Week 2 Discussion

Agonist-to-Antagonist Spectrum of Action of Psychopharmacologic Agents

An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist, and an inverse agonist causes an action opposite to that of the agonist (Kowalski, Dowben, & Keltner, 2017).  Psychopharmacologic agents can have three different types of agonist-to-antagonist actions.  The first type of agent is a full agonist.  With a full agonist, dosages can be increased eventually to completely block the receptor sites and produce an increasing effect (Institute for Effective Diagnosis, 2014).  With a full antagonist agent, the same is true, but with the end result being the increasing blockage of an effect.  In between a full agonist and a full antagonist are partial agonists, which will only produce a partial effect, regardless of the drug dosage (Institute for Effective Diagnosis, 2014).

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

G protein-coupled receptors consist of a single polypeptide that is threaded over the membrane, while ion channels are composed of pores that open and close upon ligand binding (Alexander et al., 2019).

G protein-coupled receptors interact with a variety of proteins for an intracellular response, while ion channels regulate the flow of ions. Also, G-couple proteins are the largest class of membrane proteins in the human genome and are the target for the majority of drugs in clinical usage, although only a minority of these receptors are exploited therapeutically (Alexander et al., 2019).  Their primary function, like ion-gated channels, is to transduce extracellular stimuli into intracellular signals (Alexander et al., 2019).  GCPRs do this differently than ion-gated channels.

Many important psychopharmacological drugs target ion channels. Ion channels are key targets of many psychotropic drugs. This is not surprising, because these targets are key regulators of chemical neurotransmission and the signal transduction cascade. Ligand-gated ion channels (LGICs) are integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane. Ion flux is passive and driven by the electrochemical gradient for the permeant ions. The channels are opened, or gated, by the binding of a neurotransmitter to an orthostatic site(s) that triggers a conformational change that results in the conducting state. Modulation of gating can occur by the binding of endogenous, or exogenous, modulators to allosteric sites (Purves, Augustine, & Fitzpatrick, 2015).

                                              The Role of Epigenetics in Pharmacologic Action

 Drug absorption, distribution, metabolism and excretion  are critical processes that must be understood for the development of safe drugs. These processes are mediated by drug-metabolizing enzymes and transporters that are expressed in various tissues, including the small intestine, liver, and kidney. These processes can limit or enhance the systemic and target organ exposure to xenobiotics. In particular, drug-metabolizing enzymes such as cytochrome P450 (P450) isoforms govern the metabolic elimination of drugs and membrane transporters such as ATP-binding cassette (ABC) transporters can affect drug absorption, distribution, and excretion processes. Thus the interplay of drug-metabolizing enzymes and transporters may determine the pharmacokinetic properties of a drug such as bioavailability, volume of distribution, and half-life, and understanding the regulation of drug-metabolizing enzymes and transporters is necessary for the prediction of consequent pharmacological and toxicological effects (Stefanska & MacEwan, 2015).

                                              How This Information May Impact the Way I Prescribe Medications to Clients

     It is important for me as an advanced nurse practitioner to understand how chemical neurotransmitter affects my patients when prescribing medications. Medications for the mind have a powerful effect. Important treatments center on altering the chemical balance of the brain. It is crucial to understand the actions of drugs on the brain, to grasp the impact of diseases upon the central nervous system, and to interpret the behavioral consequences of psychiatric medicines.  Writing a prescription to treat a mental health disorder is easy, but it may not always be the safest or most effective route for patients symptoms (Kowalski, Dowben, & Keltner, 2017).

 

An example in which a psychiatric mental health nurse practitioner must be aware of the medication’s action is when prescribing Selective serotonin reuptake inhibitors (SSRIs) to the elderly.  SSRIs are widely prescribed to treat depression. Although these drugs presumably have the same mechanism of action, they vary in several clinically important ways, including how long they remain in the body and the extent to which they interfere with the metabolism of other medications. The elderly, as a group, tend to take many medications on a daily basis. Because the aging body eliminates drugs less efficiently and is more sensitive to pharmacotherapeutic side effects, adverse reactions resulting from drug-drug interactions are not only more common but also potentially more severe and longer-lasting in older patients. Choosing an agent with a low propensity for drug interactions is therefore especially important for the management of late-life depression. All drug combinations should be carefully monitored among elderly patients who are frail or medically ill.

