Foundational Neuroscience Essay Assignment Paper
As a psychiatric mental health nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat clients, you must not only understand the pathophysiology of psychiatric disorders, but also how medications for these disorders impact the central nervous system.
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In this discussion, you will; analyze the agonist-to-antagonist spectrum of action of psychopharmacologic agents; Compare the actions of g couple proteins to ion gated channels; Analyze the role of epigenetics in pharmacologic action; Analyze the impact of foundational neuroscience on the prescription of medications
To prepare for this Discussion:
Review this week’s Learning Resources.
Reflect on concepts of foundational neuroscience.
ACTUAL ASSIGNMENT
PLEASE Addressed each of the following numbers with a subtopic, all the references used must have an in-text citation in each paragraph. All Articles used should come from USA and must be within last five years only that is from 2014 to 2018. Please do not begin a paragraph with author name(s) (PLEASE USE parenthetical/in-text citations). Foundational Neuroscience Essay Assignment Paper.
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
Compare and contrast the actions of g couple proteins and ion gated channels.
Explain the role of epigenetics in pharmacologic action.
Explain how this information may impact the way you prescribe medications to clients. Include a specific example of a situation or case with a client in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.
References/Resources
Stahl, S. M. (2013).
Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications
(4th ed.). New York, NY: Cambridge University Press *Preface, pp. ix–x. Foundational Neuroscience Essay Assignment Paper.
Note:
To access the following chapters, click on the
Essential Psychopharmacology, 4th ed
tab on the Stahl Online website and select the appropriate chapter. Be sure to read all sections on the left navigation bar for each chapter.
Chapter 1, “Chemical Neurotransmission”
Chapter 2, “Transporters, Receptors, and Enzymes as Targets of Psychopharmacologic Drug Action”
Chapter 3, “Ion Channels as Targets of Psychopharmacologic Drug Action” Foundational Neuroscience Essay Assignment Paper
Agonist to Antagonist Spectrum
Most drugs act as either agonists or antagonists at receptors in response to chemical messages in the brain. An agonist, which can be described as partial or inverse, binds to the receptor to produce an effect. Antagonists also bind to receptors but does not produce a response, rather blocks that receptor to a natural agonist (Pleuvry, 20004). It is important to acknowledge that agonists and inverse agonists can be reversed by competitive antagonists. In reference to atypical psychotropic drugs (APD), the blockade of serotonin receptors (5-HT2A) along with the weak antagonism of dopamine receptor (D2) is critical in potency and efficacy, as typical APD have tendency to antagonize D2 receptors more potently than 5-HT2A receptors (Kusumi, Boku, & Takahashi, 2014).
G-coupled Protein and Ion-gated Channels
G-protein linked receptors are important to clinicians with to target specific receptors with psychotropic drugs (Stahl, 2013). Nonetheless, all agonists do not produce an active state of G-protein-coupled-receptors as in constitutive activity of receptors for benzodiazepines, serotonin, and other G-protein linked receptors. Contrarily, ion channels function as a result of neurotransmitter ligands at receptors. Numerous drugs act at ion-channel complexes altering flow of ions through the channels due to the transduction of the signal at receptors (Stahl, 2013). As a result of the changes of flow of ions, drugs that act on ionotropic receptors tend to act immediately while G-protein linked receptors act at lower frequencies.
Epigenetics in Pharmacologic Action
The lack of response to standard therapies in certain individuals because of various molecular alterations can be due to genetic heterogenecity and epigenetic alterations (Rasool et al., 2015). Epigenetic modifications can occur as a result of various chemical compounds in the biological system, changing gene expression. Environmentally and biologically influenced alterations can lead to disorders, therefore clients with epigenetic alterations may require drugs used for personalized medicine based on their personal genomic profile.
