Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.

Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.

Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.

Week 1: Introduction to Neuroscience Discussion

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.

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. 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). Week 1: Introduction to Neuroscience Discussion.

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Week 2 Assignment Rubric

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

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. 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).

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.

Discussion: Foundational Neuroscience

As a psychiatric nurse practitioner, it is essential for you to have a strong background in foundational neuroscience. In order to diagnose and treat patients, you must not only understand the pathophysiology of psychiatric disorders but also how medications for these disorders impact the central nervous system. These concepts of foundational neuroscience can be challenging to understand. Therefore, this Discussion is designed to encourage you to think through these concepts, develop a rationale for your thinking, and deepen your understanding by interacting with your colleagues.

Photo Credit: Getty Images/Cultura RF

For this Discussion, review the Learning Resources and reflect on the concepts of foundational neuroscience as they might apply to your role as the psychiatric mental health nurse practitioner in prescribing medications for patients.

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.

Read a selection of your colleagues’ responses.

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.

Note: For this Discussion, you are required to complete your initial post before you will be able to view and respond to your colleagues’ postings. Begin by clicking on the “Post to Discussion Question” link and then select “Create Thread” to complete your initial post. Remember, once you click on Submit, you cannot delete or edit your own posts, and you cannot post anonymously. Please check your post carefully before clicking on Submit!

Submission and Grading Information

Grading Criteria

To access your rubric:

Week 2 Discussion Rubric

Post by Day 3 of Week 2 and Respond by Day 6 of Week 2

To Participate in this Discussion:

Week 2 Discussion

 

Week 2: Neurotransmitters and Receptor Theory

Receptors and neurotransmitters are like a lock-and-key system. Just as it takes the right key to open a specific lock, it takes the right neurotransmitter to bind to a specific receptor. Not surprisingly, as it concerns psychopharmacology, the pharmacotherapeutics that are prescribed must trigger the release of certain neurotransmitters that bind to the correct receptors in order to elicit a favorable response for the patient. The mechanism of this binding and the response that follows reflects receptor theory and lies at the foundation of pharmacology.

This week, you will continue your examination of neuroanatomy and neuroscience as you engage with you colleagues in a Discussion. You will also explore the potential impacts of foundational neuroscience on the prescription of pharmacotherapeutics.

Learning Objectives

Students 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

Learning Resources

Required Readings (click to expand/reduce)

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.

Required Media (click to expand/reduce)

The University of British Columbia. (n. d.). Neuroanatomy videos. http://neuroanatomy.ca/videos.html

Note: Please review all of the media under the neuroanatomy series.

Optional Resources (click to expand/reduce)

Pathopharmacology: Disorders of the Nervous System: Exploring the Human Brain

Dr. Norbert Myslinski reviews the structure and function of the human brain. Using human brains, he examines and illustrates the development of the brain and areas impacted by disorders associated with the brain. (15m)

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Explain the agonist-to-antagonist spectrum of action of psychopharmacologic agents.

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