 6630 Week 1 Discussion: Foundational Neuroscience
A Sample Answer For the Assignment: NUR 6630 Week 1 Discussion: 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.
NUR 6630 Week 1 Discussion Foundational Neuroscience
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
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
NUR 6630 Week 1 Discussion: Foundational Neuroscience
Full agonists allow a receptor site to open up an ion channel to the maximum amount and frequency which is allowed by that particular binding site which causes the maximum amount of downstream signal transduction possible to be utilized at the binding site. The ion channel can open more frequently than with a full agonist alone but requires the help of a second receptor site.
An antagonist causes a stabilization in the receptor sites in resting phases which is the same mechanism of action at the receptor site when an agonist is not present. Because there are no changes whether an antagonist is present or not, it is said to be neutral or silent.
In response to partial agonists, receptors modify in a way that causes ion channels to open more frequently and to a greater extent than they would in a resting state, but not as frequently as they would in the presence of a full agonist. As with full agonists, antagonists counteract partial antagonists and return the receptor site to its resting state.
Partial agonists increase ion flow and downstream signal transduction, but not to the extent of a full agonist, compared to the resting state. The receptor output must be balanced to prevent too much or too little downstream action from occurring when there are unstable neurotransmissions within the brain. Stabilizers are another name for partial agonists, which have the ability to maintain a steady response between the extremes of an excessive or insufficient action potential (Stahl, 2013).
Compare and contrast the actions of g couple proteins and ion gated channels.
A class of receptors linked to G proteins are a major target of psychotropic drugs. The G couple proteins have the structure of seven transmembrane regions, spanning the membrane seven times. Each region of the membrane is arranged around a central core which contains a binding site for a neurotransmitter. Drugs can interact at a particular neurotransmitter binding site or at other sites, also called allosteric sites within a receptor.
This binding can lead to various modifications of receptor actions by either partially or fully mimicking or blocking any neurotransmitter function which would normally occur at a specific receptor site. Downstream molecular processes can be changed by drug actions as when phosphoproteins are activated or inactivated which results in a difference in which enzymes, receptors, or ion channels are modified by the neurotransmission.
These drug actions can also lead to changes in which genes are expressed, altering which proteins are synthesized and which functions are amplified, from synaptogenesis, to receptor and enzyme synthesis, to communication with downstream neurons innervated by the neuron with the G-protein-linked receptor. As a result, drug-induced alterations at the G-protein-linked receptor site can cause actions on psychiatric disorders or symptoms (Stahl, 2013).
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Like G proteins, ligand-gated ion channels are a type of receptor which also forms an ion channel. For this reason, they are both ligand-gated ion channel and also ionotropic receptors or ion-channel-linked receptors. They have dual functions, hence the two names. Ligand-gated ion channels consist of long strings of amino acids which are gathered as subunits around an ion channel.
There are many binding sites around these subunits for neurotransmitters, ions and drugs. Complex proteins have sites where ions can pass through a channel or bind to the channel, or where a neurotransmitter can act as a binding site and where natural substances or drugs can bind to a site different than where the neurotransmitter binds resulting in an increase or decrease to the sensitivity of a channel opening. In psychopharmacology, the ion channels that are the most important are those that control sodium, calcium, chloride, and potassium.
Full agonists will directly change the receptor site to open the ion channel. Antagonists will cause a steady state at the receptor in its resting state which is similar to how a receptor responds when there is no agonist present. Alternatively, drug-induced modifications which occur with ionotropic receptors cause immediate effects by changing the flow of ions resulting in an immediate clinical onset as when medications such as anxiolytics and hypnotics are used. Some drugs that act at the G-protein-linked receptor sites may have a delayed response caused by an instigation in cellular functions that become activated by the signal transduction cascade (Stahl, 2013).
NUR 6630 Week 1 Discussion: Foundational Neuroscience
Explain the role of epigenetics in pharmacologic action.
RNA and proteins are transcribed from an unique DNA sequence within cells. Humans have more than 20,000 genes, however not all of them are expressed in the brain. While genetics can explain how a gene is expressed as a particular RNA or protein, epigenetics goes one step further by determining if the gene itself is actually expressed.
The epigenome, on the other hand, is defined as the “narrative” of all the “words” in the genome that come together to form a cohesive whole. Every neuron and cell in the body has the same genetic make-up as potential proteins. How a neuron becomes a neuron, for example, or how it becomes a liver cell instead of a neuron, depends on whether or not specific genes are activated or silenced.
Mental problems can result if genes with aberrant sequences are expressed rather than silenced in neurons that are malfunctioning. If faulty genes are expressed and/or normal genes are repressed, the development of the brain will be affected. Neurotransmission, genetic make-up, medicines, and the environment are just a few of the things that play a role in determining whether or not genes are expressed or repressed. A person’s drug usage, stress, and other mental health issues all influence into whether or not medicine and counseling will help them better their condition (Stahl, 2013).
Explain how this knowledge may affect your prescriptions for patients. The psychiatric mental health nurse practitioner must be knowledgeable of the medication’s action in a specific setting or case with a patient.
