Discussion: Foundational Neuroscience

Discussion: Foundational Neuroscience

Discussion one Foundational neuroscience
COLLAPSE

Foundational Neuroscience

Antagonist and agonist are terms that describe how ions and Psycopharmicaological agents on the receptors in the brain. Agonists have and intrinsic efficacy ‘the ability to increase the activity of the receptor’ (Berg & Clarke, 2018). Discussion: Foundational Neuroscience Chemicals That are agonist Travel into the post synaptic cleft binding to receptors allowing for a neuron to activate. Glutamate is an excitatory ion that travels into the post synaptic cleft and asked rapidly by opening channels for sodium and calcium causing postsynaptic depolarization (Camorodon & Roffman, 2016). Antagonist work in an opposite way to the excitatory ion or agonist. Antagonists are ions that have a zero-affinity binding to the target receptor without producing a response (Berg & Clarke, 2018). The antagonist such as N-methyl-D-aspartate (NMDA) act as a glutamate inhibitor (Liu et al., 2019). Inhibiting NMDA inhibiting the postsynaptic receptor for glutamate, prevents glutamate’s excitatory actions on the postsynaptic neuron. G Coupled proteins work and a slow way, using second messenger systems involving sequential multienzyme cascades. Second messenger systems convert receptor signals altering the function of multiple target organs (Camorodon & Roffman, 2016). There are seven membrane spanning G-protein coupled receptors and their embedded within the cell membrane, once activated by second messenger systems the intercellular processes are triggered. The rapid neurotransmitter systems are the ion channels, as opposed to using secondary messengers, ions rapidly alter membrane potential neuronal activity (Camorodon & Roffman, 2016). Epigenetic play an important role in the way people develop and may suffer from mental illnesses. Childhood mistreatment results in a variation in epigenetic processes, such as DNA math myelination resulting in increased suicide and depression scores (Cecil et al., 2016). Taking into consideration that a person’s environment can affect their genes puts people with high stressors and child abuse at high risk for developing mental illnesses. Taking into consideration that patients may have problems such as increased neuronal activity due to receptors being blocked, receptors receiving too much of a ion, prevention of transport to the postsynaptic nerve there are many considerations to treating these patients. For example, serotonin is released into the synaptic cleft via VMAT vessels if the patient has a genetic disposition due to birth or epigentic abuse the patient may not be releasing enough serotonin or having too much of an up take in the postsynaptic left, can be prescribed serotonin transporters (Camorodon & Roffman, 2016) Discussion: Foundational Neuroscience. Serotonin transporters prolong serotonin’s action allowing for these effects of serotonin released to work longer, therefore treating the patient’s depression by allowing seritonion to stay longer.

Reference

Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The international journal of neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

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.

Cecil, C. A., Smith, R. G., Walton, E., Mill, J., McCrory, E. J., & Viding, E. (2016). Epigenetic signatures of childhood abuse and neglect: Implications for psychiatric vulnerability. J Psychiatr Res, 83, 184-194. https://doi.org/10.1016/j.jpsychires.2016.09.010

Liu, J., Chang, L., Song, Y., Li, H., & Wu, Y. (2019). The Role of NMDA Receptors in Alzheimer’s Disease. Frontiers in neuroscience, 13, 43. https://doi.org/10.3389/fnins.2019.00043

REPLY QUOTE EMAIL AUTHOR

19 days ago
Discussion: Foundational NeuroscienceAFOLAKE OYINLOLA 
RE: Discussion one Foundational neuroscience
COLLAPSE

Good job Corey!

In support of your post, I agree that Epigenetic play an important role in the way people develop and may suffer from mental illnesses Discussion: Foundational Neuroscience. Childhood mistreatment results in a variation in epigenetic processes, such as DNA math myelination resulting in increased suicide and depression scores. According to Moosavi and Motevalizadeh Ardekani (2016), said that in the last decade, this subject has attracted many interests, especially in complicated disorders such as behavior plasticity, memory, cancer, autoimmune disease, and addiction as well as neurodegenerative and psychological disorders. Apart from the childhood mistreatment that can result in various epigenetic processes, modifications of epigenetic often happen during an organism’s lifetime; however, these changes can be transferred to the next generation if they occur in germ cells. DNA methylation status has high stability and serves as a special epigenetic memory of specific cells throughout all periods in the cell cycle. DNA methylation, as a very impressive epigenetic agent, could influence the development of mutations, DNA faultless and durability, gene expressions, and chromatin modifications.

