Foundational Neuroscience Essay

Foundational Neuroscience Essay Main Post

                            The Agonist-to-antagonist spectrum of action of psychopharmacologic agents

       Agonists are drugs that bind to target receptors and can alter receptor activity to produce a response. They therefore have both affinity as well as intrinsic efficacy. Antagonists on the other hand have affinity but lack intrinsic efficacy which means that they do not induce a response though they can bind to the target receptor. Drugs that are partial agonists can not only bind but also activate a specific receptor but are partially effective when compared to a full agonist at a receptor Foundational Neuroscience Essay. Inverse agonists on the other hand can bind as an agonist to a receptor but produces a pharmacological response or effect that differs from that of the agonist. that can reduce the constitutive activity of a receptor. Generally, a full agonist elicits the utmost response a system is capable of, while a partial agonist elicits a below maximum response. Although it is clear that the intrinsic efficacy of a partial agonist is less than that of a full agonist, full agonists can also differ in intrinsic efficacy Notably, a drug can be an agonist, an antagonist, and an inverse agonist at the same time acting at the same receptor. Therefore, even though affinity gets a drug to a receptor, it does not direct what functional outcome of the drug-receptor interaction (Berg & Clarke, 2018) Foundational Neuroscience Essay.

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                                   The actions of g couple proteins and ion gated channels

       G couple proteins receptors are made up of a group of seven-transmembrane domain-containing proteins that team up with G proteins or GRT-binding proteins over cell membranes stimulating various cellular responses by controlling the activity of ion channels and many enzymes. G proteins control a large amount of ion channels. Ion gated channels as transmembrane unlock passage of neurotransmitters, and let ions pass through neurons. G-proteins act as transducers that pair neurotransmitter binding to the control of postsynaptic ion channels.  Ligand-gated ion channels as membrane proteins have a pore that regulates the flow of selected ions across the plasma membrane. Ion channels as pore-forming proteins fused into the cell membranes of cells, and the channels let distinct ions go across cell membranes, depending on the electrochemical ion gradients in the middle of inside and outside of the cell. G protein-mediated modulations of ion channel activity indirectly includes sympathetic stimulation in the heart. For instance Noradrenaline coming from the nerve termini activates Gs by binding to the beta1-adrenergic receptor, augmenting adenylyl cyclase leading to  conversion of ATP to cyclic AMP directly activating the pore-forming cyclic nucleotide-gated non-selective cation channel subunit, leading to an increased heartbeat (Inanobe & Kurachi, 2014) Foundational Neuroscience Essay.

                            The role of epigenetics may contribute to pharmacologic action

       Epigenetics describes the way an individual’s behaviors and environments can give rise to changes that impact the way genes function. Although genes play a crucial role in the health of an individual, behaviors and environment affect health too, for instance active lifestyle or exercise and diet. Epigenetic changes can be reversed unlike genetic change.  Although they can change the way the body reads a DNA sequence, they do not however change the DNA sequence (Centers for Disease Control and Prevention [CDC], 2020).

Due to current advancements in understanding real function of the entire genome, pharmacology has to adjust itself to embrace ways of fighting diseases more global‐response sense instead of the traditional drug‐receptor sense. The design of drugs may focus on making them capable of being more broad‐acting over a variety of epigenetic large‐scale incidents instead of making them to be exact to a certain gene or protein subtype. These epigenetic regulatory mechanisms that are in a larger‐scale proportion may cross more than one gene or proteins family and may even regulate large genes groups. Some diseases like cancer that usually has many different mutation variations that are complex, unpredictable, not easily detectable, and difficult to treat, giving rise to relapse. Epigenetics of cancers might be the answer to more effective treatments (Stefanska & MacEwan, 2015). Epigenetics may affect the way drugs, psychopharmacologic agents, and treatments work for individuals. That a drug like Abilify (Aripiprazole) works for one patient does not mean it will work for the other.

                      How information may impact the way I prescribe medications to patients

       This information may impact the way I prescribe medications to patients, as individual body make up is different. The psychiatric mental health NP must understand that patient safety is the priority when prescribing medications, and that has to take into consideration the drug’s mechanism of action and drug to drug interactions. Proper evaluation is important to make the right diagnosis so that the patient can get the right treatment that will improve the outcome of care. Patients also have to be monitored for side effects and educated on the importance of drug compliance.

       For instance, a 69-year-old male patient with depression prescribed daily dose of 25 mg orally of Zoloft (Sertraline) an SSRI that works by altering a chemical messenger (serotonin) in the brain. Zoloft (Sertraline) an SSRI is usually the first line of treatment of moderate to severe as SSRIs impede the serotonin reabsorption into neurons, thereby increasing the activity of serotonin in the brain. Zoloft (Sertraline) which is used to treat depression acts as a Dopamine transporter (DAT) inhibition and sigma-1 receptor binding and is not only FDA approved, but is safe for long-term use. Common side effects include dry mouth, bruising, tremors, sexual dysfunction, and gastrointestinal constipation, and bruising. The NP in this case has to consider low doses for special populations like the elderly and risk reduction of sociality for individuals from ages 65 years and above, as well as risk of SIADH and changes for persons with hepatic and kidney impairments (Potter, 2019). As an NP in this case , I would take the patients age into consideration when prescribing, and avoid wanting to give higher doses of medications but rather start with drugs that are low dose, as well as safer, and tolerable like Zoloft with the goal of keeping the patient at lower doses that will not compromise the frug effectiveness. It is also important to monitor for side effects like erectile dysfunction.

