Pharmacological Treatment Options Research Articles

Conventional and Novel Treatment Strategies for Porokeratoses: A Narrative Review.

Porokeratoses are a heterogenous group of autoinflammatory keratinization disorders all characterized by the presence of a cornoid lamella. In addition to gene mutations affecting the mevalonate pathway, environmental factors such as UV radiation, immunosuppression, trauma, and infection are also thought to contribute to porokeratoses. To date, there are no management guidelines or levels of evidence for commonly used pharmacologic and non-pharmacologic treatment options for porokeratoses. Conventional treatment strategies encompass topical and systemic drugs (e.g., salicylic acid, topical glucocorticoids, and retinoids), phototherapy, laser, and surgical interventions. Better insights into the pathogenesis of porokeratoses have paved the way for the development of novel therapeutic approaches, such as topical statins or the use of monoclonal antibodies. This narrative review aims to summarize both conventional and novel treatment options, including their level of evidence, advantages, and disadvantages.

Pathophysiology and therapeutic options for cirrhotic portal hypertension.

Portal hypertension represents the primary non-neoplastic complication of liver cirrhosis and has life-threatening consequences, such as oesophageal variceal bleeding, ascites, and hepatic encephalopathy. Portal hypertension occurs due to increased resistance of the cirrhotic liver vasculature to portal blood flow and is further aggravated by the hyperdynamic circulatory syndrome. Existing knowledge indicates that the profibrogenic phenotype acquired by sinusoidal cells is the initial factor leading to increased hepatic vascular tone and fibrosis, which cause increased vascular resistance and portal hypertension. Data also suggest that the phenotype of hepatic cells could be further impaired due to the altered mechanical properties of the cirrhotic liver itself, creating a deleterious cycle that worsens portal hypertension in the advanced stages of liver disease. In this Review, we discuss recent discoveries in the pathophysiology and treatment of cirrhotic portal hypertension, a condition with few pharmacological treatment options.

Atopic Dermatitis: Clinical Aspects and Treatments.

To review issues related to atopic dermatitis, including its classification, clinical presentation, potential triggers, and treatment options. This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. After participating in this educational activity, the participant will:1. Synthesize a differential diagnosis for atopic dermatitis (AD).2. Explain the classification of AD cases.3. Select triggers or exacerbating factors for AD.4. Explain pharmacologic and nonpharmacologic treatment options for patients with AD.

Novel and complementary treatment approaches in attention-deficit/hyperactivity disorder.

To provide an updated review of novel and complementary treatment approaches for children and adolescents with attention-deficit/hyperactivity disorder. The evidence for complementary attention-deficit/hyperactivity disorder treatments is often promising, but limited to small, unblinded studies. Recent evidence from larger, more rigorous studies reveals that most of these treatments have modest efficacy. Omega-3 polyunsaturated fatty acids, saffron, broad spectrum micronutrients, and physical exercise have potential benefits that seem to outweigh known risks. However, neurofeedback, cognitive training, and trigeminal nerve stimulation need further research to determine whether specific sub-groups of children/adolescents with attention-deficit/hyperactivity disorder would benefit long-term with their associated tolerable risks. There is not sufficient evidence for complementary treatments to be recommended as substitutes for first-line pharmacological and psychosocial treatment options. Nonetheless, some adjuvant therapies to currently recommended attention-deficit/hyperactivity disorder treatments can be safe. Physicians should be familiar with existing and emerging complementary treatments to help guide families.

Pharmacologic Treatment of Chronic Constipation.

Chronic constipation is a common disease that can impair the quality of life, with a prevalence of 14% globally and 16.5% in South Korea. Straining, hard stools, the sensation of incomplete evacuation, the sensation of anorectal blockage, and manual maneuvers to facilitate defecation are the related symptoms of chronic constipation. On the other hand, medications commonly referred to as laxatives are the essentials of treatment for constipation compared to non-pharmacological treatment, such as lifestyle modifications, biofeedback, or surgery. Unfortunately, there is still an unmet need to determine if pharmacological treatment for constipation is being administered appropriately. Therefore, there are many disadvantages as to whether the indications and side effects of laxatives are adequately considered and prescribed as the primary treatment modality for constipation in a real clinical situation in Korea. Laxatives are generally recommended as the next step for patients in whom organic causes have been excluded and have not responded to initial non-pharmacologic therapies such as dietary fiber intake and exercise. Laxatives can be classified as bulk-forming laxatives, osmotic laxatives, stimulant laxatives, and other novel laxatives. On the other hand, there are distinct mechanisms underlying constipation, and appropriate administration is the most decisive. Therefore, the present investigators prepared this review to discuss appropriate pharmacological strategies for chronic constipation in Korea. Moreover, this paper also includes suggestions for appropriate pharmacological treatment options for special patient populations.

