Therapeutic Drug Classes Research Articles

Tunicamycin Potentiates Antifungal Drug Tolerance via Aneuploidy in Candida albicans.

ABSTRACTHow cells exposed to one stress are later able to better survive other types of stress is not well understood. In eukaryotic organisms, physiological and pathological stresses can disturb endoplasmic reticulum (ER) function, resulting in “ER stress.” Here, we found that exposure to tunicamycin, an inducer of ER stress, resulted in the acquisition of a specific aneuploidy, chromosome 2 trisomy (Chr2x3), in Candida albicans. Importantly, the resulting aneuploidy also conferred cross-tolerance to caspofungin, a first-line echinocandin antifungal, as well as to hydroxyurea, a common chemotherapeutic agent. Exposure to a range of tunicamycin concentrations induced similar ER stress responses. Extra copies of one Chr2 gene, MKK2, affected both tunicamycin and caspofungin tolerance, while at least 3 genes on chromosome 2 (ALG7, RTA2, and RTA3) affected only tunicamycin and not caspofungin responses. Other Chr2 genes (RNR1 and RNR21) affected hydroxyurea tolerance but neither tunicamycin nor caspofungin tolerance. Deletion of components of the protein kinase C (PKC) or calcineurin pathways affected tolerance to both tunicamycin and caspofungin, supporting the idea that the ER stress response and echinocandin tolerance are regulated by overlapping stress response pathways. Thus, antifungal drug tolerance can arise rapidly via ER stress-induced aneuploidy.

Phone a pharmacist: Telepharmacy services at freestanding emergency departments

AbstractIntroductionEmergency medicine (EM) pharmacy practice has experienced significant growth in the past decade, but the scope of services provided for freestanding emergency departments (FSEDs) has not been previously described.ObjectivesThe primary objective was to describe EM pharmacist interventions provided through telepharmacy services for three FSEDs.MethodsThis was a retrospective chart review conducted in three FSEDs that are part of a large health system. EM pharmacists provide remote clinical coverage for the FSEDs. Pharmacist interventions for FSED patients between 1 January 2017 and 31 December 2018 were eligible for inclusion. Documentation related to non‐direct patient care activities was excluded. Drug therapy recommendations were categorized by therapeutic drug class and the proportion associated with Institute for Safe Medication Practices (ISMP) high‐alert medications was analyzed. The clinical significance of a random sample of drug therapy recommendations was rated using a validated scale. Data was analyzed descriptively and a weighted Kappa statistic was calculated to assess inter‐rater reliability.ResultsA total of 4313 interventions met inclusion criteria with drug therapy recommendations accounting for 38.4% of all interventions. Of 1664 drug therapy recommendations, there were 1424 linked to a medication with the most frequently implicated therapeutic classes being antimicrobial agents (n = 732; 51.4%), vaccines (n = 168; 11.8%), and cardiovascular agents (n = 90; 6.3%). ISMP high‐alert medications accounted for 11% (n = 157) of these recommendations with antithrombotic agents (n = 51; 32.5%), insulin (n = 34; 21.7%), and opioids (n = 20; 12.7%) most frequently implicated. In a random sample of drug therapy recommendations, 19.2% were rated as significant errors by both reviewers with moderate inter‐rater reliability (κ = 0.55; SE 0.09). When assessing the value of service, 59% of interventions were rated as significant by both reviewers with fair inter‐rater reliability (κ = 0.22; SE 0.05).ConclusionEM pharmacists provided clinically significant drug therapy recommendations through telepharmacy services which may represent a novel approach to optimize patient care in FSEDs.

Correlation between Stroke Risk and Systolic Blood Pressure in Patients over 50 Years with Uncontrolled Hypertension: Results from the SYSTUP-India Study.

