Discussion: Foundational Neuroscience

Week 2 Discussion: Foundational Neuroscience

Agonist-to-Antagonist Spectrum of Action

The agonist-to-antagonist spectrum of action plays an important role in understanding psychopharmacologic agents. Neurotransmitters that naturally occur in the body can act as agonist that stimulate receptors; and psychopharmacologic agents can do the same (Stahl, 2013). If a drug stimulates a receptor less than the naturally occurring neurotransmitter, it is considered a partial agonist. Partial agonists can both increase and block neurotransmitter activity when there is deficient or excessive activity (Stahl, 2013).  Antagonists do not produce any activity without an agonist, since an antagonist works to block the action of agonists (Stahl, 2013). When there is an inverse agonist, it does not increase or block the signal transduction like an agonist or antagonist (Stahl, 2013). An inverse agonist causes an action that is opposite of the agonist, and results in the receptor decreasing the standard transduction level of the signal (Stahl, 2013).

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Knowing which neurotransmitters need to be either stimulated, blocked, increased, or decreased will help determine which psychopharmacologic agents will be most effective in achieving the desired outcome. In psychopharmacology, conventional and atypical antipsychotic drugs tend to be antagonist or partial agonists of dopamine (Stahl, 2013). Atypical antipsychotics can also be antagonists or inverse agonists of serotonin while hypnotic medications to improve insomnia are an example of agonists of melatonin (Stahl, 2013). Discussion: Foundational Neuroscience

Actions of G Couple Proteins and Ion Gated Channels.

Ion gated channels and g couple proteins both play a role in receiving neurotransmitter signals that cause changes in neuronal activity and are commonly targeted by pharmacological interventions (Stern et al., 2015). Ion gated channels are open or gated by the binding of a neurotransmitter that activates the channel and causes a quick synaptic transmission (Alexander et al., 2017). When a presynaptic neuron releases a neurotransmitter, the gated ion channel receives the signal from the neurotransmitter and quickly transmits it to activate a post-synaptic response that is usually excitatory or inhibitory (Alexander et al., 2017). Discussion: Foundational Neuroscience

G couple proteins work through second messenger systems that sequentially alter the functionality of multiple different target proteins and transmit signals more slowly than the rapid effect of ion gated channels (Stern et al., 2015). While ion gated channels can rapidly alter neuronal activity and membrane potential, G-protein coupled receptors (GPCRs) are slower to alter neuronal activity because they involve multiple-enzyme cascades and can cause post-translational modifications that can transmit or terminate the received signals (Stern et al., 2015).

Epigenetics and Pharmacologic Action

Epigenetics is defined as “mechanisms leading to changes in gene expression that do not involve changes in DNA sequences” (Prabhakar et al., 2017, p. 73). It is possible that the changes that occur in gene function could be heritable, but the effects of the gene changes may also be treatable or reversible (Stern et al., 2015). Long non-coding RNAs (lncRNAs) play a large role in epigenetics and the regulation of gene expression (Prabhakar et al., 2017). If pharmacologic treatments can target lncRNAs, they may be able to epigenetically modulate biochemical pathways that address the effects of the gene changes and make the pharmacologic action more effective (Prabhakar et al., 2017). Discussion: Foundational Neuroscience

Impact When Prescribing Medications

As a psychiatric mental health nurse practitioner, it is important to be aware of the action of medications that you choose to prescribe. The above information regarding the agonist-to-antagonist spectrum, ion gated channels, g couple proteins, and epigenetics is important to consider when deciding the best psychopharmacologic approach to treating patients. Anxiety disorder is a common disorder that patients seek treatment for. Selective serotonin reuptake inhibitors (SSRI) are common anxiolytic medications. If serotonin is the neurotransmitter that is being targeted to treat the anxiety, the agonist-to-antagonist spectrum of action needs to be considered to determine what type of pharmacologic action is needed. Generally, an agonist action is needed to increase serotonin at the receptor sites to treat the anxiety (Stahl, 2013).

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You also need to consider whether the signal will be transmitted quickly via an ion gated channel, or more slowly via g-coupled protein receptors and a second messenger system. Another consideration specific to treating anxiety, is that at least one third of patients with anxiety do not respond to currently available drugs (Peedicayil, 2020). Therefore, epigenetics and epigenetic drugs should be considered, as evidence suggests that epigenetic mechanisms of gene expression can contribute to the pathogenesis of anxiety and other psychiatric disorders (Peedicayil, 2020). Discussion: Foundational Neuroscience

References

Alexander, S. P., Peters, J. A., Kelly, E., Marrion, N. V., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., Davies, J. A., & CGTP Collaborators. (2017). The concise guide to pharmacology 2017/2018: Ligand-gated ion channels. British Journal of Pharmacology, 174, S130–S159. https://doi.org/10.1111/bph.13879

Peedicayil, J. (2020). The potential role of epigenetic drugs in the treatment of anxiety disorders. Neuropsychiatric Disease and Treatment, 16, 597–606. https://doi.org/10.2147/ndt.s242040

Prabhakar, B., Zhong, X., & Rasmussen, T. P. (2017). Exploiting long noncoding RNAs as pharmacological targets to modulate epigenetic diseases. Yale Journal of Biology and Medicine, (90), 73–86. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369047/pdf/yjbm_90_1_73.pdf

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical application (4th ed.). Cambridge University Press. https://books.google.com/books?hl=en&lr=&id=BBtMzTV8OMgC&oi=fnd&pg=PR9&dq=psychopharmacological+agonist+to+antagonist+spectrum+of+action+&ots=Hhnpt4RsLW&sig=lTv2dLHW58MpmvZsJzRcAIzkJGA#v=onepage&q=antagonist&f=false

Stern, T. A., Maurizio, F. M., Wilens, T. E., & Rosenbaum, J. F. (2015). Massachusetts general hospital psychopharmacology and neurotherapeutics (1st ed.). Elsevier. Discussion: Foundational Neuroscience

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