Discussion: Foundational Neuroscience

Initial Posting
  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.

A molecule, such as a hormone, neurotransmitter, or drug that binds to a cell receptor site causing cell to become more active, causing a specific physiological response that can be natural or artificial (Christie, 2016). An antagonist a substance that blocks the action of another, as a drug that binds to a receptor for a hormone, neurotransmitter, or another drug blocking the action of that substance without producing any physiologic effect itself (Grandy, 2016). A partial agonist are drugs that can activate the receptors, and can decrease the response of an activated receptor by a stronger agonist (Kenakin, 2017). An inverse antagonist binds to the receptor and decreases the activity of the receptor, which reverses the effect of the binding agonist (Berg & Clarke, 2018).

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

The G-protein coupled receptors (GPCRs) are the largest and most versatile protein family. The g protein has the most abundant membrane receptors, responsible for specific functions in human. This makes them a great attraction for drug binding and interaction (Johnson & Lovinger, 2016). Ion gated channels bind to a receptor opening a channel that only allows specific ions to pass, once the channel is open the membrane may be polarized or depolarized (Bylund, 2014).

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

Epigenetics is the study of changes in gene expression that does not involve change the DNA sequence, thus a change in phenotype, not genotype, and affects how cells read genes (Rasool et al, 2015). “Epigenetic mechanisms in health and disease has uncovered changes in DNA methylation and chromatin structure that may contribute to psychiatric disorders” (Schuebel, Gitik, Domschke, & Goldman 2016). Recent studies in epigenetics have revealed a correlations between DNA and depression; using epigenetics can help personalized a patient’s medication regimen, especially if they are not responding to traditional medicines (Rasool et al, 2015).

  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

 

Understanding how a drug will affect the patient and the way the patient’s body will affect the drug is critical when prescribing medications (Laureate Education, n.d.). Knowing that labs should be obtained periodically certain medication like lithium for bipolar to monitor therapeutic ranges, kidney function and toxicity. Lithium can cause renal insufficiencies.

 

  1. Nurse practitioner must be aware of the medication’s action.

In order to safely prescribed medications and prevent adverse reactions, a Nurse Practitioner should have an understanding of drug-drug interactions and food-drug interactions (Laureate Education, n.d.). It is impossible to know all interactions, so the clinician should have resources readily available, such as a drug book or PDA (Laureate Education, n.d.). Understanding the medication’s action will require the Nurse Practitioner to have knowledge of pharmacokinetics and pharmacodynamics in particular age groups. For example, if prescribing a medication to an elderly patient that excretes through the kidneys, the clinician should understand that as a person ages, kidney functioning decreases, which depending on the drug that  can cause toxicity (Ponticelli, Sala, & Glassock, 2015). The goal is to effectively treat the patient without causing harm.

 

References

Berg, K. & Clarke, W. (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

Bylund, D. (2014). Reference Module in Biomedical Science. Science Direct. Retrieved from https://www.sciencedirect.com/referencework/9780128012383/biomedical-sciences

Christie, M. (2016 April 28). Explainer: how do drugs work? The Conversation. Retrieved from https://theconversation.com/explainer-how-do-drugs-work-48665

Grandy, D. (2016). Neuropathology of Drug Addictions and Substance Misuse. Science Direct. Retrieved from https://www.sciencedirect.com/book/9780128002124/neuropathology-of-drug-addictions-and-substance-misuse.

Johnson, K., & Lovinger, D. (2016). Presynaptic G Protein-Coupled Receptors: Gatekeepers of Addiction? Frontier in Cellular Neuroscience. Retrieved from https://www.frontiersin.org/articles/10.3389/fncel.2016.00264/full

Kenakin, T. (2017). Pharmacology in Drug Discovery and Development Understanding Drug Response. Science Direct. Retrieved from https://www.sciencedirect.com/book/9780128037522/pharmacology-in-drug-discovery-and-development.

