Nursing homework help
FYI HERE RESPOND TO TWO COLLEAGUES: Please include 2 in test citations and references in each response
By Day 3 of Week 2
Post a response to each of the following:
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.
2-Compare and contrast the actions of g couple proteins and ion gated channels.
3-Explain how the role of epigenetics may contribute to pharmacologic action.
4-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.
By Day 6 of Week 2
Respond to at least two of your colleagues on two different days in one of the following ways:
If your colleagues’ posts influenced your understanding of these concepts, be sure to share how and why. Include additional insights you gained.
If you think your colleagues might have misunderstood these concepts, offer your alternative perspective and be sure to provide an explanation for them. Include resources to support your perspective.
Colleague 1
The future role of epigenetics in understanding and treating mental illness is increasingly a promising one. Because of its direct role on gene behavior (Szyf, 2019) it will provide clinicians with not only a deeper knowledge of the biologic reaction of the human brain to stressful or noxious stimuli across its lifespan, but also improve medications that specifically target these complex biologic reactions. This will be particularly beneficial for the developing brain beginning in utero and into early adulthood where continued maturation of the central nervous system (CNS) makes it particularly vulnerable to adverse events (Barker, 2018; Szyf, 2019). A particular area of focus in epigenetic research concerns DNA methylation (DNAm). This is a chemical process involving changes in genetic material in response to stimulation that can then produce ‘behavioral phenotypes’ (Szyf, 2019, p 369). Barker (2018) further explains, “…if adversity-related DNAm is a causal link in the aetiology of a mental health problem – then reversing epigentic marks might help in remission of these problems” (p. 3). Nursing homework help
One example of the result of an epigenetic process involves the use of the drug cannabis. According to Hurd et al., (2019) prenatal, perinatal and adolescent exposure to the chemical tetrahydrocannabinol (THC), the substance responsible for psychoactive results, can lead to changes in gene expression that can affect mental health across the lifespan. During prenatal development maternal exposure to THC can cause changes in receptors called cannabinoid 1 receptors (CB1Rs) that are in the mesocorticolimbic brain where high concentrations of dopamine, glutamate and GABA are thought to contribute significantly to addiction and psychiatric disorders (Hurd et al, 2019). Lactating mothers can also transfer these substances to their breastfeeding babies. One outcome of this exposure is the impact these substances have during the development of the neurotransmitter, GABA (Hurd et al., 2019). GABA in the developing brain starts out as an excitatory neurotransmitter and does not achieve its inhibitory characteristic until the brain gradually matures (Hurd et al., 2019). According to Hurd et al. (2019) “The timing of this shift is a decisive moment in the neurodevelopmental trajectory, and pertubations during this critical period are linked to numerous disorders” (p. 8252). During adolescence the central nervous system continues to develop especially the reward system located in the mesolimbic dopamine pathway via the endocannabinoid (eCB) ligands (Hurd et al., 2019). When the development of this area of the brain is disrupted by a substance like THC, it can increase vulnerability to drug addition (Hurd et al., 2019).
Limitations in epigenetic research do exist. For example, access to the living human tissue of the CNS, although ideal for this field of study, is not plausible. Instead, information from saliva, buccal epithelial cells, and blood, where peripheral inflammation and change in the immune response can be observed, are extrapolated to further understand how the changes correlate to mental illness (Barker, 2018). Despite this limitation, information gleaned from these peripheral tissues, especially blood, hold promising information for the future of epigenetic research of mental illness (Barker, 2018). Barker (2018) further adds, “Moreover, there is good evidence from animal studies, and increasing evidence in humans, that peripheral inflammatory markers can affect brain areas implicated in certain psychiatric disorders. Consequently, adversity-related immune processes and DNAm may be well measured in blood samples’ (p. 5).
Neuron cells in the central nervous system communicate via two main types of signaling pathways: the ion channel and G couple protein. Due to their importance in maintaining homeostasis in the central nervous system, and therefore mental health, both processes have been extensively researched for their involvement in psychiatric and neurological disorders with numerous drug developments that target their structures to help treat disease (Pluimer et al., 2020; Held & Toth, 2021).
Hundreds of ion channels are located in the central nervous system and with their respective proteins act directly on the cell membrane to control interneuron communication (Held & Toth, 2021). Once an electrical impulse in the neuron cell reaches the cell’s membrane that synaptic activity, which is tightly regulated by ion channel, increases the permeability of the cell membrane (membrane potential) to the influx of ion proteins (Held & Toth, 2021). Compared to the G couple protein process, ion channel communication occurs rapidly (Stern et al., 2016). Transient Receptor Potential (TRP) channels are a group of 28 cation channels responsible for sensing external and internal stimulation (Held & Toth, 2021). For instance, the channel TRPM2 is selective for calcium ions that are critical for healthy brain functioning and is thought to be involved in ‘oxidative stress’ that occurs with aging and neurodegenerative diseases (Held & Toth, 2021). Another widely studied TRP ion channel is the TRPM3 which is found in large numbers in the choroid plexus, the cerebellum, the forebrain, and the hippocampus (dentate gyrus) where it helps to regulate movement, cerebral spinal fluid, and memory (Held & Toth, 2021). Dysregulation of TRPM3 has also been implicated in certain brain pathologies involving learning disabilities including Kabuki Syndrome and autism suggesting its critical role in early brain development (Held & Toft, 2021). Other areas of TRPM3 involvement include mood and anxiety disorders, including post-partum depression and seizures (Held & Taft, 2021).
