- 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.
Agonist agents are chemicals that stimulate a reaction by binding to a target site made explicitly for that chemical. If the site or chemical is incorrect, the two cannot bind and will not elicit another reaction. An antagonist is also a chemical that binds to a specific location, but instead of producing a reaction, it blocks an agonist chemical that would then elicit a reaction. Both antagonist and agonist can create an excitatory or inhibitory response depending on the desired effect. Partial agonists induce less than the full response when they occupy the receptor. An example of a partial agonist would be buprenorphine, which binds to the opioid receptor site but only elicits a partial effect (Whelan, P. J., et al.,2012). The benefits of buprenorphine partial effects, versus. Methadone that creates a full effect does not produce the same euphoria and respiratory effect as methadone. This partial effect can help with misuse, side effects, and the eventual withdrawal of the medication. An inverse agonist will cause the exact opposite reaction as the usual chemical messenger for that site (Camprodon, J. A., et al., 2016). Beta-blockers and antihistamines are examples of inverse agonists. Beta-blockers, like carvedilol, not only block an increase in heart rate and blood pressure, they can also lower heart rate and blood pressure (Khilnani, G., et al., 2011).
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Compare and contrast the actions of g couple proteins and ion gated channels.
Ion gated channels are the primary neurotransmitter site locations on the pre and post-synaptic sites that open ion channels to elicit the next neuron to receive a signal. A Gated ion channel creates a rapid membrane potential creating fast neuron activity (Camprodon, J. A., et al., 2016). G-protein-coupled receptors (GPCRs) are a slower secondary neurotransmitter site, triggers a multi-enzyme cascade. When they receive a specific neurotransmitter, the GPCRs, located on plasma membranes, release Alpha, Beta, or Gamma subunits into the cell membrane to be converted into new chemical reactions or signals that either create or inhibit a response (Camprodon, J. A., et al., 2016).
3. Explain how the role of epigenetics may contribute to pharmacologic action.
Epigenetic differences have been shown to change a pharmacological reaction that an individual may have versus someone with a different gene expression. DNA methylation is an excellent example of how these differences can occur. The methylation of DNA is responsible for multiple processes. Gene expression, imprinting, chromatin organization, and X-chromosome inactivation are examples (Rasool, M., et al., 2018). Methylation can affect how medications work on cells by decreasing or increasing their effectiveness and metabolizing too quickly or slowly. DNA tests are available for patients to determine their responses to drugs.
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 a psychiatric mental health nurse practitioner must be aware of the medication’s action.
A good example of why a mental health nurse practitioner needs to understand the Mechanism of Action (MOA) of medications is with multiple drugs that can create steven Johnson syndrome. Steven Johnson’s syndrome is a medical emergency that can be caused by too much serotonin. Two examples are Lamictal and selective serotonin reuptake inhibitors (SSRIs). SSRIs block the ion channels that generally pull back the extra serotonin between the pre and post synapse of two neurons. By blocking the reuptake ion channel on the pre-synaptic site, there is more serotonin available for the post-synaptic neuron to receive serotonin through their ion channels. Lamictal, another medication used for an anti-seizure and commonly bipolar disease, is also believed to increase serotonin. Specifically, Lamictal has an increased chance to cause SJS with patients who have recently started taking the medication (Frey et al., 2017). The risk for SJS can also be increased using another medicine that raises serotonin levels. Knowing the mechanism of action and the results of the MOA can help nurse practitioners and their patients stay safe.
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.
Frey, N., Jossi, J., Bodmer, M., Bircher, A., Jick, S., Meier, C., & Spoendlin, J. (2017). The Epidemiology of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in the UK. Journal of Investigative Dermatology. Retrieved 9 September 2021, from https://www.sciencedirect.com/science/article/pii/S0022202X17301768.
Khilnani, G., & Khilnani, A. K. (2011). Inverse agonism and its therapeutic significance. Indian journal of pharmacology, 43(5), 492–501. https://doi.org/10.4103/0253-7613.84947.
Rasool, M., Malik, A., Naseer, M.I. et al. The role of epigenetics in personalized medicine: challenges and opportunities. BMC Med Genomics 8, S5 (2015). https://doi.org/10.1186/1755-8794-8-S1-S5
Whelan, P. J., & Remski, K. (2012). Buprenorphine vs methadone treatment: A review of evidence in both developed and developing worlds. Journal of neurosciences in rural practice, 3(1), 45–50. https://doi.org/10.4103/0976-3147.91934
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.
