Foundational Neuroscience

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Foundational Neuroscience

The term foundational neuroscience refers to a three-course series that explores the structure and function of the nervous system – from the inner workings of a single nerve cell to the staggering complexity of the brain and the social interactions it enables (Harvard Edu. 2020)

According to studies, cases of mental and psychiatric conditions have been on the increase. As a result of this crisis, there is a need for quality psychiatric health care that encompasses appropriate knowledge by health practitioners of dealing with these issues (Harvard Edu. 2020). This involves a deep understanding of the pathophysiology of psychiatric disorders and understanding the impact of certain drugs on a specific disorder. It has been advocated those psychiatric patients be referred to as clients as it is more favorable for mental health. This discussion will address the agonist and antagonistic agents, g- g-couple proteins and ion-gated channels, and the role of epigenetics in psychopharmacology.

The agonist-to-antagonist spectrum of action of psychopharmacologic agents.

 Also known as the agonist spectrum, describes the range of effects that can be exerted by psychopharmacological agents. For example, it describes how some medications/drugs can stimulate receptors in the brain just like natural neurotransmitters and how other drugs can block/prevent this action (Stahl, 2013). For example, benzodiazepines (Valium) increase/mimic the GABA neurotransmitter (agonist) and Flumazenil decreases/blocks this neurotransmitter (antagonist).  The agonist-to-antagonist spectrum psychopharmacologic agents work at the sites of neurotransmission and conduct their effects based on a spectrum of agonist-to-antagonist (Stahl, 2013). The spectrum ranges from true agonist to inverse agonist. Some examples of effects between the two ends are partial agonist, silent antagonist, and partial inverse agonist.

Agonist

Agonist is a chemical substance that binds to and activates certain receptors on cells. Agonistic drugs are drugs that modify or change the state of receptors to trigger a biological response. Oxycodone, morphine, heroin, fentanyl, methadone, and endorphins are all examples of opioid receptors (Stahl, 2013). According to Stahl (2013), a full agonist allows the receptor to fully open the ion channel which allows the downstream signal transduction to occur maximally. An agonist is any drug that activates specific brain receptors, thereby causing the full effects of the drug to take place

Partial Agonist

A partial agonist is any drug that acts as an agonist, but the degree of receptor activation is reduced. The receptor has a resting state. When a partial agonist is in contact with the receptor in a resting state, the ion channel will partially open, allowing some downstream signal transduction (Stahl, 2013).

Antagonist

Antagonistic drugs refrain or stop minimizing any biological response by blocking any presenting receptors (Camprodon et al., 2016). The antagonist will return the receptor to a resting state (Stahl, 2013). Constitutive activity still occurs in the presence of an antagonist, which is the minor ion flow despite being in a resting state (Stahl, 2013). When a drug is classified as an antagonist, it means that it blocks the receptors, so they are not able to bind to the agonist. In the realm of opioids, an example of an agonist is Heroin, the antagonist is Naloxone, while the the partial agonist is Buprenorphine. To illustrate this example, Heroin is an addictive agonistic substance. In the case of heroin overdose, Naloxone, an antagonist can be used to reverse the binding and block receptors from binding with free-floating Heroin. The pharmacological treatment for heroin addiction often includes the partial agonist, Buprenorphine. Buprenorphine allows partial binding to opioid receptors, thus reducing withdrawal symptoms and curving drug cravings (Camprodon et al., 2016).

Inverse Antagonist

Inverse agonists are the last type on the spectrum. Inverse agonists cause receptor changes, leading to the closing of the ion channels and eventual inactivation if not reversed (Stahl, 2013).

G Couple Proteins and ion-gated channels

G couple proteins and ion-gated channels are both major membrane receptors. The binding of a signaling molecule to a G-coupled protein receptor results in G protein activation, which in turn triggers the production of any number of second messengers, leading to G-coupled proteins helping to regulate a person’s immune system, growth, taste, smell, behavior, and mood (Rosenbaum et.al, 2009). Gated ion channels are proteins that open to allow ions such as Na+, K+, Ca2+or Cl- to pass through the cell membrane in response to a ligand such as a neurotransmitter (Stahl, 2013).

