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 generates a required or full response to the intended chemical and receptor in the brain but an antagonist is a drug that binds to the receptor and hinders the receptor from producing a response. This is important to enable drugs to produce the required effect that is individualized for each patient. Agonists cause an action and antagonist opposes the action. Agonists are drugs with both affinity and inherent efficacy. In other words, agonists attach to the target receptor and can modify the receptor activity to generate a response. Antagonists on the other hand have affinity but no inherent efficacy; hence they can stick to the target receptor and do not generate any response. Antagonist generally minimizes the probability of occupancy by an agonist by virtue of occupying a portion of the receptor population.
Agonists can have various inherent efficacies and thus can be described as full or partial agonists based on the drug framework (Berg & Clarke 2018). A full agonist according to Berg & Clarke study, generates the full response a system is made for while a partial agonist generates a submaximal response. Also, an Inverse agonist is a drug that binds to the same receptor as an agonist but induces an opposite pharmacological response to that of the agonist. This means that its effect on the target cell is inconsistent with that of the agonist.
For example, the pharmacological management for the recovery from opioid use disorder includes the opioid agonist or antagonist therapy. Full agonist opioids activate the opioid receptors in the brain giving rise to the full opioid effect while the antagonist blocks opioids by attaching to the opioid receptors and causing no opioid effect ( US Department of health and Human services, n.d).
Compare and contrast the actions of g couple proteins and ion gated channels
Appropriate neurotransmission needs precise interplay of so many neurotransmitter receptors at pre- and post-synaptic compartments. Transmission at most mammalian synapses requires neurotransmitter activation of two receptor subtypes, G protein-coupled receptors (GPCRs) and ligand-gated ion channels (Johnson & Lovinger, 2016). G protein–coupled receptors (GPCRs) mediate most cellular responses to external stimuli, such as light, odors, hormones, and growth factors. They interfere with the sense of vision, smell, taste, and pain and are involved in cell recognition and communication. Ion channels aid ion influx across the membrane and is the foundation of electrical excitation of neurons ( Li etal., 2014). Ion channel receptors are essential in the nervous system, allowing for signaling, fast and direct conversion of a chemical neurotransmitter message to an electrical current.
While the ligand-gated ion channels can moderate fast synaptic responses, the G protein-coupled receptors (GPCRs) have slower neuromodulatory actions. The GPCRs constitute a large portion of neurotransmitter receptors needed in virtually all phases of the nervous system function and are also targets for majority of pharmacotherapeutic agents. Ion channel -linked receptors open a channel in the membrane enabling the passage of ions while G-protein-linked receptors activates a membrane protein known as G-protein, which helps to interact with an ion channel or an enzyme in the membrane.
Explain how the role of epigenetics may contribute to pharmacologic action
Epigenetics is the study of how an individual’s behaviors and environment can result in changes that affect the functioning of genes (Centers for Disease Control and Prevention, 2020). Epigenetic changes can be reversed., they do not change the DNA sequence, but rather can change the way the body reads a DNA sequence. Epigenetic regulation of gene activity is shown to be involved in the evolution of diseases such as cancer and neurodegenerative disorders like Alzheimer’s. Recent classification of drugs regulates epigenetic mechanisms to counteract disease found in human beings (Stefanska & MacEwan, 2015). Personalized medicines are given to patients after collecting genomic information such as the levels of RNA, proteins and metabolites that could aid medical decision making.
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 impact this information will have on my ability to prescribe medications is raising my concern for patient’s safety and need for critical thinking. This will create the awareness that each prescription should be individualized based on each patient’s presenting symptoms, overall goal of treatment and long-term effect of the medication. Knowing the pharmacokinetics, pharmacodynamics is essential in determining which drug should be prescribed for each patient. Pharmacogenomics provides understanding of the actual drug for each patient at the exact concentration and time. With the concern of multiple drug responses, factors including nutrition, age, body weight, sex, genetic behavior, infections, co-medications, and organ function are relevant to be considered with treatment of a disease and the ideal medication that should be prescribed.
For example, in the management of Alzheimer’s disease, using donepezil (Acetylcholinesterase inhibitors), it is important to educate the patient and family that gastrointestinal problems could be side effects from the medication. This could aid adherence to the medication with reduced abrupt discontinuation. Also, donepezil can lead to side effects such as seizures, bradycardia, and heart block, therefore reviewing each patient’s medical history and determining the best medication that is patient centered is essential to promote health and achieve positive outcomes from medications. Donepezil and other cholinomimetic agents can cause seizures; therefore healthcare professionals should be cautious in prescribing this medication in individuals with a history of seizure disorder ( Kumar & Sharma, 2020).
Centers for Disease Control and Prevention. (2020). Genomics & Precision Health. https://www.cdc.gov/genomics/disease/epigenetics.htm
Kumar, A., Sharma, S. (2020). Donepezil. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK513257/
Li, S., Wong, A., Liu, F. (2014). Ligand-gated ion channel interacting proteins and their role in neuroprotection. Frontiers in Cellular Neuroscience, 8 (125). doi: 10.3389/fncel.2014.00125. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4023026/
Stefanska, B., MacEwan, D. (2015). Epigenetics and pharmacology. British Journal of Pharmacology, 172(11), 2701-2704. doi: 10.1111/bph.13136. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/
US Department of health and Human services. (n.d). Pharmacological treatment. Indian Health Service. https://www.ihs.gov/opioids/recovery/pharmatreatment/