Evaluation and Pharmacologic Management of Paroxysmal Sympathetic Hyperactivity in Traumatic Brain Injury.

Paroxysmal sympathetic hyperactivity (PSH) can occur in up to 10% of severe traumatic brain injury (TBI) patients and is associated with poorer outcomes. A consensus regarding management is lacking. We provide a practical guide on the multi-faceted clinical management of PSH, including pharmacological, procedural and non-pharmacological interventions. In addition to utilizing a standardized assessment tool, the use of medications to manage sympathetic and musculoskeletal manifestations (including pain) is highlighted. Recent studies investigating new approaches to clinical management are included in this review of pharmacologic treatment options. While studies regarding pharmacologic selection for PSH are limited, this paper suggests a clinical approach to interventions based on predominant symptom presentation (sympathetic hyperactivity, pain and/or muscle hypertonicity) and relevant medication side effects.

Case report: CBD: THC medical cannabis in the treatment of neuropathic pain

Chronic neuropathic pain affects millions of adults worldwide, creating a direct impact on quality of life. The control of neuropathic pain is a challenge in daily clinical practice. Current pharmacological treatment options for neuropathic pain afford substantial benefit for only a few people, often with adverse effects that outweigh the benefits. There is a need to explore other treatment options, with different mechanisms of action for treatment of this pathology. The use of cannabis and cannabinoid products is a growing area of research for the treatment of different pathologies including neuropathic pain. The studies developed so far and what is observed in the clinical practice, demonstrate the importance of this medication in a pathology of such complexity and difficult control, besides of that, more randomized controlled studies are needed to confirm medical cannabis an adjunct medication in the treatment of neuropathic pain. This case report aims to demonstrate the validity of joining GMP cannabis products as an adjuvant therapy for an effective with low profile side effects treatment leading to an improvement in quality of life.

Challenges and pitfalls of youth-onset type 2 diabetes.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) are increasing. The rise in frequency and severity of childhood obesity, inclination to sedentary lifestyle, and epigenetic risks related to prenatal hyperglycemia exposure are important drivers of the youth-onset T2DM epidemic and might as well be responsible for the early onset of diabetes complications. Indeed, youth-onset T2DM has a more extreme metabolic phenotype than adult-onset T2DM, with greater insulin resistance and more rapid deterioration of beta cell function. Therefore, intermediate complications such as microalbuminuria develop in late childhood or early adulthood, while end-stage complications develop in mid-life. Due to the lack of efficacy and safety data, several drugs available for the treatment of adults with T2DM have not been approved in youth, reducing the pharmacological treatment options. In this mini review, we will try to address the present challenges and pitfalls related to youth-onset T2DM and summarize the available interventions to mitigate the risk of microvascular and macrovascular complications.

Pharmacotherapy of Chronic Neuropsychiatric Conditions During Pregnancy

Many pregnant persons will experience neuropsychiatric conditions during pregnancy, including migraine, attention deficit disorder, depression, and anxiety. Treatment of each of these conditions requires shared decision-making among the individual, family, and health care team. Although medications may include risk, the benefits often outweigh the potential fetal risks. In this article, we review pharmacologic treatment options for each of these conditions and appropriate use in pregnancy to maintain the stability of conditions and to optimize maternal and fetal outcomes.

Epigenetics of Fear, Anxiety and Stress - Focus on Histone Modifications.