Comparison between G-couple protein and ion-gated channel and their actions

 The ion-gated channels, commonly known as, ligand-gated channels consolidate rapid postsynaptic responses while G-proteins consolidate slow postsynaptic responses (Camprodon et al., 2016). In terms of structure, the ion-gated channels are pores that open and close at the ligand binding while G-proteins include a single polypeptide. The G-protein receptors interact with proteins while ion channels regulate the flow of ions. G Couple Proteins and Ion-Gated Channels. Neurotransmission occurs not only electrically such as with ion-gated channels but also occurs chemically at receptors. G-protein linked receptors have seven transmembranes that each have a receptor to bind a neurotransmitter (Stahl, 2013). The first messenger is an extracellular neurotransmitter, and it passes the message to the second messenger system (Stahl, 2013). When the first messenger binds to the receptor, it changes the shape allowing the binding of the G protein, which then changes confirmation to allow binding with an enzyme (Stahl, 2013). Once bound, cyclic adenosine monophosphate is synthesized leading to the second messenger continuing neurotransmission to other messengers (Stahl, 2013).

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

Epigenetics not only has a role in the development of psychiatric and mental health disorders, but it can also affect the way medications work for each person. DeSocio (2016) describes synaptogenesis as the development of new neuronal connections that occur more rapidly during childhood but continue through adulthood as well. When stress hormones are present at high levels, there is a decrease in synaptogenesis (DeSocio, 2016).  Epigenetics can be defined in many ways, but the basis is that gene function can be altered without changing the DNA and RNA code. This functional change in the gene can also be inherited (Camprodon & Roffman, 2016, p. 64). As a result, epigenetics can determine how a medication works and what illnesses an individual may develop. If a medication works on a specific gene, but that gene has an altered function, the drug’s efficacy may change. For example, individuals with altered dopamine formation and receptor binding may have an affinity toward drug addiction or a degree of natural tolerance (Saad et al., 2019, p. 1534). For non-addictive substances, this logic holds as to why some medications work for one person, but not another individual.

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.

The above concepts of foundational neuroscience analyses will have an impact on how and what a psychiatric mental health nurse practitioner will prescribe to all clients. The knowledge learned will enable the provider to determine exactly which medication will help each client the most for their illness whether it be short-term or long-term. The PMHNP will be made more aware of the effectiveness of all medications used and their action for the client's individual needs. Examples of the effects and actions are used to treat clients with anxiety and insomnia such as benzodiazepines which have an immediate effect on clients. Benzodiazepines can act as a full agonist on a positive allosteric modulator (PAM) by exhibiting an anxiolytic, hypnotic, anticonvulsant, amnestic, and muscle relaxant action (Stahl, 2013). Benefit-risk assessments must be considered by all providers when prescribing specific drugs to certain groups of clients. Extra care should be considered for clients, such as pregnant women, children, and the elderly because of their vulnerable states (Alshammari, 2016). An advanced psychiatric mental health nurse practitioner must be able to match the client's symptoms with the correct medication to sometimes control their difficult symptoms (Laureate Education, 2016).

References

Alshammari, T. M. (2016). Drug safety: The concept, inception, and its importance in patients’ health. Saudi Pharmaceutical Journal, 24 (4), 405-412. doi: 10.1016/j.jsps.2014.04.008

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.

DeSocio, J. E. (2015). Epigenetics: An Emerging Framework for Advanced Practice Psychiatric Nursing. Perspectives in Psychiatric care/Volume 52, Issue 3/.201-207. https://doi.org/10.1111/ppc.12118Links to an external site.

Harvard University (2020). Fundamentals of Neuroscience: Electrical Properties of the Neuron. Retrieved September 4, 2023, from https://www.edx.org>lrstn>harva…

Laureate Education (Producer). (2016i). Introduction to psychopharmacology [Video file]. Retrieved from https://class.waldenu.eduLinks to an external site.

Rosenbaum, M. J., Clemmensen, L. S., Bredt, D. S. et al. Targeting receptor complexes: a new dimension in drug discovery. Nat Rev Drug Discov 19, 884-901 (2020). https://doi.org/10.1038/s41573-020-0086-4

Saad, M. H., Rumschlag. M., Guerra, M. H., Savonen, C. L., Jaster, A. M., Olson, P. D., Alazizi, A., Luca, F., Pique-Regi, R., Schmidt, C. J., & Bannon, M, J. (2019). Differentially expressed gene networks, biomarkers, long noncoding RNAs, and shared responses with cocaine identified in the midbrains of human opioid abusers. Scientific Reports, 9, pp. 1534. Retrieved from https://www.nature.com/articles/s41598-018-38209-8

Stahl, S. M. (2013). Stahl's Essential Psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York, NY: Cambridge University Press.