Details:

The first step of the EBP process is to develop a question from the nursing practice problem of interest.

Select a practice problem of interest to use as the focus of your research.

Start with the patient and identify the clinical problems or issues that arise from clinical care.

Following the PICOT format, write a PICOT statement in your selected practice problem area of interest, which is applicable to your proposed capstone project.

The PICOT statement will provide a framework for your capstone project (the project students must complete during their final course in the RN-BSN program of study).

Conduct a literature search to locate research articles focused on your selected practice problem of interest. This literature search should include both quantitative and qualitative peer-reviewed research articles to support your practice problem.

Select six peer-reviewed research articles which will be utilized through the next 5 weeks as reference sources. Be sure that some of the articles use qualitative research and that some use quantitative research. Create a reference list in which the six articles are listed. Beneath each reference include the article’s abstract. The completed assignment should have a title page and a reference list with abstracts.

Suggestions for locating qualitative and quantitative research articles from credible sources:

1. Use a library database such as CINAHL Complete for your search.
2. Using the advanced search page check the box beside “Research Article” in the “Limit Your Results” section.
3. When setting up the search you can type your topic in the top box, then add quantitative or qualitative as a search term in one of the lower boxes. Research articles often are described as qualitative or quantitative.

To narrow/broaden your search, remove the words qualitative and quantitative and include words that narrow or broaden your main topic. For example: Diabetes and pediatric and dialysis. To determine what research design was used, review the abstract and the methods section of the article. The author will provide a description of data collection using qualitative or quantitative methods.

Prepare this assignment according to the guidelines found in the APA Style Guide, located in the Student Success Center. An abstract is not required.

This assignment uses a rubric. Please review the rubric prior to beginning the assignment to become familiar with the expectations for successful completion.

Comment 1

A colleague recently was diagnosed with breast cancer. The American Cancer Society (ACS) has an easy website to navigate for information. There is a search bar for questions that may be posed. One can begin with cancer from A to Z. Breast cancer has many headers such as about, risk and prevention, early diagnosis and prevention, understanding the diagnosis, treating, reconstruction surgery, living as a survivor, and non-cancerous breast conditions. A patient can even find easy reading for those with breast cancer. They have downloadable information under pdfs with similar headings. Related topics, news and stories, and more resources are available. Their site has a handy tool bar and toll-free phone number for those who prefer to use that resource. At the end of their page is another way to approach subjects. For example, to find information about rides to treatment one can just navigate to the bottom of the page, rather than using the search bar. Reach to Recovery is a phenomenal resource, allowing you to speak with a person that has survived breast cancer (Cancer Caregiver Support, n.d.).

Factors that are associated with cancer risk are tobacco use and secondhand smoke, inactivity, obesity, nutrition and diet, alcohol, ultraviolet light, and cancer-associated infections such as HPV. Six infections are listed. I live in Connecticut and it is estimated that there will be 21,240 new cases diagnosed and 6,590 deaths this year. In my state, there is a partnership with Center for Disease Control (CDC). State specific cancer issues are identified and a plan has been developed with goals and strategies for improvement. For example, at St. Francis Hospital, Men’s Health Institute has the goal of providing free services to the underinsured or uninsured and to address the disparities affecting African-Americans. I feel that research and medication and treatment trials will make an enormous impact in the future. The ACS is always trying to raise not only awareness but funding for further research. I think that statistics will change to percentages rather than number of people in diagnosis and mortality because we are living longer. I believe there will be some cures that will decrease certain kinds of cancers in the future as well as people being more aware.

ACS conducts Palliative Care Research. It has come to mean pain relief with treatments and management of side effects; it is not only specific to terminal cancers. According to the website, the ACS is funding more than $26 million for survivorship and quality of life research. Included is the improvement of lives of children with cancer and studies of survivors. The research has the goal of relieving cancer pain and managing side effects. I would imagine a person newly diagnosed would be most worried about prognosis and pain. This research is tantamount to cancer patients (American Cancer Society, 2018).

