Foundational neuroscience peer responses | Nursing homework help

Respond to two of your colleagues 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.

Peer one 

Patricia Kensah

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.

          Psychopharmacologic drugs have a wide range of effects, known as the agonist-to-antagonist spectrum. Drugs that increase the body’s response to a stimulus are called agonists, whereas those that decrease it are called antagonists. Inverse agonists have the opposite effect of agonists, while partial agonists are agonists and antagonists. Substances with psychopharmacologic effects are used to treat mental health problems. They influence the brain through influencing certain neurotransmitter systems. The spectrum of action from agonist to antagonist describes the range of effects these medications have on brain receptors. To activate a receptor, chemicals called agonists must first bind to it. Action-wise, they’re like a key in a lock, mimicking the effects of endogenous neurotransmitters. One type of agonist is a full agonist, while another is a partial agonist. Different from partial agonists, full agonists fully activate the receptor. In contrast to agonists, antagonists bind to a receptor but do not trigger its activation. Instead, they inhibit the receptor’s function by blocking the binding of endogenous neurotransmitters or other agonists. Full and partial antagonists are distinguished by the degree to which they inhibit receptor activity.

          On the agonist-antagonist spectrum, partial agonists and antagonists occupy a special place. While the endogenous neurotransmitter is abundant, a partial agonist can block its effects, but when it is depleted, the agonist properties of the molecule become more prominent. In COPD, the combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β2 adrenergic agonist (LABA) elicited bronchodilation superior to that by monotherapy with either of these agents (Jude et al., 2023). On the other hand, inverse agonists are medications that have the opposite effect as agonists while binding to the same location. If an inverse agonist were to bind to a receptor, it would become less active in the absence of an agonist. The performance of partial and inverse agonists can affect the success of psychopharmacologic therapy. Certain psychiatric diseases may not respond as well to partial agonists as they would to complete agonists because of the diminished effect they create. Inverse agonists should be used with caution because they could potentially cause unpleasant side effects.

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

          One may classify receptors that respond to neurotransmitters into two categories: G protein-coupled receptors (GPCRs) and ion gated channels. G protein-coupled receptors (GPCRs) are transmembrane proteins that can be activated by a wide range of ligands, such as neurotransmitters, hormones, and other signaling molecules. A change in gene expression, ion channel function, and other physiological activities may result from their activation of a downstream signaling pathway. When a ligand binds to a GPCR, the receptor undergoes a conformational change that can either activate (called an agonist) or inhibit (called an antagonist) signal transduction pathways. Approximately one third of the drugs on the market target GPCRs and are used to treat various human diseases including cardiac malfunction, asthma, and migraines (Jooseong et al., 2022). Nevertheless, ion gated channels are transmembrane proteins that open to enable the influx or egress of ions when bound to certain ligands, such as neurotransmitters. When an ion enters or leaves a neuron’s cytoplasm, the membrane potential shifts, causing either depolarization or hyperpolarization.

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

          Changes in gene expression that do not result from shifts in the DNA sequence are referred to as epigenetics. In other words, epigenetics studies gene expression. Environment, food, and stress may also contribute to this phenomenon. Pharmacologic therapy may be affected by gene expression, which affects how the body reacts to medicine. Modifications to the DNA molecule, such methylation or acetylation, or to the proteins that interact with DNA, like histones, can result in these shifts. Genes involved in neurotransmitter synthesis, receptor expression, and other brain functions can be affected by epigenetic modifications that modify their expression.  The attenuation of the stress-induced reduction of MK-801’s antiseizure efficacy may be due to the increased acetylation of histone proteins in the nucleosomal core and promotion of gene expression (Researcher, 2008). It is possible that long-term consequences of psychopharmacologic treatments are influenced by epigenetic alterations, though this is yet an area of research. Changes in DNA methylation have been observed, for instance, in patients taking depressive medications; these modifications may contribute to the drugs’ therapeutic effects.

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.

          It is imperative for a psychiatric mental health nurse practitioner to have a thorough understanding of the agonist-antagonist spectrum of action and the actions of various types of receptors to prescribe the most effective medication for their patients. If a patient is taking an agonist, the nurse practitioner must know how to treat and prevent side effects. The Vitamin D Receptor (VDR) ligand-binding domain undergoes conformation change upon the binding of VDR agonists/antagonists. Helix 12 ((H)12) is one of the important helices at VDR ligand binding and its conformational changes are controlled by the binding of agonists and antagonists’ molecules (Nagamani et al., 2023). The nurse practitioner must also know how to handle decreasing efficacy if a patient is taking an antagonist. A patient with major depressive disorder, for instance, may need a full agonist antidepressant rather than a partial agonist. Knowing about epigenetics can also help with making treatment choices and keeping track of how well drugs are working. For instance, a patient’s body’s response to a medicine could be affected by their history of stress. If the patient’s family has a history of the illness, that’s another red flag. Thus, it is crucial to modify the drug according to the individual patient’s requirements in to boost the therapy’s chances of success.

                                                                          References

Jooseong Oh, Hyi-thaek Ceong, Dokyun Na, & Chungoo Park. (2022). A machine learning

          model for classifying G-protein-coupled receptors as agonists or antagonists. BMC

           Bioinformatics23(S9), 1–10. https://doi.org/10.1186/s12859-022-04877-7Links to an external site.