Drugs are one of the key treatment modalities in psychiatry, understanding their pharmacology is critical for all people involved in the treatment of psychiatric disorders. Drugs are generally small synthetic molecules. These act in several different ways; agonist; antagonist; dose-response curve; partial agonist; receptors.  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 autoreceptors may have. Antagonists block the effects of endogenous neurotransmitters and oppose normal synaptic transmission. 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; hence they are sometimes called agonist–antagonists (Nutt and Lingford-Hughes, 2007).

References

Nutt, D., & Lingford-Hughes, A. (2007). Key concepts in psychopharmacology. Retrieved from  http://www.med.monash.edu.au/assets/docs/scs/psychiatry/psychopharmacology/nutt-pharmacodynamics-2007.pdf

Moosavi, A., & Motevalizadeh Ardekani, A. (2016). Role of Epigenetics in Biology and Human Diseases. Iran Biomed J.246-58. doi: 10.22045/ibj.2016.01.

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceCarline Timothee 
RE: Discussion one Foundational neuroscience
COLLAPSE

Hello Miller.

I enjoyed reading your discussion. Indeed agonists and antagonists have opposing actions when they bind to receptors. Agonists are drugs that bind to receptors, emitting a similar response as the intended chemical or receptor (Nguyen, 2018). Antagonists are drugs that bind to receptors on the primary or another site, stopping the receptor from producing any response. One stimulates the intended response while the other blocks or slows the intended response (Azhagiya Singam et al., 2019). For instance, Atropine is an antagonist competitive of the receptor muscarinic acetylcholine receptors. It inhibits some parasympathetic system functions, including heart rate, salivation, and pupil dilation. It is often used to treat bradycardia by slowing the heart rate and lowering the amount of saliva produced during specific surgeries. I liked your illustration of the G-coupled proteins. They are cell surface receptors that respond to multiple external stimuli. The binding of a molecule to the G coupled proteins leads to G protein activation that triggers the production of any amount of second messengers. Second messenger systems directly connect signaling molecules, including cytokines, growth factors, and neurotransmitters and gene expression changes responsible for nerve cell differentiation, proliferation, and maturation (Newton et al., 2016). Indeed epigenetic involves behaviors and the environment that can cause alterations that impact how genes work, impacting growth. Epigenetic changes are often reversible and do not alter the DNA sequence but can affect how the body reads a DNA sequence. I agree that mental health issues can affect epigenetics because epigenetic marks can be affected by environmental stressors such as traumatic life events that change their status. The change in status contributes to mental health disorders development. Thank you for the informative post.

References

Azhagiya Singam, E. R., Tachachartvanich, P., La Merrill, M. A., Smith, M. T., & Durkin, K. A. (2019). Structural Dynamics of Agonist and Antagonist Binding to the Androgen Receptor. The journal of physical chemistry. B, 123(36), 7657–7666. https://doi.org/10.1021/acs.jpcb.9b05654

Newton, A. C., Bootman, M. D., & Scott, J. D. (2016). Second Messengers. Cold Spring Harbor perspectives in biology, 8(8), a005926. https://doi.org/10.1101/cshperspect.a005926 Discussion: Foundational Neuroscience

Nguyen, A. (2018, May). Agonists and antagonists. https://lx.uts.edu.au/pharmacology/article/agonists-and-antagonists/

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceFidelia Chukwuto 
RE: Week 2 Discussion Response 2
COLLAPSE

Corey,

Thanks for the detailed educative post. I agree that epigenetics plays a vital role in the way people develop. Drug-metabolizing enzyme genes may be influenced by epigenetics. The term “epigenetic regulation” refers to heritable variables that affect genomic changes. Epigenetics examines how the actions and environment might alter how the gene functions. While genetic alterations are irreversible, epigenetic modifications may be reversed. It may also be used as a treatment for medical issues. A change in the expression of drug-metabolizing enzyme genes may impact drug metabolism (Stefanska & MacEwan, 2015). It has recently been discovered that heritable reasons with genomic modifications that do not need changes in DNA sequence, such as epigenetic control, affect drug-metabolizing enzyme genes (John & Rougeulle, 2018).