Comment 2

It was fascinating to learn of “liquid biopsy” as an emerging technology. I learned from the National Cancer Institute that liquid biopsy is “A test done on a sample of blood to look for cancer cells from a tumor that are circulating in the blood or for pieces of DNA from tumor cells that are in the blood. A liquid biopsy may be used to help find cancer at an early stage. It may also be used to help plan treatment or to find out how well treatment is working or if cancer has come back” (NCI, 2018). It is technically known as rapid plasma genotyping, and has a plausable rate of accuracy, according to researches from the study at Dana Farber Cancer Institute, where the study took place. According to the website from Dana Farber Cancer Institute, they are working on not only this technology, but target cancer therapy technology, where they pinpoint the origin of cancer, and create a tumor profile. 

comment1

Diabetes mellitus is characterized by glucose intolerance, chronic hyperglycemia, and disturbances of carbohydrate, protein, and fat metabolism (Huether & Mccance, 2016). Generally, a diagnosis of diabetes mellitus is based on elevated plasma glucose concentrations and measurement of glycosylated hemoglobin (A1C). Genetic susceptibility in combination with other environmental risk factors such as obesity place someone at higher risk for DM II. Obesity contributes to metabolic syndrome, altered adipokines, increased fatty acids, inflammation, and hyperinsulinemia, increasing insulin resistance further (Huether & Mccance, 2016).

Acute complications such as diabetic ketoacidosis and hyperosmolar hyperglycemic nonketotic syndrome are life threatening (in the short term), but not as common as the long-term life-threatening chronic complications of diabetes mellitus. Most long-term complications related to hyperglycemia are sequelae of hyperglycemia on the micro and macro vasculature.

Identify a long-term complication of the vasculature (micro or macro) related to diabetes, the clinical manifestations, and other health concerns they may contribute to.

comment2

According to (Lewis, Bucher, Heitkemper, & Harding, 2017), angiopathy is the leading cause of end organ disease secondary to chronic hyperglycemia. There are several theories as to why these complications exist that include toxic byproducts of high glucose metabolism such as sorbitol, the collection of glucose molecules in the basement membranes of capillaries, and a derangement of red blood cell function (Lewis, Bucher, Heitkemper, & Harding, 2017).  The microvascular complications are related to the thickening of the capillary membranes that result in micro occlusions. The micro occlusions lead to small herniations with swelling that lead to ischemia and tissue damage most commonly to tissues like the retina and the glomeruli of the kidneys (Lewis, Bucher, Heitkemper, & Harding, 2017).

  

Answer the following questions and write a paper (3 pages) about the problem of lack of knowledge regarding the differences of effect between first-in-class imported medications and me-too drugs.

· Introduction

· Why we need to fix this problem?

· How to study this problem?

· What is the Significant of the problem?

· What are the consequences of solving this problem?

· Theoretical Background of Me-too drugs

· Conclusion

TO DO A REPLY COMMENT TO POST 1 and 2 WITH TWO APA REFERENCES EACH ABOVE 2013.

POST 1

An agonist to antagonist to inverse agonist spectrum

     Psychoactive medications vary in how they affect activity at the synapse.  Agonists increase the neurotransmitter effect while antagonists block the neurotransmitter effect (Barron, 2018). There are gradients of how medications act creating a spectrum of influence on receptors.  Agonists can occur naturally as neurotransmitters that stimulate receptors.  Some medications also act as agonists to stimulate receptors, but medications can stimulate receptors to varying degrees (Stahl, 2013).  This creates the spectrum of how medications variably affect neurotransmitters.  The medications that stimulate receptors but do so less than full agonists are partial agonists or stabilizers.  Antagonists have no activity of their own except to block the activity of the agonists, sometimes antagonists are called silent (Stahl, 2013).  At the opposite end of the spectrum from agonists are inverse agonists. These medications block agonists and decrease activity to below the normal baseline level when there is no agonist present (Stahl, 2013). 

G Couple proteins and Ion gated channels

     Ion gated channels are proteins that form pores in cell membranes (Inanobe & Kurachi, 2014).  These pores are the channels that allow movement across the cell membrane and are controlled by several mechanisms. The pore may open due to the voltage difference across the membrane (Ianonobe & Kurachi, 2014).  Ligand-gated channels have a domain extracellular that associates with small chemicals and regulatory proteins (Ianonobe & Kurachi, 2014).  A domain is a protein that has its own stable structure (Genscript, 2018). Ion channels gated by ligands can be opened or closed by a neurotransmitter that is specific to a ligand binding and causing a very short, brief open active state that occurs in milliseconds (Inanobe & Kurachi, 2014).  The ligand-gated channels can also be opened when metabotropic receptors that have G protein-coupled receptors are stimulated by G protein signaling (Inanobe & Kurachi, 2014).  The G protein-coupled ion gated open response is slower and is longer lived than the neurotransmitter ion channel opening (Ianonobe & Kurachi, 2014).  In summary, an ion gated channel is a throughway to the cell and this throughway is stimulated to be opened or closed by various mechanisms.  One of the ways the ion gated channel is stimulated to open is through G couple proteins. 