Jude, J. A., Dainty, I., Karmacharya, N., Jester, W., & Panettieri, R. (2023). The

          Bronchoprotective Effects of Dual Pharmacology, Muscarinic Receptor Antagonist and β

          2 Adrenergic Receptor Agonist Navafenterol in Human Small Airways. Cells (2073-

           4409)12(2), 240. https://doi.org/10.3390/cells12020240

Nagamani, S., Jaiswal, L., & Sastry, G. N. (2023). Deciphering the importance of MD

          descriptors in designing Vitamin D Receptor agonists and antagonists using machine

           learning. Journal of Molecular Graphics and Modelling118.

           https://doi.org/10.1016/j.jmgm.2022.108346

Researchers from Department of Veterans Affairs discuss findings in gene therapy. (2008,

           September 4). Gene Therapy Weekly, 106.

Peer 2

Janny Rodriguez

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 mechanism of action of psychopharmacologic agents can be agonist, antagonist, partial agonist, or inverse agonist. The abnormal concentrations of neurotransmitters play a great role in the development of psychotic and neurodegenerative diseases, and psychopharmacologic agents are designed to influence their actions differently. The drug can act as an agonist and increase the effect of the neurotransmitters after binding to synaptic receptors. Or the drug can be an antagonist and block the receptor site so that the neurotransmitter cannot bind and produce its effects. Partial agonists are drugs that don’t produce the maximum possible effect and have lower efficacy than agonists. Inverse agonists produce an effect inverse of a classical agonist after binding to the same receptor (Azzam et al., 2019). For example, full agonists of opioids include heroin and oxycodone. Naltrexone is an opioid antagonist, whereas buprenorphine is an example of a partial agonist.

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

            G protein-coupled receptors (GPCRs) and ion gated channels are two types of membrane receptors involved in signal transduction in cells. GPCRs are transmembrane receptors that transduce extracellular signals to the cytosol and mediate necessary cellular responses. The ligand (hormone or a neurotransmitter) binds to the GPCRs, and the GPCRs then interact with G proteins that activate downstream effectors such as enzymes or ion channels. GPCRs activated cascade is slow, leading to multiple and complex diverse cellular responses (Liu et al., 2021).

            Ion channels are remarkable proteins that form a pore in the lipid bilayer membrane and allow the passage of ions in response to a stimulus. Ion channels are classified according to the type of stimulus that opens and closes them. They can be voltage-gated, ligand-gated, photon mediated, light-gated, etc. They play a role in the generation of electric signals in the neurons, which are produced within milliseconds. The cellular response is simpler, and a single type of ion flux is mediated (Shad et al., 2018).  

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

            Epigenetics is the study of the impact of different factors on gene expression. Epigenetic mechanisms can cause alterations in the chromosome without directly altering the DNA sequence and regulate the gene expression (Al Abou et al., 2022). These mechanisms include DNA methylation, histone modification, and microRNA (miRNA) and can produce heritable phenotypic changes. These changes play a role in the pharmacologic action as they can alter the therapeutic effects, impact the medication efficacy, or may result in the development of adverse effects like addiction.

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 impacts the way one prescribes medications to patients. Epigenetic information is important as these mechanisms can play a role in the pathogenesis of multiple diseases. In such cases, drugs that can reverse or inhibit these epigenetic changes should be identified. A mental health nurse practitioner must be aware of the medication’s action to prescribe the most appropriate drug for the patient and predict the side effects. An example can be while treating an older adult for insomnia, OTC drugs, off-label prescription medications, or medications with regulatory approval for treating insomnia can be used. Trazodone is an antidepressant commonly prescribed for insomnia; however, a nurse must be aware that hypotension is a common side effect of this medicine, increasing the fall risk in older patients. Similarly, OTC antihistamines with anticholinergic activity can cause confusion and other side effects which are not tolerable for older patients (Neubauer, 2022).

References

Al Aboud, N. M., Tupper, C., & Jialal, I. (2022). Genetics, epigenetic mechanism. StatPearls [Internet]. https://www.ncbi.nlm.nih.gov/books/NBK532999/

Azzam, A. A. H., McDonald, J., & Lambert, D. G. (2019). Hot topics in opioid pharmacology: mixed and biased opioids. British Journal of Anaesthesia, 122(6). https://www.bjanaesthesia.org.uk/article/S0007-0912(19)30187-4/fulltext#secsectitle0010

Liu, N., Wang, Y., Li, T., & Feng, X. (2021). G-Protein Coupled Receptors (GPCRs): Signaling pathways, characterization, and functions in insect physiology and toxicology. International Journal of Molecular Sciences22(10). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156084/#:~:text=The%20main%20function%20of%20GPCRs,proteins%20and%20their%20downstream%20effectors.

Neubauer, D. N. (2022). Pharmacotherapy for insomnia in adults. UpToDate. https://www.uptodate.com/contents/pharmacotherapy-for-insomnia-in-adults#:~:text=Antidepressants%20prescribed%20for%20insomnia%20(eg,patients%20%5B10%2C24%5D

Shad, K. F., Salman, S., Afridi, S., Tariq, M., & Asghar, S. (2018). Introductory chapter: Ion channels: Ion channels in health and sickness. IntechOpen. https://www.intechopen.com/chapters/63380

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