Prior to prescribing any medication, it is critical to have a thorough understanding of its pharmacodynamics, pharmacokinetics, and toxicology. In addition, one must be aware of genetics and factors that influence medicine absorption and uptake. From a social worker’s perspective, Farmer (2014) argues that a new understanding of mental illness is emerging.
In an effort to rethink mental disorder diagnosis, the National Institute of Mental Health has worked on a project (the Research Domain Criteria RDoC). When it comes to studying mental disease, the RDoC makes use of data from the fields of genetics and neuroscience. An emphasis is being placed on investigating the biological underpinnings of mental diseases, and this includes a new knowledge of various aspects of functioning related to positive and negative valence systems, cognitive systems, systems for social activities, and arousal/modulatory systems.
Additionally, client behavior and self-reports are taken into account. Mental disease diagnosis will be linked with neurobiology and better treatments will be discovered. It’s important to realize that psychotropic drugs function by altering the concentration of a neurotransmitter in the brain and central nervous system. Axons transmit chemical and electrical signals to receptive neurons, while synapses serve as a point of communication between neurons and the site of an action potential.
This brain activity is the source of human behavior. It is important for us as PMHNPs to have an understanding of how a medicine works and how it affects the primary neurotransmitters (acetylcholine and norepinephrine) and how they are changed by specific medications. Medications affect patients in varied ways, depending on their age, gender, color, and ethnicity, for example. Racially and ethnically diverse populations may have different pharmacokinetic and pharmacodynamic profiles, which are impacted by genetic and environmental variables, including lifestyle, behavior, and social contact. In order for a medication to work for one person, it must be paired with their genes and their surroundings (Farmer, 2014).
Patients with mental health issues including major depressive disorder and drug addiction can benefit from understanding that numerous genes are involved rather than the “one gene and one disease” model. There is hope that better understanding of epigenetic modifications (such as acetylation and deacetylation of histones and DNA methylation) could lead to more effective treatments for mental health issues (Mahgoub & Monteggia, 2013).
When prescribing SSRIs or SNRIs, PMHNPs should keep in mind that these drugs require time to have a therapeutic impact. As a patient, you need to know that you won’t feel “well” right away, and you should be encouraged to stick with your medicine and therapy regimen.
References
Farmer, R. L. (2014). Interface between psychotropic medications, neurobiology, and mental illnesses. Smith College Studies in Social Work, 84(2-3), 255-272.
Mahgoub, M., & Monteggia, L. M. (2013). Epigenetics and psychiatry. Neurotherapeutics, 10, 734-741.
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.
To prepare for this Discussion:
Review this week’s Learning Resources.
Reflect on concepts of foundational neuroscience.
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!
By Day 3
Post a response to each of the following:
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
Compare and contrast the actions of g couple proteins and ion gated channels.
Explain the role of epigenetics in pharmacologic action.
Explain how this information may impact the way you prescribe medications to clients. Include a specific example of a situation or case with a client 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
Respond to two colleagues 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.
Week 1 discussion
Discussion: Foundational Neuroscience
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.
Learning Objectives
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
Note: To access this week’s required library resources, please click on the link to the Course Readings List, found in the Course Materials section of your Syllabus.
Required Readings
Note: All Stahl resources can be accessed through the Walden Library using this link. This link will take you to a log-in page for the Walden 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)
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.
Foundational Neuroscience
Question 1
The psychopharmacologic drug effects of medications are based on the spectrum of agonist to an antagonist. Agonists are molecules that mimic the specific impacts of biological neurotransmitters by binding to and stimulating the receptor sites to produce a response similar to that elicited by a biological molecule. An antagonist, on the other hand, blocks the actions of neurotransmitters.
While these represent two extreme aspects of psychopharmacologic drug effects, the agonist spectrum to antagonist ranges from full agonists, partial agonists, silent antagonists, inverse agonists, and irreversible agonists. Full agonists generally lead to the full ion channel opening for maximal signal transduction (Huang et al., 2020).
On the other hand, partial agonists partially improve signal transduction and elicit responses that do not match the full agonist. Silent antagonists have the impact of returning receptors to their resting states. Inverse antagonists ideally surpass and antagonism and have the effect of blocking constitutive activity (Fuller et al., 2019).
On the other hand, the irreversible agonists bind and activate receptors but do not activate the receptor. Given that their binding is permanent, they generally lead to receptor destruction. Therefore, the psychopharmacological action of a drug depends on the available position in the agonist to antagonist spectrum.
Question 2
G-coupled proteins are a family of membrane proteins activated by a spectrum of structurally diverse molecules. These molecules are made up of seven different protein units spanning the membrane up to seven-time. They serve to transmit signals after neurotransmitters bind to the receptors. Drug binding to the receptor sites leads to a partial or full blocking of the functions of the neurotransmitters. Ion-gated channels, on the other hand, are controlled electrically.
Unlike ions, G-proteins can freely diffuse through the membrane and change their behaviors (Yudin, & Roh
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