NURS 6630 week 2 Discussion: Foundational Neuroscience

Agonist-To-Antagonist Spectrum of Action of Psychopharmacologic Agents

In medicine, drugs can act either as agonist or antagonist. As an agonist, drugs bind to target receptor, changing its activity to produce a response. Agonist medications activates the full receptor in the brain while a partial agonist produces a sub-maximal response when in contact with a receptor (Berg & Clarke, 2018). On the other hand, antagonist, binds to target receptors but produces no response, hence preventing agonist from occupying the receptor. Inverse agonists lower the activity of a receptor replicating the opposite effect of an agonist (Berg & Clarke, 2018).

Actions of g Couple Proteins and Ion Gated Channels.

GPCR, found in eukaryotes, comprise of the largest known class of plasma membrane receptors. They act as principal targets for most of prescribed drugs and binds to many different types of ligands (Weir, 2019. They convert signals from extracellular ligands to signals in intracellular relay proteins, and when bonded with nucleotide guanosine triphosphate (GTP), hydrolyze it to form GDP. Ion gated channels are proteins that regulates the flow of selected ions passively across the plasma membrane. As a gated channel, they only open under specific conditions like for specific ligands (ligand-gated ion channels), or for a specific electrical potential (voltage-gated channels).

Role of Epigenetics and Pharmacologic Action

Epigenetics describes thestudy of genetic information, changes and modifications coded in gene expression. Its study has led to the understanding of many disease processes and the manufacturing of drugs to counteract such diseases (Stefanska & MacEwan, 2015). Diseases such as cancers and neurodegenerative disorders, are often associated with epigenetic alteration, can be generated by a single base mutation. With genome testing /screening, pharmacological treatments are personalized with precise disease management and prediction (Rasool et al., 2015)

Pharmacogenomics and The Impact on Mental Health Patients

Pharmacogenomics help clinicians personalized treatment to patients based on their individual’s genetic pattern and response to drugs (Butler, 2018). In the psychiatry environment, knowing the genetic make-up of patients and how they respond to specific medications can help providers predict the tolerability and metabolic impact to patients. For instance, individuals with genetic variant with CYP2C9 gene alleles with reduced enzyme activity will require a reduced dose of most medications compared to patients with a normal CYP2C9. Lithium toxicity can easily occur in patients with reduced or no enzyme activity as they metabolize medications slower leading to build of the drug in the system. The reverse can occur with patients with duplications/multiplications of the wild-type allele (Butler, 2018), metabolizes medications faster and may require a higher dose of medications.

References

Berg, K. A., & Clarke, W. P. (2018). Making sense of pharmacology: Inverse Agonism and functional selectivity. International Journal of Neuropsychopharmacology21(10), 962-977. https://doi.org/10.1093/ijnp/pyy071

Butler, M. (2018). Pharmacogenetics and psychiatric care: A review and commentary. JOURNAL OF MENTAL HEALTH AND CLINICAL PSYCHOLOGY2(2), 17-24. https://doi.org/10.29245/2578-2959/2018/2.1120

Rasool, M., Malik, A., Naseer, M. I., Manan, A., Ansari, S. A., Begum, I., Qazi, M. H., Pushparaj, P. N., Abuzenadah, A. M., Al-Qahtani, M. H., Kamal, M. A., & Gan, S. H. (2015). The role of epigenetics in personalized medicine: Challenges and opportunities. BMC Medical Genomics8(S1). https://doi.org/10.1186/1755-8794-8-s1-s5

Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British Journal of Pharmacology172(11), 2701-2704. https://doi.org/10.1111/bph.13136

Weir, C. J. (2019). Ion channels, receptors, agonists and antagonists. Anaesthesia & Intensive Care Medicine21(1), 62-68. https://doi.org/10.1016/j.mpaic.2019.10.022

 

responses

I appreciate your example of how genetic variations can contribute to impaired metabolism of psychotropic medications in critical ways. Especially with medications such as Lithium that have such a narrow therapeutic window.  Kronfol et al. (2020) describe changes to the p450 system that can occur with aging due to reduced DNA methylation of CYP2E1 genes in mice. As prescribers, it is also important to understand how metabolism of medications changes with aging and why this occurs. Hopefully the ability to genetically test for specific variations will continue to expand.