Studying the proper drug and dose and its mechanism of action is critical for mental health nursing, particularly in terms of improving patients’ health. Benzodiazepines, such as alprazolam, clonazepam, diazepam, lorazepam, and midazolam, are typical anxiolytics prescribed to mental health patients (Versed). Anxiety is a common side effect of many drugs. As with alcohol, the long-term use of benzodiazepines may impact the brain comparable to that of alcohol and is associated with various mental health issues, including depression and anxiety and post-traumatic stress disorder (PTSD). Discussion: Foundational Neuroscience This might lead to memory loss because long-term treatment takes in erroneous information.

Reference

John, R. M., & Rougeulle, C. (2018). Developmental epigenetics: Phenotype and the flexible epigenome. Frontiers in Cell and Developmental Biology, 6.

https://doi.org/10.3389/fcell.2018.00130

Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British journal of

   pharmacology, 172(11), 2701–2704. https://doi.org/10.1111/bph.13136

REPLY QUOTE EMAIL AUTHOR

17 days ago
Discussion: Foundational NeuroscienceSean Haggerty 
RE: Discussion one Foundational neuroscience
COLLAPSE

Week 2 – Response 2 – S. Haggerty

Corey, thank you for your informative post. Environmental alterations to epigenetics scratch the surface for the etiology of psychiatric disorders. Schizophrenia is considered the most poorly understood disorder. Genetics and hereditary evidence explain the link to schizophrenia; however, firm conclusions are inconclusive loci. Individualized genetic risk factors are unidentifiable. Epigenetics bridges the gap between significant inheritance and the lack of genetic makers. Phenotype alterations have no impact on the DNA genetic sequencing, which has no lasting permeant effect. However, these cross-generation lines impact the predisposed risks. Altered histone acetylation is derived from maternal behavior, increasing DNA methylation (Föcking et al., 2019).

Treatment of psychiatric disorders consists of therapeutics based around homogenous molecules, effecting similar pathways, and set dosing strategies. Epigenetics can confirm predictive drug responses in given psychiatric disorders. Thus, guiding treatment rather than subjectively selecting drugs typically takes weeks for evaluation. They deliver a more specific individualized treatment (Zhou et al., 2021).

References

Föcking, M., Doyle, B., Munawar, N., Dillon, E., Cotter, D., & Cagney, G. (2019). Epigenetic factors in schizophrenia: Mechanisms and experimental approaches. Molecular Neuropsychiatry, 5(1), 6–12. https://doi.org/10.1159/000495063

Zhou, J., Li, M., Wang, X., He, Y., Xia, Y., Sweeney, J. A., Kopp, R. F., Liu, C., & Chen, C. (2021). Drug response-related dna methylation changes in schizophrenia, bipolar disorder, and major depressive disorder. Frontiers in Neuroscience, 15. https://doi.org/10.3389/fnins.2021.674273

WK 2 discussion
COLLAPSE
  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.

Agonists are drugs with both affinity and intrinsic efficacy, which means they have both, the ability to attach to a target receptor and modify activity, that generates a response.  Antagonist only have ability to bind to a target receptor Discussion: Foundational Neuroscience. When the concentration of the agonist expands the increasing the concentration of the agonist, the chance that an agonist will inhibit the occupancy increases. A full agonist usually produces the highest response and a partial agonist produces a less than optimal response. When treatment with an inverse agonist treatment is prolonged, in can result in an increased response to an agonist at the same receptor.  The inverse agonist becomes a barrier, blocking other agonists form the receptor. Chronic use of inverse agonists can cause drug insensitivity (Berg & Clarke, 2018).

