Pharmacotherapeutic Principles Research Articles

Local Anesthetics: Review of Pharmacological Considerations

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is not so regular, and the negative effects are so low, that providers can overlook a lot of their pharmacotherapeutic principles understandable. The purpose of this continuing education article is important for various local anesthesia formulas in current use. Local anesthetics inhibit nerve conduction by inhibiting the passage of sodium ions through channels or ionophores within neural membranes. Usually these channels are present at rest, during which access to sodium ions is prohibited. When the neuron is excited, the channel adopts an activated or open state, in which sodium ions spread to the cell and begin depolarization. After a sharp change in membrane voltage, the sodium channel adopts an inactive state, at which point the active transport mechanisms return sodium ions outward. After this repolarization, the canal receives a normal state of rest. Valuing these sodium channel States helps explain the privileged sensitivity of local anesthetics for different classes of neuronal fibers

FGF/FGFR Pathways in Multiple Sclerosis and in Its Disease Models.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS) affecting more than two million people worldwide. In MS, oligodendrocytes and myelin sheaths are destroyed by autoimmune-mediated inflammation, while remyelination is impaired. Recent investigations of post-mortem tissue suggest that Fibroblast growth factor (FGF) signaling may regulate inflammation and myelination in MS. FGF2 expression seems to correlate positively with macrophages/microglia and negatively with myelination; FGF1 was suggested to promote remyelination. In myelin oligodendrocyte glycoprotein (MOG)35–55-induced experimental autoimmune encephalomyelitis (EAE), systemic deletion of FGF2 suggested that FGF2 may promote remyelination. Specific deletion of FGF receptors (FGFRs) in oligodendrocytes in this EAE model resulted in a decrease of lymphocyte and macrophage/microglia infiltration as well as myelin and axon degeneration. These effects were mediated by ERK/Akt phosphorylation, a brain-derived neurotrophic factor, and downregulation of inhibitors of remyelination. In the first part of this review, the most important pharmacotherapeutic principles for MS will be illustrated, and then we will review recent advances made on FGF signaling in MS. Thus, we will suggest application of FGFR inhibitors, which are currently used in Phase II and III cancer trials, as a therapeutic option to reduce inflammation and induce remyelination in EAE and eventually MS.

A Team-based Assignment to Integrate Basic Science and Pharmacotherapeutic Principles for Anticancer Agents

Objective. To implement and evaluate an active-learning, team-based assignment centered on anticancer agents for the integration of basic science and pharmacotherapeutic principles. Methods. Student teams were assigned a specific anticancer agent and were expected to answer a series of questions on the written section of the assignment, followed by a presentation to the class. Each assignment was assessed using a grading rubric that was mapped to the 2013 CAPE educational outcomes. Student perceptions of the assignment were assessed using a short survey. Results. Student cohort performance on the assignment was in the B range (83%) with a mean of 33.2 out of 40. Using the grading rubric, the 12 student cohorts performed particularly well under professionalism (Domain 4.4) that focuses on personal and professional development from CAPE 2013 with means >4 on a 1-5 scale. Student impressions of the assignment suggested that students believed the assignment had a positive effect on their learning and should be continued. Conclusion. The assignment provided a focused review of basic science and pharmacotherapeutic principles and enabled integration of concepts relating to the therapeutic application of anticancer agents, and management of anticancer agent mediated adverse effects. The assignment could contribute toward preparing students for the evolving role of the pharmacist in the management of cancer.

A Team‐based Assignment to Integrate Basic Science and Pharmacotherapeutic Principles for Anticancer Agents