References

Alexander, S., Christopoulos, A., Davenport, A. P., Kelly, E., Marthie, A., Peters, J. A., … Davies, J. A. (2019). G protein-coupled receptors. IUPHAR/BPS Guide to Pharmacology, 176(S1), S21-S141.https://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=694

Institute for Effective Diagnosis. (2014). Full agonists, partial agonists, antagonists. Retrieved from http://effectivediagnosis.org/full-agonists-partial-agonists-antagonists/

Kowalski, P. C., Dowben, J. S., & Keltner, N. L. (2017). My dad can beat your dad: Agonists, antagonists, partial agonists, and inverse agonists. Perspectives in Psychiatric Care, 53(2), 76-79. http://dx.doi.org/ 10.1111/PPC.12208

Purves, D., Augustine, G. J., & Fitzpatrick, D. (2015). Neuroscience (2 ed.). Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK10855/

http://dx.doi.org/10.1111/bph.13136  

Stefanska, B., & MacEwan, D. J. (2015). Epigenetics and pharmacology. British Journal of Pharmacology, 172(11), 2701-2704.

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!

Neuroscience Overview

 

 Psychopharmacological treatment effects come from the alteration of neurotransmitter binding in the synapse through several types of actions. Agonism is when neurotransmitters are made more available to the postsynaptic cell. This can be done by stimulating synthesis or release of the transmitter, and also by blocking the reuptake or breakdown (Caprodon & Roggman, 2016). Antagonism is when a drug binds to a receptor but does not cause any action. The outcome of this is that other agents cannot bind to those same receptors and activate the associated response (Salahudeen & Nishtala, 2017). Partial agonists bind to and stimulate action on some but not all available receptors. In inverse agonism, a drug binds to the receiving cell but causes the opposite of the cell’s intended effect (Salahudeen & Nishtala, 2017). 

     Once there is an activation of a receptor at the postsynaptic neuron, communication can occur in various ways. Two examples are ion gated channels and G-protein coupled receptors (GPCRs) (Caprodon & Roggman, 2016). The activation of ion gated channels can alter the electrical potential of a neuron at the level of the cell membrane and cause relatively quick effects. In contrast, activated GPCRs have more complicated effects that alter the cell via a series of sequential steps and take longer for their intended effect (Caprodon & Roggman, 2016).

 Epigenetics in psychiatry is the study of how identifiable biological/genetic predispositions of the individual interact with environmental experiences to cause mental health symptom expression (Caprodon & Roggman, 2016). While pharmacological treatment can be more challenging as a result of these interactions, it can also be used to balance out or correct dysfunctional neuronal pathways (Caprodon & Roggman, 2016). 

 

Clinical Implications

 

 Understanding the above drug functionality can allow for more precision when prescribing psychopharmacological agents. Medications can be utilized to increase or decrease the actions of cells and stimulate or block certain responses based on a patient’s specific symptoms. This knowledge is also essential when moderating the side effects of medication interventions (Delacretaz et al., 2019). An example of how this all comes together would be for a person being treated with antipsychotic medications. Some intended effects come from antagonism of D2 receptors (Caprodon & Roggman, 2016), however, this same action in the hypothalamus often produces increased appetite, weight gain, and long-term metabolic changes (Delacretaz et al., 2019). Some people have also been found to have a genetic variation that increases their risk of this particular negative outcome if they are prescribed antipsychotic medications (Delacretaz et al., 2019). Prescribers with this knowledge must be cautious in prescribing and vigilant for weight gain early in treatment. 

 

References

 

Camprodon, J. A., & Roffman, J. L. (2016). Psychiatric neuroscience: Incorporating pathophysiology into clinical case formulation. Massachusetts General Hospital Psychopharmacology and Neurotherapeutics. Elsevier.

 

Delacrétaz, A., Glatard, A., Dubath, C., Gholam-Rezaee, M., Sanchez-Mut, J. V., Gräff, J., von Gunten, A., Conus, P., & Eap, C. B. (2019). Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients. Clinical Epigenetics, 11(1), 1.

 

Salahudeen, M. S., & Nishtala, P. S. (2017). An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice. Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society, 25(2), 165–175. https://doi.org/10.1016/j.jsps.2016.07.002