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

G-protein-coupled receptors help facilitate the biological response of hormones and neurotransmitters. Agonists help regulate receptor-G protein communication by increasing their association rate. (Sungkaworn, Jobin, Burnecki, Weron, Lohse & Calebiro, 2017). The processing of neuronal information greatly depends on the ion channels. Ion channels have the capability to aid or prevent transmembrane ion flux (Phillips, Nigam & Johnson, 2020).

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

Recent research has indicated there is a correlation between Genetic and epigenetic backgrounds when discussing the variation and drug response in Schizophrenia. According to Swathy and Banerjee (2017) there is a correlation between epigenetics, genetic and environmental factors, which contribute to the complexity of the disease.  There seems to be a correlation between altered miRNA expression or epimutations in the form of aberrant DNA methylation and histone that cause schizophrenia drug response. Research shows that antipsychotic drugs can also change the epigentic stability and induce pharmacoepigenomic effects (Swathy & Banerjee, 2017).

  1. 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.

The information will change my approach to how I prescribe medications by individualizing treatment for each patient with consideration of how the medication will impact the patient on a long- term basis. I will also consider family history, drug interactions and genetic testing, as well as current health status and the need for continued monitoring during medication use. All medications may not be effective for every patient. Psychiatric Mental Health Nurse Practitioner may need to trial several different medications before the treatment is effective.

References

Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The international journal of neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

Phillips MB, Nigam A, Johnson JW. Interplay between Gating and Block of Ligand-Gated Ion Channels. Brain Sci. 2020 Dec 1;10(12):928. doi: 10.3390/brainsci10120928. PMID: 33271923; PMCID: PMC7760600.

Sungkaworn, T., Jobin, M., Burnecki, K., Weron, A., Lohse, M. J., & Calebiro, D. (2017). Single-molecule imaging reveals receptor–G protein interactions at cell surface hot spots. Nature, 550(7677), 543-547,547A-2A. doi:http://dx.doi.org/10.1038/nature24264

Swathy, B., & Banerjee, M. (2017). Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy. Epigenomics, 9(5), 721-721–736. doi:http://dx.doi.org/10.2217/epi-2016-0106

REPLY QUOTE EMAIL AUTHOR

19 days ago
Discussion: Foundational NeuroscienceKristine Umiten 
RE: WK 2 discussion
COLLAPSE

Hello Nicole,

Your discussion paper was precise and straight to the point. I liked how you made schizophrenia an example of epigenetics. According to (Lockwood et al., 2022), “there are several recognized risk factors for psychosis, including trauma history and substance use”. Chemical substances happen when there is substance abuse, while chemical imbalances of the brain occur when a person goes through trauma. With schizophrenia that is what normally happens. Genes or genetics may play a role in having schizophrenia, however, there are triggers to causing the symptoms of mania and instability in thinking clearly.

As a psychiatric mental health nurse practitioner, prescribing medications will be a huge part in maintaining balance of mental illness with life’s challenges. The day-to-day interaction with different types of people, especially at work, can be hard with someone who, for example, has schizophrenia or bipolar disorder. Therefore, as practitioners, we have to evaluate and treat these patients with medications, therapy, and/or approve them for disability, depending on the severity of their mental capacity to work and live the best normal life as possible. (Nguyen et al., 2019), states that “opioid use disorder (OUD) has become an increasingly grave public health concern, especially in the United States where approximately 80% of the global opioid supply is consumed”. As providers who can prescribe, we have to be very careful of all medications especially opioids given to patients who have mental disorders such as schizophrenia. It can be detrimental to their health and can be fatal as well.

