Pharmacotherapeutic Modalities Research Articles

Pharmacotherapy of acute ST-elevation myocardial infarction and the pharmacist's role, part 2: Complications, postrevascularization care, and quality improvement.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the later phases of inpatient care are reviewed. Published descriptions and validation of clinical pharmacist roles specific to the acute management of STEMI are limited. This high-risk period from presentation through revascularization, stabilization, and hospital discharge involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. A companion article reviewed STEMI pharmacotherapy from emergency department presentation through revascularization. Herein we complete the pharmacotherapy review for the STEMI patient across the inpatient phases of care, including the management of peri-infarction complications with vasoactive and antiarrhythmic agents, considerations for postrevascularization antithrombotics, and assessments of supportive therapies and secondary prevention. Key guideline recommendations and literature developments are summarized from the clinical pharmacist's perspective alongside suggested pharmacist roles and responsibilities. Considerations for successful hospital discharge after STEMI and pharmacist involvement in associated institutional quality improvement efforts are also provided. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population and call for further research delineating pharmacists' impact on patient and institutional STEMI outcomes.

Pharmacotherapy of acute ST-elevation myocardial infarction and the pharmacist's role, part 1: Patient presentation through revascularization.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Key pharmacotherapeutic modalities and considerations for the patient with ST-elevation myocardial infarction (STEMI) across the critical initial phases of care are reviewed. Despite established value in the emergency department (ED), cardiac care, and intensive care settings, there is currently little published literature describing or supporting clinical pharmacist roles in the acute management of STEMI. The high-risk period from hospital presentation through revascularization and stabilization involves complex pharmacotherapeutic decision points, many operational medication needs, and multiple layers of quality oversight. While rife with opportunities for pharmacists to optimize care, this timeframe appears inconsistently targeted by clinical pharmacy services, which may halt after ED evaluation and then resume upon postcatheterization cardiac unit admission. Herein we review the key pharmacotherapeutic modalities and considerations for the patient with STEMI across the critical initial phases of care. These include supportive therapies prior to revascularization, the host of antithrombotics involved in revascularization by percutaneous coronary intervention and/or fibrinolysis, and other periprocedural medications. Important practice guidelines and clinical resources are summarized from the clinical pharmacist perspective, and roles and responsibilities of the responding pharmacist are suggested. A companion article will extend the review to periprocedural adverse event management, key early decision-making regarding long-term risk reduction, and pharmacist involvement in institutional quality improvement efforts. We aim to support inpatient pharmacy departments in advancing clinical services for this critical patient population, and we call for further research delineating pharmacist impact on patient and institutional STEMI outcomes. Patients presenting with STEMI rapidly traverse multiple phases of care and receive a host of antithrombotic and supportive medications during acute management, presenting many important pharmacotherapeutic decision points and roles for pharmacists.

Advances in the management of alcohol-associated liver disease.

Alcohol-associated liver disease (ALD) is a significant global health challenge, encompassing a spectrum from steatotic liver disease to cirrhosis and alcohol-associated hepatitis, and contributed to 25% of global cirrhosis deaths in 2019. The identification of both modifiable (e.g. heavy drinking, metabolic syndromes) and non-modifiable risk factors (e.g. genetic predispositions) is crucial for effective disease management. Alcohol use assessment and treatment, by using both behavioral therapy and pharmacotherapeutic modalities, nutrition support, and optimization of liver disease modifiers, form the cornerstone of management. Advances in medical therapies, such as fecal microbiota transplantation and novel agents such as IL-22, are being explored for their therapeutic potential. A unifying theme in ALD care is the need for a personalized approach to management, accounting for the spectrum of the disease and individual patient characteristics, to tailor interventions effectively. Finally, it is essential to address the challenges to effective ALD treatment, including socioeconomic, logistical, and stigma-related barriers, to improve patient outcomes. This review discusses the current knowledge on ALD, including epidemiology, pathophysiology, risk factors, and management strategies, highlighting the critical role of integrated care models.

