FOUNDATIONAL NEUROSCIENCE NURS 6630

FOUNDATIONAL NEUROSCIENCE NURS 6630

FOUNDATIONAL NEUROSCIENCE NURS 6630

Neuroscience is the scientific study of the human central nervous system to understand the brain’s dysfunction that can lead to disease, mental disorders, and physical impairment (Karmarkar & Plassmann, 2019). The complex design of a neuron is the basic understanding of communication by sending impulses to other body organs. The brain controls human behavior and the functions of body organs. The anatomy and physiology of the brain help understand the part of the brain affected by mental illness. For example, poor concentration and cognitive skills dysfunction is the forebrain pathology. Additionally, one can understand the mode of action of psychopharmacology. For example, antidepressants may function by inhibiting the serotonin or epinephrine receptors.

An Agonist-To-Antagonist Spectrum of Action and How Partial and Inverse Agonists Influence Psychopharmacologic

An antagonist binds at the receptors by blocking any event of an agonist, hence, blocking the biological response. For example, naloxone is a competitive opioid antagonist and has no effects with opioid co-administration (Gicquelais, et al, 2019). An agonist binds to a receptor causing activation of the receptor, hence, the biological response. A partial agonist activates the receptors partially with lesser effect on the brain. For example, buprenorphine is a partial agonist, and therefore, an antagonist may block its opioid function without activating its receptors. An inverse receptor binds with constitutively active receptors and inhibits receptor activity by exerting opposite pharmacological effects that suppress spontaneous receptor signaling.

Comparison between Actions of G Couple Proteins and Ion Gated Channels

G coupled proteins GPCRs are integral membrane proteins that convert extracellular responses to hormones, neurotransmitters, olfaction, and taste signals. The GPCRs work by binding to the hormones, neurotransmitters, and growth factors to initiate a cellular response. The three types of G-couple receptors are alpha, beta, and gamma, in which the ligands bind and activate (Yudin & Rohacs 2019). Ion gated channels are integral membrane proteins of excitable cells that allow a flux of ions to pass only under defined circumstances. These channels are voltage-gated sodium channel neurons and ligand-dated acetylcholine receptors of the cholinergic synapses. The ion gated channel pull and bonds to the agonist changing the protein while g coupled proteins are used by the cells to convert intracellular signals into responses.

The Role of Epigenetics In the Pharmacologic Action

Epigenetics regulate gene activity by switching off the gene activity or activating the gene activity. Epigenetics plays a role in the phenotypic activity of the cell in diseases such as cancer and neurodegenerative disorders such as Alzheimer’s disease. Epigenetics modify gene expressions after drug administration to counteract the disease states in humans. Epigenetics proves its effectiveness in treating psychiatric and neurodegenerative disorders to its ability to modify gene expressions.

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The Significance of the Information to Psychiatric Mental Health Nurse Practitioner

A psychiatric mental health nurse practitioner should have basic knowledge of the concepts of foundational neuroscience. Understanding the function of agonists, inverse and partial agonists, and antagonists prevent co-administration of drugs that agonize and antagonize the same receptors. For example, in treating a patient with a depressive mood disorder, prescribing antipsychotics such as fluphenazine worsens the depressive mood because it antagonizes the dopaminergic D1 and D2 receptors depressing the release of the hypothalamic hormone.

References

Gicquelais, R. E., Bohnert, A. S., Thomas, L., & Foxman, B. (2020). Opioid agonist and antagonist use and the gut microbiota: associations among people in addiction treatment. Scientific reports, 10(1), 1-11. https://doi.org/10.1038/s41598-020-76570-9

Karmarkar, U. R., & Plassmann, H. (2019). Consumer neuroscience: Past, present, and future. Organizational Research Methods, 22(1), 174-195.

https://doi.org/10.1177%2F1094428117730598

Yudin, Y., & Rohacs, T. (2019). The G‐protein‐biased agents PZM21 and TRV130 are partial agonists of μ‐opioid receptor‐mediated signalling to ion channels. British journal of pharmacology, 176(17), 3110-3125. https://doi.org/10.1111/bph.14702

FOUNDATIONAL NEUROSCIENCE NURS 6630

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2 months ago

Ifeanyi Duruewuru

RE: Intial post Basirat

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Hello Basirat,

I really enjoyed reading your article, it was very informative. However, in addition to your points about the agonist-antagonist spectrum, I will like to share additional insight I found interesting too.