​

References

Lockwood, L., Miller, B., & Youssef, N. A. (2022). Epigenetics and first-episode psychosis: A systematic review. Psychiatry Research, 307, 114325. https://doi.org/10.1016/j.psychres.2021.114325

Nguyen, T., Andraka-Christou, B., Simon, K., & Bradford, W. (2019). Provider-directed marketing may increase prescribing of medications for opioid use disorder. Journal of Substance Abuse Treatment, 104, 104–115. https://doi.org/10.1016/j.jsat.2019.06.014 Discussion: Foundational Neuroscience

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceStephanie Schrag 
RE: WK 2 discussion.Schrag.Response1
COLLAPSE

Nichole,

Thank you for your wonderful post this week.  Your last couple statements about needing to trial several medications before finding one that would work best for the patient is something I have seen often in the field.  It is often necessary but also must be done carefully to avoid over medicating patients.  While this is a concern throughout the mental health field, it is especially of concern for pediatric and older patients.  For both age groups there is a gap in knowledge and research.  For older patients providers often must take research based on younger patients and try to adapt it for older patients due to the lack of specific research for this age group and can lead to issues with poly-pharmacy and side effects (Tournier, et al., 2019).

As for pediatric patients, providers find themselves with similar issues to those providers caring for elderly patients.  Similarly, pediatric mental health providers must often use research and drug information aimed at adult patients when trying to prescribe for their pediatric population.  This can lead to poly-pharmacy concerns, adverse drug interactions and other issues as providers use off label drugs to treat their pediatric patients (Bogler, et al., 2019).

References

Bogler, O., Roth, D., Feinstein, J., Strzelecki, M., Seto, W., & Cohen, E. (2019). Choosing Medications Wisely: Is it Time to Address Paediatric Polypharmacy? Paediatrics & Child Health, 303-305.

Tournier, I., Hanon, C., Vasseur-Bacle, S., Deloyer, J., Moraitou, M., Tzanakis, E., . . . Fondharmant, L. (2019). Mental Health Care Networks in Older Adults: A Narrative Review. Journal Plus Education, 179-187.

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceCorey Miller 
RE: WK 2 discussion
COLLAPSE

Response 3

Hello, Nicole

The agonist antagonist relationship between ions at the receptor sites helps drive the psychopharmacological properties of drugs in people. Drugs like naloxone and opioids both have high affinity to the mu opioid receptors in the brain (Chimbar & Moleta, 2018). The agonist antagonist properties of these drugs give the lifesaving benefits. G couple proteins travel slow due to the need to summon secondary messenger system to transport the signal down a neuron (Camprodon & Roffman, 2016). The ion gated channels are a faster transport system due to the direct signaling pathways. Epigenetics are important to due to changes that occur to the methylation of neurons and changes in the DNA resulting in PTSD and depression (Sheerin et al., 2017). Patients who underwent child abuse had been shown to have the Methylation changes and DNA changes that predisposed them to PTSD and Depression. A thorough history can help providers identify areas of depressions, PTSD and other issues that arise from environmental or epigenetic influences. The  patients history may not show any  familial history of depression or PTSD but history obtained of trauma and abuse may give an indication to psychiatric illness Discussion: Foundational Neuroscience.

Reference

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

Chimbar, L., & Moleta, Y. (2018). Naloxone Effectiveness: A Systematic Review. J Addict Nurs, 29(3), 167-171. https://doi.org/10.1097/jan.0000000000000230

Sheerin, C. M., Lind, M. J., Bountress, K. E., Nugent, N. R., & Amstadter, A. B. (2017, 2017/04/01/). The genetics and epigenetics of PTSD: overview, recent advances, and future directions. Current Opinion in Psychology, 14, 5-11. https://doi.org/https://doi.org/10.1016/j.copsyc.2016.09.003

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceJessica Bell 
RE: WK 2 discussion
COLLAPSE

Approaches to Treatment: Week 2 Reply 2

Nichole,

You have some good information in your post this week. However, there could have been more information included. A worthy note regarding inverse agonist, is that they bind to receptor cells just as agonists do, but that they produce an opposite response of the agonist, and both agonists and inverse agonists can be stopped by an antagonist (Berg & Clarke, 2018). Another interesting fact is that when epigenetics lead to the turning off of genes, certain medications that interact with that genes receptors and expressions can be rendered ineffective for that patients illness (Rasool et al., 2015). Therefore, it is clear that the study and use of epigenetics can assist in being able to prescribe more patient specific medications. I do like that you mentioned that sometimes it requires several medication trials to find the right medication for some patients. Hopefully with the advancement of epigenetics and medications, the amount of medication trials a patient undergoes can be significantly decreased. Good job and good luck!