Neuron signaling is also performed by the G-protein-coupled receptors (GPCRs). According to Pluimer et al. (2020), “GPCRs constitute the largest superfamily of membrane proteins in eukaryotes. Their capacity to bind a wide variety of ligands and diverse signaling profiles position them as ideal candidates for drug-target therapies” (p. 139). In fact, the Food and Drug Administration has approved between 20% – 30% of all the current drugs on the market, including opioids, anti-psychotics, and anti-histamines, to target GPCRs (Pluimer et al., 2020; Vedel et al., 2020). Unlike ion channels, GPCRs, of which there are five (Glutamate, Rhodospsin, Adhesion, Frizzled and Secretin), exert their influence through a complex slower process of chain reactions involving second-messenger systems (Stern et al., 2016). According to the International Union for Basic and Clinical Pharmacology Committee of Receptor Nomenclature and Drug Classification, (NC-IUPHAR) there are, at present, 121 ‘orphan GPCR’ receptors, meaning an ‘endogenous ligand’ has not yet been identified for that receptor, including one for GPR 139, which is thought to have a role in Parkinson’s Disease, alcohol addiction, hyperalgesia, phenylketonuria schizophrenia, attention deficit hyperactivity disorder, depression and fetal development (Vedel et al., 2020). Nursing homework help
Colleague 2
Top of Form
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.
Paul Ehrlich (1854–1915) is credited with being the first person to suggest the notion of highly precise interactions between medications and receptors. corpora non agunt nisi fixata (drugs do not act unless they are bound) (Weir, 2020). However, before moving on to talk about how different drugs interact with one another, it is necessary to define what exactly a receptor is. A neurotransmitter, hormone, or inflammatory mediator are all examples of endogenous chemical mediators that may be recognized by receptors, which are proteins. Pharmacologists define a receptor as a protein that identifies one of these endogenous chemical mediators (Weir, 2020). Following the binding of the mediator (agonist) to the receptor, a cascade of events takes place, which eventually results in a change in the function of the host cell. For instance, the binding of GABA to GABAA receptors inhibits neuronal activity by causing an inward flow of chloride ions (Cl) via an integral ion channel. This flow of chloride ions (Cl) is responsible for the inhibition of neuronal function. When referring to a target whose function is changed by an external drug rather than an endogenous mediator, it is common practice to use the word “receptor” in a more general sense (Weir, 2020).
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An agonist is a substance that binds to a receptor, which then causes the receptor to become activated and causes the function of the receptor’s host cell to change. Agonists are characterized by having both affinity and efficacy. The ability of an agonist (or drug) to bind to a receptor is referred to as its affinity (Weir, 2020). Affinity is defined as the ratio of the binding rate (k + 1) to the dissociation rate (k 1), which is to say that affinity (kA) = k + 1/k 1. Affinity is frequently measured experimentally through the utilization of radioactive binding techniques. On the other hand, efficacy is a term that refers to the capability of the medication to activate the receptor once it has successfully attached to the receptor (Weir, 2020). Full agonists are capable of producing a maximal response or maximal efficacy (this may occur when only a fraction of receptors are occupied, hence the concept of’spare’ receptors), whereas partial agonists are not capable of producing a full response even in the presence of high concentrations of agonist (Weir, 2020).
Competitive receptor antagonists are classed as either reversible or irreversible. Competitive antagonists bind to the receptor and therefore possess affinity, but they are unable to produce a response and thus lack efficacy (Weir, 2020). Furthermore, they prevent the agonist from binding and so block its ability to activate the receptor. It is possible to overcome irreversible competitive antagonism. To put it another way, the effects of an antagonist attaching to an agonist binding site may be neutralized by raising the concentration of a competing agonist. In contrast, irreversible competitive antagonists form a covalent bond with the receptor, and it is not possible to circumvent the receptor blockage by raising the concentration of the agonist (i.e. the effect is insurmountable). Because of this, the agonist has less of an opportunity to exert its full impact when there is an irreversible antagonist present (Weir, 2020). Nursing homework help
Inverse agonists are substances that, according to their name, have the opposite impact of agonists on the body. This recently discovered phenomenon is only conceivable in the event that the receptor is capable of action in the absence of an agonist (i.e. it has constitutive activity). In this circumstance, a competitive antagonist by itself will not have any impact on constitutive activity (since there is no agonist present), but an inverse agonist will create a concentration-dependent drop in receptor activity. This will occur because an agonist is not present (Weir, 2020).