Objectives To assess mean systolic and diastolic blood pressure (SBP and DBP) levels in patients ≥50 years with uncontrolled hypertension (HTN) and evaluate the correlation between BP and stroke risk. It also assessed therapeutic drug classes prescribed in these patients. Methods A cross-sectional, observational study was conducted at 176 outpatient centers across India, including patients aged ≥50 years with elevated SBP (≥140 mmHg). The relationship between stroke risk, calculated using Stroke Riskometer™, and mean SBP, mean DBP, and other risk factors was evaluated using Pearson correlation coefficient and logistic regression analysis. Results The study included 3791 patients (men, 60.0%; mean age: 62.1 ± 8.3 years; mean BMI: 27 kg/m2) with mean SBP 157.3 ± 12.8 mmHg and mean DBP 89.8 ± 9.7 mmHg. Five-year stroke risk in 33.9% and 10-year stroke risk in 70% patients were moderate to severe. A ~4% increase in both 5- and 10-year stroke risk with each 1 mmHg increase in mean SBP (p < 0.0001) was seen. However, mean DBP did not exhibit any significant correlation with 5-year (p = 0.242) or 10-year (p = 0.8038) stroke risk. There was a positive correlation between mean SBP and patient age, comorbid diabetes, and smoking and alcohol habits (p < 0.0001). Comorbid diabetes and smoking increased 5- and 10-year stroke risk by 2- to 5-fold. Irrespective of the risk category, most patients received antihypertensive therapy with an angiotensin receptor blocker. Conclusion Findings corroborate an association between stroke risk and mean SBP. These real-world clinical findings indicate that efforts are required to improve primary prevention of stroke and reduce the prevalence of recurrent stroke in India.

Next generation proteomics with drug sensitivity screening identifies sub-clones informing therapeutic and drug development strategies for multiple myeloma patients

With the introduction of novel therapeutic agents, survival in Multiple Myeloma (MM) has increased in recent years. However, drug-resistant clones inevitably arise and lead to disease progression and death. The current International Myeloma Working Group response criteria are broad and make it difficult to clearly designate resistant and responsive patients thereby hampering proteo-genomic analysis for informative biomarkers for sensitivity. In this proof-of-concept study we addressed these challenges by combining an ex-vivo drug sensitivity testing platform with state-of-the-art proteomics analysis. 35 CD138-purified MM samples were taken from patients with newly diagnosed or relapsed MM and exposed to therapeutic agents from five therapeutic drug classes including Bortezomib, Quizinostat, Lenalidomide, Navitoclax and PF-04691502. Comparative proteomic analysis using liquid chromatography-mass spectrometry objectively determined the most and least sensitive patient groups. Using this approach several proteins of biological significance were identified in each drug class. In three of the five classes focal adhesion-related proteins predicted low sensitivity, suggesting that targeting this pathway could modulate cell adhesion mediated drug resistance. Using Receiver Operating Characteristic curve analysis, strong predictive power for the specificity and sensitivity of these potential biomarkers was identified. This approach has the potential to yield predictive theranostic protein panels that can inform therapeutic decision making.

Slowing Diabetic Kidney Disease Progression: Where Do We Stand Today?

This article aims to provide an overview of the major clinical trials conducted within the past 20 years, addressing this critical clinical need. Specifically, we will review several therapeutic drug classes that have demonstrated renoprotective potential by halting the progression of DKD.

PCN226 The Association between Polypharmacy and the Health-Related Quality of Life in Older Adults with Cancer

There is a dearth of literature on the impact of polypharmacy on patient-reported outcomes among older adults with cancer. The objective of this study was to determine the association between polypharmacy and health-related quality of life (HRQoL) in older adults with cancer. This is a cross-sectional retrospective study using data from 2012-2016 longitudinal panels of the Medical Expenditure Panel Survey (MEPS). Adults aged > 65 years and with a diagnosis of cancer during the baseline year were included in the study. Polypharmacy was assessed based on the number of medications and defined as taking 5 or more therapeutic drug classes concurrently. HRQoL was measured using the physical component summary (PCS) score and mental component summary (MCS) score reported based on the 12-item short form (SF-12) health survey. Statistical comparisons were performed using chi-square and Student’s t tests. Multivariable regression was used to examine the associations between the number of medications and the HRQoL measures. In this study, 1,508 adults 65 years and above with cancer were included. Polypharmacy was found among 63.06% of these individuals. For the eligible population, mean PCS scores were: 38.06 (SE=0.526) (polypharmacy) and 44.93 (SE=0.555) (no polypharmacy). Mean MCS scores were: 51.77 (SE=0.368) (polypharmacy) and 53.71 (SE=0.42) (no polypharmacy). Polypharmacy was found more often among women, the south region, patients with private insurance, and patients with 3 or more CCI score. In adjusted models, each increase of a drug class used decreased PCS (coefficient=-0.735; P < .001) and MCS (coefficient=-0.303; P < .001) scores significantly. Our results suggest that an increase in number of medications decreases HRQoL scores among older adults with cancer. Interventions to reduce the number of medications taken such as deprescribing, may need to be developed to improve HRQoL among older adults with cancer.