Kind Regards,

Jessica

Reference

Berg, K. A., & Clarke, W. P. (2018). Making Sense of Pharmacology: Inverse Agonism and Functional Selectivity. The international journal of neuropsychopharmacology, 21(10), 962–977. https://doi.org/10.1093/ijnp/pyy071

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 genomics, 8 Suppl 1(Suppl 1), S5. https://doi.org/10.1186/1755-8794-8-S1-S5

REPLY QUOTE EMAIL AUTHOR

17 days ago
Discussion: Foundational NeuroscienceSteven St. Onge WALDEN INSTRUCTOR MANAGER 
RE: WK 2 discussion
COLLAPSE

Hi Nichole,

Great summary here.  Can you share why we would combine a partial agonist such as Buprenorphine with an antagonist such as Naloxone into a single medication such as Suboxone?  As you are probably aware, oral naloxone has nearly 0% bioavailability when given orally.  If none of the drug is absorbed, why use it in the combination? Discussion: Foundational Neuroscience

Thanks!

REPLY QUOTE EMAIL AUTHOR

Hide 1 reply

17 days ago
Discussion: Foundational NeuroscienceNICHOLE HOLLAND 
RE: WK 2 discussion
COLLAPSE

Dr. St. Onge,

Thank you for your feedback. There is potential for abuse when Buprenorphine is taken alone. Naloxone is not absorbed orally so when it is

combined with buprenorphine it decreases the chance of abuse (Kumar, Viswanath Saadabadi, 2021). As an opioid antagonist naloxone is an opioid

antagonist and has no impact on sublingual use of buprenorphine, but it helps block intravenous or intranasal abuse of the drug (Velander, 2018).

References

Kumar R, Viswanath O, Saadabadi A. Buprenorphine. [Updated 2021 Aug 6]. In: StatPearls [Internet]. Treasure Island (FL): Stat Pearls Publishing;

2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459126/

Velander J. R. (2018). Suboxone: Rationale, Science, Misconceptions. The Ochsner journal, 18(1), 23–29.

REPLY QUOTE EMAIL AUTHOR
Week 2 discussion
COLLAPSE
  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.

The agonist spectrum is when psychotropics facilitate neurotransmitters to stimulate receptors either fully or partially (Stern, 2016). This is like dimming the lights in a room they could be turned on fully which makes the room brighter (Stahl, 2013). In a partial agonist effect, it dims the light in the room. The agonist spectrum is directly related to the G-Protein-linked receptors (Stahl, 2013). Agonists are thought to produce a change in G- protein-linked receptors which lead to full receptor activation and full signal transduction down the axon. Without an agonist, the same effect may be occurring at the site but at a very low transduction rate. The same effect could be true in areas where there is a high concentration of certain receptors (Stahl, 2013). This is like the higher concentration of dopamine receptors in the frontal lobe of the brain. The two ways drugs act to stimulate G-protein-linked receptors with full agonist action. Several drugs bind directly to the receptor site and produce the same full agonist effect.  Some psychotropics can indirectly produce a full agonistic effect by blocking the inactivation mechanisms of the neurotransmitter.

Regarding antagonist, they provide an inhibitory effect on neurotransmitter sites. Antagonist also produce a change in the G- Protein- linked receptors that causes no change in the signal transduction. So, Antagonist can be neutral and produce no changes at the site (Stern, 2016). So, in some areas antagonistic effects are desirable and in other areas of the brain the effects are not desirable. This is like the dopamine in the mesolimbic pathway.  If there is too much dopamine in the mesolimbic pathway it stimulates positive psychotic symptoms. I like to think of positive symptoms as symptoms that extenuate the human experience like hallucinations and delusions.