Fear-, anxiety- and stress-related disorders are among the most frequent mental disorders. Given substantial rates of insufficient treatment response and often a chronic course, a better understanding of the pathomechanisms of fear-, anxiety- and stress-related disorders is urgently warranted. Epigenetic mechanisms such as histone modifications - positioned at the interface between the biological and the environmental level in the complex pathogenesis of mental disorders - might be highly informative in this context. The current state of knowledge on histone modifications, chromatin-related pharmacology and animal models modified for genes involved in the histone-related epigenetic machinery will be reviewed with respect to fear-, anxiety- and stress-related states. Relevant studies, published until 30th June 2022, were identified using a multi-step systematic literature search of the Pub- Med and Web of Science databases. Animal studies point towards histone modifications (e.g., H3K4me3, H3K9me1/2/3, H3K27me2/3, H3K9ac, H3K14ac and H4K5ac) to be dynamically and mostly brain region-, task- and time-dependently altered on a genome-wide level or gene-specifically (e.g., Bdnf) in models of fear conditioning, retrieval and extinction, acute and (sub-)chronic stress. Singular and underpowered studies on histone modifications in human fear-, anxiety- or stress-related phenotypes are currently restricted to the phenotype of PTSD. Provided consistent validation in human phenotypes, epigenetic biomarkers might ultimately inform indicated preventive interventions as well as personalized treatment approaches, and could inspire future innovative pharmacological treatment options targeting the epigenetic machinery improving treatment response in fear-, anxiety- and stressrelated disorders.

Novel Method to Assess Treatment Effcacy in Preclinical Peripheral Arterial Disease Studies

Background: Peripheral arterial disease (PAD), a condition caused by atherosclerotic narrowing or occlusion of blood vessels in the lower extremities, affects ~200 million adults globally and lacks effective treatment options to improve limb function. Cilostazol is the only approved pharmacological treatment option for PAD patients, but its effect on walking performance is modest and the drug is not widely used clinically. Over the past several decades, numerous therapies (drug, gene, and cell-based) have shown promise in the preclinical setting but failed to achieve primary outcomes in clinical trials. While the failure of therapeutic translation is complex, most preclinical studies have employed perfusion recovery as a primary outcome variable whereas most clinical trials in PAD patients employ the six-minute walk test. Although perfusion is an important contributor to limb function and walking performance, assessing preclinical therapeutics solely via perfusion recovery may be a flawed approach. Objective: To address the need for a more comprehensive method to assess the effcacy of preclinical PAD therapeutics, we aimed to develop a protocol to assess hindlimb function that incorporates assessment of muscle power and perfusion across a six-minute testing period. Methods: To assess muscle contractile performance, the tibialis anterior or plantarflexor muscles were carefully exposed and the distal tendon mounted to the force-length controller (Aurora Scientific) and the muscles were stimulated via the sciatic nerve in anesthetized C57BL6 mice. After obtaining isometric forces, a six-minute functional test was performed using repeated isotonic (shortening) contractions against a submaximal load (30% or 45% of the reference force). Muscle fatigue was measured as a change in power across the testing period. Throughout the test, laser Doppler flowmetry was used to measure muscle blood flow. Hindlimb ischemia was used as an experimental model of PAD. Results: In healthy mice without PAD, the test produced the expected dose-dependent relationship between fatigue and workload with contractions performed at 30% of the reference force having less fatigue compared to 45% of the reference force ( P=0.0051), without a significant difference in muscle blood flow between the conditions. Compared the mice that received a sham surgery, those subjected to hindlimb ischemia displayed significantly lower maximal isometric forces (1514 ± 118 mN vs. 880 ± 85 mN, P=0.0001) and power at 35% maximal force (280 ± 12 vs. 105 ± 46 watts/kg, P=0.0002). Whereas sham mice lost ~25% power across the six-minute test, HLI mice displayed a ~70% loss of power. Regarding muscle blood flow, sham mice increased blood flow ~250% whereas HLI mice were only able to increase blood flow to ~105% ( P<0.001). Conclusions: This newly developed protocol successfully combines isotonic muscle function and limb perfusion assessments in the hindlimb of mice and can detect differences between healthy and PAD mice. Future work is needed to fully evaluate the accuracy and sensitivity of this method to select therapeutics in preclinical PAD models. This study was supported by National Institutes of Health (NIH) grant R01-HL149704 (T.E.R.). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy and tolerability of brexpiprazole - a new antipsychotic drug from the group of dopamine D2 receptor partial agonists.