Epigenetics in pharmacologic action

     Genes are inherited from each parent.  But epigenetics looks at if the gene is developed into its specific RNA and protein or if the gene is silenced and ignored (Stahl, 2013).  Childhood stress has been found to deactivate the receptors for glucocorticoids (Rosenfield & Ziff, 2018).  Because the receptors are deactivated people grow up with disrupted feedback.  The glucocorticoids continue to be made by the body in greater amounts because they are not detected normally.  DNA methylation occurs and creates a barrier to normal genetic codes (Rosenfield & Ziff, 2018).  Long-term effects from childhood stressors are chronic inflammation, diabetes, heart disease, obesity, schizophrenia and major depressive disorder (Rosenfield & Ziff, 2018).  Cells including neurons respond to life stressors by reacting to genetics.  Genes may be silenced or activated but the expression of genetics can vary depending on stress (Stahl, 2013).

Possible Impact on Clients

     Psychopharmacology is important because of the impact interactions can have on patients.  As future prescribers, it is important to be aware of patient differences and how illness affect patient’s ability to metabolize medications (Laureate Education, 2012).  It is also important to be aware of drug interactions with other medications, foods, and metabolism.  For example, Wellbutrin is primarily metabolized by CYP2B6.  So, Wellbutrin can react with other medications that are inhibitors or inducers of CYP2B6 (Drugs.com, 2018).  Plavix and Ticlid are CYP2B6 inhibitors and can increase bupropion levels (Drugs.com, 2018).  People also metabolize medications differently.  There are four classes of metabolizers from ultra-extensive metabolizers to poor metabolizers (Barron, 2018).  Knowing the type of metabolizer that the patient is can be helpful in tailoring their medication and dosage.  Epigenetics teaches us that people with trauma can have their gene expression altered by DNA methylation.  Trauma can lead to metabolic type diseases as well as depression and schizophrenia.  As a client example, a 17-year-old male was admitted for being increasingly physically and verbally abusive to his entire foster family.  The client had pushed down a foster brother and punched and kicked his foster mom and dad.  This client had been taken away from his biological mom around age 5 due to her drug use, neglect then jail.  He was then placed with his maternal grandmother who could not handle his behavior.  The client then was placed in numerous foster homes for brief periods of time.  He acted appropriately in the Psychiatric care center, so he could control his behavior when multiple security/ authority figures were present.  The client had been on Wellbutrin at home and when he had symptoms of insomnia and aggression his Wellbutrin was increased.  He was taken off Wellbutrin and started on another medication.  Some of the more common side effects of Wellbutrin are sleep disturbance (45%), agitation (32%), irritability, and anxiety (Drugs.com, 2018).  This patient’s history of trauma and aggression set him up for depression, anxiety and irritability then when he had increased symptoms with the medication it was increased to the maximum dose as an outpatient.  He became increasingly agitated and then violent which led to his admission to an inpatient psychiatric facility. 

References

Barron, S. (2018). Psychopharmacology. Nobia textbook series:  Psychology. https://doi.org/nobaproject

Drugs.com. (2018). Wellbutrin. Retrieved from https://www.drugs.com/pro/wellbutrin.html

Genscript. (2018). Domain. Retrieved from https://www.genscript.com/molecular-biology-glossary/819/domain

Inanobe, A., & Kurachi, Y. (2014, February). Membrane channels as integrators of G-protein mediated signaling. Biochimica et Biophysica Acta (BBA) Biomembranes, 1838(2), 521-531. https://doi.org/10.1016/j.bbamem.2013.08.018

Laureate Education. (2012). Introduction to advanced pharmacology[Video file]. Retrieved from Walden University