Comparative efficacy and safety of pharmacotherapies for alcohol withdrawal: a systematic review and network meta-analysis.

There have been few head-to-head clinical trials of pharmacotherapies for alcohol withdrawal (AW). We, therefore, aimed to evaluate the comparative performance of pharmacotherapies for AW. Six databases were searched for randomized clinical trials through November 2021. Trials were included after a blinded review by two independent reviewers. Outcomes included incident seizures, delirium tremens, AW severity scores, adverse events, dropouts, dropouts from adverse events, length of hospital stay, use of additional medications, total benzodiazepine requirements, and death. Effect sizes were pooled using frequentist random-effects network meta-analysis models to generate summary ORs and Cohen's d standardized mean differences (SMDs). Across the 149 trials, there were 10 692 participants (76% male, median 43.5 years old). AW severity spanned mild (n = 32), moderate (n = 51), and severe (n = 66). Fixed-schedule chlormethiazole (OR,0.16; 95% CI, 0.04-0.65), fixed-schedule diazepam (OR,0.16; 95% CI, 0.04-0.59), fixed-schedule lorazepam (OR = 0.19; 95% CI, 0.08-0.45), fixed-schedule chlordiazepoxide (OR = 0.21; 95% CI, 0.08-0.53), and divalproex (OR = 0.22; 95% CI, 0.05-0.86) were superior to placebo at reducing incident AW seizures. However, only fixed-schedule diazepam (OR,0.19; 95% CI, 0.05-0.76) reduced incident delirium tremens. Oxcarbazepine (d = -3.69; 95% CI, -6.21 to -1.17), carbamazepine (d = -2.76; 95% CI, -4.13 to -1.40), fixed-schedule oxazepam (d = -2.55; 95% CI, -4.26 to -0.83), and γ-hydroxybutyrate (d = -1.80; 95% CI, -3.35 to -0.26) improved endpoint Clinical Institute Withdrawal Assessment for Alcohol-Revised scores over placebo. Promazine and carbamazepine were the only agents significantly associated with greater dropouts because of adverse events. The quality of evidence was downgraded because of the substantial risk of bias, heterogeneity, inconsistency, and imprecision. Although some pharmacotherapeutic modalities, particularly benzodiazepines, appear to be safe and efficacious for reducing some measures of alcohol withdrawal, methodological issues and a high risk of bias prevent a consistent estimate of their comparative performance.

A comparative study on the pharmacovigilance scoring of causality assessment grading and staging of topical pharmacotherapy of ofloxacin 0.3% ophthalmic solution in bacterial conjunctivitis and ofloxacin 0.3% otic solution in otitis externa

Background: Topical pharmacotherapeutic modalities would minimalize systemic adverse effects. Ofloxacin, the bactericidal racemic mixture, has inhibitory effects on DNA gyrase, DNA topoisomerase IV and IL-1α, IL-6, and IL-8. This was a comparative study for pharmacovigilance scoring of causality assessment grading and staging of topical ofloxacin pharmacotherapy in bacterial conjunctivitis and otitis externa.Methods: Group A=50 bacterial conjunctivitis patients were prescribed topical ophthalmic 0.3% ofloxacin, 2 drops in each eye after every 3 hours for 2 days, and 2 drops in each eye after every 6 hours for next 5 days; and group B=50 otitis externa patients were prescribed topical otic 0.3% ofloxacin, 3 drops in each ear after every 6 hours for first 2 days, and 5 drops in each ear after every 12 hours for next 5 days. Comparative adverse drug reactions occurrence, like transient ocular burning or discomfort, ocular irritation, redness, stinging, pruritis, photophobia, ocular watering and dryness in group A, and pruritis, headache, dizziness, mild ear pain, rashes, and hypersensitivity reactions in group B, were analysed with adverse event case report forms, on days 0, 3, 5, 7, 10, 15, 30, and on follow-ups, with causality assessment scores, from adverse drug reactions grading and staging.Results: The occurrence of adverse effects were statistically non-significant, in both groups, with causality assessment scoring for group A: -11, none on average=Unlikely causality, and group B: -11, none on average= Unlikely causality.Conclusions: Topical ofloxacin therapy in group A and group B patients, were safe and tolerable; with nil causality of association of adverse drug reactions.

