Discussion 2

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Jan 9, 2024

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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. The Agonist-to-antagonist spectrum comprises the full agonist, partial agonist, antagonist, and inverse agonist (Stahl, 2021). Simply described, and agonist is an agent that will bind to the target receptors and stimulate them, precipitating an action or response. Full agonists stimulate receptors, and depending on the drug structure and its intrinsic efficacy, they will produce a maximal response, whereas partial agonists stimulate receptors to a lesser extent, and will not produce a maximal response (Stahl, 2021). Antagonists are agents that bind to receptors, blocks the agonists, and inhibit their action. Despite their inhibitory activity, antagonists are not the opposite of agonist, nor can they have any activity independently from the agonists (Stahl, 2021). Inverse agonist, as their name states, have activities inversed or opposite to that of the agonists. Inverse agonists will block the agonist agents, and in the absence of agonists, can drop the activity below the baseline (Stahl, 2021). 2. Compare and contrast the actions of g couple proteins and ion gated channels . Most psychotropic drugs aim at the G-protein receptors and Ion-channels receptors. Psychotropic drug at the G-proteins receptors operates in a spectrum; going from full agonists to partial agonist, to antagonist, and inverse agonist. According to Stahl (2021), each drug that targets the G-protein receptors triggers a change in that receptor that will determine the location on the agonist-to-antagonist spectrum where it will act. Ion gated channels are organized in two classes: ligand-gated and voltage-gated. The ligand-gated channels have two functions; as they act as a type of receptors and as ion channels. They are made of long strings of protein and packed as subunits that have transmembrane

regions, their opening is controlled by neurotransmitters, and they act across an agonist to inverse agonist spectrum like the g-protein receptors (Stahl, 2021). The ligand-gated can be found in 5 states, ranging from resting, to open, closed, desensitized, and inactivated, and these states will determine the opening capacity of the channel, that ranges from maximal opening; usually caused by a full agonist, to maximal closing, usually caused by inverse agonist (Stahl. 2021). The voltage-gated channels opening is controlled by an ionic charge across the membrane in which they are found. Both the ligand-gated and the voltage gated channels work in conjunction during neurotransmission, leading to the release of an electrical and chemical message during brain communication (Stahl, 2021). 3. Explain how the role of epigenetics may contribute to pharmacologic action. Toth (2021) describes epigenetics as the study of the regulation of a genes’ transcriptional potential, and adds that epigenetic modifications include methylation of cytosine bases and chemical modifications of histones and nonhistone proteins. The Center for Disease Control and Prevention (2022) defines epigenetics as the study of how an individual’s behaviors and environment can cause changes that affect the way their genes work and states that epigenetic changes imply DNA methylation, histone modification, and non-coding RNA. Unlike genetic changes, epigenetic do not alter one’s DNA sequence, but they can change how one’s body reads a DNA sequence. Taking into consideration the two above definitions, it emerges that the knowledge of some’s epigenome is crucial in establishing a personalized treatment plan, knowing that epigenetic modification vary among individuals. (CDC, 2022). For example, certain gene mutations will make and individual prone to developing breast cancer, whereas some epigenetic changes might increase or decrease the changes of another individual to end up

developing breast cancer. Knowing someone’s epigenome will guide in the choice of the treatment including the pharmacological agent. 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 . Knowing the pathophysiology of a disease, the epigenome of the affected individual, and the mechanism of action of pharmacologic agents indicated in the treatment of the identified pathology is key in determining the most appropriate treatment for this specific individual. This is explained by the fact that two individuals started on Escitalopram 10 mg daily for depression might not have the same response for example. While the first individual might report improvement withing a few days or weeks, the second individual on the contrary might experience adverse effects from the medication and worsening symptoms, thus requesting a trial with a medication from another class of antidepression. Once the diagnosis is established, the nurse practitioner or provider can identify the defective neurotransmitter, which will help determine if the prescribed agent needs to act as an antagonist, agonist, inverse agonist, full or partial agonist and so on. Far from just being a random test-and-trial, the treatment of brain disorder greatly depends on the knowledge of most of the information discussed above.

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References: Center for Disease Control and Prevention (2022). Genomics and Precision Health . Retrieved fromhttps://www.cdc.gov/genomics/disease/epigenetics.htm Stahl, S. M. (2021). Stahl's essential psychopharmacology: Neuroscientific basis and practical applications (5th Ed.) Cambridge University Press. Toth, M. (2021). Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain. Annual Review of Pharmacology and Toxicology Vol. 61:181-201.https://doi.org/10.1146/annurev-pharmtox-030220-022920

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