Rosenfield, I., & Ziff, E. (2018). Epigenetics:  The evolution revolution. Retrieved from https://www.nybooks.com/articles/2018/06/07/epigenetics-the-evolution-revolution/

Stahl, S. M. (2013). Stahl’s essential psychopharmacology:  Neuroscientific basis and practical applications (4th ed.). Retrieved from https://stahlonline-cambridge-org.ezp.waldenulibrary.org

POST 2

Agonist to Antagonist Spectrum

     Most drugs act as either agonists or antagonists at receptors in response to chemical messages in the brain.  An agonist, which can be described as partial or inverse, binds to the receptor to produce an effect.  Antagonists also bind to receptors but does not produce a response, rather blocks that receptor to a natural agonist (Pleuvry, 20004).  It is important to acknowledge that agonists and inverse agonists can be reversed by competitive antagonists.  In reference to atypical psychotropic drugs (APD), the blockade of serotonin receptors (5-HT2A) along with the weak antagonism of dopamine receptor (D2) is critical in potency and efficacy, as typical APD have tendency to antagonize D2 receptors more potently than 5-HT2A receptors (Kusumi, Boku, & Takahashi, 2014).

G-coupled Protein and Ion-gated Channels

     G-protein linked receptors are important to clinicians with to target specific receptors with psychotropic drugs (Stahl, 2013).  Nonetheless, all agonists do not produce an active state of G-protein-coupled-receptors as in constitutive activity of receptors for benzodiazepines, serotonin, and other G-protein linked receptors.  Contrarily, ion channels function as a result of neurotransmitter ligands at receptors.  Numerous drugs act at ion-channel complexes altering flow of ions through the channels due to the transduction of the signal at receptors (Stahl, 2013).  As a result of the changes of flow of ions, drugs that act on ionotropic receptors tend to act immediately while G-protein linked receptors act at lower frequencies. 

Epigenetics in Pharmacologic Action 

      The lack of response to standard therapies in certain individuals because of various molecular alterations can be due to genetic heterogenecity and epigenetic alterations (Rasool et al., 2015).  Epigenetic modifications can occur as a result of various chemical compounds in the biological system, changing gene expression.  Environmentally and biologically influenced alterations can lead to disorders, therefore clients with epigenetic alterations may require drugs used for personalized medicine based on their personal genomic profile.

Impact on How Medicine is Prescribed

     Understanding the agonistic/antagonistic effects of medications along with the prescribing of medications specific to G-protein coupled receptors, and personalized medication profiles required by epigenetic alterations found in certain cases is important to PMHNP’s who may prescribe psychotropic medications to these clients.  Studies have found an existence of constitutive receptor activity in benzodiazepine receptors and G-protein coupled receptors and may be present in mutated strains exhibiting underactive behavior that can lead to inherited diseases such as congenital hypothyroidism and diabetes insipidus (Rasool et al., 2015).  For schizophrenic clients at greater risk for developing extrapyramidal symptoms (EPS), it is known that risperidone equally occupies D2 and 5-HT2A receptors increasing the frequency of EPS, while clozapine more potently occupies 5-HT2A receptors than D2 receptors, rarely producing EPS (Kusumi, Boku, & Takahashi, 2014).  It is the responsibility of the PMHNP to understand their clients’ profiles and medical histories in order to properly prescribe the most effective medications with the least adverse effects. 

                                                                                            REFERENCES

Kusumi, I., Boku, S., & Takahashi, Y. (2014).  Psychopharmacology of atypical antipsychotic drugs: From the recpetor binding profile to neuroprotection and neurogenesis.  Psychiatry and Clinical Neurosciences, 69(5): 243-258. doi: 10.1111/pcn.12242.

Pleuvry, B. (2004).  Receptors, agonists, and antagonists.  Anaesthesia & Intensive Care Medicine, 5(10): 350-352.  doi: 10.1383/anes.5.10.350.52312.

Rasool, M., Malik, A., Naseer, M., Manan, A., Ansari, S., Begum, I.,…Gan, S. (2015).  The role of epigenetics in personalized medicine: Challenges and opportunites.  BMC Medical Genomics, 8(Suppl 1): S5.  doi: 10.1186/1755-8794-8-S1-S5. 

Stahl, S. (2013).  Stahl’s essential psychopharmacology: Neuroscientific basis and practical applications (4th ed.).  New York, NY: Cambridge University Press.