The efficacy of triazavirin (riamilovir)-based treatment for coronavirus disease 2019 (COVID-19) in clinical trials and preliminary practical experiences

Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has plagued the human population as 2019 turned into 2020, when first cases were confirmed to be infected with the pathogen in Wuhan City, the largest mega-city and capital of Hubei Province in Central China. Since this time, many pharmacotherapeutic modalities were suggested and used to treat the patients suffering from COVID-19. Triazavirin (TZV; riamilovir) is a synthetic non-toxic broad-spectrum antiviral drug belonging into an azolotriazine class. Several hypotheses and suggestions based on the knowledge about morphology, structure of virion, genome, replication cycle and functions of particular proteins within SARS-CoV-2 as well as in silico analyzes were published aiming to employ TZV for the treatment of COVID-19. Results and conclusions from a well-known randomized controlled trial registered under the Registration No. ChiCTR2000030001, which was carried out in China in 2020, indicated not only the anti-SARS-CoV-2 efficacy of given aza analogue of guanine but also some limitations of these outcomes in the context of their general interpretability and applicability. Thus, a primary aim of this review article was to provide more complex view on pharmacotherapeutic interventions based on TZV against COVID-19/SARS-CoV-2. The focus was on relevant results and conclusions from clinical trials as well as practical experiences with given antiviral agent considering not only real benefits of chosen therapeutic strategies but also several obstacles connected with them.

Human brain organoids in Alzheimer’s disease

Alzheimer’s disease (AD) is a progressive neurological disorder that typically involves neuronal damage leading to the deterioration of cognitive and essential body functions in aging brains. Major signatures of AD pathology include the deposition of amyloid plaques and neurofibrillary tangles, disruption of the blood-brain barrier, and induction of hyper-activated proinflammation in the brain, leading to synaptic impairment and neuronal loss. However, conventional pharmacotherapeutic modalities merely alleviate symptoms, but do not cure AD, partly because drug screening has used model systems with limited accuracy in terms of reflecting AD pathology in human brains. In this regard, several AD organoids have received substantial attention as alternatives to AD animal models. In this review, we summarize the key characteristics required for the generation of a pathologically relevant AD brain organoid. We also overview major experimental organoid models of AD brains, such as spheroids, three-dimensional (3D) bioprinted constructs, and 3D brain-on-chips, and discuss their strengths and weaknesses for AD research. This review will provide valuable information that will inspire future efforts to engineer authentic AD organoids for the study of AD pathology and for the discovery of novel AD therapeutic strategies.

Современные концепции и перспективы воздействия на катарактогенез

This paper highlights current pharmacotherapeutic modalities for various metabolic disorders which result in cataract. This therapy is preferable for the prevention and treatment of lens opacities due to less financial costs and ease of use. A novel strategy of the medical treatment for cataract was developed. Several compounds prevent the generation of lens protein aggregates and to contribute to their degradation. Oxidative stress, excessive quinoid substances, and activation of aldose reductase promote cataract progression. Quinoid theory suggests that quinones, which are produced because of impaired metabolism of aromatic amino acids (tryptophan, tyrosine etc.) are important for cataractogenesis. Lens opacity occurs when its water-soluble proteins denature and transform into dense compounds under the influence of quinones. Many studies clearly demonstrate that Catalin (pirenoxine) eye drops provide anti-cataract effect on all layers of the lens, in particular, cortex and posterior capsule. High therapeutic efficacy and long-term safety allow for recommending Catalin to slow the progression of cataract, in particular, early cataracts in patients under 59 years of age. Further studies are needed to assess the effects of pirenoxine in various cataracts and risk of cataracts. Cited published data best illustrate the crux of this issue. Keywords: lens, cataract, antioxidants, quinoid compounds, cataractogenesis, medical treatment, pirenoxine, oxidative stress. For citation: Kovalevskaya M.A., Vladimirova Yu.V., Filina L.A., Kokorev V.L. Current conceptions and promising tools to prevent cataractogenesis. Russian Journal of Clinical Ophthalmology. 2021;21(1):24–28. DOI: 10.32364/2311-7729-2021-21-1-24-28.