Mechanisms and Models in Heart Failure: A Translational Approach.

Despite multiple attempts to develop a unifying hypothesis that explains the pathophysiology of heart failure with a reduced ejection fraction (HFrEF), no single conceptual model has withstood the test of time. In the present review, we discuss how the results of recent successful phase III clinical development programs in HFrEF are built upon existing conceptual models for drug development. We will also discuss where recent successes in clinical trials do not fit existing models to identify areas where further refinement of current paradigms may be needed. To provide the necessary structure for this review, we will begin with a brief overview of the pathophysiology of HFrEF, followed by an overview of the current conceptual models for HFrEF, and end with an analysis of the scientific rationale and clinical development programs for 4 new therapeutic classes of drugs that have improved clinical outcomes in HFrEF. The 4 new therapeutic classes discussed are ARNIs, SGLT2 (sodium-glucose cotransporter 2) inhibitors, soluble guanylate cyclase stimulators, and myosin activators. With the exception of SGLT2 inhibitors, each of these therapeutic advances was informed by the insights provided by existing conceptual models of heart failure. Although the quest to determine the mechanism of action of SGLT2 inhibitors is ongoing, this therapeutic class of drugs may represent the most important advance in cardiovascular therapeutics of recent decades and may lead to rethinking or expanding our current conceptual models for HFrEF.

ASSESSMENT OF CENTRAL AORTIC BLOOD PRESSURE IN PATIENTS WITH HYPERTENSION: RESULTS FROM A PAN-INDIA ASSESS CABP REGISTRY

Abstract Objective: Although central aortic blood pressure (CABP) has shown to be better predictor of cardiovascular events than brachial BP in randomized trials, the real-world clinical practice data are scarce. Our study aimed to assess brachial and CABP and illustrate the correlation between them in patients with hypertension. It also aimed to assess the therapeutic drug classes prescribed in hypertensive patients. Design and method: This was a single-visit, prospective, non-interventional, observational study of hypertensive outpatients. Data collection included clinical and demographic characteristics, brachial (sphygmomanometer) and CABP (Agedio B900 device (IEM, Stolberg, Germany) and antihypertensive treatment. Results: A total of 3989 patients were enrolled with the mean age of 56.6 ± 12.2 years. About 58.6% were male and 66.4% were obese. Mean systolic (SBP) and diastolic blood pressure (DBP) was 156 ± 15.2/ 95.6 ± 12.9 mm Hg. Mean arterial pressure was 119.4 ± 21.8 mm Hg and heart rate was 83.1 ± 14.6 bpm. The central blood pressure parameters were: central systolic blood pressure (CSBP), 139.8 ± 16.3 mm Hg; central diastolic blood pressure (CDBP), 96.1 ± 13.2 mm Hg; central pulse pressure (CPP), 43.4 ± 15.3 mm Hg; augmentation index (%), 29.1 ± 16.6; pulse wave velocity, 8.8 ± 3.8 m/s. A positive correlation was observed between SBP and CSBP (r = 0.6809, p &lt; 0.0001); DBP and CDBP (r = 0.7413, p &lt; 0.0001); and PP and CPP (r = 0.638, p &lt; 0.0001). About 83.1% patients were taking antihypertensive medications and 76.94% (n = 3163) patients were receiving monotherapy: ACE inhibitors, 6.96%, angiotensin receptor blockers, 30.92%, beta-Blockers, 12.6%, calcium channel blockers, 17.93%, diuretics, 8.54%, and alpha/central blockers, 0.17%. Combinations of two and three drugs were received by 21.6% and 1.46%, respectively Conclusions: Brachial BP was positively correlated to CABP in hypertensive patients. Majority of patients were receiving angiotensin receptor blockers as antihypertensive monotherapy.