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

The actions of G coupled proteins and ion gated channels assist in the transmission of electrical signals that are then transitioned to chemical signals. Once an electrical signal stimulates the presynaptic axon terminal it causes the release of the neurotransmitter that is stored in that axon (Sadock et al., 2015). The major electrical channels are calcium and sodium channels. So, the electrical impulses open the calcium and sodium channels respectively. The channels open by the electrical impulses change the ionic charge across the membrane of the axon (Stahl, 2013). The action potential moves down the neuron until it reaches the presynaptic nerve terminal this causes the release of calcium in the terminal. This causes the release of the chemical contents into the synapse. This is how the electrical stimulus turns into a chemical process.

In fact, neurotransmitter receptors facilitate triggering either a rapid or slow effector system. Rapid effect neurotransmitter receptors are either ion channels or coupled to ion channels. The excitatory neurotransmitters like glutamate and NMDA are ion channels. G- protein receptors work via a slower second messenger system. This means that they usually include multiple processes to get the desired effect.  Se3cond messenger systems convert receptor signals into a coordinated set of cellular effects by altering the function of multiple target proteins (Stern, 2016). This influences a wide range of proteins. Ion channels that control neural firing, synaptic proteins that regulate synaptic efficacy, and cytoskeletal elements that determine cellular morphology.

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

Epigenetics runs parallel to genetics but, very different. Genetics is the DNA code for what a cell can transcribe into specific cell types of RNA or translate into specific proteins. There are 20,000 genes in the human genome and not all genes are expressed this is due to epigenetics (Stahl, 2013). Epigenetics is a parallel system that determines whether a gene is made into its specific RNA and protein, or if it’s ignored or silenced. Epigenetics is influenced by environmental factors and or genetic susceptibility (Stern, 2016). This is where the debate environmental factors versus the genetic factors in the development of mental disorders. In practice, In seeing patient family members if one medication works for the mother or father then the medication has a higher efficacy in the child (Sadock et al., 2015).

  1. 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.

In a client with bipolar disorder, the balance between inducing mania, depression, and, euthymia is very difficult. Starting an SSRI on a patient with bipolar disorder can cause mania via the second messenger system by providing too much serotonin in the frontal lobe which can cause an increase in dopamine in the mesolimbic system (Stahl, 2013).  Mania is expressed as insomnia, elevated mood (Euphoria), and can be expressed as rage in some patients. Prescribing a medication that can have an antagonistic effect on dopamine like Vraylar, Seroquel, Zyprexa, or Geodon can prevent mania. Treating with an antidepressant in Bipolar depression is controversial but, if you have antimanic medications like anticonvulsants and antipsychotics is very important.

References

Stern, T. A. (2016). Massachusetts General Hospital: Psychopharmacology and neurotherapeutics. Elsevier.

Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4 edition). Cambridge University Press.

Sadock, B. J., Sadock, V. A., & Ruiz, P. (2015). Kaplan & Sadock’s synopsis of psychiatry: Behavioral sciences/clinical psychiatry (Eleventh edition). Wolters Kluwer.

REPLY QUOTE EMAIL AUTHOR

19 days ago
Discussion: Foundational NeuroscienceSteven St. Onge WALDEN INSTRUCTOR MANAGER 
RE: Week 2 discussion
COLLAPSE

Hi Antonio,

Nice job with your post.  Can you please share with your peers some examples of antagonists and partial agonists?  Thanks!

REPLY QUOTE EMAIL AUTHOR

Hide 1 reply

19 days ago
Discussion: Foundational NeuroscienceAntonio Ingram 
RE: Week 2 discussion
COLLAPSE

Hello, Mr. St. Onge

There are three different opioid receptors they are Mu, Kappa, and delta. The receptor that is most relevant in opioid abuse is the MU receptor (Arcangelo et al., 2017). The MU receptor is where the opioids exert most of their desired effects like euphoria, analgesia, and addictive effects. Opioids can interact with receptors in different ways by an agonist, antagonist, and partial agonist(Arcangelo et al., 2017).