ObjectiveTo implement and evaluate an active‐learning, team‐based assignment centered on anticancer agents for the integration of basic science and pharmacotherapeutic principles.DesignStudents enrolled in the integrated hematologic and oncologic disorders course were divided into 5–6 students/group. Each group was assigned a specific anticancer agent and was expected to answer a series of questions designed to measure students learning abilities and competencies, followed by a presentation to the class.AssessmentEach assignment was assessed using a grading rubric that was mapped to the 2013 Center for the Advancement of Pharmacy Education (CAPE) outcomes to assess whether expected abilities and competencies are being met within a PharmD curriculum. Student learning was evaluated using performance on the assignment and examination questions. Student perceptions of the assignment were assessed using a short survey.ResultAssessments for student learning abilities and competencies were performed based on the team‐based assignment and presentation as well as three examinations, in which the first exam was taken place prior to the team‐based assignment and in‐class activities. Overall mean score on examination 1 was 75%, examination 2 and examination 3 were 81% and 77%, respectively. When only questions related to drugs covered in the assignment were analyzed, we found that students performed better on examination 2 and 3 that were completed after the team‐based assignment vs. examination 1. Student performance on 14 of the 53 questions on examination 2 that were related to the drugs covered as part of the assignment was 93.7%. Students performed better on assignment related questions on examination 2 compared to unrelated questions. Student performance on 21 of the 61 questions on examination 3 that were related to the drugs covered as part of the assignment was 85.9%. Although, student performance was better on assignment related questions on examinations 2 and 3 compared to unrelated questions, this differences were not significant (p=0.253). Finally, Student perceptions of the effectiveness of the team‐based assignment were also positive and majority of the students (83%) agree or strongly agreed that the assignment improved their knowledge and understanding of anticancer agents and should.ConclusionThe assignment provided a focused review of basic science and pharmacotherapeutic principles and enabled integration of concepts relating to the therapeutic application of anticancer agents and management of anticancer agent mediated adverse effects. The assignment could contribute toward preparing students for the evolving role of the pharmacist in the management of cancer.

Nanotechnology approaches for pain therapy through transdermal drug delivery.

The paper focuses on the advances in the field of pain treatment by transdermal delivery of specific drugs. Starting from a short description of the skin barrier, the pharmacodynamics and pharmacokinetics including absorption, distribution, action mechanism, metabolism and toxicity, aspects related to the use of pain therapy drugs are further discussed. Most recent results on topical anesthetic agents as well as the methods proved to overcome the skin barrier and to provide efficient delivery of the drug are also discussed. The present review is proposing to summarize the recent literature on the pharmacotherapeutic principles of local anesthetics and non-steroidal anti-inflammatory drugs, generally used to alleviate pain but also the drugs as nanoformulations with potential applications in transdermal delivery. A special attention is given to efficient formulations meant for transdermal penetration enhancement of anesthetics where the drug is encapsulated into macrocyclic molecules (cyclodextrins, cyclodextrin derivatives), liposomes or polymer nanoparticles and hydrogels.

Pharmacotherapy Considerations in the Management ofTransgender Patients: A Brief Review.

Transgender and transsexual individuals have unique health care needs and risks compared with the population at large. It is estimated that 1 in 100,000 individuals in the United States is a transgender woman and 1 in 400,000 is a transgender man, although these estimates of prevalence are likely conservative. Transgender individuals are at an increased risk of tobacco, alcohol, and substance abuse; they have an increased lifetime suicide attempt risk; and they are more likely to experience significant stressors in their lives. Transgender patients may elect to transition their appearance to the gender with which they identify. Hormone treatment (and possibly sex reassignment surgery) is a significant part of this transition, and pharmacists must understand the pharmacotherapeutic principles involved so they can better recommend therapeutic agents, provide dosing recommendations, and anticipate and manage adverse effects. It is critical to be culturally sensitive when providing care for transgender patients including using their preferred gender identity, preferred names, and preferred pronouns. It is also essential to be able to identify transgender and transsexual patients correctly within electronic health records to ensure that appropriate care and monitoring are provided. For pharmacists, this means they should know the biologic sex for performing calculations such as creatinine clearance and to prevent teratogenic agents from reaching a transgender or transsexual man who could be pregnant or is capable of becoming pregnant. Promoting knowledge of transgender health issues will enable pharmacists to provide better, more holistic care to their transgender patients.

DSM-5 Sleep-Wake Disorders Classification: Overview for Use in Clinical Practice

Mental health clinicians should appreciate that sleep is a fundamental human behavior and that inadequate sleep has adverse medical, psychiatric, and psychosocial consequences. Sleep disturbances interact with common mental disorders; the two are mutually exacerbating, and both must be appropriately addressed to ensure optimal outcomes for our patients. Sleep is by the brain, of the brain, and for the brain.

