Respond to at least two of your colleagues 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.
-Both responses should be at least a paragraph in length and have 2 references each.
FRIZETTEs Answers
- 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 is a drug that binds to the receptor and produces a reaction that is comparable to the chemical and receptor intended (Nguyen, 2018).. An antagonist, on the other hand, is a medication that binds to the receptor either at the primary location or at a different place, preventing the receptor from eliciting a response. Agonists work by simulating the actions of normal neurotransmitters (Nguyen, 2018).The antagonist is the reverse of the agonist. It attaches to receptors and prevents them from inducing the intended effect (Nguyen, 2018).
A partial agonist binds to a receptor but does not produce the same level of response as a complete agonist at the same receptor site, or only partially mimics the function of the endogenous neurotransmitter it mimics (American psychological association, 2022).
Inverse agonists work on the receptor to create the physiological impact that another agonist at the same receptor would induce (American psychological association, 2022). By stabilizing inactive conformations, inverse agonists inhibit receptor activation. It inhibits agonist effects and suppresses or prevents spontaneous or constitutive receptor activity (Burstein, 2019).
- Compare and contrast the actions of g couple proteins and ion gated channels.
G-protein coupled receptors (GPCRs) are the most common type of plasma membrane receptor, with rhodopsin and adrenergic receptors being the most well-known examples (Hille, 2009). They are plasma membrane proteins that convert signals from external ligands to intracellular relay proteins, which are heterotrimeric GTP binding proteins (G proteins) (Hille, 2009). The G proteins cause pleiotropic changes in a variety of targets by connecting to many downstream second messengers and effectors. As a result, the extracellular signal is frequently amplified, resulting in powerful, diverse, and cell-specific responses. Growth-factor receptors (e.g., insulin, NGF, BDNF, etc.) signal via tyrosine kinases, do not require heterotrimeric G proteins, and often control gene expression as well as second-messenger signals. GPCRs and growth-factor receptors, on the other hand, have some common signaling enzymatic pathways (Hille, 2009).
G protein coupled receptors (GPCRs) are one of the largest families of validated pharmacological targets, as they are involved in nearly all physiological functions and pathological processes (Zhao et al., 2016). G protein coupled receptors (GPCRs) are membrane proteins that allow cells to translate extracellular signals such as hormones and neurotransmitters into intracellular responses, as well as responses to vision, olfaction, and taste signals (Zhao et al., 2016).
Ion channels are pore-forming protein complexes that allow ions to flow freely across cell membranes’ hydrophobic cores, they are found in all cells’ plasma membranes and intracellular organelle membranes, where they perform vital physiological functions such as establishing and shaping electrical signals that underpin muscle contraction and relaxation, neurotransmitter release, cognition, hormone secretion, sensory transduction, and maintaining electrolyte balance and blood pressure. Gating, or the stimulus that ‘opens’ the channel, whether chemical or mechanical, is used to classify them (Pharmacology education project, n.d.).
G-proteins are activated by neurotransmitters and subsequently dissociate from the receptor, interacting directly with ion channels or binding to other effector proteins, such as enzymes, which produce intracellular messengers that open or close ion channels (Purves et al., 2001). G-proteins can thus be thought of as transducers that link neurotransmitter binding to postsynaptic ion channel control (Purves et al., 2001).
- Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetics is the study of how your behavior and environment can influence how your genes function (CDC, 2020). Epigenetic modifications are reversible and do not alter your DNA sequence; nevertheless, they can alter how your body interprets DNA sequences (CDC, 2020). In response to illicit drug use, epigenetic alterations in DNA methylation and chromatin remodeling have been discovered (Neilsen et al., 2012). The status of epigenetic chromatin may have a role in the development of persistent substance misuse. Epigenetic changes that control transcription are triggered when a substance of abuse is administered. Reward, psychomotor activity, drug seeking, and relapse may all be influenced by variations in gene expression (Neilsen et al., 2012). Epigenetic variables such as DNA methylation and histone changes can influence an individual’s predisposition to acquire drug addiction, as well as their reaction to drugs of abuse and pharmacotherapy for addictions (Neilsen et al., 2012).