A Novel Prodrug Approach for Central Nervous System-Selective Estrogen Therapy.

Beneficial effects of estrogens in the central nervous system (CNS) results from the synergistic combination of their well-orchestrated genomic and non-genomic actions, making them potential broad-spectrum neurotherapeutic agents. However, owing to unwanted peripheral hormonal burdens by any currently known non-invasive drug administrations, the development of estrogens as safe pharmacotherapeutic modalities cannot be realized until they are confined specifically and selectively to the site of action. We have developed small-molecule bioprecursor prodrugs carrying the para-quinol scaffold on the steroidal A-ring that are preferentially metabolized in the CNS to the corresponding estrogens. Here, we give an overview of our discovery of these prodrugs. Selected examples are shown to illustrate that, independently of the route of administrations and duration of treatments, these agents produce high concentration of estrogens only in the CNS without peripheral hormonal liability. 10β,17β-Dihydroxyestra-1,4-dien-3-one (DHED) has been the best-studied representative of this novel type of prodrugs for brain and retina health. Specific applications in preclinical animal models of centrally-regulated and estrogen-responsive human diseases, including neurodegeneration, menopausal symptoms, cognitive decline and depression, are discussed to demonstrate the translational potential of our prodrug approach for CNS-selective and gender-independent estrogen therapy with inherent therapeutic safety.

Pharmacotherapy in Acutely Anemic Jehovah's Witnesses: An Evidence-Based Review.

To determine the pharmacological treatment methods available to anemic Jehovah's Witnesses (JW). MEDLINE and PubMed were searched from inception through February 2018 using the search terms Jehovah's Witnesses, treatment, erythropoietin, hemoglobin-based oxygen carrier, Sanguinate, Hemopure, bleeding, and anemia. All clinical trials, cohort studies, case-control studies, and observational trials involving pharmacotherapy in anemic JW patients were evaluated. Case reports and bibliographies were also analyzed for inclusion. Two studies involving the use of erythropoietin (EPO) and one study involving recombinant factor VIIa were included. Information was also included from other pharmacotherapeutic modalities that had case report data only. Current published evidence is limited with regard to evidence-based management of JW patients. High-dose EPO, intravenous iron supplementation, and hemostatic agents have demonstrated good clinical outcomes in case reports. EPO doses as high as 40 000 units daily have been advocated by some experts; however, pharmacokinetic studies do not support dose-dependent effects. Hemoglobin-based oxygen carriers (HBOCs) are currently not Food and Drug Administration approved. They are available through expanded access programs and may represent a lifesaving modality in the setting of severe anemia. There are currently not enough data to make definitive recommendations on the use of pharmacological agents to treat severe anemia in the JW population. Further evidence utilizing EPO and HBOCs will be beneficial to guide therapy.

The nephroprotective potential of peloid therapy used for the rehabilitation of the patients presenting with chronic pyelonephritis

This review article presents the data on the mechanism of action of peloid therapy from the perspective of its defibrosing effect, the structure and functions of the extracellular matrix under the normal and pathological conditions. In addition, role of this treatment modality in the progression of tubulointerstitial fibrosis which determines the severity and prognosis of chronic pyelonephritis is considered. The researchers are currently carry out the extensive studies aimed at the search of the methods for the primary and secondary prevention of chronic pyelonephritis. A wide range of pharmacotherapeutic modalities are currently used for this purpose. Moreover the development of long-acting anti-relapse medications is currently underway along with the further improvement of high-tech reconstructive surgical methods for the intervention on the organs of the urinary system. At the same time, the nephroprotective potential of the natural physical factors, such as therapeutic muds, e.g. peloids, remains poorly explored even though their well apparent thermophysical properties, unique organic and mineral composition, and saturation with biologically active compounds are well known long ago. The systemic response to peloid therapy manifests itself as the changes in the metabolism of the intercellular matrix and collagen of the connective tissue associated with the alterations in the process of fibrogenesis and the development of tubulointerstitial disorders. The direct and indirect influence of peloids on the connective tissue is possible. The indirect effects are attributable to the peloid impact on the antioxidant status, immunity, hormonal regulation, and metabolic processes. These findings suggest the necessity of the relevant experimental and clinical studies for the evaluation of the influence of peloid therapy on the structure and metabolism of the connective tissue in the kidneys including dynamics of the markers of inflammation, proliferation and fibrogenesis, and the hormonal status of the patients suffering from chronic pyelonephritis based on the application of the modern technologies in accordance with the requirements of evidence-based medicine.