Brexpiprazole is a new antipsychotic drug from the group of dopamine D2/D3 receptor partial agonists. It represents a development of the second-generation antipsychotics and is an important addition to the pharmacological treatment options for schizophrenia. The purpose of this article is to present, illustrated by the case of brexpiprazole, how advances in the pharmacological properties of new antipsychotics translate into improved results in the treatment of schizophrenia, not only in terms of symptom reduction, but also in terms of functional improvement. The ratio of activation to blocking of the D2/D3 receptor is lower for brexpiprazole than for aripiprazole and cariprazine, which may translate into a lower risk of akathisia. Brexpiprazole has also stronger antihistaminic activity, which is likely to be associated with a stronger sedative effect, a lower risk of akathisia, excessive agitation and insomnia. Brexpiprazole meets the traditional requirements for an antipsychotic drug's efficacy, i.e., compared to placebo, it brings a greater reduction in schizophrenia symptoms in short-term studies and prevents schizophrenia relapses in long-term follow-up. The highest antipsychotic efficacy was found with the highest registered dose (4 mg/day). In addition to reducing positive symptoms, brexpiprazole treatment also leads to a reduction in negative and depressive symptoms, as well as anxiety. It has also a positive effect on patients' social and personal functioning and quality of life. This action of the drug is in line with the expectations of patients and their families regarding effective treatment. It should not only reduce symptoms, but also enable a return to health, i.e., a state that, in addition to optimal health and a sense of psychological well-being, also makes it possible to maintain proper social relations.

Pharmacological treatments for psychotic depression

Despite the overall efficacy of antidepressant and antipsychotic combination therapy for the treatment of psychotic depression, data on the most appropriate choice of individual drugs for the combination treatment are limited. Researchers recently conducted a network meta‐analysis to compare the efficacy and safety of various pharmacological treatment options for patients who had major depressive episodes with psychotic features (Oliva et al., 2024).

Efficacy of patient education and duloxetine, alone and in combination, for patients with multisystem functional somatic disorder: Study protocol for the EDULOX trial

BackgroundMultisystem functional somatic disorder is characterized by specific patterns of persistent physical symptoms with a complex biopsychosocial etiology. The disorder can lead to disability and personal suffering. Current treatment options require specialized settings, therefore patients often wait a long time to receive specific treatment.Patient education is considered important in most treatment programs, but has only been investigated sparsely as a stand-alone treatment. Pharmacological treatment is limited to tricyclic antidepressants in low doses with no antidepressant properties. Duloxetine has been found effective in single organ functional disorders. As a treatment for multisystem functional somatic disorder, duloxetine could reduce symptoms and treat comorbid anxiety and depression. It may furthermore enhance the effect of patient education through a hypothesized effect on cognitive functioning. The purpose of the EDULOX trial is to study psycho-EDUcation and duLOXetine alone and in combination. MethodsThis is a nested study design. The parent trial “EDULOX1” (n = 424) will compare a patient education program with enhanced usual care in an open-labelled, randomized controlled trial. In addition to this, eligible participants will furthermore receive either duloxetine or active placebo in the nested, double-blinded, randomized controlled trial, “EDULOX2” (n = 212). Patient and clinician reported outcomes will be collected through questionnaires. ConclusionThe EDULOX trial may establish evidence for treatments applicable for the majority of patients with multisystem functional somatic disorder. If effective, duloxetine would be a more tolerable pharmacological treatment option that can target comorbid depression and anxiety, and potentially boost the effect of patient education.Trial registration numberThe study is registered at www.clinicaltrials.gov (NCT06232473) and the internal list of research projects at the Region of Central Denmark (Case number 1-16-02-305-23). Approval from the Danish Medical Research Ethics Committees (Case number: 2212291) and the Danish Medicines Agency was obtained under EudraCT Number: 2022-002780-30 and Sponsor's Protocol Code Number: 9515.

Identification and characterization of migraine in pregnancy: A Norwegian registry-based cohort study.