2- Compare and contrast the actions of g couple proteins and ion gated channels.
Ion channel receptors are an essential part of the signaling process that occurs in the nervous system. They make it possible for a chemical neurotransmitter message to be rapidly and directly converted into an electrical current. Ionotropic receptors are known to be controlled by protein-protein interactions with other ion channels, G-protein coupled receptors, and intracellular proteins (Li et al., 2014). This has become abundantly clear over the course of the last several decades. The interactions between ion channel receptors and these other proteins have the potential to regulate these other proteins as well. This bidirectional functional cross-talk is necessary for key cellular processes like as excitotoxicity in pathological and disease states like stroke, and it is also vital for the fundamental dynamics of activity-dependent synaptic plasticity. Protein interactions with ion channel receptors constitute a potential target for therapeutic intervention in neuropsychiatric disorder (Li et al., 2019). As a result, protein interactions with ion channel receptors may boost the computational capacity of neuronal signaling cascades (Li et al., 2014).
In order for there to be effective neurotransmission, there must be a specific interaction between the many different types of neurotransmitter receptors that are present in the pre- and post-synaptic compartments. In the neurological system, ligand-gated ion channels are an extremely important part of the process of intercellular communication. Ion channels are the cell’s mechanism for transporting ions across membranes, and as such, they are the fundamental component of the electrical activity that neurons undergo. G protein coupled receptors, also known as GPCRs, are integral membrane proteins that are utilized by cells to translate extracellular information into intracellular responses. These responses may include reactions to hormones and neurotransmitters, as well as reactions to taste, smell, and vision cues (Li et al., 2014).
3-Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics may be defined in a number of different ways, but it generally refers to the concept that the function of a gene can be altered without a corresponding change in the genetic code, and that this variation in gene function may also be heritable. This may often take place as a result of a change in the structure of the DNA molecule, such as the formation of chromatin around a gene, which modifies the expression of that gene. The human genome contains many genes, but only few of them are ever used. Through the study of epigenetics, one may decide whether a gene will be translated into its corresponding RNA and protein, or if it will be ignored or silenced (Mahgoub & Monteggia, 2013). Epigenetic processes allow for the modification of the structure of chromatin found in the nucleus of a cell, which in turn allows for the activation or silencing of genes. This may take place as a result of methylation, acetylation, phosphorylation, or any one of a number of other activities that are controlled by neurotransmission, medicines, and the surrounding environment (Mahgoub & Monteggia, 2013). Nursing homework help
It was formerly believed that genes did not alter throughout the course of a person’s lifespan; nevertheless, it is now recognized that epigenetics may change in adult neurons that have differentiated. Neurons are able to be altered by a variety of factors, including child maltreatment, nutritional inadequacies, psychotherapy, drug misuse, and other similar situations; as a result of these events, genes may either be activated or silenced. These results may sometimes be favorable, but more often than not, they are not. Increasing amounts of evidence point to the possibility that epigenetic mechanisms, which are able to cause changes in gene expression that are both stable and long-lasting in response to environmental occurrences and behavioral experiences, may play a role in the processes that contribute to the pathophysiology of psychiatric disorders (Mahgoub & Monteggia, 2013).
The goal is that with a greater knowledge of how epigenetic processes underlie mental diseases, it will be possible to better identify how individual genes that may contribute to these disorders are impacted by epigenetic alterations. Researchers will discover new pathways of treatment approaches to satisfy the demands of people who are suffering from mental disease if they have a better grasp of how epigenetic processes carry out long-lasting and adaptive alterations in gene activity and expression (Mahgoub & Monteggia, 2013)
4-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.
This information plays a critical role in determining how medicine is recommended to patients, making it very important. When a practitioner has a thorough awareness of the agonist-to-antagonist spectrum of action, they are in a better position to accurately anticipate the clinical effects of psychopharmacologic drugs. Providers may benefit from having knowledge about the activity of certain neurotransmitters and where these neurotransmitters fall on the spectrum of agonists to antagonists, as this can help them choose the most effective therapy to deliver the desired therapeutic result. An illustration of this can be found in the treatment for substance abuse. If medical professionals have a better understanding of the mechanism by which a partial agonist can inhibit the use of a full agonist by occupying receptor sites, they will be better able to explain why drugs like Suboxone are used to treat addiction.
When a patient presents with anxiety that will require both short-term and long-term management, the psychiatric mental health nurse practitioner must be aware of the action of the medication. This is an additional specific example of a situation in which the psychiatric mental health nurse practitioner must be aware of the action of a medication. The knowledge that benzodiazepines alter ion flow and begin working nearly instantly, but the effects of an SSRI for long-term use will be delayed, has the potential to impact the prescription choices made by medical professionals. In this circumstance, it may be reasonable to prescribe a benzodiazepine as an initial treatment until the effects of the SSRI begin to take hold. Nursing homework help