Impact on How Medicine is Prescribed
Understanding the agonistic/antagonistic effects of medications along with the prescribing of medications specific to G-protein coupled receptors, and personalized medication profiles required by epigenetic alterations found in certain cases is important to PMHNP’s who may prescribe psychotropic medications to these clients. Studies have found an existence of constitutive receptor activity in benzodiazepine receptors and G-protein coupled receptors and may be present in mutated strains exhibiting underactive behavior that can lead to inherited diseases such as congenital hypothyroidism and diabetes insipidus (Rasool et al., 2015) Foundational Neuroscience Essay Assignment Paper. For schizophrenic clients at greater risk for developing extrapyramidal symptoms (EPS), it is known that risperidone equally occupies D2 and 5-HT2A receptors increasing the frequency of EPS, while clozapine more potently occupies 5-HT2A receptors than D2 receptors, rarely producing EPS (Kusumi, Boku, & Takahashi, 2014). It is the responsibility of the PMHNP to understand their clients’ profiles and medical histories in order to properly prescribe the most effective medications with the least adverse effects.
Agonist-to-antagonist Spectrum of action of psychopharmacological agents
An agonist produces a conformational change in the G-protein-linked receptor that turns on the synthesis of second messenger to the greatest extent possible (i.e., the action of a full agonist.
Antagonists Spectrum of action produce a conformational change in the G-protein-linked receptor that causes no change in signal transduction – including no change in whatever amount of any constitutive activity that may have been present in the absence of agonist.
Compare and contrast the actions of g couple proteins and ion gated channels
Ion Channels
There are two major classes of ion channels, and each class has several names. One class of ion channels is opened by neurotransmitters and goes by the names ligand-gated ion channels, ionotropic receptors, and ion-channel-linked receptors. The other major class of ion channel is opened by the charge or voltage across the membrane and is called either a voltage-sensitive or a voltage-gated ion channel. Ion channels that are opened and closed by actions of neurotransmitter ligands at receptors acting as gatekeepers. When a neurotransmitter binds to a gatekeeper receptor on an ion channel, that neurotransmitter causes a conformational change in the receptor that opens the ion channel. ). A neurotransmitter, drug, or hormone that binds to a receptor is sometimes called a ligand. Thus, ion channels linked to receptors that regulate their opening and closing are often called ligand-gated ion channels. Since these ion channels are also receptors, they are sometimes also called ionotropic receptors or ion-channel-linked receptors Foundational Neuroscience Essay Assignment Paper.
G Linked receptors
G-protein receptors are the most common targets of psychotropic drugs, and their actions can lead to both therapeutic and side effects. Drug actions at these receptors occur in a spectrum, from full agonist actions, to partial agonist actions, to antagonism, and even to inverse agonism. Natural neurotransmitters are full agonists, as are some drugs used in clinical practice. However, most drugs that act directly on G-protein-linked receptors act as antagonists. A few act as partial agonists, and some as inverse agonists. Each drug interacting at a G-protein-linked receptor causes a conformational change in that receptor that defines where on the agonist spectrum it will act.
G-protein-linked receptors are a large superfamily of receptors that interact with many neurotransmitters and with many psychotropic drugs. Clinicians needs to ensure understanding the targeted specific receptors with psychotropic drugs utilized in clinical practice
Role of Epigenetics in Pharmacologic action
Genetics is the DNA code for what a cell can transcribe into specific types of RNA or translate into specific proteins. However, just because there are over 20 000 genes in the human genome. So, the plot of how a normal neuron becomes a malfunctioning neuron in a psychiatric disorder, as well as how a neuron becomes a neuron instead of a liver cell, is the selection of which specific genes are expressed or silenced. In addition, malfunctioning neurons are impacted by inherited genes that have abnormal nucleotide sequences, which if expressed contribute to mental disorders. Thus, the story of the brain depends not only on which genes are inherited but also on whether any abnormal genes are expressed or even whether normal genes are expressed when they should be silent or silenced when they should be expressed. Neurotransmission, genes themselves, drugs, and the environment all regulate which genes are expressed or silenced, and thus all affect whether the story of the brain is a compelling narrative such as learning and memory, a regrettable tragedy such as drug abuse, stress reactions, and psychiatric disorders, or therapeutic improvement of a psychiatric disorder by medications or psychotherapy Foundational Neuroscience Essay Assignment Paper.
it now seems that previously silenced genes can become activated and/or previously active genes can become silenced. When this happens, both favorable and unfavorable developments can occur in the character of neurons. Favorable epigenetic mechanisms may be triggered in order for one to learn (e.g., spatial memory formation) or to experience the therapeutic actions of psychopharmacologic agents. On the other hand, unfavorable epigenetic mechanisms may be triggered in order for one to become addicted to drugs of abuse or to experience various forms of “abnormal learning,” such as when one develops fear conditioning, an anxiety disorder, or a chronic pain condition. Genes modify behavior and behavior modifies genes. Genes do not directly regulate neuronal functioning. Foundational Neuroscience Essay Assignment Paper. Rather, they directly regulate the proteins that create neuronal functioning. Changes in function have to wait until the changes in protein synthesis occur and the events they cause start to happen.
