Feb 23, 2024 Discussion Foundational Neuroscience Assignment
Discussion: Foundational Neuroscience Assignment
A Sample Answer For the Assignment: Discussion: Foundational Neuroscience assignment
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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Discussion Foundational Neuroscience Assignment
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
Pharmacological agents produce both agonist and antagonist actions in different receptors in the human body. The agonist and antagonist actions of pharmacological agents work against one another. The agonists combine with the receptor to produce an action in the body. On the other hand, antagonist action hinders or opposes the action by a receptor, thereby, leading to a failure of an occurrence of an event.
The effect of agonists is attributed to the combination it has with compounds or chemical substances to promote the desired action while that of antagonist entails the combination with chemicals or blockage of neurotransmitters to cause interference with action. Partial and inverse agonists have an effect on the efficacy of psychopharmacological agents. Partial agonists bind to a specific receptor to produce partial efficacy at that receptor that is relative to the effect of full agonist.
The partial enhancement of the actions of the receptor results in a net decline in the activation of the receptor hence, average activity of the receptor in producing the desired action. Inverse agonists work by binding to a receptor as an antagonist to produce an action that is opposite to that of the agonist (Demler, 2019). Inverse agonists mimic the agonist activity of the receptors, hence, the desired therapeutic activity of psychopharmacological agents.
G-couple proteins and ion-gated channels are the mechanisms in which cells communicate to produce actions. They comprise of the cell-surface receptors that play the roles of signal transfer in multicellular organisms. The two however differ in a number of aspects. Ion-gated channels have receptors that bind to a ligand to cause opening of channels via membranes to allow the passage of specific ions. Ion-gated channels do not allow the passage of fatty acids and amino acids because they are hydrophobic in nature. Ion-gated channels therefore mediate rapid, post-synaptic responses.
G-proteins channels on the other hand have receptors that bind and active G-protein on cell membranes. The activation of G-proteins results in cyclic series that cause entry of proteins such as amino acids and fatty acids into the cell to produce action (Hood & Khan, 2020). The G-proteins therefore mediate slow post-synaptic responses.
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Epigenetics has a role in pharmacologic actions of drugs. Firstly, changes in the expression of enzymes that metabolize drugs may affect the action as well as metabolism of a drug. For example, changes in enzymes due to aspects such as DNA methylation affects the metabolism of drugs, leading to their altered effectiveness.
The addition of methyl group to the cytosine pyrimidine ring causes silencing of transcription, thereby, hindering the binding of co-activators and transcription factors that are needed for metabolism and action of drugs. The second influence of epigenetics is the genetic variations in the transporters of drugs. A genetic change in the transporters of drugs such as ATP binding cassette transporters and solute carrier transporter affect the binding and action of pharmacological agents (Castelo-Branco & Jeronimo, 2020).
The above information will affect my prescribing of medications to patients. For instance, it will translate into my understanding of the disease process and the targets of the medications that I prescribe to the patients. The implication of the information also entails the need for comprehensive patient assessment to identify any relevant patient history that may affect the effectiveness of the prescribed medications.
I should also be aware of the contraindications of specific medications to patients with history of allergies or comorbid conditions (Hood & Khan, 2020). Therefore, the information will inform my safe prescribing in my professional role as an advanced practice nurse.
References
Castelo-Branco, P., & Jeronimo, C. (2020). Histone Modifications in Therapy. Elsevier Science.
Demler, T. L. (2019). Pharmacotherapeutics for Advanced Nursing Practice, Revised Edition. Jones & Bartlett Learning.
Hood, P., & Khan, E. (2020). Understanding Pharmacology in Nursing Practice. Springer Nature.
NURS 6630 Discussion: Foundational Neuroscience
Discussion: Foundational Neuroscience
Week 2 Discussion
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.