- 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 psychiatric mental health nurse practitioner, it is important to obtain and gather patient’s information and perform a thorough assessment, including the patient’s past medical and psychiatric history, current and previous prescribed medications, current lifestyle, drugs, alcohol, and smoking history before prescribing medications. The possible side effects, adverse effects, indications and how it might affect the patient’s well being. Possible drug- drug or drug-food interactions should also be considered. These factors should be assumed that can impact the way medications are prescribed. Assess the appropriateness of psychopharmacology as well as the patient’s willingness to receive it. Psychotropic medication should only be administered after potential side effects, risk factors for negative outcomes, and the hazards of continued use, if any, have been considered (AMA, 2022).
References:
AMA. (2022). Psychopharmacology guide on prescribing psychotropic medications. https://www.ama-assn.org/delivering-care/public-health/psychopharmacology-guide-prescribing-psychotropic-medications#:~:text=Evaluate%20appropriateness%20of%20psychopharmacology%2C%20along,if%20any%2C%20of%20prolonged%20usage.
American psychological association. (2022). Agonists. https://dictionary.apa.org/agonist
American psychological association. (2022). Partial agonists. https://dictionary.apa.org/partial-agonist
Burstein, E.S. (2019). Should inverse agonists be defined by pharmacological mechanism or clinical effect? https://www.cambridge.org/core/journals/cns-spectrums/article/should-inverse-agonists-be-defined-by-pharmacological-mechanism-or-clinical-effect/6B771F914A9C40CB6C882DD5A42B4FD7
Centers for disease control and prevention. (2020). What is epigenetics? https://www.cdc.gov/genomics/disease/epigenetics.htm
Hille, B. (2009). G protein-coupled receptor. http://www.scholarpedia.org/article/G_protein-coupled_receptor
Nguyen, A. (2018). Agonists and antagonists. https://lx.uts.edu.au/pharmacology/article/agonists-and-antagonists/
Nielsen, D. A., Utrankar, A., Reyes, J. A., Simons, D. D., & Kosten, T. R. (2012). Epigenetics of drug abuse: predisposition or response. Pharmacogenomics, 13(10), 1149–1160. https://doi.org/10.2217/pgs.12.94
Parmacology education project. (n.d.). Ion channels. https://www.pharmacologyeducation.org/pharmacology/ion-channels
Purves, D., Augustine, G.J., & Fitzpatrick, D. (2001). Two families of postsynaptic receptors. https://www.ncbi.nlm.nih.gov/books/NBK10855/#:~:text=Neurotransmitter%20binding%20to%20metabotropic%20receptors,open%20or%20close%20ion%20channels.
Zhao, J., Dend, Y., Jiang, Z., & Qing, H. (2016). G protein-coupled receptors (GPCRs) in Alzheimer’s disease: A focus in BACE1 related BPCRs. Frontiers in aging neuroscience. https://doi.org/10.3389/fnagi.2016.00058
ASIA’s Answers
Agonist-to-Antagonist Spectrum of Impact on Psychopharmacologic Agents
The properties of a medication are vital to know to make sure that the medication interacts with the body properly. The agonist to antagonist spectrum of action is how psychiatric drugs have the potential to cause an effect in an individual who is prescribed these types of medications. Antagonist medication that targets these receptors will stop the other item from having the ability to make an impact. Agonist medication that targets these receptors will do the opposite and help to increase the impact that this item has on the body. Based on if the medication has an affinity for agonist or antagonist receptors will determine what the medication binds to. According to (Lee et al., 2018) psychiatric medications have receptors that they bind to that include antagonist or agonist properties to help treat the illness that the medication was created for. Partial agonist medication has shown to be more beneficial and cause less side effects such as decreased sedation according to (Reynolds, 2021). Binding with an inverse agonist has proven in the treatment of diseases such as depression, schizophrenia, and Alzheimer’s disease (Nirogi et al., 2021).
G Couple Proteins vs. Ion Gated Channels
G couple proteins and ion gated channels can both be found in the tissue of the brain and throughout the body. However, both items have different roles depending on the type of neurotransmitter that they belong to in a certain area of the body. According to (Camprodon & Roffman, 2016) nicotinic acetylcholine ion channels allow for an increased influx of sodium and calcium in the post synaptic area of the neuron. Clonidine is an example of a medication that utilizes g coupled proteins to reduce the activity of locus coeruleus neurons to produce a calming effect when a person is going through opiate withdrawals (Camprodon & Roffman, 2016).
Role of Epigenetics and Pharmacologic Action
Epigenetics is a term that has been adopted in the psychiatry world that describes how the function of a gene may be changed based on what a person has inherited according to (Camprodon & Roffmanm 2016). Understanding epigenetics can help a person to understand how a person’s body may react to a medication based on their DNA that they have acquired from their family. Epigenetics should be taken into consideration before prescribing a medication since this could play an impact in how the drug will react in the body.