Agonists activate receptors in the brain. Agonists bind to the target receptors and turn them on. Full MU agonist activates mu receptors. Opioids with the greatest abuse potential are the full agonist, for example, methadone, and oxycodone (Stahl, 2013). Discussion: Foundational Neuroscience Partial agonist possesses some properties of both antagonist and full agonist. Partial agonists bind to receptor sites and activate them but, not to the effect of a full agonist.  In partial agonist medications like buprenorphine, they don’t produce an increasing effect over a certain level.

Stahl, S. M. (2013). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Applications (4 edition). Cambridge University Press.

Arcangelo, V. P., Peterson, A. M., Wilbur, V., & Reinhold, J. A. (Eds.). (2017). Pharmacotherapeutics for advanced practice: A practical approach (Fourth edition). Wolters Kluwer.

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeurosciencePamela Tachang 
RE: Week 2 discussion
COLLAPSE

Antonio, Epigenetics, as you point out, can be influenced by environmental factors or even hereditary helplessness (Stern, 2016). Muscle cells can turn “on” qualities that make proteins important for their work and turn “off” qualities that are important for a nerve cell’s work by using epigenetics. While you’re alive, your epigenetics are always shifting (Stern, Fava, Wilens, and Rosenbaum, 2016). A quality statement can depend on a variety of factors, like the climate, but aggregates depend on the qualities that code for them. As a branch of study, epigenetics is concerned with examining how natural factors influence aggregate progress through affecting quality articulation (Langdon et al, 2021). DNA methylation, a topic central to epigenetics, can be influenced by a wide range of environmental factors, including development chemicals. These elements can be hereditary and natural, and they have a direct impact on how we express our feelings.

References

Langdon, R. J., Yousefi, P., Relton, C. L., & Suderman, M. J. (2021). Epigenetic modelling of former, current and never smokers. Clinical Epigenetics, 13(1), 206. https://doi.org/10.1186/s13148-021-01191-6

Stern, T. A., Fava, M., Wilens, T. E., & Rosenbaum, J. F. (2016). Psychopharmacology and Neurotherapeutics. London: Elsevier.

REPLY QUOTE EMAIL AUTHOR

18 days ago
Discussion: Foundational NeuroscienceAFOLAKE OYINLOLA 
RE: Week 2 discussion
COLLAPSE

Hello Antonio!

The agonist spectrum is when psychotropics facilitate neurotransmitters to stimulate receptors either fully or partially is supported by me and your idea of using a dimming or fully turning on lights in a room can make the room brighter to explain this gives me a clearer eye-opener to it. According to Mailman and Murthy (2010), stated that functional selectivity is the term that describes drugs that cause markedly different signaling through a single receptor (e.g., a full agonist at one pathway and antagonist at a second) and this impacts the understanding of the mechanism of action of some drugs and has relevance to drug discovery. Mania defines bipolar disorder, but depression is the major challenge of treatment because they are more frequent, longer, with a major prognostic impact in terms of disability and suicide. Antidepressants are the treatment of choice for patients with depression, but not bipolar disorder. It has been traditionally accepted that antidepressants are effective, but they were inducing a significant risk of destabilization of bipolar disorder, because of the transitions to mania and rapid cycling (Courtet et al., 2010) Discussion: Foundational Neuroscience. To better treat depression in bipolar disorder, a psychiatrist must have guidelines that caution that antidepressants should be used conservatively in the treatment of bipolar disorder to prevent further risk.

Reference

Courtet, P., Samalin, L., Olié, E. (2011). Les antidépresseurs dans le trouble bipolaire [Antidepressants in bipolar disorder]. Encephale. 37 Suppl 3:S196-202. French. doi: 10.1016/S0013-7006(11)70053-7. PMID: 22212875.

Mailman, R. B., & Murthy, V. (2010). Third generation antipsychotic drugs: partial agonism or receptor functional selectivity?. Current pharmaceutical design, 16(5), 488–501. https://doi.org/10.2174/138161210790361461