Book Review: Essentials of clinical psychopharmacology, third edition

CPNP members maintain a suggested reading list to provide information on peer recommended resources and convenient access to the highest quality neuropsychopharmacology publications. A reminder that if you shop with CPNP, by following the links below to Amazon, a small commission will be paid to CPNP which helps to financially support our mission to improve the minds and lives of individuals with psychiatric and/or neurologic disorders.You can help grow this list of resources by suggesting a book.Book: Essentials of Clinical Psychopharmacology, Third EditionThis third edition of Essentials of Psychopharmacology is, like its predecessors, based on the premier textbook in the field, The American Psychiatric Publishing Textbook of Psychopharmacology, now in its fourth edition. The Essentials format is designed to deliver core knowledge to the busy trainee or practitioner in a succinct and accessible manner. Essentials of Psychopharmacology provides a complete overview of clinically focused pharmacotherapeutic principles of vital interest to psychiatry residents, primary care physicians, and other health care professionals. Updated with the latest research findings since the publishing of the fourth edition of the Textbook, the Essentials features new chapters on recently introduced medications and updated chapters on others. The book is divided into two parts: Classes of Psychiatric Treatments, which systematically reviews psychotropic medications within each drug class (e.g., antidepressants and anxiolytics, antipsychotics), and Psychopharmacological Treatment, which outlines current pharmacotherapeutic approaches in the major psychiatric disorders as well as in specific patient populations. Although the latter part has been streamlined in this new edition, coverage of critical information such as approved indications, drug interactions, side effects, and other prescribing factors remains comprehensive. Clinicians seeking a reliable reference and guide to the core knowledge base and practice of clinical psychopharmacology can do no better than this new edition of Essentials of Psychopharmacology.Essentials of Clinical Psychopharmacology is a compressed version of the APA's Textbook on Psychophamacology. Part 1 entitled “Classes of Psychiatric Treatment” includes chapters that explain drug classes and chapters devoted to specific agents (e.g., chapters on fluoxetine, clozapine, etc.). Each chapter gives a short history/discovery of the agent, pharmacological profile, and review of the literature pertaining to indications and efficacy. A “specific issues” section within each chapter highlights clinical pearls and a brief conclusion section states where the agent can be utilized in practice. Part 2 entitled “Psychopharmacologic Treatment” includes drug information from the perspective of treating specific diagnoses with topics including depression, bipolar disorder, schizophrenia, anxiety disorders, and substance-related disorders. There are also chapters devoted to the treatment of child and adolescent disorders and psychopharmacology during pregnancy and lactation. Each chapter is approximately 20 pages in length with some reference tables and figures included throughout. The book provides a good overview of psychotropics especially for students and residents that are learning psychopharmacology. The text is also useful as a quick reference guide for clinicians practicing in a variety of disciplines and settings. In conclusion, this publication is a good reference resource for core material in psychopharmacology.

Local Anesthetics: Review of Pharmacological Considerations

Local anesthetics have an impressive history of efficacy and safety in medical and dental practice. Their use is so routine, and adverse effects are so infrequent, that providers may understandably overlook many of their pharmacotherapeutic principles. The purpose of this continuing education article is to provide a review and update of essential pharmacology for the various local anesthetic formulations in current use. Technical considerations will be addressed in a subsequent article.

Integration of pharmacists into a patient-centered medical home

To define the joint principles of the patient-centered medical home (PCMH) and describe the integration of pharmacists into a PCMH. Family medicine residency training program in North Carolina from 2001 to 2011. Mountain Area Health Education Family Health Center is a family medicine residency training program that is part of the North Carolina Area Health Education Center system. The goal of the organization is to train and retain health care students and residents. The practice is recognized as a level III PCMH by the National Committee for Quality Assurance (NCQA) and seeks to provide quality, safe, patient-centered care according to the joint principles of PCMH. Pharmacists, nurses, nutritionists, care managers, Spanish translators, and behavioral medicine specialists work collaboratively with physicians to provide seamless, comprehensive care. The Department of Pharmacotherapy is embedded in the family medicine clinic. Three pharmacists and two pharmacy residents are involved in providing direct patient care services, ensuring access to community resources, assisting patients with transitions of care, providing interprofessional education, and participating in continuous quality improvement initiatives. The pharmacists serve as clinical pharmacist practitioners and provide medication therapy management services in a pharmacotherapy clinic, anticoagulation clinics, and an osteoporosis clinic and via an inpatient family medicine service. Multiple learners such as student pharmacists, pharmacy residents, and family medicine residents rotate through the various pharmacy clinics to learn about pharmacotherapeutic principles and the role of the pharmacist in PCMH. PCMH is a comprehensive, patient-centered, team-based approach to population management in the primary care setting. Pharmacists play a vital role in PCMH and make fundamental contributions to patient care across health care settings. Such innovations in the ambulatory care setting create a unique niche for pharmacists to use their skills.

