NURS 6630 Discussion: Foundational Neuroscience

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Week 2 Main Post
  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.

Agonists bind to a receptor and produces a normal appropriate response.  Agonists mimic the actions of the naturally occurring neurotransmitters. Antagonists produce the opposite action of agonists (Berg & Clarke, 2018).  Antagonists prevent receptor binding, which blocks the natural effects of neurotransmitters.  Partial agonists work like an agonist but only produce a minimal response.  Partial agonists can bind to as many receptors but cannot produce a response.  When partial agonists bind without an effect, they are essentially blocking the receptor site and serving as an antagonist (Berg & Clarke, 2018).  This would alter the effects of pharmacological effects of medications.  An inverse agonist binds to the same receptors as agonists but produce the opposite effect (Aronson, n.d.).  Inverse agonists deactivate a receptor instead of activating them.

 

  1. Compare and contrast the actions of g couple proteins and ion gated channels.

Ion gated channels are a rapid-effect receptor.  Ions rapidly flow through channels across the plasma membrane (Camprodon & Roffman, 2016).  These cellular membranes open or close when signaled which allows certain ions to pass when the channel is open.

G couple proteins are a slower messenger system that includes Ligand binding sites (Camprodon & Roffman, 2016).  There is an extracellular transmembrane. G couple proteins transfer signals from the cell membrane to inside the cell.

 

  1. Explain how the role of epigenetics may contribute to pharmacologic action.

Epigenetics is essentially how gene function can be altered without specific alterations in a code or sequence changes.  Epigenetics is also how physical changes affect the way genes are expressed.  A medications mechanism of action and side effects can be affected by epigenetics.  Changes can include modifications of DNA, remodeling, and can cause DNA methylation; a methyl group may be added or deleted, which can affect neurotransmitters such as norepinephrine and dopamine (Hodgson et al., 2019).  For example, a study by Lockwood & Youssef (2017), noted that rats had an increase in leptin that were given valproic acid which can be associated with weight gain.  This side effect could be attributed to the epigenetic changes or the valproic mechanism of action.  There are many studies that continue to explore the side effect changes for antipsychotics and how they are related to epigenetics.

 

  1. 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.

This information is crucial when prescribing medications.  It is important for nurse practitioners to understand the agonist and antagonist actions.  If this concept is not fully understood, prescribed medications could essentially be counter-acted at the receptor site.  The medication response could also be maximized or decreased. The goal of prescribing medication is to relieve symptoms and not to cause harm.  For example, Haldol is an antagonist for dopamine, this limits dopamine uptake at the receptor sites.  In patients that have a severe overdose, an agonist can be given to counteract the Haldol and reduce the extrapyramidal effects.  Ropinirole is a dopamine receptor agonist and will work to decrease the antagonist effects of Haldol and essentially stimulate the dopamine receptors (PubChem, n.d.).

 

Reference

Aronson, J. (n.d.). The Hitchhiker’s Guide to Clinical Pharmacology Pharmacodynamics: How Drugs Work. https://www.cebm.net/wp-content/uploads/2016/05/Pharmacodynamics-How-drugs-work.pdf

Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. International Journal of Neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

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.

 

Hodgson, N. W., Waly, M. I., Trivedi, M. S., Power-Charnitsky, V.-A., & Deth, R. C. (2019). Methylation-related metabolic effects of D4 dopamine receptor expression and activation. Translational Psychiatry, 9(1). https://doi.org/10.1038/s41398-019-0630-3

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

PubChem. (n.d.). Ropinirole. Pubchem.Ncbi.Nlm.Nih.Gov. Retrieved December 9, 2020, from https://pubchem.ncbi.nlm.nih.gov/compound/ropinirole

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!

Thank you for your insightful post. I find the mechanisms of ligands fascinating.  An allosteric binding is when a ligand binds in a site that is not the primary receptor site and the interaction increases or decreases the action of the agonist (Kowalski et al., 2017).  An example of a positive allosteric modulation is when oxygen molecules bind to hemoglobin, in which oxygen is the substrate and the effector (Kowalski et al., 2017).  An inverse agonist is similar to an antagonist in such that it binds with the receptor and the result is not what the endogenous ligand would produce but instead of being the opposite effect, the effect is muted (Khilnani & Khilnani, 2011).  Antihistamines were categorized as antagonists but new research has shown they act as inverse agonists stabilizing the effects of histamine (Khilnani & Khilnani, 2011).  In addition, several antipsychotic drugs (“D2 receptor antagonists”), such as clozapine, have shown inverse agonist properties as the mechanism of action in their therapeutic effects (Kowalski et al., 2017).

References

Khilnani, G., & Khilnani, A. (2011). Inverse agonism and its therapeutic significance. Indian Journal of Pharmacology, 43(5), 492. https://doi.org/10.4103/0253-7613.84947

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/10.1111/ppc.12208