Migraine is common in women of reproductive age. Migraine's episodic manifestation and acute and preventive pharmacological treatment options challenge studying drug safety for this condition during pregnancy. To improve such studies, we aimed to develop algorithms to identify and characterize migraines in electronic healthcare registries and to assess the level of care. We linked four registries to detect pregnancies from 2009-2018 and used three algorithms for migraine identification: i) diagnostic codes, ii) triptans dispensed, and iii) a combination of both. We assessed migraine severity using dispensed drugs as proxies. ICD-10 diagnostic subcodes of migraine (G43) allowed the allocation of four subtypes: complicated and/or status migrainosus; with aura; without aura; other/unspecified. We included 535,089 pregnancies in 367,908 women with available one-year lookback. The prevalence of migraines identified was 2.9%-4.3% before, and 0.8%-1.5% during pregnancy, depending on algorithm used. Pregnant women with migraine were mostly managed in primary care. Primary care data in combination with drug dispensation records were instrumental for identification of migraine in electronic healthcare registries. Data from secondary care and drug dispensations allow better characterization of migraines. Jointly, these algorithms may contribute to improved perinatal pharmacoepidemiological studies in this population by addressing confounding by maternal migraine indication.

Mitragynine (Kratom)-Withdrawal behaviour and cognitive impairments can be ameliorated by an epigenetic mechanism.

Kratom is a preparation from Mitragyna speciosa, which is used as a natural drug preparation for many purposes around the world. However, an overdose of Kratom may cause addiction-like problems including aversive withdrawal states resulting in cognitive impairments via unknown mechanisms. Its main psychoactive alkaloid is mitragynine, showing opioid-like properties. Here, we analysed the neuropharmacological effects of mitragynine compared with morphine withdrawal in rats and searched for a pharmacological treatment option that may reverse the occurring cognitive deficits that usually aggravate withdrawal. We found that withdrawal from 14-day mitragynine (1-10mg·kg-1·day-1) treatment caused dose-dependent behavioural withdrawal signs resembling those of morphine (5mg·kg-1·day-1) withdrawal. However, mitragynine (5 and 10mg·kg-1·day-1) withdrawal also induced impairments in a passive avoidance task. Mitragynine withdrawal not only reduced hippocampal field excitatory postsynaptic potential (fEPSP) amplitudes in basal synaptic transmission and long-term potentiation (LTP) but also reduced epigenetic markers, such as histone H3K9 and H4K12 expression. At the same time, it up-regulates HDAC2 expression. Targeting the epigenetic adaptations with the HDAC inhibitor, SAHA, reversed the effects of mitragynine withdrawal on epigenetic dysregulation, hippocampal input/output curves, paired-pulse facilitation, LTP and attenuated the cognitive deficit. However, SAHA amplified the effects of morphine withdrawal. The data from this work show that changes in histone expression and downstream hippocampal plasticity may explain mitragynine, but not morphine, withdrawal behaviours and cognitive impairments. Thus, it may provide a new treatment approach for aversive Kratom/mitragynine withdrawal and addiction.

Therapeutic role of yoga in hypertension.

Systemic hypertension is an established risk factor for coronary artery disease and cerebrovascular accident and control of blood pressure reduces the risk of a major cardiovascular event. Both non-pharmacological and pharmacological treatment options are available to treat hypertension. Yoga, recently received more attention as a treatment modality for various lifestyle disorders, even though practiced in India since ancient times. In this review, we are analyzing the role of yoga in the treatment of systemic hypertension.

Isradipine, an L-type calcium channel blocker, attenuates cocaine effects in mice by reducing central glutamate release

Substance abuse disorder is a chronic condition for which pharmacological treatment options remain limited. L-type calcium channels (LTCC) have been implicated in drug-related plasticity and behavior. Specifically, dopaminergic neurons in the mesocorticolimbic pathway express Cav1.2 and Cav1.3 channels, which may regulate dopaminergic activity associated with reward behavior. Therefore, this study aimed to investigate the hypothesis that pre-administration of the LTCC blocker, isradipine can mitigate the effects of cocaine by modulating central glutamatergic transmission. For that, we administered isradipine at varying concentrations (1, 7.5, and 15 μg/μL) via intracerebroventricular injection in male Swiss mice. This pretreatment was carried out prior to subjecting animals to behavioral assessments to evaluate cocaine-induced locomotor sensitization and conditioned place preference (CPP). The results revealed that isradipine administered at a concentration of 1 μg/μL effectively attenuated both the sensitization and CPP induced by cocaine (15 mg/kg, via i. p.). Moreover, mice treated with 1 μg/μL of isradipine showed decreased presynaptic levels of glutamate and calcium in the cortex and hippocampus as compared to control mice following cocaine exposure. Notably, the gene expression of ionotropic glutamate receptors, AMPA, and NMDA, remained unchanged, as did the expression of Cav1.2 and Cav1.3 channels. Importantly, these findings suggest that LTCC blockage may inhibit behavioral responses to cocaine, most likely by decreasing glutamatergic input in areas related to addiction.