An interesting study in mice by Kabir et al. (2017) linked alterations in genes, to alterations in specific calcium channel pathways, that than disrupt  signaling of dopamine in ventral tegmental areas (VTA). This connection may shed some light on the pathology around behaviors such as cocaine abuse and depression in humans which are associated with dysfunction in dopamine activity in the VTA (Kabir et al., 2017). The authors found that medications to correct the calcium channel dysfunction resulted in changes in the mice behavior. This study shows both the complexity of the  neuropsychiatric underpinnings of behavior and sheds light into possible ways that medications can be used to alleviate illness.

Thank you for a thought provoking post.

References

Kabir, Z.D., Martínez-Rivera, A. & Rajadhyaksha, A.M. (2017). From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms. Neurotherapeutics 14, 588–613 (2017). https://doi-org.ezp.waldenulibrary.org/10.1007/s13311-017-0532-0

Kronfol, M.M., Jahr, F.M., Dozmorov, M.G. (2020). DNA methylation and histone acetylation changes to cytochrome P450 2E1 regulation in normal aging and impact on rates of drug metabolism in the liver. GeroScience 42, 819–832 (2020). https://doi-org.ezp.waldenulibrary.org/10.1007/s11357-020-00181-5

 

The use of medications and how they exert their pharmacological process can be said to be a biological/scientific process that if not fully understood can cause more harm for the patient that it is intended for. Hence, it is important to always educate one’s self, even acquiring the license to practice.

There are different principles that needs to be put into consideration before a provider prescribes medications for patients. One of these pharmacological actions is the agonist-to-antagonist spectrum of action. The agonist-to-antagonist spectrum of action pharmacological agent describes how some medications are agonists, thereby causing a direct binding effect to the receptor sites to cause the desired action, while there are some that are antagonist, which would just bind to the receptor sites without eliciting any response or produce an undesired/unexpected action (Bolin et al., 2016).

Another action that should be considered is the actions of g couple proteins and ion gated channels. The g couple proteins and ion gated channels are neurotransmitter receptors that binds to postsynaptic sites from the presynaptic sites to get a response (Alexander et al., 2019). In understanding how they differ, Ion gated channels would elicit a rapid response within/across the cell membrane (Alexander et al., 2019), while g-couple protein activate a response at a slower rate outside of the membrane.

Finally, epigenetics would put into consideration a person’s DNA without alteration to develop a pharmacological treatment. Using epigenetics as you have mentioned would be very beneficial in the treatment of inheritable diseases like cancer (Fu & Imani, 2018). Hence, constant education is needed so has to be current on new research about these types of medications that would help people with the same DNA.

All these actions alongside side effects and comorbidities have to be considered in order to develop a pharmacological treatment that would be effective in treating patients. Thanks for an education post.

 

 

 

 

References

Alexander, S. P. H., Mathie, A., Peters, J. A., Veale, E. L., Striessnig, J., Kelly, E., Armstrong, J.

F., Faccenda, E., Harding, S. D., Pawson, A. J., Sharman, J. L., Southan, C., & Davies, J. A. (2019). THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology, 176 Suppl 1, S142–S228. https://doi-org.ezp.waldenulibrary.org/10.1111/bph.14749

Bolin, B. L., Alcorn III, J. L., Reynolds, A. R., Lile, J. A., & Rush, C. R. (2016). Human drug

discrimination: A primer and methodological review. Experimental and clinical             psychopharmacology, 24(4), 214.

Fu, J., & Imani, S. (2018). Epigenetics in cancer. Science Press. https://search-ebscohost-

com.ezp.waldenulibrary.org/login.aspx?direct=true&db=cat06423a&AN=wal.EBC5684596&site=eds-live&scope=site.

 

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!

 

Discussion Week 2
On the cellar level the ligand gated ion channel an agonist can bind to a receptor and cause the same phycological response as a natural ligand.  An antagonist binds to the receptor and do not cause a phycological response but block that receptor preventing the natural ligand from going into that receptor. For example, most antipsychotic drugs act as dopamine receptor antagonist.  Blocking reuptake of dopamine (Howland, 2016).  Some antipsychotic drugs also act as inverse agonist at the serotonin receptor causing an opposite effect. An inverse agonist produces a opposite effect of the agonist.

In regard to the efficacy of a drug treatments, the NP has to provide a very good patient assessment to provide the patient with an accurate diagnosis.  The NP having knowledge, can correctly prescribe the drug (agonist, antagonist or reverse agonist) that will act on the on the targeted neurotransmitter to produce the desired effect in the patient.

