Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents, including how partial and inverse agonist
TuesdayJun 6 at 10:32pm
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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.
In today’s world drugs are made up to be either agonists, antagonists, or partial agonists. An agonist refers to a chemical that binds to a receptor, the receptor activates, and a biological response is produced. In contrast, an antagonist blocks the action of an agonist, as an antagonist it will cause the opposite effect on the body (Stahl, 2013). Agonists can have different intrinsic efficacies and could be classified as full or partial agonists. A full agonist typically produces the maximal response possible, whereas a partial agonist produces a lesser agonist effect on a receptor (Berg & Clarke, 2018). For example, aripiprazole is a partial agonist Lowering dopaminergic neurotransmission in the mesolimbic pathway and enhancing dopaminergic activity in the mesocortical pathway (Berg & Clarke, 2018). So, when Aripiprazole is administered, the drug will occupy brain receptors where dopamine is elevated and will partially block the effects of dopamine, decreasing psychosis. However, if dopamine levels are low then aripiprazole will act as an agonist to increase dopamine transmission in these regions. These dual effects of partial agonists mean that they are sometimes called agonist–antagonists. This drug produces less extrapyramidal effects because it is a weak agonist. Therefore, never blocks dopamine function as much as an antagonist (Ghaemi. 2019). An inverse agonist binds to the same receptor binding sites as an agonist and not only antagonizes the effects of an agonist but exerts the opposite by suppressing spontaneous receptor signaling (Ghaemi. 2019).
Compare and contrast the actions of g-couple proteins and ion-gated channels.
Two receptor proteins perform their functioning in the opening and closing of postsynaptic ion channels. The ionotropic receptor is linked directly to ion channels. These receptors have two functions, the first one is an extracellular site binding neurotransmitters, and the second one is a membrane-spanning domain to form an ion channel (Jiangi et al., 2023) Therefore, inotropic receptors combine transmitter-binding and channel functions into one single molecular entity and are called ligand-gated ion channels. Such receptors are multimers and are comprised of four or five individual proteins subunit. Each of the monomeric subunits forms a functionally independent pore channel (Jiangi et al., 2023). The second neurotransmitter is the metabotropic receptor. This neurotransmitter’s movement of ions depends upon one or more metabolic steps. There are no ion channels in these receptors, but the channels are affected by the activation of intermediate molecules called G-proteins. For this same reason, metabotropic receptors are also referred to as G-protein-coupled receptors (Jiangi et al., 2023) ). Metabotropic receptors are monomeric proteins having an extracellular domain for neurotransmitter binding and an intracellular domain for binding to G-proteins. Neurotransmitter binding to metabotropic receptors activates G-proteins, after which it dissociates from the receptor and interact directly with ion channels or bind to other effector proteins, like enzymes to make intracellular messengers to open or close ion channels. Therefore, G-proteins work as transducers that couple neurotransmitter binding to the regulation of postsynaptic ion channels (Jiangi et al., 2023).
Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics is a term that describes how genetic information is coded because of changes in your behavior or environment. Scientists are starting to learn and understand the actual function of the entire genome. According to Stefanska and MacEwan, (2015), drugs may have to be able to be more broad-acting over a range of epigenetic large-scale events instead of being designed to a particular ligand or specific to a particular gene or protein subtype. Thinking of epigenetics on a larger scale, epigenetic regulatory mechanisms may be involved with more than one gene or family of proteins that could regulate large groups of genes. Thinking in this manner we may find epigenetic variations could be responsible cause for any particular disease. Believing this way just targeting one protein of the multiple pathways involved in a disease could prove futile. For example, diseases such as cancer can mutate into different variations which are difficult to detect, predict, and effectively treat, leading too often to relapse. According to Stefanska and MacEwan, (2015), Epigenetics of cancers may be the key to more effective treatments.
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.
When a nurse practitioner prescribes a medication, the prescriber needs to take a thorough health history and individualize the medication based on the person not just what illness they could have and what genetic implications and treatment options. According to McClarty et al. (2018), Antipsychotics are commonly prescribed for the treatment of psychosis along with behavioral and psychological symptoms of dementia in the elderly. This treatment can be ineffective and causes side effects in these patients. The provider should remember that advanced age affects drug metabolism and clearance, additional pharmacokinetic and pharmacodynamic changes due to aging-induced epigenetic alterations also impact processes important for antipsychotic function. Epigenetic mechanisms account for some of the altered efficacy and increased side effects seen in elderly patients involving histone modifications that can adversely affect the efficacy of antipsychotics and increase their side effects in elderly patients (McClarty et al., (2018). We need further investigation of this mechanism will benefit elderly patients who need treatment for psychosis.
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.
Ghaemi, N. (2019). Clinical psychopharmacology: Principles and practice. Oxford University Press, USA. Kew, J. N., & Davies, C. H. (Eds.). (2010). Ion channels: from structure to function. Oxford University Press, USA.
Jiang, C., He, X., Wang, Y., Chen, C. J., Othman, Y., Hao, Y., Yuan, J., Xie, X. Q., & Feng, Z. (2023). Molecular Modeling Study of a Receptor-Orthosteric Ligand-Allosteric Modulator Signaling Complex. ACS chemical neuroscience, 14(3), 418–434. https://doi.org/10.1021/acschemneuro.2c00554Links to an external site.
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.
Stahl, S. M. (2013). Ion Channels as Targets of Psychopharmacologic Drug Action. In Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (3rd ed.). New York, NY: Cambridge University Press.
Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology.
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