NUR 6630 Week 1 Discussion: Foundational Neuroscience
Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.
Full agonists allow a receptor site to open up an ion channel to the maximum amount and frequency which is allowed by that particular binding site which causes the maximum amount of downstream signal transduction possible to be utilized at the binding site. The ion channel can open more frequently than with a full agonist alone but requires the help of a second receptor site. An antagonist causes a stabilization in the receptor sites in resting phases which is the same mechanism of action at the receptor site when an agonist is not present. Because there are no changes whether an antagonist is present or not, it is said to be neutral or silent.
Compare and contrast the actions of g couple proteins and ion gated channels.
Partial agonists cause changes in receptors so that ion channels open to a greater extent and with more frequency that at a resting state but less than when a full agonist is present. Antagonists reverse partial antagonists just as it reverses full agonists and result in the receptor site returning to its state of rest. Partial agonists produce ion flow and downstream signal transduction which is more than at a resting state but less than that of a full agonist. When there are unstable neurotransmissions within the brain, a balance must be found to stabilize the receptor output so that there is not too much or too little downstream action occurring Foundational Neuroscience Essay Assignment Paper. Partial agonists are also referred to as stabilizers since they are typically able to cause an even reaction between extremes of too much or too little action potential (Stahl, 2013).
A class of receptors linked to G proteins are a major target of psychotropic drugs. The G couple proteins have the structure of seven transmembrane regions, spanning the membrane seven times. Each region of the membrane is arranged around a central core which contains a binding site for a neurotransmitter. Drugs can interact at a particular neurotransmitter binding site or at other sites, also called allosteric sites within a receptor. This binding can lead to various modifications of receptor actions by either partially or fully mimicking or blocking any neurotransmitter function which would normally occur at a specific receptor site. Downstream molecular processes can be changed by drug actions as when phosphoproteins are activated or inactivated which results in a difference in which enzymes, receptors, or ion channels are modified by the neurotransmission. These drug actions can also lead to changes in which genes are expressed, altering which proteins are synthesized and which functions are amplified, from synaptogenesis, to receptor and enzyme synthesis, to communication with downstream neurons innervated by the neuron with the G-protein-linked receptor. As a result, drug-induced alterations at the G-protein-linked receptor site can cause actions on psychiatric disorders or symptoms (Stahl, 2013).
Like G proteins, ligand-gated ion channels are a type of receptor which also forms an ion channel. For this reason, they are both ligand-gated ion channel and also ionotropic receptors or ion-channel-linked receptors. They have dual functions, hence the two names. Ligand-gated ion channels consist of long strings of amino acids which are gathered as subunits around an ion channel. There are many binding sites around these subunits for neurotransmitters, ions and drugs. Complex proteins have sites where ions can pass through a channel or bind to the channel, or where a neurotransmitter can act as a binding site and where natural substances or drugs can bind to a site different than where the neurotransmitter binds resulting in an increase or decrease to the sensitivity of a channel opening. In psychopharmacology, the ion channels that are the most important are those that control sodium, calcium, chloride, and potassium. Full agonists will directly change the receptor site to open the ion channel. Antagonists will cause a steady state at the receptor in its resting state which is similar to how a receptor responds when there is no agonist present. Alternatively, drug-induced modifications which occur with ionotropic receptors cause immediate effects by changing the flow of ions resulting in an immediate clinical onset as when medications such as anxiolytics and hypnotics are used. Some drugs that act at the G-protein-linked receptor sites may have a delayed response caused by an instigation in cellular functions that become activated by the signal transduction cascade (Stahl, 2013).
Explain the role of epigenetics in pharmacologic action.