Laureate Education (producer). (n.d.) Introduction to advanced pharmacology [Video File]. Baltimore, MD: Author

Rasool, M., Malik, A., Naseer, M. I., Manan, A., Ansari, S., Begum, I., Qazi, M. H., Pushparaj, P., Abuzenadah, A. M., Al-Qahtani, M. H., Kamal, M. A., & Gan, S. (2015). The role of epigenetics in personalized medicine: challenges and opportunities. BMC medical genomics8 Suppl 1(Suppl 1), S5. https://doi.org/10.1186/1755-8794-8-S1-S5

Schuebel, K., Gitik, M., Donschke, K., & Goldman, D. (2016). Making Sense of Epigenetics. International Journal of Neuropsychopharmacology, 19(11). https://doi.org/10.1093/ijnp/pyw058

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!

Week 2 Initial Post
  1. Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact psychopharmacologic treatments’ efficacy.

An agonist is a drug that binds with the receptor and changes the receptor activity to produce a response with neurotransmitters and hormones. An antagonist will bind with the receptor but will not cause any changes to occur with the receptor activity. Opioids are agonists; they activate the opioid receptors. Naloxone is an antagonist as it attaches to the opioid receptors, blocking the opioids, but does not activate the opioid receptors.

A partial agonist is a substance that can activate receptors but cannot elicit the maximum response from the receptor system; for example, tramadol is a partial agonist of the mu receptor. An inverse agonist: substances that bind to the same binding site of the agonist in the receptor and produce an opposite pharmacological effect of a receptor agonist; for example, a benzodiazepine is an inverse agonist.

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse agonism and functional selectivity. The International Journal of Neuropsychopharmacology21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

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

 

A neurotransmitter can affect a postsynaptic cell’s activity by two different receptor proteins: ionotropic or ligand-gated ion channels and metabotropic receptors.

G-proteins can be understood as transducers that combine neurotransmitter binding to postsynaptic ion channel regulation. – Ion channel -linked receptors attach a ligand and open a channel through the membrane that permits specific ions to move through. G-protein-linked receptors bind a ligand and initiate a membrane protein called a G-protein, which then networks with an enzyme or an ion channel in the membrane

Lodish H, Berk A, Zipursky SL, et al. Molecular Cell Biology. (4th ed.) New York: W. H. Freeman; 2000. Section 21.5, Neurotransmitter Receptors.  https://www.ncbi.nlm.nih.gov/books/NBK21586/

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

 

Epigenetics is a gene regulation mechanism where DNA, RNA, and even proteins undergo reversible modifications that alter the genes’ expression patterns and can be transferred to the next generation. Epigenetic modifications are not only regulated by mutations but also by the environment. Most of these modifications are methylation, acetylation, phosphorylation, ubiquitylation, and sumoylation. The best known epigenetic modification in DNA is DNA methylation, where the addition or removal of a methyl group (CH3) predominantly occurs in the cytosine bases repressing the genes. DNA interacts with proteins and is also packed into chromatins. These histone proteins undergo epigenetic modifications like acetylation, phosphorylation, and methylation to either activate or repress the gene transcription. This epigenetic modification of histone proteins results in chromatin remodeling. The acetylation of the K14 and K9 lysines histone H3 tails by histone acetyltransferase enzymes is known to cause transcriptional activation.

Cholewa-Waclaw,J., Adrian Bird, A., von Schimmelmann, M.,   Schaefer, A., Yu, H., Song, H., Madabhushi,R., and Tsai, L. (2016). The role of epigenetic mechanisms in the regulation of gene expression in the nervous system. Journal of Neuroscience 36 (45): 11427-11434; DOI: 10.1523/JNEUROSCI.2492-16.2016

 

  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.

When prescribing medication, it is essential to know the various drugs that all providers prescribe to the patient. It is crucial to ensure that the patient is not taking any antagonist medications if prescribed an agonist medication due to the agonist drug’s nullifying effect; otherwise, the patient will receive no benefit from the medication. To not provide the patient with too much of a response as would be the case with two agonist medications for synergistic effect, care must be taken. For example, if a patient were to take aspirin and warfarin, the result would be excessive bleeding.

If we use two agonists, it will have a synergistic effect, and the total response that we will get will be maximum, whereas if we use an agonist and an antagonist, the antagonistic effect will result in a decreased response, for example, phenobarbital and warfarin result sin a reduced impact.

Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The International Journal of Neuropsychopharmacology21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

Drugs.com (2020). https://www.drugs.com/drug-interactions/warfarin.html

 

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