Ion gated channels pull and bond to the agonist changing the protein.  G coupled proteins are proteins used by the cell to convert intracellular signals into responses (Zhao, Deng, Jiang, Oing, 2016).

Epigenetics is modifications in gene expression that is controlled by various fundamental epigenetic mechanisms leading to various physical and psychiatric diseases.  As a result, traditional treatment may often prove ineffective with these patients because these mechanisms regulate cellular and gene expression, just to name a few (Rasool, et al., 2015).

As practitioner, my patient assessment may also include an education and discussion concerning pharmacogenomics.  Particularly, if the patient comes to me after having been on various medication treatments that were unsuccessfully.   Knowledge of a medications action is important for example; treating a patient with Bipolar I that is exhibiting depression symptoms but also reported that he maxed out his credit card last week on video games. With the knowledge that an antidepressant should not be given because the action of the antidepressant would cause the patient to go into mania.

 

References

 

Berg, K., A., Clarke, W., P. (2018).  Making Sense of Pharmacology: Inverse Agonism and

Functional Selectivity, International Journal of Neuropsychopharmacology, Volume 21, Issue 10, October 2018, Pages 962–977, https://doi.org/10.1093/ijnp/pyy071

 

Howland, R. H. (2016). Pimavanserin: An inverse agonist antipsychotic drug. Journal of

Psychosocial Nursing & Mental Health Services, 54(6), 21-24. doi:http://dx.doi.org.ezp.waldenulibrary.org/10.3928/02793695-20160523-01

 

Rasool, M., Malik, A., Naseer, M. I., Manan, A., Ansari, S., Begum, I., Qazi, M. H., Pushparaj,

P., Abuzenadah, A. M., Al-Qahtani, M. H., Kamal, M. A., & Gan, S. (2015). The role of epigenetics in personalized medicine: challenges and opportunities. BMC medical genomics8 Suppl 1(Suppl 1), S5. https://doi.org/10.1186/1755-8794-8-S1-S5

 

Zhao, J., Deng, Y., Jiang, Z., Oing, H. (2016). G Protein-Coupled Receptors (GPCRs) in

Alzheimer’s Disease; A Focus om BACE1 Related GPCRs. Frontier in Aging Neuroscience.,  https://doi.org/10.3389/fnagi.2016.00058

 

Response

Interesting post you have here, i like how you describe all the terms.

Agonist-to-antagonist spectrum of action is crucial in the human body when discussing pharmacology. It expresses the action of the two antagonize each other. An agonist produces action and the antagonist opposes the action which means the two spectrum operates in opposite direction. This describes the mechanism of drug interaction in the human body.

There are agonist, partial agonist, inverse agonist and antagonist. The inverse agonist is the drug that bind to a receptor as an agonist but block or reduces the effect of the agonist. The partial agonist will bind a receptor partially not like the full agonist (Stahl, 2013). An agonist drug is a drug that bind and active a receptor. An antagonist at the other hand is the drug that bind a receptor but will not activate the receptor. The antagonist will decrease the action of the receptor from binding to another agonist.

G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases. They are also fascinating molecules from the perspective of membrane-protein structure and biology G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases. They are also fascinating molecules from the perspective of membrane-protein structure and biology. The g-couple proteins and ion gated channel are receptor which are useful in their different area and can interact by binding to ligand and cause a chemical response. This action is mostly triggered by the presence of neurotransmitters (Stahl, 2013)

G- couple protein also known as G-protein-coupled receptors (GPCRS) are receptors that live on cell membrane and able to bind with ligands to cause a change. These GPCRS receptors are responsible for most physiological processes such as light, odour, hormones, and pain. G-protein can be used to predict poor prognosis in some cancer, and some of these protein function as a potential biomarker for some diagnosis (Zhu, Huang & Jin, 2018).

Ion gated channel allow the regulation of movement of ions thorough the cell membrane. The ion gated channel are transmembrane protein complexes that conduct the flow of ion channel in response to binding of a neurotransmitter.

 

Stahl, S. M. (2013). Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.). New York. NY: Cambridge University Press

 

Zhu, X., Huang, G., & Jin, P. (2018). Clinicopathological and prognostic significance of aberrant G Protein-Couple Receptor 110 (GPR110) expression in gastric cancer. Pathology- Research and Practice. https://doi-org.ezp.waldenulibrary.org/10.1016/j.prp.2018.12.004

 

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