A cross-sectional study on current prescription trends and errors in outpatient department of a Bangladeshi secondary care district hospital.

Context:The rational prescription leads to a healthy and good-quality life of a patient. Irrational, inappropriate, and unnecessary prescriptions are major therapeutic issues in Bangladesh, which can cause severe consequences.Aim:This cross-sectional study was conducted to evaluate the prescription patterns and errors as well as to review the most frequently prescribed drug classes among outpatients at a secondary hospital in Pabna, a district of Bangladesh.Methods:A total of 400 prescriptions were reviewed from March 2019 to May 2019. In this study, statistical data analysis was implemented by IBM SPSS Statistics V22 and data revealed in frequencies, mean, and percentage. Spearman's rank correlation coefficient was calculated to show the correlation between bivariate coded variables.Results:The results revealed that majority of the prescription were prescribed for females (73.5%) where proton-pump inhibitors (PPIs), analgesics, vitamins, and single antibiotics were most frequently prescribed medicine for the female patients compared to male patients. Almost half of the collected prescription contained four medicines (47%). Maximum number of prescriptions contained two (30.5%) essential drugs and among 1402 medicines of 400 prescriptions, antiulcerants were most frequently prescribed medicine (23.32%) where esomeprazole was highly prescribed generic drug (44.75%). Moreover, Spearman's rank correlation coefficient suggested that PPIs and analgesics were frequently prescribed medicines at a time for the patients (0.182). According to the age group, the study also got some significant variations in prescribing pattern. However, most common prescription errors were prescriber's name not mentioned (100%), diagnosis not mentioned (96.75%), dose not indicated (15.41%), and wrong drug name (0.36%).Conclusion:Findings of the current study represent the existing prescribing trends of different therapeutic classes of drugs and common prescription errors in a secondary health facility of Bangladesh. From this study, it is observed that physicians prescribed rationally in some cases but need to ensure rationality in all prescriptions. Continuous monitoring of drug use, development of prescribing guidelines, and training are recommended to ensure and implement good-quality prescribing practices for promoting the rational and cost-effective use of drugs.

SODIUM-GLUCOSE LINKED COTRANSPORTER 2 INHIBITOR: A NEW HORIZON IN THE TREATMENT OF TYPE-2 DIABETES

Hyperglycemia is a key therapeutic focus in the management of patients with type 2 diabetes (T2D) mellitus. The various therapeutic classes of antidiabetic drugs presently existing in the market are not sufficiently effective in maintaining long-term glycemic control in most of the diabetic patients, even when used in combination. The undesirable adverse effects of these drugs, such as hypoglycemia, weight gain, and hepatic and renal toxicity, have escalated the demand for the discovery of new and safer antidiabetic drugs. The progressive nature of T2D requires practitioners to periodically evaluate patients and intensify glucose-lowering treatment once glycemic targets are not attained. Sodium-glucose cotransporter 2 inhibitors (SGLT2-is) are the new class of antidiabetic medications that are approved (2013) by the Food and Drug Administration recently for treating diabetes. These inhibitors block the SGLT2 protein involved in glucose reabsorption from the proximal renal tubule resulting in escalated glucose excretion and lower blood glucose levels. These inhibitors exhibit favorable effects beyond glucose control, such as consistent body weight, blood pressure, and serum uric acid reductions. This review highlighted the brief updates of SGLT2-i, their benefits, and adverse effects.

Abstract PS16-22: Targeting resistance to current CDK4/6 therapies by RGT-419B, an inhibitor with optimized kinase activity spectrum