       The NP has to bear in mind that studies shows that a once a day drug such as Wellbutrin XL (Bupropion XL), a norepinephrine and dopamine reuptake inhibitor, is known to improve sexual function. Wellbutrin XL (Bupropion XL) is also generally well tolerated with no major safety concerns. It also works well with Zoloft in managing the side effects of sexual dysfunction that may result from Zoloft (Shen et al., 2019) Foundational Neuroscience Essay

                                                                                References

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse agonism and functional selectivity. International Journal

       of Neuropsychopharmacology21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

Centers for Disease Control and Prevention. (2020). What is Epigenetics? https://www.cdc.gov/genomics/disease/epigenetics.htm

Inanobe, A., & Kurachi, Y. (2014). Membrane channels as integrators of g-protein-mediated signaling. Biochimica et Biophysica Acta

       (BBA) – Biomembranes1838(2), 521–531. https://doi.org/10.1016/j.bbamem.2013.08.018

Potter, D. R. (2019). Major Depression Disorder in Adults: A Review of Antidepressants. International Journal of Caring Sciences12(3),

       936–1942. https://web-b-ebscohost-com.ezp.waldenulibrary.org/ehost/pdfviewer/pdfviewer?vid=7&sid=b2d9f73d-7902-43bf-82

       b0-903ed3e0bb63%40sessionmgr101

Shen, Y., Zhao, Q., Yu, Y., Tan, Y., Zhang, H., Xu, X., Wang, Z., Li, Y., Hu, J., Zhong, J., & Li, H. (2019). Efficacy and safety of        bupropion hydrochloride extended-release versus escitalopram oxalate in Chinese patients with major depressive disorder: Results

       from a randomized, double-blind, non-inferiority trial. Journal of Affective Disorders257, 143–149. https://doi.org/10.1016/j.jad.2019.07.023

Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British Journal of Pharmacology172(11), 2701–

       2704. https://doi.org/10.1111/bph.13136

 

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. Foundational Neuroscience Essay

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. Foundational Neuroscience Essay
  • 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 such a thorough discussion post. The way you succinctly summarized the agonist-antagonist spectrum helped solidify that information a bit more for me. It was also interesting to understand that the affinity a drug has to a receptor does not change (higher is typically better), but the intrinsic efficacy can be manipulated by scientists and is valuable at different levels. These different levels represent the agonism/antagonism continuum (Berg & Clarke, 2018).

In investigating epigenetics further, I found some information about DNA methylation and learned about it’s crucial role in activating or repressing gene expression. Specifically, how disruption of DNA methylation of HTR2A can lead to Major Depression. DNA methylation is also associated with turning off repetitive types of coding as well to maintain stability (Kuehner et al., 2019). Although the science and exploration of methylation in the brain is continuing to grow, alteration to intrinsic patterns have been associated with things like early life stressors and abuse (Kuehner et al., 2019). Foundational Neuroscience Essay

Thank you again for a thought provoking post.

Adria

References

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

Kuehner, J. N., Bruggeman, E. C., Wen, Z., & Yao, B. (2019). Epigenetic Regulations in Neuropsychiatric Disorders. Frontiers in Genetics, 10, 268. https://doi.org/10.3389/fgene.2019.00268

 

Thank you for your explanation. I like what you said about epigenetics and how genes, including behaviors, age, disease state, and environment, play an important in individuals’ health.  As individuals, we have to be conscious of our surroundings and the things that can affect us. We have to include diet, exercise nutritious foods in our lifestyle. Doing our parts will be beneficial in the long run. Although genetic change can be a regular and natural occurrence, the change in epigenetics can also lead to a damaging effect such as cancers.  The environment is being researched as an essential influence on epigenetic tags and also on diseases. For example, Pollution has become a significant focus in the research area as scientists are finding that air pollution may affect methyl tags on DNA  and increase one’s risk for neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Fortunately, Vitamin B may protect against harmful epigenetic effects of pollution and may be able to combat the harmful effects that particular matter has on the body (“Epigenetic: Fundamentals,” n.d) Foundational Neuroscience Essay

References:

Epigenetics and drug discovery. (2018, July 27). Drug Discovery from Technology Networks. https://www.technologynetworks.com/drug-discovery/articles/epigenetics-and-drug-discovery-306821

Epigenetics: Fundamentals. (n.d.). https://www.whatisepigenetics.com/fundamentals/#:~:text=Epigenetics%20is%20the%20study%20of,how%20cells%20read%20the%20genes. Foundational Neuroscience Essay

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