Respond to two colleagues 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. Main Post Agonist-to-Antagonist Spectrum of Action Molecules that bind to receptors are referred to as ligands (“Pharmacology Corner: Agonists and Antagonists”, 2015). Ligands are capable of binding to receptor sites and producing a biological response. These ligands are called agonists (“Pharmacology Corner”, 2015). The opposite effect can also take place. Ligands that block the responses of agonists are referred to as antagonists. An agonist binds to a receptor site, activates it, and causes a signal to be transmitted. This reaction is called a biological response (“Pharmacology Corner,” 2015). Conversely, an antagonist also binds to a receptor site, but blocks binding from any other agonists, thus preventing any biological response (“Pharmacology Corner”, 2015). Several types of agonists exist on a spectrum. Their place on this spectrum is measured by comparing their binding ability versus endogenous agonists already present in the body (“Pharmacology Corner”, 2015). Endogenous agonists are present in the body. Super agonists produce a greater biological response than endogenous agonists. Next on the spectrum are full agonists, which mimic the efficacy of the endogenous agonists. Next in line are the partial agonists, which only exert a partial biological response as their name suggests (“Pharmacology Corner”, 2015). The next group of agonists are the inverse agonists which act in two ways. They inhibit the normal receptor site activity, and exert the opposite pharmacological activity at the same time. Last on the spectrum are the irreversible agonists which permanently bind and activate the receptor site. Since this action is permanent, it only occurs once and results in the destruction of the receptor (“Pharmacology Corner”, 2015). G-Couple Proteins and Ion-Gated Channels Receptors called G-protein-coupled receptors (GPCRs) facilitate most physiological responses to neurotransmitters, hormones, and stimulants in the environment. As such, they have great potential to be targeted for the treatment of many diseases (Rosenbaum, Rasmussen, & Kobilka, 2009). GPCRs comprise the largest group of membrane proteins and are responsible for most cellular responses to neurotransmitters and hormones. They also contribute significantly to the human senses of vision, smell, and taste (Rosenbaum et al., 2009). GPCRs are made up of seven alpha-helical segments separated by intracellular and extracellular looped areas (Rosenbaum et al., 2009). The fastest and least complex of signal pathways occur with signals whose receptors are gated ion channels (Ahern & Rajagopal, 2019). Gated ion channels consist of many transmembrane proteins that create a hole, or a channel in the cell membrane. Each ion channel will allow the passage of a certain ionic species depending on its type. They are called gated because the passage is controlled by a gate which must be opened to allow the ions to pass (Ahern & Rajagopal, 2019). The opening of the gates is controlled by the binding of a signal to the receptor. This causes the immediate passage of millions of ions across the membrane (Ahern & Rajagopal, 2019). Epigenetics in Pharmacologic Action Epigenetics refers to genetic information that exists beyond the information contained solely in the individual’s genetic code (Stefanska & MacEwan, 2015). Human diseases can be caused by a single base genetic mutation. Scientists have made great strides in unraveling the genetic code, recording the first complete sequence of the human genome in 2001 (Stafanska & MacEwan, 2015). These advances have prompted scientists to think beyond treating illness through drugs activating receptors, but in a more global fashion. Epigenetic mechanisms are systems that are able to alter or cancel genetic activation, and are present in all genes (Stefanska & MacEwan, 2015). These mechanisms may affect more than one gene or group of proteins, and can even regulate large groups of genes. Cancer is one disease in which the understanding of epigenetics can be key to more effective treatment (Stefanska & MacEwan, 2015). Specific Client Example One example of a common client issue is the opioid epidemic. Naloxone (Narcan) is an opioid antagonist that binds to the opioid receptors in the patient’s brain, reversing or blocking the effects of the opioid (“Opioid overdose reversal with naloxone (Narcan, Evzio)”, 2018). This is essential to save the patient’s life who has accidentally or intentionally overdosed on opiate drugs. Naloxone can quickly restore a normal breathing pattern in a person whose respirations have slowed or stopped as a result of the opiate (“Opioid overdose reversal”, 2018). Naloxone (Narcan) can be administered using a pre-filled delivery device that is sprayed into the nostril while the patient lies supine. This device is simple to use and requires no assembly (“Opioid overdose reversal”, 2018). References Ahern, K., & Rajagopal, I. (2019). Ligand-gated Ion Channel Receptors. Retrieved from https://bio.libretexts.org/Bookshelves/Biochemistry/Book:_Biochemistry_Free_and_Easy_(Ahern_and_Rajagopal)/08:_Signaling/8.2:_Ligand- gated_Ion_Channel_Receptors.Opioid overdose reversal with naloxone (Narcan, Evzio). (2018). Retrieved from drugabuse.gov.Pharmacology Corner: Agonists and Antagonists. (2015). Retrieved from aegislabs.com/agonistsRosenbaum, D.M., Rasmussen, S.G.F., & Kobilka, B.K. (2009). The structure and function of G-protein-coupled receptors. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967846/#_ffn_sectitle.Stefanska, B., & MacEwan, D.J. (2015). Epigenetics and pharmacology. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4439868/#_ffn_sectitle. Reply Quote Email Author
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