ChemInform Abstract: Pharmacology of Immunosuppressive Drugs

Immunosuppressive therapy of solid organ transplantation has become more potent, effective and selective since the results of earlier use of prednisone and azathioprine post renal transplantation. Calcineurin inhibitors and mycophenolate mofetil have been important additions to the effective antirejection armamentarium. Today, cyclosporin, tacrolimus, azathioprine, mycophenolate and prednisone are all effective immunosuppressive agents and are the cornerstone of immunosuppressive protocols used posttransplant. However, the use of these agents is hindered by a 20% rate of rejection, lack of selectivity and a high rate of major adverse drug reactions which ultimately lead to a decrease in patient and graft survival. A number of clinical trials are underway to compare efficacy, safety and tolerability of different combination protocols to improve patient and allograft survival and decrease adverse drug reactions. Clinical knowledge of the pharmacology, pharmacokinetics, pharmacodynamics, adverse drug reactions and therapeutic drug monitoring of antirejection agents is essential for designing an effective immunosuppressive protocol for individual solid organ transplant recipients. The clinical application of pharmacotherapeutic principles into the clinical practice will improve both long-term patient and allograft survival while minimizing systemic toxicity of immunosuppressive drugs.

Antibiotics in otorhinolaryngology practice

This study investigated utilization of antibacterial agents at the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman and at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, in the period February-March 2001. All antibacterial agents were classified as group J, regarding Anatomic-Therapeutic-Chemical Classification. Data on drug utilization were presented in Defined Daily Doses (DDD). Patients who were under observation were all treated with antibiotics. In regard to prescribed treatment in the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, most outpatients were treated with macrolide antibiotics--in 26.21%; combination of penicillin and beta-lactamase inhibitors in 20.83% and pyranosides in 16.12%. At the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad, macrolides and lincosamines were most frequently used--in 20.46%; cephalosporins in 19.87% and penicillins susceptible to beta-lactamase in 18.85%. It is extremely positive and in agreement with current pharmacotherapeutic principles that in both institutions peroral ampicillins have not been prescribed. Aminoglycosides have been prescribed in less than 1% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, whereas they were much more frequently prescribed at the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad--in 11.25%. Although there is a positive postantibiotic effect in regard to these antibiotics and it is recommended to use them once a day, in both examined institutions aminoglycosides were given twice a day. In regard to bacterial identification it was done in 80.76% of patients of the Ear, Nose and Throat Department of the Outpatient Service of the Health Center Novi Sad-Liman, while in the Ear, Nose and Throat Clinic of the Clinical Center Novi Sad it was done only in 32.42%. Although treatment performed on empirical basis and clinical findings is usually correct, a greater percentage of antibiotic prescriptions should be confirmed by antibiograms providing optimal therapy and decreased degree of resistance.

Pharmacology of immunosuppressive drugs.

Immunosuppressive therapy of solid organ transplantation has become more potent, effective and selective since the results of earlier use of prednisone and azathioprine post renal transplantation. Calcineurin inhibitors and mycophenolate mofetil have been important additions to the effective antirejection armamentarium. Today, cyclosporin, tacrolimus, azathioprine, mycophenolate and prednisone are all effective immunosuppressive agents and are the cornerstone of immunosuppressive protocols used posttransplant. However, the use of these agents is hindered by a 20% rate of rejection, lack of selectivity and a high rate of major adverse drug reactions which ultimately lead to a decrease in patient and graft survival. A number of clinical trials are underway to compare efficacy, safety and tolerability of different combination protocols to improve patient and allograft survival and decrease adverse drug reactions. Clinical knowledge of the pharmacology, pharmacokinetics, pharmacodynamics, adverse drug reactions and therapeutic drug monitoring of antirejection agents is essential for designing an effective immunosuppressive protocol for individual solid organ transplant recipients. The clinical application of pharmacotherapeutic principles into the clinical practice will improve both long-term patient and allograft survival while minimizing systemic toxicity of immunosuppressive drugs.