Abstract Cyclin-dependent kinases (CDKs) 4/6 inhibitors are a powerful class of therapeutic drugs for the treatment of advanced metastatic breast cancer. However, the currently approved CDK4/6 inhibitors palbociclib, ribociclib and abemaciclib have dose-limiting toxicities that require treatment holidays or reductions to sub-optimal doses, thus limiting full target inhibition. The residual CDK4/6 activity, together with persistent signaling through CDK2/cyclin E are among key resistant mechanisms that can compromise full clinical benefit. RGT-419B is a 3rd generation CDK inhibitor with an optimized kinase activity spectrum that has been discovered employing a Computer Accelerated Rational Design technology platform. RGT-419B has potent sub-nM CDK4 activity with desired degrees of selectivity against kinases such as CDK6, CDK9 and GSK3β to enable full target engagement with an improved safety profile. Furthermore, single digit nM CDK2 kinase activity has been incorporated into the design of RGT-419B to combat Cyclin E/CDK2-driven resistance. In vitro, RGT-419B showed more robust activity against palbociclib-resistant ER+ breast cancer cells than abemaciclib. In ER+ T47D breast cancer cells with overexpression of Cyclin E1, RGT-419B exhibited better antiproliferation activity than either abemaciclib or palbociclib. RGT-419B also demonstrated more durable in vivo tumor growth inhibition when compared with abemaciclib in an ER+ breast cancer xenograft model. The optimized kinase activity spectrum of RGT-419B provides an opportunity to treat ER+ breast cancer patients refractory to the existing CDK4/6 inhibitors, as either a single agent or in combination with other therapies. Citation Format: Zhi Xie, Jing Han, Zhilong Hu, Hu He, Xianqiang Sun, Fei Zhang, Jing Lin, Lili Yao, Xinjuan Wang, Liufeng Mei, Yangyang Liu, Guoyun Zhu, Xi Chen, Xiaotian Zhu, Wenge Zhong. Targeting resistance to current CDK4/6 therapies by RGT-419B, an inhibitor with optimized kinase activity spectrum [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-22.

Dual Roles of Metal-Organic Frameworks as Nanocarriers for miRNA Delivery and Adjuvants for Chemodynamic Therapy.

MicroRNA (miRNA) represents a promising class of therapeutic nucleic acid drugs, while delivery challenges remain that impede the advancement of miRNA therapy, largely because of in vivo instability and low delivery efficiency. Herein, we discover the dual roles of metal-organic framework (MOF) nanoparticles (ZIF-8) as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. The miR-34a-m@ZIF-8 complex demonstrated efficient cellular uptake and lysosomal stimuli-responsive miRNA release. Zn2+ triggered the generation of reactive oxygen species, which consequently induced apoptosis of tumor cells. Released miR-34a-m led to a remarkable decrease in expression of Bcl-2 at both mRNA and protein levels and enhanced cancer cell apoptosis. In vivo experiments showed high efficacy of using miR-34a-m@ZIF-8 to suppress tumor growth via synergistic gene/chemodynamic therapy in a mouse model of triple-negative breast cancer. Our work demonstrates MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy.

Artemisinin Derivatives Inhibit Non-small Cell Lung Cancer Cells Through Induction of ROS-dependent Apoptosis/Ferroptosis.

Non-small cell lung cancer (NSCLC) is one of the major cancer-related causes of morbidity and mortality worldwide. Despite the progress in lung cancer treatment, there is still an urgent need to discover novel therapeutic agents for NSCLC. Natural products represent a rich source of bioactive compounds. Through a natural compound library screening assay, we found that a group of anti-insect drugs had significant inhibitory effect on the proliferation of NSCLC cells. Among the anti-insect drugs, two derivatives of artemisinin, i.e., artesunate (ART) and dihydroartemisinin (DHA), a group of well-known anti-malarial drugs, have been shown to possess selective anti-cancer properties. Mechanistically, we found that ART and DHA induced apoptosis of A549 cells as evidenced by decreased protein level of VDAC and increased caspase 3 cleavage. Furthermore, cystine/glutamate transporter (xCT), a core negative regulator of ferroptosis, was downregulated by ART and DHA. The mRNA level of transferrin receptor (TFRC), a positive regulator of ferroptosis, was upregulated by ART and DHA. ART/DHA-induced apoptosis and ferroptosis in NSCLC cells were partly reversed by N-Acetyl-L-cysteine (NAC), a ROS scavenger, and ferrostatin-1, a ferroptosis inhibitor, respectively. These results suggest that artemisinin derivatives have anti-NSCLC activity through induction of ROS-dependent apoptosis/ferroptosis. Our findings provide the experimental basis for the potential application of artemisinin derivatives as a class of novel therapeutic drugs for NSCLC.