According to Berg and Clarke (2018), Agonists have intrinsic efficacy (the ability to increase the activity of a receptor), and inverse agonists are said to have negative intrinsic efficacy (the ability to decrease the activity of a receptor). Just as agonist intrinsic efficacy for a receptor varies with the structure of the agonist (resulting in strong agonists and weaker [partial] agonists), inverse agonists also have different degrees of negative intrinsic efficacy, resulting in strong and weak (partial) inverse agonists.

Inverse agonists are ligands that selectively bind to the inactive state of the receptor (Kenakin, 2017). If any receptor happens to be in an active state spontaneously, then an inverse agonist will reverse the resultant constitutive activity. However, the main pharmacological effect of inverse agonists is receptor antagonism, that is, inverse agonists will block the effect of agonists and the effect on constitutive activity is only relevant if the system is spontaneously active (Kenakin, 2017). There is a property of inverse agonists that may be therapeutically relevant in nonconstitutively active systems (Kenakin, 2017).

References

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse agonism and functional selectivity. The international journal of neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

Kenakin, T. P. (2017). Pharmacology in Drug Discovery and Development (Second Edition). ScienceDirect. Retrieved June 10, 2022, from https://doi.org/10.1016/B978-0-12-803752-2.00004-1

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Darius II Opada

Week 2 Discussion: Foundational Neuroscience- OpadaD

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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.

 

An agonist produces a conformational change in the G-protein-linked receptor that turns on the synthesis of the second messenger to the greatest extent possible. The full agonist is generally transmitted by the naturally occurring neurotransmitter itself. Hence, downstream proteins are maximally phosphorylated, and genes are maximally impacted. (Stahl, 2021; Pleuvry, 2004)

There are two ways to stimulate the G proteins directly with full agonist action. First, several drugs directly bind to the neurotransmitter site on the G protein-linked receptor itself and can produce the same signal transduction as a full agonist. For example, the G-protein receptor and pharmacological subtype directly targeted by antipsychotic or antimanic drugs for the neurotransmitter dopamine is the D2. Secondly, many drugs can indirectly act to boost the levels of the natural full agonist neurotransmitter, and this increased amount of natural agonist binds to the neurotransmitter site of the G protein-linked receptor. For example, the G protein-linked receptor and pharmacological subtype indirectly by dopamine reuptake inhibitors (e.g., amphetamine, Adderall) are D1, D2, D3, D4, and D5 (Stahl, 2021; Pleuvry, 2004)

On the other hand, when blocking the action of the natural neurotransmitter, this is called antagonists. Antagonists produce a confrontational change in the G protein-linked receptors that causes no signal transduction and blocks the action of everything in the agonist spectrum. In short, the antagonists will block both agonists and partial agonists (Pleuvry, 2004; Stahl, 2021)

Meanwhile, Partial agonists produce signal transduction that is something more than antagonists but less than full agonists. Depending upon how close this partial agonist is to a full agonist or to silent antagonists on the agonist spectrum will determine the impact of a partial agonist on downstream signal transduction events. (Pleuvry, 2004; Stahl, 2021)

Ion gated channels are key targets of many psychotropic drugs. There are two main types of ion-gated channels: ligand-gated ion channels and voltage-sensitive ion channels. The opening of ligand gated-ion channels is regulated by neurotransmitters whereas the opening of voltage-sensitive ion channels is regulated by the charge across the membrane in which they reside. Ligand-gated ion channels are both ion channels are receptors and are commonly called inotropic receptors. Ligands act at a ligand-gated ion channel across an agonist’s spectrum from full to partial, to antagonists, and to an inverse agonist. The most common sub-types of volume-sensitive ion channels are the voltage-sensitive sodium channels and the voltage-calcium channels (Stahl, 2021)

 

 

 

1. Compare and contrast the actions of g couple proteins and ion gated channels.

 

Comparison of G-Protein receptors directly and indirectly targeted (Stahl, 2021)

