Discussion: Foundational Neuroscience – Solved Sample

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 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.

An agonist is a drug substance that binds to and activates a cell receptor to produce a psychological response similar to the signal ligand (Pleuvry, 2004). For example, salbutamol is a moderately selective beta 2 – receptor agonist that produces smooth muscle relaxation. Contrarily, the antagonist is a drug substance that binds to a cell’s receptor to oppose or reduce the cell’s actions, limiting the cell’s receptor’s ability to be stimulated by other antagonists (Pleuvry, 2004). For example, ranitidine acts as an antagonist to H2 receptors, reducing the secretion of stomach acid.

Partial agonists are drugs that have lower efficacy when binding and activating a cell’s receptor (Kenakin, 2016). Tramadol, for example, is a mild mu agonist opioid that can trigger low levels of opioid physical dependency because it acts as a partial agonist. An inverse agonist, on the other hand, is a drug that attaches itself to a receptor like an agonist but produces the opposite pharmacological reaction. (Berg & Clarke, 2018). For example, naloxone is an inverse agonist against the mu-opioid receptor.

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

G couple proteins act as the receptors for several cell components such as neurotransmitters, ions, hormones, etc. Therefore, G couple proteins facilitates communication between cells and their sorrounding (Camprodon & Roffman, 2016). G couple proteins binds with agonists to activate particular heterotrimeric G proteins, causing substance secretion from cell wall forming an ion opening. Activated G-proteins, for example, stimulate adenylyl cyclase, which modulates the production of cyclic AMP [cAMP], which is involved in, among other things, sensory perceptions, hormones, and nerve transmission. Ion channels are openings in the cell membrane that enable ions to enter and exit the cell. (Camprodon & Roffman, 2016). Ion channels are vital in shaping action potential, regulating cell volume, and establishing a resting potential by gating ion flow across the epithelial and secretory cells (Camprodon & Roffman, 2016).

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

Epigenetics is a mechanism of gene regulation where DNA, RNA, and even proteins undergo reversible modifications that alter the genes’ hereditary expression patterns (Rasool et al., 2015). The epigenetic alterations influence normal and disease states associated with chronic illnesses like cancers and neurodegenerative disorders (Camprodon & Roffman, 2016). The epigenetic alterations are regulated by mutations, environment/lifestyle, or disease state. They include methylation, where the addition or removal of a methyl group (CH3) predominantly occurs in the cytosine bases repressing the genes. Epigenetic diagnostic testing provides information by collecting genomic information crucial in decision making regarding the management of these conditions by pharmacological means.

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.

It is important to consider the basic principles of agonist-antagonist interaction/reactions of various drug substances in order to make appropriate clinical decisions. The aim of drug therapy is to produce a specific pharmacologic response with the desired strength and length while preventing adverse drug reactions. Thus, the knowledge of agonists and antagonists helps in determining the therapeutic efficacy of different drug combinations. For example, an asthmatic person cannot use bisoprolol for high pressure and at the same time use albuterol used in preventing and treating wheezing and shortness of breath. Bisoprolol is a beta-blocker/antagonist and has a restrictive effect on albuterol. Equally, epigenetics knowledge is necessary when determining personalized treatment for individuals diagnosed with diseases associated with epigenetic alterations. For instance, regulating treatment efficiency and transport of drugs requires an understanding and manipulation of drug-metabolizing genes.

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References

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.  

Kenakin, T. (2016). Pharmacology in drug discovery and development: Understanding drug response. Academic Press.

Pleuvry, B. J. (2004). Receptors, agonists and antagonists. Anaesthesia & Intensive Care Medicine, 5(10), 350–352. https://doi.10.1383/anes.5.10.350.52312  

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

Rosenbaum, D. M., Rasmussen, S. G., & Kobilka, B. K. (2009). The structure and function of G-protein-coupled receptors. Nature, 459(7245), 356-363. https://doi.10.1038/nature08144

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