The application of the herbal tea for the combined treatment of the patients presenting with chronic acalculous cholecystitis

The objective of the present study was to evaluate the effectiveness of the application of the herbal tea having an original composition for the combined treatment of the patients presenting with chronic acalculous cholecystitis. A total of 84 patients with this condition at the age varying from 18 to 60 years were available for the examination. The patients of the control group (n = 42) were treated with the use of the basal pharmacotherapeutic modalities while those in the main group (n - 42) received. in addition. the herbal tea of original composition following the specially elaborated regimen for its consumption. It was shown that the inclusion of this herbal tea in the sstandard pharmacotherapy resulted in the significant reduction of the activity of the key enzymes of the hepatobiliary system. such as alanine aminotransferase. aspartate aminotransferase. alkaline phosphatase. and gamma-glutamyl transferase. Simultaneously. the motor function of the gallbladder was considerably improved while the severity of the clinical symptoms of the disease decreased. These beneficial changes were less apparent in the control patients treated with standard pharmacotherapy alone.

The medical rehabilitation of the children presenting with atopic dermatitis (a literature review)

Atopic dermatitis takes the predominant position in the structure of skin pathologies in the children of various age. Both the scientifically based forecasts and the data of numerous investigations give evidence not only of the significant increase in the number of patients presenting with this condition but also of the growing severity of this disease. Taken together, these facts account for the serious medico-social importance of the problems arising in connection with this pathology. The introduction of the eliminative actions, a hypoallergenic diet, local and systemic pharmacotherapeutic modalities do not always allow to prevent or arrest the inflammatory process and achieve the long-standing remission. The high frequency of undesirable reactions to the pharmacological products turns the attention of many clinicians to the application of the non-pharmacological factors and methods for the treatment of atopic dermatitis in the children. The main objectives of physical therapy in the case of atopic dermatitis include the normalization of the state of the central and vegetative nervous system, the achievement of hyposensitization, sedative, anti-toxic, and anti-inflammatory effects, as well as the application of the dissolving, trophic, and antipruritogenic agents, strengthening of the general health status of the children.

Anxiety disorders in late life: A comprehensive review

Anxiety disorders are not uncommon in late life. These disorders are associated with greater rates of comorbidities with other psychiatric and medical disorders. Anxiety disorders are also associated with greater morbidity and mortality in late life. These disorders are often under- and misdiagnosed in older individuals given their symptomatic overlap with other medical disorders and drug side effects. Additionally, the diagnostic criteria for anxiety disorders have been developed for younger individuals and not for older adults. Although limited, data from controlled studies indicate that both psychotherapeutic and pharmacotherapeutic modalities are beneficial in the treatment of anxiety disorders in late life.

Prostate cancer: emerging pharmacotherapeutic modalities

Prostate cancer is the most common cancer in the world due to factors like old age, family history, ethnicity, diet and some elements exposure, with lot of controversies regarding prevention of prostate cancer. Though the exact pathogenesis is not clear, epidemiological evidence supports a relationship between prostate cancer and hormone levels. In this review article we are focusing on the advances in different pharmacotherapeutic modalities i.e. Chemoprevention, Prostate-Specific Antigen, Hormone Therapy, Anti-Inflammatory Drugs, SERM, Vaccines, Cryotherapy, Watchful Waiting, Radiotherapy and Androgen Deprivation Therapy etc. and new possibilities with strategies to provide maximal benefits while effectively balancing risks for the prostate cancer treatment.