The pattern of reported adverse drug reactions with reference to specific drug class and organ system

Background: Adverse drug reactions (ADRs) represent a major public health problem. The overall ADR rate is estimated to be 6.5 and 28% of these are preventable.ADR incidence in Indian population ranges between 1.8-25% with 8% resulting in hospitalization. Hence, the present study was undertaken to study the pattern of reported adverse drug reactions with reference to specific drug class and organ system in a tertiary care hospital.Methods: A cross-sectional retrospective study was carried to analyse the ADRs reported over a period of one year (January-December 2019). Individual case safety reports (ICSRs) of all patients of suspected adverse drug reactions seen in various out-patient departments and admitted in the wards of the hospital were included in the study. The ICSRs were analysed for patient demography, causality, severity and with reference to specific drug class and organ system.Results: Among 382 reported ADRs, 27.2% of the ADRs were reported as serious. The most common therapeutic class of drugs causing ADRs where Antimicrobial agents (36.07%). The skin is the most common affected organ system (25.39%).Conclusions: A coordinated system of identifying the ADRs early in the course of treatment and recognizing the preventable ADRs is required by the health care system. The coordination of prescribing physicians and pharmacovigilance personnel can produce better trend of reporting the ADRs.

Cefixime and Metals Complex Interaction: A systemic review on Drug-metals interaction

The review study work comprises of interaction studies of cefixime with different group of drugs and metals to know about the alteration in pharmacological activity of cefixime by other drugs or vice versa. Cefixime is included among the cephalosporin third generation drug class which is active against a wide range of Gram positive and Gram negative bacteria. Since the presence of different therapeutic class of drugs like cefixime may affect the bioavailability as well as pharmacokinetics of other drugs and metal in the blood or tissues, therefore in order to study the potential interaction of cefixime with different therapeutic class of drugs and metals which can show several type of toxicity or may develop drug resistance in the body is the main reason to perform this study. About 102 articles were screened from different databases related to Cefixime and its interaction for this review. This review study claims that there is a possible interaction between cefixime and other drugs&amp; metals which are confirmed by different method like GLC, HPLC, and Disk Diffusion Method. Drug resistance and unwanted adverse drug reactions are a common thing for different underlying factors which becomes an alarming issue. That’s why this is significant.

Cefixime and Metals Complex Interaction: A systemic review on Drug-metals interaction

The review study work comprises of interaction studies of cefixime with different group of drugs and metals to know about the alteration in pharmacological activity of cefixime by other drugs or vice versa. Cefixime is included among the cephalosporin third generation drug class which is active against a wide range of Gram positive and Gram negative bacteria. Since the presence of different therapeutic class of drugs like cefixime may affect the bioavailability as well as pharmacokinetics of other drugs and metal in the blood or tissues, therefore in order to study the potential interaction of cefixime with different therapeutic class of drugs and metals which can show several type of toxicity or may develop drug resistance in the body is the main reason to perform this study. About 102 articles were screened from different databases related to Cefixime and its interaction for this review. This review study claims that there is a possible interaction between cefixime and other drugs&amp; metals which are confirmed by different method like GLC, HPLC, and Disk Diffusion Method. Drug resistance and unwanted adverse drug reactions are a common thing for different underlying factors which becomes an alarming issue. That’s why this is significant.

Body composition outcomes and visceral fat reduction in weight loss program participants taking antidepressant medication

ObjectiveAntidepressants are one of the most commonly prescribed therapeutic drug classes in the United States. Studies support a bidirectional link between major depressive disorder and obesity. As such, it is critical to understand how these medications may impact weight loss. In this study, we assessed changes in body composition in participants taking versus not taking antidepressant medications during a comprehensive weight loss program focused on reduction of visceral adipose tissue. MethodsData was analyzed from 2200 subjects completing a commercially available expert supervised very low calorie diet (VLCD)-based program. Overall, 23% of the subjects reported taking at least one antidepressant medication. Endpoints assessed include weight, BMI, body fat, body water, and visceral adiposity. ResultsOur data show participants taking prescription antidepressants did not negatively impact improvement in any outcome, we found both groups achieved clinically relevant progress. Improvements from baseline were statistically significant and clinically relevant for all outcome measures in both groups. ConclusionInterestingly, while antidepressants may be linked to weight gain and inhibition of one's ability to lose weight, our data show subjects currently taking at least one antidepressant achieved clinically relevant improvements in body composition outcomes on par with those not taking medications in a VLCD-based weight loss and metabolic health program.