In genetics, there is a DNA code which transcribes specific types of RNA or proteins within cells. While there are greater than 20,000 genes within the human genome, not every gene is expressed, even within the brain. Epigenetics goes a step further than genetics in that there is a determination whether a given gene is made into specific RNA and protein or instead it is just simply ignored or silenced. Further definition states that if a genome is a glossary of all “words” related to protein, than the epigenome is the “story” of all of those “words” into something that is cohesive. The genomic makeup of potential proteins is the same within every single neuron and cell in the body. What causes a normal neuron to malfunction, as in psychiatric diagnoses, or how a neuron winds up a neuron rather than a liver cell is all the result of whether or not specific genes are expressed or silenced. Neurons that are functioning improperly are often impacted by genes with abnormal sequences and if these genes are expressed rather than silenced, mental disorders can ensue. Brain development is not only dependent on inherited genes, but whether or not abnormal genes are expressed, and/or normal genes are silenced. There are many factors which regulate whether or not genes are expressed or silenced and include neurotransmission, the gene makeup, drugs and environment. All of these factors help decide whether or not the brain is one full of learning and memories or drug abuse, stress and psychiatric disorders and whether or not there can be improvement with medications and therapy (Stahl, 2013).
Explain how this information may impact the way you prescribe medications to clients. Include a specific example of a situation or case with a client in which the psychiatric mental health nurse practitioner must be aware of the medication’s action.
In depth knowledge regarding medications, pharmacokinetics and pharmacodynamics are important prior to prescribing. In addition to this, one must understand genetics and factors regarding medication uptake and absorption. Foundational Neuroscience Essay Assignment Paper Farmer (2014) discusses psychopharmacological treatment from a social work perspective and states that a new way of thinking about mental illness is evolving. The National Institute of Mental Health has worked on a project (the Research Domain Criteria RDoC) to change the thought process behind mental illness diagnoses. The RDoC utilizes data regarding pathophysiology, especially related to genomics and neuroscience when it comes to understanding mental illness. Investigation of the biological underlying of mental disorders is being focused on and a new understanding of different dimensions of functioning related to positive and negative valence systems, cognitive systems, systems for social processes, and arousal/modulatory systems are being included and studied as well as the analysis of genes, molecules, cells, neural circuits, physiology. Client behaviors and self-reports are also considered. The idea is to link neurobiology with mental illness diagnoses and find better medications to treat specific mental disorders. We must understand that psychotropic medications work in the brain and CNS to affect the level of a neurotransmitter. Human behavior is the result of neural activity where an axon sends chemical and electrical messages to receiving neurons and a synapse is a communication point between neurons and where an action potential takes place. As PMHNPs, we must understand the mechanism of action in how a medication works, whether it is an agonist or antagonist, and how the major neurotransmitters (acetyl-choline, norepinephrine, dopamine, serotonin, gamma aminobutyric acid, glutamate) are affected by specific medications. Medications have different effects based on factors such as client age, gender, race and ethnicity. More studies are needed how race and ethnicity may affect medications as pharmacokinetics and pharmacodynamics, as are influenced by genetic factors as well as the environment which includes lifestyle, behavioral patterns, and social interactions. One person’s response to a medication will be determined by gene–environment interaction (Farmer, 2014) Foundational Neuroscience Essay Assignment Paper.
Understanding that psychiatric disorders such as major depressive disorder, drug addiction, and schizophrenia can have multiple gene involvements rather than “one gene/one disease” relation can assist with finding the right medications and treatments for clients. Understanding epigenetic modifications (histone acetylation and deacetylation, DNA methylation) and how these can result in changes in gene expression is looking to be the future of treating psychiatric disorders (Mahgoub & Monteggia, 2013).
PMHNPs must be aware at this time, when prescribing medications such as an SSRI or SNRI, these medications take time to reach therapeutic effect. Patients must be well educated that they will not feel “better” instantly and must be counseled to stay the course with medication compliance and therapies to achieve maximum benefit.
References
Farmer, R. L. (2014). Interface between psychotropic medications, neurobiology, and mental illnesses.
Smith College Studies in Social Work, 84
(2-3), 255-272.
Mahgoub, M., & Monteggia, L. M. (2013). Epigenetics and psychiatry.
Neurotherapeutics, 10
, 734-741.
Stahl, S. M. (2013).
Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications
(4th ed.). New York, NY: Cambridge University Press Foundational Neuroscience Essay Assignment Paper.