Prescribing Medications as a PMHNP
Looking a patient in a holistic view is important for a nurse practitioner to do before prescribing medication. Epigenetics is an example of why treatment plans need to be created based off the individual who is receiving treatment. A medication plan that works for one patient may not work for another patient who has the same diagnosis. An example of a situation when a psychiatric nurse practitioner must be aware of the actions a medication could have on a person is prescribing Clozaril to an adolescent. A high rate of adverse effects and limited studies are available for adolescents who are prescribed Clozaril (Clozapine effectiveness assessed in RCTs of children and adolescents, 2018). Medications and dosing must be taken into consideration when prescribing to an adolescent due to the body processing drugs differently than an adult.
References
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.
Clozapine effectiveness assessed in RCTs of children and adolescents. (2018). Brown University Child &
Adolescent Psychopharmacology Update, 20(12), 1–3. https://doi.org/10.1002/cpu.30351
Lee, E. S., Vidal, C., & Findling, R. L. (2018). A Focused Review on the Treatment of Pediatric Patients
with Atypical Antipsychotics. Journal of Child & Adolescent Psychopharmacology, 28(9), 582–
Nirogi, R., Benade, V., Daripelli, S., Subramanian, R., Kamuju, V., Bhyrapuneni, G., Muddana, N. R.,
Mekala, V. R., Petlu, S., Jayarajan, P., Badange, R., Shinde, A., & Jasti, V. (2021). Samelisant
(SUVN-G3031), a potent, selective and orally active histamine H3 receptor inverse agonist for
the potential treatment of narcolepsy: pharmacological and neurochemical
characterisation. Psychopharmacology, 238(6), 1495–1511. https://doi.org/10.1007/s00213-
021-05779-x
Reynolds, G. P. (2021). High dose antipsychotic polypharmacy and dopamine partial agonists – time to
rethink guidelines? Journal of Psychopharmacology (Oxford, England), 35(9), 1030–1036.
https://doi.org/10.1177/02698811211026456
Responding to Classmate Answers
Student’s Name
Institutional Affiliation
Course
Instructor’s Name
Date
Responding to Classmate Answers
Response to Frizette
I agree with several points put forward by Frizette in the discussion post. All the information provided reflects what is written in various literature. The discussion is clear and easy to understand. I agree with the explanation regarding the agonist to antagonist spectrum. Indeed, an agonist is a drug that binds to the receptor to produce the intended action. On the other hand, antagonist drugs bind to the receptor to prevent specific reactions or responses. I agree with Frizette’s answer that GPCRs are plasma membrane proteins that convert extracellular signals into intracellular responses. Ion gated channels control synaptic transmission between neurons. Epigenetics occurs when changes in the environment and behavior impact one’s DNA sequence. Epigenetics changes occur throughout the life span.
Response to Asia
The discussion post by Asia is very insightful and educative. As stated in the post, antagonist and agonist medications work in opposite ways. While one allows for certain actions, the other one tries to inhibit such responses. Understanding such basics is important to every health worker. Regarding the G-protein coupled receptors, they are useful in enhancing signal transmission in the cell membrane. On the other hand, ion gated channels help control synaptic transmission between neurons. The insight about epigenetics is satisfactory as addressed by Asia. Epigenetics begin before one is born. It continues to occur as people age. All the information provided in the discussion post is relevant and reliable, therefore, I agree with the answers provided by Asia.
Nguyen, A. (2018). Agonists and antagonists. https://lx.uts.edu.au/pharmacology/article/agonists-and-antagonists/
Lee, E. S., Vidal, C., & Findling, R. L. (2018). A Focused Review on the Treatment of Pediatric Patients with Atypical Antipsychotics. Journal of Child & Adolescent Psychopharmacology, 28(9), 582–605. https://doi.org/10.1089/cap.2018.0037
Peedicayil, J., In Grayson, D. R., & In Avramopoulos, D. (2021). Epigenetics in psychiatry. Academic Press.
Yudin, Y., & Rohacs, T. (2019). The G‐protein‐biased agents PZM21 and TRV130 are partial agonists of μ‐opioid receptor‐mediated signaling to ion channels. British journal of pharmacology, 176(17), 3110-3125. https://doi.org/10.1111/bph.14702