Discussion: Foundational Neuroscience assignment

Discussion: Foundational Neuroscience

Week 2 Discussion

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.

Pharmacology is the study of how drugs interact with biological processes; while psychopharmacology is the study of the effects of drugs on brain processes such as cognition, mood, and other psychological phenomena (Fields, 2019). Psychopharmacological drugs are generally small synthetic molecules that act in a number of different ways such as agonist, antagonist, partial, and inverse agonists. Agonists act to mimic the action of an endogenous neurotransmitter, though their net action is not necessarily to promote synaptic transmission because of the effect that presynaptic auto-receptors may have (Stahl

2013). Antagonists block the effects of endogenous neurotransmitters and oppose normal synaptic transmission, although in some cases if they act predominantly on presynaptic receptors they may increase neuronal firing and so increase neurotransmitter release. Partial agonists act somewhat like agonists in that they directly act on receptors, but if used in the presence of an agonist, they compete for the receptor and so can have partial blocking properties, therefore are called agonist-antagonists (Stahl, 2013). Inverse agonists on the other hand bind to the same receptors as an agonist but typically have the opposite effect on the target cell. The main pharmacological effect of inverse agonists is receptor antagonism in that the inverse agonists block the effect of agonists and the effect on constitutive activity is only relevant if the system is spontaneously active (Norris & Carr 2013).  Overall, the agonist-antagonist spectrum reaches from agonists through antagonists to partial and inverse agonists. Naturally occurring neurotransmitters are agonists. It is a common misconception that antagonists are the opposite of agonists because they block the actions of agonists. However, inverse agonists are really the opposite of agonists. Antagonist can block anything in the agonist spectrum, including inverse agonists. If an agonist is not as strong as the full agonist, it is called a partial agonist (Stahl, 2013). Examples of the psychopharmalogical actions of an agonist would be to reduce anxiety or pain. An antagonist would block agonists from reducing anxiety or pain and would block inverse agonists from causing pain. However, an antagonist would neither reduce nor cause pain in itself.

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

G couple proteins represent the most abundant family membrane proteins in the human genome, which are activated by a spectrum of structurally diverse ligands. They have seven different protein segments which span the membrane seven times and transmit signals for binding sites for neurotransmitters (Stahl, 2013). This will allow for therapeutic drug actions to occur. Once drugs attach to these receptor sites, a full or partial blocking function of neurotransmitters occurs. The molecular changes can ultimately be affected by the drug actions, and cause changes in which phosphoproteins are activated or inactivated, or determine which enzymes, receptors, or ion channels are modified by neurotransmission (Stahl, 2013). Ion gated channels are electrically controlled. Unlike ions, G-couple proteins can diffuse through the membrane and ultimately change a cell’s behavior, and ions cannot diffuse due to their charge. Ion gated channels control access in and out of neurons. Dependent on the class of ion channels, they may be opened by neurotransmitters or voltage. A comparison that relates to both ion channels and g-protein-linked receptors is the agonist spectrum. Both g couple proteins and ion gated channels are types of protein receptors which are embedded in cell membranes that bind to a molecule. Medications that change the flow of ions can cause a clinical effect, unlike drugs that target g protein-linked receptor sites, which takes a more extended period (Stahl, 2013)

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

Epigenetics consists of heritable genetic modification that alter gene function and expression without changes in DNA sequence (Dos Santos, 2018). There are several epigenetics mechanisms such as: histone protein modification, covalent DNA modification, and regulation of noncoding RNA. Epigenetics enables drug metabolism and transport throughout the body with changes to the phenotype instead of the genotype (Des Santos 2018). Epigenetics determines if some genes will become a specific RNA and protein, or if it will be turned off, based on the structure of chromatin, neurotransmission, genes, drugs, or the environment. All of these can affect the brain in various ways and can result in inefficient information processing. Epigenetics also affect the way medications work for each person. Drugs may not be designed to be specific to a particular gene or protein subtype; they may indeed have to be able to be more broad‐acting over a range of large‐scale epigenetic event (Stefanska & MacEwan, 2015).

