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Julian Fils Julian Fils: (Week Two)Neurotransmitters and Receptor TheoryCOLLAPSE
Discussion: Neurotransmitters and Receptor Theory
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist functionality may impact psychopharmacologic treatments’ efficacy.
In simple terms, an agonist creates a specific action, and the antagonist opposes a particular activity. Neurotransmitters that occur naturally stimulate receptors and are thus agonists. Some medications also stimulate receptors and are therefore agonists as well. The mechanism of partial agonists or stabilizers the drugs stimulate the receptors lesser than natural neurotransmitter. It is a common misconception that antagonists are the opposite of agonists because they block agonists’ actions. However, although antagonists prevent agonists’ efforts, they have no activity of their own in the agonist’s absence (Stern et al., 2016).
For this reason, antagonists are sometimes called “silent.” Inverse agonists, on the other hand, do have opposite actions compared to agonists. That is, they not only block agonists but can also reduce activity below the baseline level when no agonist is present. Thus, the agonist spectrum reaches from full agonists to partial agonists through “silent” antagonists and finally inverse agonists (Stahl, 2013).
Compare and contrast the actions of g couple proteins and ion gated channels
Neurotransmitters trigger G-protein-linked and ion-channel-linked cascades. There are four elements linked to the G-protein-linked system. The first element is the neurotransmitter, also referred to as the first messenger. The second is the G-protein coupled receptors which have seven transmembrane regions. The third element a G protein, which is a connecting protein. The fourth element is an enzyme that can synthesize a second messenger when activated (Stahl, 2013). The first steps involve the neurotransmitter binding to the receptor. It also changes the form of the receptor, which allows it to fit with the G protein. Then, the G protein binding is conformed to the receptor of the neurotransmitter. The two receptors (neurotransmitter and the G protein) work with each other, which then bind to enzyme E and synthesizes the second messenger (Stahl, 2013).
Ion channel receptors are a vital component of nervous system signaling, allowing rapid and direct conversion of a chemical neurotransmitter message to an electrical current. Efficient neurotransmission requires the precise interplay of various neurotransmitter receptors at pre-and post-synaptic compartments. Ligand-gated ion channels play a central role in intercellular communication in the nervous system. Ion channels are the cellular machinery for ion flux across the membrane and, therefore, the basis of the electrical excitation of neurons. Ligand-gated ion channels are oligomeric protein assemblies that convert a chemical signal into an ion flux through the post-synaptic membrane and are involved in essential brain functions such as attention, learning, and memory (Li et al., 2015).
Explain how the role of epigenetics may contribute to pharmacologic action
Epigenetics describes genetic information that is ‘beyond’ or ‘above’ that information coded solely by our genetic code (Stefanska & MacEwan, 2015). Prior research has shown that the initial epigenetic pattern was set during life and gave each neuron its life-long personality. However, recent studies have shown that these neurons are changing. Depending on what happened to them, such as stress, child abuse, dietary deficiencies, psychotherapy, drug abuse, or psychotherapeutic medications, the previously silent genes are now activated once active genes can become silenced. Thus, causing favorable and unfavorable developments. Favorable epigenetics may trigger learning or experience therapeutic effects on medications, and inimical epigenetic mechanisms may trigger drug abuse, addiction, anxiety disorder, or chronic pain (Stahl, 2013).
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.
As prescribers, psychiatric nurse practitioners must understand the biological and physical aspects of prescribing medication to the mental health population. These medications directly affect the receptors and neurons; therefore, it is imperative to understand the mechanism of action. Recently at work, a geriatric psychiatric patient with a urinary tract infection was having difficulty sleeping. The nurse asked about trazodone as a PRN for sleep. The Psychiatrist explained that trazodone inhibition of the reuptake of serotonin makes it an antidepressant. It is essential to know it also blocks alpha- receptors that can give the side effect of orthostatic hypotension, especially in older patients. What is also crucial is to note that the anticholinergic effects of trazodone cause delirium and confusion.
In this example, a study was conducted by Lockwood & Youssef (2017), where the study of epigenetic effects on the Brain-Derived Neurotrophic Factor (BDNF) in patients with bipolar disorder types I and II and major depressive disorder. In this study, methylation was investigated when patients were in various mood states, including manic, hypomanic, mixed, euthymic, and depressed. The effects of valproic acid and lithium and the impact on BDNF were studied. The results have shown that in a mixed or manic state, BDNF methylation levels approximated that of the control subjects. In addition to that, the patients that were in euthymic or depressed states had significantly higher BDNF methylation levels (Lockwood & Youssef, 2017).
Li, S., Wong, A. H. C., & Liu, F. (2015). Ligand-gated ion channel interacting proteins and their role in neuroprotection. Frontiers in Cellular Neuroscience, 8. https://doi.org/10.3389/fncel.2014.00125
Lockwood, L., & Youssef, N. (2017). Systematic review of epigenetic effects of pharmacological agents for bipolar disorders. Brain Sciences, 7(12), 154. https://doi.org/10.3390/brainsci7110154
Stahl, S. (2013). Stahl’s essential psychopharmacology print and online bundle: Neuroscientific basis and practical applications. Cambridge University Press.
Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British Journal of Pharmacology, 172(11), 2701–2704. https://doi.org/10.1111/bph.13136
Stern, T. A., M Fava, Wilens, T. E., & Rosenbaum, J. F. (2016). Massachusetts general hospital psychopharmacology and neurotherapeutics. Elsevier.
Deepinder Bhandohal Week 2 DiscussionCOLLAPSE
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.
Agonists are agents that activate receptors upon their binding, similar to the effect of neurotransmitters, hormones, and other endogenous regulators. Antagonists on the other hand do not affect the action of the receptor but act by blocking the receptor’s effectiveness to prevent binding of other drugs or endogenous molecules for activation. Therefore, an antagonist is a drug that has a receptor binding affinity but do not initiate any intrinsic activity (Seyedabadi, Ghahremani, & Albert, 2019).
Partial agonists have moderate activity compared to full agonists, often producing half the effect. A partial agonist can thus be an agonist-antagonist as it blocks the binding of other molecules while producing limited activity. An inverse agonist binds to the agonist binding site on the receptor but elicits an opposite pharmacological effect. Therefore, partial and inverse agonists influence the efficacy and outcomes of the treatments.
2. Compare and contrast the actions of G-coupled proteins and ion gated channels.
G-protein coupled receptors (GPCRs) constitute a large family of receptors on the cellular plasma membranes that utilize a G protein to transmit signals inside the cell. Disorders in G-protein coupled receptors may result in diseases as they serve multiple functions within the body. Different responses are elicited by the G-protein coupled receptors following the interaction of G-protein subunits with other proteins within the cell. The subunits (α subunit, and another made up of the β and γ subunits) are produced from the division of G-protein following the binding with guanosine triphosphate. The interaction of these subunits with other proteins triggers diverse signaling pathways within the cell (Seyedabadi, Ghahremani, & Albert, 2019).
Ion channels are proteins that enable the flow of specific ions into and out of the cell. There are three types of gated ion channels; mechanically-gated ion channels, voltage-gated ion channels, and ligand-gated ion channels. Ligand-gated ion channels are ionotropic receptors that close or open in response to ligand binding. Voltage-gated ion channels open or close in response to changes in the membrane potentials. Membrane proteins activated by a GPCR can interact with ligand-gated ion channels to prompt their opening or closing (Alexander et al., 2019).
3. Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics is gene regulation where the gene expression patterns are changed following reversible modification of DNA, RNA, or proteins. Epigenetic alterations enable the understanding and identification of diseases like neurodegenerative disorders or cancers. DNA methylation is an example of disease-causing alterations. Responses to drugs vary based on the cellular changes caused by epigenetic alterations or genetic heterogeneity (Rosenthal & Burchum, 2018).
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.
Prescribing medications needs to take account of the patient’s characteristics especially the family history and the genetic implications on diagnosis and treatment. McClarty, Fisher, and Dong (2018) point out the effect of age on dementia treatment, especially when using antipsychotics for the psychological, behavioral, and psychosis symptoms. The treatment has various side effects and is often ineffective due to the effects of aging on drug metabolism and clearance. Age-induced epigenetic alterations also result in pharmacodynamic and pharmacokinetic changes that influence the antipsychotic action of the medication (Nguyen et al., 2020). Epigenetic changes also cause an increase in side effects and altered efficacy of antipsychotics due to histone modifications. Awareness of these changes would inform the prescription decision, especially for the antipsychotics to ensure minimal side effects and maximum efficacy of the selected medication (Camprodon & Roffman, 2016).
Alexander, S., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., Armstrong, J. F., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators (2019). The Concise Guide to Pharmacology 2019/20: Ion channels. British journal of pharmacology, 176 Suppl 1(Suppl 1), S142–S228. https://doi.org/10.1111/bph.14749
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.
Guidelines on prescribing practice in mental health: A systematic review. Psychiatry Research, 284. https://doi-org.ezp.waldenulibrary.org/10.1016/j.psychres.2019.112671
McClarty, B. M., Fisher, D. W., & Dong, H. (2018). Epigenetic Alterations Impact on Antipsychotic Treatment in Elderly Patients. Current treatment options in psychiatry, 5(1), 17–29.
Nguyen, T., Seiler, N., Brown, E., & O’Donoghue, B. (2020). The effect of Clinical Practice
Rosenthal, L. D., & Burchum, J. R. (2018). Lehne’s pharmacotherapeutics for advanced practice providers. St. Louis, MO: Elsevier.
Seyedabadi, M., Ghahremani, M. H., & Albert, P. R. (2019). Biased signaling of G protein coupled receptors (GPCRs): Molecular determinants of GPCR/transducer selectivity and therapeutic potential. Pharmacology & therapeutics, 200, 148–178. https://doi.org/10.1016/j.pharmthera.2019.05.006
2 SOURCES ON EACH DISCUSSION
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