Drug administration in patients with renal insufficiency. Minimising renal and extrarenal toxicity.

Renal insufficiency has been associated with an increased risk of adverse effects with many classes of medications. The risk of some, but not all, adverse effects has been linked to the patient's degree of residual renal function. This may be the result of inappropriate individualisation of those agents that are primarily eliminated by the kidney, or an alteration in the pharmacodynamic response as a result of renal insufficiency. The pathophysiological mechanism responsible for alterations in drug disposition, especially metabolism and renal excretion, is the accumulation of uraemic toxins that may modulate cytochrome P450 enzyme activity and decrease glomerular filtration as well as tubular secretion. The general principles to enhance the safety of drug therapy in patients with renal insufficiency include knowledge of the potential toxicities and interactions of the therapeutic agent, consideration of possible alternatives therapies and individualisation of drug therapy based on patient level of renal function. Although optimisation of the desired therapeutic outcomes are of paramount importance, additional pharmacotherapeutic issues for patients with reduced renal function are the prevention or minimisation of future acute or chronic nephrotoxic insults, as well as the severity and occurrence of adverse effects on other organ systems. Risk factors for the development of nephrotoxicity for selected high-risk therapies (e.g. aminoglycosides, nonsteroidal anti-inflammatory drugs, ACE inhibitors and radiographic contrast media) are quite similar and include pre-existing renal insufficiency, concomitant administration of other nephrotoxins, volume depletion and concomitant hepatic disease or congestive heart failure. Investigations of prophylactic approaches to enhance the safety of these agents in patients with renal insufficiency have yielded inconsistent outcomes. Hydration with saline prior to drug exposure has given the most consistent benefit, while sodium loading and use of pharmacological interventions [e.g. furosemide (frusemide) dopomine/dobutamine, calcium antagonists and mannitol] have resulted in limited success. The mechanisms responsible for altered dynamic responses of some agents (benzodiazepines, theophylline, digoxin and loop diuretics) in renally compromised patients include enhanced receptor sensitivity secondary to the accumulation of endogenous uraemic toxins and competition for secretion to the renal tubular site of action. Application of the pharmacotherapeutic principles discussed into clinical practice will hopefully enhance the safety of these agents and optimise patient outcomes.

Imbalance of neuronal excitability as a cause of psychic disorder.

Electrical activity of neurons is characterized by an equilibrium between excitation and inhibition, maintained by negative feedback mechanisms at the cellular, synaptic and neurohumoral level. A central mechanism is the interaction between excitatory calcium currents and inhibitory potassium currents, linked by intracellular calcium concentration. These conductances are located in the somato-dendritic part of the neuron and fundamentally influence spontaneous activity and the processing of synaptic input. The electrical equilibrium is altered by different neuromodulators, such as biogenic amines, peptides, and steroids and by several drugs. Neuromodulatory desequilibration towards increased excitability may occur task-related in a transient way or in a cascade of desequilibrating and partially compensating mechanisms, producing distinct grades of functional impairment. Pharmacotherapeutic principles interfere with this process. It is postulated, that the imbalance between excitation and inhibition is a central factor in the origin of psychic disorder.

Benefits and limitations of major pharmacological treatment for depression.

An extensive amount of research in clinical psychiatry, psychopharmacology, and the neurosciences has led to effective pharmacological treatments for affective disorders. These impressive developments have suffered from several limitations. In the case of antidepressant drugs, the delayed onset of antidepressant effect, troublesome side effects, possible lethality after an overdose, and the 20 to 30 percent of depressed patients not responsive to them have made these drugs less than a panacea. In addition to the limitations of the drugs themselves, there is frequently inattention to pharmacotherapeutic principles by clinicians. There is definitely a need for further research in the field, especially regarding major unresolved issues such as the proper selection of patients for whom antidepressants are indicated, clinical and biological predictors of treatment response, and the development of new antidepressants with superior efficacy and safety as well as an earlier onset of action. Meanwhile, an empathic psychotherapeutic alliance coupled with careful clinical and pharmacological monitoring are the essential prerequisites for successful antidepressant treatment.