Pharmacology is the study of how drugs interact with biological processes; while psychopharmacology is the study of the effects of drugs on brain processes such as cognition, mood, and other psychological phenomena (Fields, 2019). Psychopharmacological drugs are generally small synthetic molecules that act in a number of different ways such as agonist, antagonist, partial, and inverse agonists. Agonists act to mimic the action of an endogenous neurotransmitter, though their net action is not necessarily to promote synaptic transmission because of the effect that presynaptic auto-receptors may have (Stahl2013). Antagonists block the effects of endogenous neurotransmitters and oppose normal synaptic transmission, although in some cases if they act predominantly on presynaptic receptors they may increase neuronal firing and so increase neurotransmitter release. Partial agonists act somewhat like agonists in that they directly act on receptors, but if used in the presence of an agonist, they compete for the receptor and so can have partial blocking properties, therefore are called agonist-antagonists (Stahl, 2013). Inverse agonists on the other hand bind to the same receptors as an agonist but typically have the opposite effect on the target cell. The main pharmacological effect of inverse agonists is receptor antagonism in that the inverse agonists block the effect of agonists and the effect on constitutive activity is only relevant if the system is spontaneously active (Norris & Carr 2013). Overall, the agonist-antagonist spectrum reaches from agonists through antagonists to partial and inverse agonists. Naturally occurring neurotransmitters are agonists. It is a common misconception that antagonists are the opposite of agonists because they block the actions of agonists. However, inverse agonists are really the opposite of agonists. Antagonist can block anything in the agonist spectrum, including inverse agonists. If an agonist is not as strong as the full agonist, it is called a partial agonist (Stahl, 2013). Examples of the psychopharmalogical actions of an agonist would be to reduce anxiety or pain. An antagonist would block agonists from reducing anxiety or pain and would block inverse agonists from causing pain. However, an antagonist would neither reduce nor cause pain in itself.
Compare and contrast the actions of g couple proteins and ion gated channels.
G couple proteins represent the most abundant family membrane proteins in the human genome, which are activated by a spectrum of structurally diverse ligands. They have seven different protein segments which span the membrane seven times and transmit signals for binding sites for neurotransmitters (Stahl, 2013). This will allow for therapeutic drug actions to occur. Once drugs attach to these receptor sites, a full or partial blocking function of neurotransmitters occurs. The molecular changes can ultimately be affected by the drug actions, and cause changes in which phosphoproteins are activated or inactivated, or determine which enzymes, receptors, or ion channels are modified by neurotransmission (Stahl, 2013). Ion gated channels are electrically controlled. Unlike ions, G-couple proteins can diffuse through the membrane and ultimately change a cell’s behavior, and ions cannot diffuse due to their charge. Ion gated channels control access in and out of neurons. Dependent on the class of ion channels, they may be opened by neurotransmitters or voltage. A comparison that relates to both ion channels and g-protein-linked receptors is the agonist spectrum. Both g couple proteins and ion gated channels are types of protein receptors which are embedded in cell membranes that bind to a molecule. Medications that change the flow of ions can cause a clinical effect, unlike drugs that target g protein-linked receptor sites, which takes a more extended period (Stahl, 2013)
Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics consists of heritable genetic modification that alter gene function and expression without changes in DNA sequence (Dos Santos, 2018). There are several epigenetics mechanisms such as: histone protein modification, covalent DNA modification, and regulation of noncoding RNA. Epigenetics enables drug metabolism and transport throughout the body with changes to the phenotype instead of the genotype (Des Santos 2018). Epigenetics determines if some genes will become a specific RNA and protein, or if it will be turned off, based on the structure of chromatin, neurotransmission, genes, drugs, or the environment. All of these can affect the brain in various ways and can result in inefficient information processing. Epigenetics also affect the way medications work for each person. Drugs may not be designed to be specific to a particular gene or protein subtype; they may indeed have to be able to be more broad‐acting over a range of large‐scale epigenetic event (Stefanska & MacEwan, 2015).