Bibliometric Analysis of the Highly Cited Articles on Biomarker Discovery for Irritable Bowel Syndrome from 1985 to 2023.

With an increasing number of patients with irritable bowel syndrome (IBS) and availability of many pharmacological treatment options, there is an urgent need to develop and validate IBS biomarkers for prognostication and selection of patients for treatment and monitoring. The usage of investigations is limited because of its invasive nature, poor patient acceptability, and sampling variability. The bibliometric analysis of biomarker discovery of IBS articles will help in understanding current research trends of biomarkers study of IBS. To study the most highly cited articles from literature search on the biomarker for IBS to provide simple educational source. A bibliometric literature review-the electronic search by terms and keywords were searched in PubMed databases. The commonly cited article was searched from 1985 to 2023. The total citation number was received from knowledge search engines like Google Scholar. Articles were classified according to number of citations, year of publication, journal name, authors, publications from continents of countries of origin, research hotspots, and article title. The articles written in English and other languages were included in the analysis. Total number of articles found was 1,449. The mean number of citations per article was 177. The citation count ranged from 24 to 1,191. The articles with citations >30 were included in the study. The majority of articles (n = 175) were published between 2016 and 2023. Among the highly cited articles, the most prevalent topic of interest was biomarker discovery. Most of the articles were original articles. The continent of origin for most of the articles was the United States of America (n = 163), Europe (n = 145), United Kingdom (n = 23), Asia (n = 23), Australia (n = 14), etc. Conclusion: The analysis of articles on biomarker discovery for IBS will help in understanding the requirement for unmet need for the discovery of biomarker for IBS. The current bibliometric study has highlighted the work of authors with advanced knowledge about discovery of the biomarker for IBS. This study will help to identify the current trends in the biomarker discovery for IBS and help for the further evolution of the field.

What a pain in the … back: a review of current treatment options with a focus on naproxen sodium.

Non-specific low back pain (LBP) represents a challenging and prevalent condition that is one of the most common symptoms leading to primary care physician visits. While established guidelines recommend prioritizing non-pharmacological approaches as the primary course of action, pharmacological treatments are advised when non-pharmacological approaches are ineffective or based on patient preference. These guidelines recommend non-steroidal anti-inflammatory drugs (NSAIDs) or skeletal muscle relaxers (SMRs) as the first-line pharmacological options for acute or subacute LBP, while NSAIDs are the exclusive first-line pharmacological option for chronic LBP. Although SMRs are generally effective for acute LBP, the available evidence does not support the view that they improve functional recovery, and their comparative efficacy to NSAIDs and other analgesics remains unknown, while studies have shown them to introduce adverse events without significantly reducing LBP. Moreover, opioids continue to be widely prescribed for LBP, despite limited evidence for effectiveness and known risks of addiction and overdose. Broader use of non-opioid pharmacotherapy, including the appropriate use of OTC options, is critical to addressing the opioid crisis. The balance of evidence indicates that NSAIDs have a favorable benefit-risk profile when compared to other available pharmacological treatment options for non-specific LBP, a condition that is primarily acute in nature and well-suited for self-treatment with OTC analgesics. While clinical guidelines do not differentiate between NSAIDs, evidence indicates that OTC naproxen sodium effectively relieves pain across multiple types of pain models, and furthermore, the 14-h half-life of naproxen sodium allows sustained, all day pain relief with reduced patient pill burden as compared to shorter acting options. Choosing the most appropriate approach for managing LBP, including non-pharmacological options, should be based on the patient's condition, severity of pain, potential risks, and individual patient preference and needs.