Differential medication overuse risk of novel anti-migraine therapeutics.

Medication overuse headache is estimated to affect 2% of the population, and is ranked in the top 20 most disabling disorders due to its high level of disability. Several therapies used in the treatment of acute migraine are thought to be associated with medication overuse headache, including opioids and triptans. With limited treatment options, it is critical to determine the risk profile of novel therapies prior to their widespread use. The current study explores the potential medication overuse risk of two novel therapeutic drug classes, namely the ditans: 5-HT1F receptor agonists, and the gepants: calcitonin gene-related peptide receptor antagonists, in a preclinical model of medication overuse. Persistent exposure of mice to the 5-HT1F agonist LY344864, but not olcegepant produced a significant reduction in hind paw and orofacial mechanical withdrawal thresholds as a surrogate readout of allodynia. In agreement, only LY344864 induced neuroplastic changes in trigeminal sensory afferents, increasing calcitonin gene-related peptide expression and basal trigeminal nociception. Our data highlight a differential medication overuse headache risk profile for the ditan and gepant classes of drugs that has important implications for their clinical use and patient education to help reduce the burden of medication overuse headache.

Medication burden in epilepsy: Exploring the impact of non-epilepsy concomitant drugs load

PurposeTo determine the burden of non-epilepsy drugs on people with epilepsy, using administrative health care data. MethodsThe Achmea Health Insurance Database (AHID) contains health claims data from 25 % of the Dutch population. From the AHID, we selected all policyholders with coverage for at least one full calendar year between 2006−2009. We included adults with diagnostic codes for epilepsy and randomly selected two frequency-matched controls per case. We labeled drugs dispensed at least twice per calendar year as chronic and excluded antiseizure medications. We estimated and compared the prevalence of chronic medication use, number of chronic medications used, number of prescriptions dispensed, Rx Risk comorbidity index, and drug burden index (DBI) between people with epilepsy and controls. ResultsNon-epilepsy chronic medication use was more frequent in people with epilepsy than controls (67 % versus 59 %, p < 0.001). People with epilepsy had an increased DBI (average 0.19 versus 0.10, p < 0.001), used more chronic medications (median 2 versus 1, p < 0.001) and had more prescriptions dispensed (median 7 versus 3, p < 0.001). The DBI and number of unique chronic medications were higher among older (>60 years) than younger (<60 years) subjects in cases and controls. Non-epilepsy chronic medication use was more prevalent in people with epilepsy across all therapeutic drug classes and most comorbidities measured using the Rx Risk score. ConclusionChronic non-epilepsy medication use is more prevalent among people with epilepsy. The medication burden is higher among elderly with epilepsy and could partially explain the lower quality of life of people with epilepsy with comorbidities.

Impact of pharmaceutical price controls on the cost of cardiovascular drugs: does essentiality matter?

ABSTRACT Background With the goal of improving the affordability of medicines, governments across the globe have instituted various forms of price controls. Since 2013, India has been regulating the prices of drugs included in its national list of essential medicines (NLEM). Here we evaluate the cost variations among available cardiovascular drugs and perform cost-analysis comparing essential and non-essential drugs. Methods Data on listed prices of selected cardiovascular drugs – essential (NLEM) and non-essential (NNLEM) – were sourced from multiple drug information compendia. Price of medications was calculated in cost-per-defined-daily-dose (DDD)-units and NLEM vs. NNLEM drugs were compared. Regression analysis was used to explore the determinants of percentage cost variation (PCV) of drugs. Results The median-cost/DDD of essential medicines was lower as compared to non-essential ones for all therapeutic drug classes, with greatest difference observed for antianginals and least for heart failure medicines. There were substantial cost variations with values in excess of 1000% for six medicines, all being essential. The regression analysis failed to demonstrate a significant effect of essentiality on PCV (β = 0.19, P = 0.314). Conclusions Our analyses demonstrate considerable cost variations for some essential cardiovascular medicines. Given the need for prolonged and often, lifelong-treatment, there is significant potential for cost savings based on chosen brand, highlighting the need for patient as well as prescriber education.