Case-Discussion: Foundational Neuroscience

Case-Discussion: Foundational Neuroscience

A Sample Answer For the Assignment: Case-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).

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.

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.

Both ion-gated channels and G-protein-coupled receptors give rise to postsynaptic actions, although with very different time courses that range from less than a millisecond to minutes, hours, or even days (Wulff & Christophersen, 2015). Ion-gated channels typically mediate rapid postsynaptic effects.

Examples include endplate potential (EPP) produced at neuromuscular synapses by Acetylcholine, Excitatory postsynaptic potential (EPSPs) produced at certain glutamatergic synapses, and IPSPs produced at certain GABAergic synapses (Wulff & Christophersen, 2015). The PSPs in ion-gated channels occur within a millisecond or two of an action potential occupying the presynaptic terminal and last for only a few tens of milliseconds or less.

In contrast, the activation of G-protein-coupled channels typically produces much slower responses, ranging from hundreds of milliseconds to minutes and even longer (Johnson & Lovinger, 2016). The comparative slowness of G-protein-coupled channels actions reflects the fact that multiple proteins are required to bind to each other sequentially to produce the final physiological response.

Role of Epigenetics in Pharmacologic Action

Epigenetics refers to genetic information that is beyond the information coded solely by our genetic code. Epigenetic regulation of gene activity has revealed to be essential in maintaining the normal phenotypic activity of cells and has a role in the development and diseases such as cancer and neurodegenerative disorders such as Alzheimer’s (Remely et al., 2015).

Epigenetics is used to develop newer classes of drugs, which regulate epigenetic mechanisms to offset disease states in humans. Epigenetic factors such as DNA methylation, histone modification, and noncoding RNAs regulate drug-metabolizing enzymes and transporters (Remely et al., 2015). These factors are thus responsible for variation in drug metabolism and response.

Epigenetic variations are associated with the underlying cause of a particular disease. Consequently, targeting one protein of the multiple pathways involved in the epigenetic variations may help treat the disease (Remely et al., 2015).

For instance, conditions such as cancer usually have several different mutation variations that are hard to detect, predict, and effectively treat, causing relapse (Remely et al., 2015). Epigenetics of cancers may be the solution to more effective treatments.

How This Information May Impact the Way I Prescribe Medications to Clients

The information on pharmacologic action may impact how I prescribe medications to clients since I have to consider if a particular drug will provide the maximum benefit to a patient based on its pharmacokinetics and pharmacodynamics.

Information on the agonist-to-antagonist spectrum can be used to identify the drugs that will bring the desired effect and which ones can cause adverse effects. A PMHNP needs to understand the agonist-to-antagonist spectrum to understand how a drug’s mechanism of action might bring the desired effect.

An example of the agonist-to-antagonist spectrum of action of psychopharmacologic agents is as follows: An agonist will act by reducing anxiety. An inverse agonist, in equivalence, will cause anxiety. A partial agonist would weakly lower anxiety, and a partial inverse agonist would weakly cause anxiety. An antagonist will block the full and partial agonists from lowering any anxiety and would also block the full and partial inverse agonists from causing any anxiety. However, an antagonist would neither reduce nor cause anxiety in itself.

References

Johnson, K. A., & Lovinger, D. M. (2016). Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction? Frontiers in cellular neuroscience, 10, 264. https://doi.org/10.3389/fncel.2016.00264

Remely, M., Lovrecic, L., De La Garza, A. L., Migliore, L., Peterlin, B., Milagro, F. I., Martinez, A. J., & Haslberger, A. G. (2015). Therapeutic perspectives of epigenetically active nutrients. British Journal of Pharmacology, 172(11), 2756-2768. http://dx.doi.org/10.1111/bph.2015.172.issue-11

Stahl, S. M., & Stahl, S. M. (2013). Stahl’s essential psychopharmacology: neuroscientific basis and practical applications. Cambridge university press.

Wulff, H., & Christophersen, P. (2015). Recent developments in ion channel pharmacology. Channels (Austin, Tex.), 9(6), 335. https://doi.org/10.1080/19336950.2015.1077650

ORDER NOW FOR AN ORIGINAL PAPER ASSIGNMENT :Case-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 medication

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.

You must proofread your paper. But do not strictly rely on your computer’s spell-checker and grammar-checker; failure to do so indicates a lack of effort on your part and you can expect your grade to suffer accordingly. Papers with numerous misspelled words and grammatical mistakes will be penalized. Read over your paper – in silence and then aloud – before handing it in and make corrections as necessary. Often it is advantageous to have a friend proofread your paper for obvious errors. Handwritten corrections are preferable to uncorrected mistakes.

Use a standard 10 to 12 point (10 to 12 characters per inch) typeface. Smaller or compressed type and papers with small margins or single-spacing are hard to read. It is better to let your essay run over the recommended number of pages than to try to compress it into fewer pages.

Likewise, large type, large margins, large indentations, triple-spacing, increased leading (space between lines), increased kerning (space between letters), and any other such attempts at “padding” to increase the length of a paper are unacceptable, wasteful of trees, and will not fool your professor.

The paper must be neatly formatted, double-spaced with a one-inch margin on the top, bottom, and sides of each page. When submitting hard copy, be sure to use white paper and print out using dark ink. If it is hard to read your essay, it will also be hard to follow your argument.

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–