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 nurse practitioner, it is imperative to understand the importance of providing individualized care to each patient. When prescribing a medication, factors such as patient’s age, medical history, social history (illicit drug and alcohol use) pharmacodynamics, pharmacokinetics, and epigenetics should be always be put into consideration so as to prevent adverse reactions and achieve the therapeutic effects desired. For example, I once cared for a twenty five year old male post-op patient who was brought in by ambulance due to a ruptured appendix. The physician had initially written an order for 1.5mg of Dilaudid every 3 hours as needed. This dosage and frequency did not address patient’s pain even for a second. I was determined to figure out why we could not manage the patient’s pain. So I once again reviewed his chart for admission notes as well as his medications, medical and social history. Patient denied any illicit drug use or being on any opioid prescription during his initial assessment. So I went to the patient and told him that I was working on putting together a plan of care to better address his pain, and that whatever information that he could give me regarding his medical/social history would be helpful. Patient then opened up and informed me that he was a “functional” heroin addict, and that he could not mention it at the time of his initial health assessment because his family members were present. The patient also stated that he was currently on Opioid Agonist Therapy (OAT) and was on methadone. According to Quinlan & Cox (2017), patients who are typically on OAT and develop acute painful conditions tend to be undertreated for acute pain. As providers encounter more frequently patients receiving OAT, it is important that a proper pain management plan is implemented to ensure that these patients achieve the desired pain relief management without worsening the addiction. From a pharmacokinetics perspective, methadone is a very potent synthetic analgesia that is used to treat chronic pain such as cancer as well we effective in the management of opioid dependence (American Addiction Centers 2019). Methadone particularly works as an agonist (full opioid receptor) and an antagonist (N-methyl-d-aspartate NMDA). From an agonist standpoint, methadone imitates the body’s natural opioids such as endorphins and enkephalins though the release of neurotransmitters involved in pain transmission (Negus & Banks 2018). Methadone uniquely differs from other opioid analgesics such as morphine because of its longer bioavailability and longer duration of action and half-life. This unique pharmacokinetic profile makes it an effective drug for treating opioid addiction in that it requires fewer doses to maintain analgesia and thus prevents withdrawal (Negus & Banks 2018).
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From a pharmacodynamics perspective, methadone is metabolized by the liver through the actions of the cytochrome P450 enzymes (Sandritter, McLaughlin, Artman, & Lowry 2017). How methadone works in the body of each patient differs as a result of many factors. The same dose given to two different patients will manifest somewhat differently based on factors such as level of addiction, kidney and liver function, genetics, etc. Methadone works by affecting the brain and nervous system’s responses to pain, and while it does not have the immediate addicting properties of illicit opioids such as heroin, improper use and management can also lead to abuse of Methadone (Sandritter, McLaughlin, Artman, & Lowry 2017). In conclusion, having an understanding of pharmacokinetics and pharmacodynamics of the medications the patient was on as well as having a more detailed health history of this patient allowed me to put together an individualized pain management plan for this patient.
References
Dos Santos, D. L. (2018). Clinical pharmacology: Epigenetic drugs at a glance. Retrieved from
https://www.longdom.org/open-access/clinical-pharmacology-epigenetic-drugs-at-a-glance-2167-0501-1000e186.pdf
Fields, D. (2019). What is psychopharmacology. Retrieved from
https://www.news-medical.net/health/What-is-Psychopharmacology.aspx
Negus, S.S., & Banks, M.L. (2018). Pharmacokinetic-pharmacodynamic (PKPD) Analysis with
drug discrimination. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5446801/
Norris, D.O., & Carr, J.A. (2013). Synthesis, metabolism, and actions of bioregulators. Retrieved
From https://www.sciencedirect.com/topics/neuroscience/inverse-agonist
Sandritter, T.L., McLaughlin, M., Artman, M., & Lowry, J. (2017). The interplay between
pharmacokinetics and pharmacodynamics. Retrieved from
https://pedsinreview.aappublications.org/content/38/5/195/tab-article-info
Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical
applications (4th ed.). New York, NY: Cambridge University Press
Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. Retrieved from
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/
Quinlan, J., & Cox, F. (2017). Acute pain management in patients with drug dependence
syndrome. Retrieved May 31, 2021 from
https://journals.lww.com/painrpts/fulltext/2017/08000/acute_pain_management_in_patients_with_drug.10.aspx
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
Post a response to each of the following: Include sub headings please.
1. Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
2. Compare and contrast the actions of g couple proteins and ion gated channels.
3. Explain the role of epigenetics in pharmacologic action.
4. 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.
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
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)
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.
Required Media (click to expand/reduce)
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