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 nurse practitioner, it is imperative to understand the importance of providing individualized care to each patient. When prescribing a medication, factors such as patient’s age, medical history, social history (illicit drug and alcohol use) pharmacodynamics, pharmacokinetics, and epigenetics should be always be put into consideration so as to prevent adverse reactions and achieve the therapeutic effects desired. For example, I once cared for a twenty five year old male post-op patient who was brought in by ambulance due to a ruptured appendix. The physician had initially written an order for 1.5mg of Dilaudid every 3 hours as needed. This dosage and frequency did not address patient’s pain even for a second. I was determined to figure out why we could not manage the patient’s pain. So I once again reviewed his chart for admission notes as well as his medications, medical and social history. Patient denied any illicit drug use or being on any opioid prescription during his initial assessment. So I went to the patient and told him that I was working on putting together a plan of care to better address his pain, and that whatever information that he could give me regarding his medical/social history would be helpful. Patient then opened up and informed me that he was a “functional” heroin addict, and that he could not mention it at the time of his initial health assessment because his family members were present. The patient also stated that he was currently on Opioid Agonist Therapy (OAT) and was on methadone. According to Quinlan & Cox (2017), patients who are typically on OAT and develop acute painful conditions tend to be undertreated for acute pain. As providers encounter more frequently patients receiving OAT, it is important that a proper pain management plan is implemented to ensure that these patients achieve the desired pain relief management without worsening the addiction. From a pharmacokinetics perspective, methadone is a very potent synthetic analgesia that is used to treat chronic pain such as cancer as well we effective in the management of opioid dependence (American Addiction Centers 2019). Methadone particularly works as an agonist (full opioid receptor) and an antagonist (N-methyl-d-aspartate NMDA). From an agonist standpoint, methadone imitates the body’s natural opioids such as endorphins and enkephalins though the release of neurotransmitters involved in pain transmission (Negus & Banks 2018). Methadone uniquely differs from other opioid analgesics such as morphine because of its longer bioavailability and longer duration of action and half-life. This unique pharmacokinetic profile makes it an effective drug for treating opioid addiction in that it requires fewer doses to maintain analgesia and thus prevents withdrawal (Negus & Banks 2018).

From a pharmacodynamics perspective, methadone is metabolized by the liver through the actions of the cytochrome P450 enzymes (Sandritter, McLaughlin, Artman, & Lowry 2017).  How methadone works in the body of each patient differs as a result of many factors. The same dose given to two different patients will manifest somewhat differently based on factors such as level of addiction, kidney and liver function, genetics, etc. Methadone works by affecting the brain and nervous system’s responses to pain, and while it does not have the immediate addicting properties of illicit opioids such as heroin, improper use and management can also lead to abuse of Methadone (Sandritter, McLaughlin, Artman, & Lowry 2017).  In conclusion, having an understanding of pharmacokinetics and pharmacodynamics of the medications the patient was on as well as having a more detailed health history of this patient allowed me to put together an individualized pain management plan for this patient.

References

Dos Santos, D. L. (2018). Clinical pharmacology: Epigenetic drugs at a glance. Retrieved from

Fields, D. (2019). What is psychopharmacology. Retrieved from

Negus, S.S., & Banks, M.L. (2018). Pharmacokinetic-pharmacodynamic (PKPD) Analysis with

drug discrimination. Retrieved from

Norris, D.O., & Carr, J.A. (2013). Synthesis, metabolism, and actions of bioregulators. Retrieved

From

Sandritter, T.L., McLaughlin, M., Artman, M., & Lowry, J. (2017). The interplay between

pharmacokinetics and pharmacodynamics. Retrieved from

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical

applications (4th ed.). New York, NY: Cambridge University Press

Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. Retrieved from

Quinlan, J., & Cox, F. (2017). Acute pain management in patients with drug dependence

syndrome. Retrieved May 31, 2021 from

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. 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.

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

Note: To access this week’s required library resources, please click on the link to the Course Readings List, found in the Course Materials section of your Syllabus.

Required Readings

Post a response to each of the following: Include sub headings please.

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

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

3. Explain the role of epigenetics in pharmacologic action.

4. 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.

Introduction to Advanced Pharmacology

In this media presentation, Dr. Terry Buttaro, associate professor of practice at Simmons School of Nursing and Health Sciences, discusses the importance of pharmacology for the advanced practice nurse. (6m)