Neurotransmitters	G-Protein receptor directly targeted	Action	G-Protein receptor indirectly targeted	Action
Acetylcholine	M1 M4 M2/3 M5	Agonist Antagonist Agonist ?	M1 (Possibly M2-M5)	Agonist via increasing acetylcholine via acetylcholinesterase inhibition
GABA	GABA-B	Agonist
Glutamate
Serotonin	5HT2A         5HT1B/1D     5HT2C 5HT6 5HT7 5HT1A	Antagonist or Inverse Agonist, and agonist   Antagonist or partial agonist   Antagonist ? Antagonist Partial Agonist	5HT1A     5HT2A   5HT2A/2C	Agonist by SSRIs/SNRIs   Agonist   Agonist by MDMA
Dopamine	D2	Antagonist or Partial agonist	D1, D2, D3, D4, D5	Agonist actions by dopamine reuptake inhibitors
Norepinephrine	Alpha 1   Alpha 2	Antagonist   Antagonist/Agonist	All NE receptors	Norepinephrine reuptake inhibitors
Melatonin	MT1   MT2	Agonist   Agonist
Histamine	H1   H2	Antagonist   Antagonist/Inverse agonist

 

COMPARISON OF LIGAND-GATED ION CHANNEL RECEPTOR SUBTYPE DIRECTLY TARGETED (Stahl, 2021)

 

Neurotransmitter	Ligand-gate ion channel receptor subtype directly targeted	Action
Acetylcholine	Alpha4, Beta2, nicotinic	Partial agonist
GABA	GABA A benzo receptors   GABA A benzo PAM sites   GABA A nonsteroid sites	Full agonist phasic inhibition   Full agonist phasic inhibition   Full agonist, tonic inhibition
GLUTAMATE	NMDA   NMDA open-channel sites	Antagonist   Antagonist
SEROTONIN	5HT3   5HT3	ANTAGONIST   ANTAGONIST

 

 

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

 

Epigenetics is the idea that a gene function may be changed without a specific alteration in the code, and this change in gene function may also be heritable (Stern, et. al., 2016). Frequently, this may occur by a change in the structure of the DNA molecule: for example, chromatin, around the gene, which alters gene expression. Epigenetics control whether a gene is read (expressed) or is not read (i.e., silenced), which is done by the structure of chromatin. Chemical modifications that can do this include not only methylation, but also acetylation, phosphorylation, other drugs, and the environment. The initial epigenetic pattern of a neuron is set during neurodevelopment to give each neuron its own lifelong personality, it now appears that some neurons respond to their narrative of experiences throughout life (child abuse, stress, dietary deficiencies, medications, psychotherapy, drug use,) with a changing character arc, hence causing alteration in their epigenome. Moreover, it now seems that silenced genes can be activated and activated genes can be silenced. When this happens, both favorable and unfavorable developments. Favorable developments may trigger a person to be able to learn or to experience the therapeutic effects of the drugs. On the other hand, unfavorable mechanisms may be triggered for one to become addicted to a drug or to experience abnormal learning (Stahl, 2021; Stefanska & MacEwan, 2015)

 

 

1. 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 a future nurse practitioner, gaining knowledge about the agonist-antagonist spectrum is really at par with knowing the disease process. Being knowledgeable of the agonist-antagonist spectrum helps a provider understand the mechanism of one drug and its side or adverse effects. For example, typical antipsychotic drugs primarily target D2 receptors in the mesolimbic pathway (Stern, et. al., 2016; Keltner, 2018, which treat positive psychotic symptoms (hallucination, delusion, ambivalence, etc.). However, typical antipsychotics also affect other receptors (D1, D3, D4, and D5) in other ways such as the nigrostriatal pathway, which causes the onset of extrapyramidal symptoms, NMS, and Parkinson-like effects. In situations such as this, a practitioner may be able to anticipate prescribing dopamine agonists like amantadine (Symmetrel) to control the EPS or switch to atypical antipsychotics, which have lower EPS and NMS adverse effects (Stern, et. al; Keltner, 2018)

References

Keltner, N. (2018). Psychiatric Nursing. 8^th ed. Elsevier

Pleuvry, B. (2004). Receptors, Agonist, and Antagonist. https://www.sciencedirect.com/science/article/pii/S1472029906003845

Stefanska, B., & MacEwan, D. (2015). Epigenetics and Pharmacology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/

Stern, T., et. al. (2016). Massachusetts General Hospital Psychopharmacology and Neurotherapeutics. 1^st ed. Elsevier

Stahl, S. (2021). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Application. 5^th ed. Cambridge