The placebo effect: Why we should care

Contrary to its definition, a placebo is far from an inert substance but carries meaningful responses that can mediate significant outcome results in pharmacotherapeutic studies. The advent of detailed studies and modern imaging techniques have provided the basis to understand the underlying mechanisms of the placebo effect, as well as its localization to determined brain centers. Designing clinical trials using principles of classical conditioning to mediate placebo effects may enhance treatment outcomes and provide novel pharmacotherapeutic modalities.

English

During the past decades, researchers involved in the development of ophthalmic pharmaceuticals have understood that ophthalmic drug delivery is a challenging subject for optimization. Normal vision is dependent upon the optimal functioning of ocular barriers and intact membranes that function to selectively regulate the environment of ocular tissues. Novel pharmacotherapeutic modalities have aimed to overcome the biological barriers which can impede efficient ocular drug delivery. To explore the impact of ocular barriers on research related to ophthalmic drug delivery and targeting, herein we provide a review of the literature of work carried out on the biological constraints and new approaches to ophthalmic drug delivery.

Atrial Fibrillation in Singapore and Malaysia: Current Trends and Future Prospects

Atrial fibrillation (AF) imposes substantial burdens of morbidity and impaired health-related quality of life, and significantly increases sufferers' risk of having a cardiovascular event, in particular a stroke. Prevalence of AF in Asia and the associated healthcare costs are likely to have been underestimated and are expected to increase due to greater awareness, population ageing and increasing prevalence of associated risk factors and comorbidities. The AF management paradigm is shifting from a conventional focus on achieving heart rate or rhythm control, towards endeavouring to use the safest agents available to reduce patients' symptoms and improve their quality of life and cardiovascular outcomes. No new anti-AF drugs have been introduced for decades and existing pharmacotherapeutic modalities have potentially serious side effects as well as sub-optimal efficacy in converting to and maintaining normal sinus rhythm and preventing recurrence. There is an unmet need for better anti-arrhythmic drugs that are well tolerated, efficacious, cost-effective and have a more favourable safety profile than current options. Although the perfect agent remains to be discovered, some promising new anti-arrhythmic drugs have the potential to overcome certain limitations of established approaches to AF management.

Invited Review: The Medical Management of Obesity and the Role of Pharmacotherapy: An Update

The prevalence of obesity in the United States has been increasing since the 1980s and has become a public health concern. The etiology of obesity is complex and includes a host of genetic influences in addition to overconsumption of energy and a sedentary lifestyle. Obesity is strongly associated with several chronic diseases, such as cardiovascular disease and diabetes, and thus accounts for significant morbidity and mortality. The previous failures of short‐term therapy for obesity have led experts to recognize that obesity is a chronic disease that should be treated with long‐term programs to ensure the best chance for maintenance of weight loss. In addition, clinical studies have demonstrated that a modest weight loss of 5% to 10% can produce significant decreases in comorbidities. This articles summarizes the current medical approach to the treatment of obesity and includes strategies for diet modification, exercise therapy, and lifestyle change. The rationale and appropriateness of pharmacotherapy are discussed, followed by case histories that highlight the management of obesity and its comorbidities by using diet, exercise, and pharmacotherapeutic modalities.

A systematized approach to the management of the depressed and anxious patient

The coexistence of depression and anxiety is a common occurrence that frequently poses diagnostic and treatment challenges in the clinical setting. As epidemiological studies continue to confirm the enormous prevalence of this comorbid condition, the separation in diagnosis and treatment between depression and anxiety has become increasingly less pronounced. Additionally, the discovery that pharmacotherapeutic modalities have a broader range of efficacy, often overlapping both depression and anxiety, has led to an evolving reclassification of treatment, away from ‘antidepressants’ and ‘anxiolytics’ toward one based on mechanism of action. A rational approach to the systematized management of the various comorbidities of depressive and anxiety disorders is discussed.