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Tinesha Rios
Dec 5, 2022 Dec 5 at 11:43am
1. Different drugs have different effects on receptors. An agonist binds to a receptor and
produces a full effect, mimicking the neurotransmitter that usually binds to that receptor.
An antagonist binds to receptors and blocks activation from other agonist producing no
effect. Examples of a agonist is hydrocodone and a antagonist is Narcan. A partial agonist
binds to a receptor and produces a partial effect not a full effect for example tramadol vs
hydrocodone. An inverse agonist binds to a receptor and produces the opposite effects as
the agonist for example antihistamines. These concepts are very important regarding the
efficacy of psychopharmacology treatments, knowing these concepts the mental health
nurse practitioner can prescribe medication appropriately and provide better explanation
to patients regarding medications.
2. Both g proteins and ion gate channels are postsynaptic receptors located on the dendrites,
however G proteins can be located elsewhere on the neurons and can activate ion-gate
channels. G proteins have a slower effect than ion gate channels. Ion gate channels can
open or close in response to membrane changes
3. Epigenetics may contribute to pharmacologic action by the way a person’s body reacts to
a certain drug. Also, it can help mental health providers treat and understand certain
mental health issues. “Current mental health epigenetic research supports the adverse
psychosocial experiences are associated with mental heath disorders such as
schizophrenia, anxiety, depression and addiction. There are also positive epigenetics
associations with counseling interventions, including cognitive behavioral therapy
mindfulness diet and exercise” (David E. Jones, Feb 26, 2021).
4. All the mechanisms mentioned earlier will impact the way I prescribe medications in
mental health. For example, for example a patient that develops addiction to opiate drugs
may benefit from a partial agonist in efforts to ween of opiates. Also having knowledge
of ones epigenetics can guide me into providing positive treatment options like
counseling interventions and medications for patients with mental health issues in an
effort to increase the efficacy of psychopharmacology treatments.
Allthough I have been always amazed on how we have used medicines, especially psychotropic meds to induce agonist or antagonist effects to treat multiple psychiatric medications, what really amazes me is how we can use and benefit from epigenetics to treat and control these disoders, and may be prevent this from being passed from a parent to his/her own offsprings (Stahl, 2021). Mountain evidence suggests that epigenetic mechanisms, which induce stable and lasting changes in gene expression in response to environmental events and behavioral experiences, may play a role in the processess that contribute to the pathophysiology of psychiatric disorders (Mahgoub & Monteggia, 2013).
Epigenetics is a process that can change gene expression, without alterations of the DNA sequence and promote stable changes in the Chromatin structure (Stahl, 2021; Maghoub & Monteggia, 2013; Stern, et. al., 2016). A good application of epigenetics in psychiatric disoderders are the following examples:
- The modification of brain derived neurotrophic factor (BDNF) as a potential therapeutic target in antidepressant action as well as in mediating antidepressant response (Mahgoub & Monteggia, 2013)
- The involvement of BDNF to addiction. Acute administration of cocaine induces release of BDNF in the ventral tegmented area (reward system)
- Involvement of histone H4 deacetylases in cocaine addiction. Histone play a crucial role in regulating gene activity by inducing modifications in chromatin structure (Mahgoub & Monteggia, 2013)
- The involvement and modification of DNA methylation within GABA in schizophrenia. There was a downward regulation of several genes expressed within the GABA neurons (Chen, et. al, as cited in Mahgoub & Monteggia, 2013)
Much emphasis has been placed right now on histone modifications and DNA methylation for using pharmacologic inhibitors in treating multiple disorders. Both histone acetylation and DNA methylation can induce lasting and stable changes in gene expression, and therefore have been implicated in adaptive behaviors and neuronal changes that accompany many psychiatric disorders.
NURS 6630C Discussion Foundational Neuroscience Walden University References:
Mahgoub, M., & Monteggia, L. (2013). Epigenetics and Psychiatry. https://ncbi.nlm.nih.gov/pmc/articles/PMC3805856
Stahl, S. (2021). Stahl’s Essential Psychopharmacology: Neuroscientific Basis and Practical Approach. 5th ed. Cambridge
Stern, T., et. al (2016). Massachusetts General Hospital Psychopharmacology and Neurotherapeutics. 1st ed. Elsevier
