Effects Of Drugs Research Articles

Role of antioxidative activity in the docosahexaenoic acid's enteroprotective effect in the indomethacin-induced small intestinal injury model.

Therapeutic effect of non-steroidal anti-inflammatory drugs (NSAIDs) has been related with gastrointestinal injury. Docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid (PUFA), can prevent gastric and small intestinal damage. Nonetheless, contribution of antioxidative action in the protective effect of DHA has not been evaluated before in the small intestine injury after indomethacin treatment. Pathogenesis of NSAID-induced small intestinal injury is multifactorial, and reactive oxidative species have been related to indomethacin's small intestinal damage. The present work aimed to evaluate antioxidative activity in the protective action of DHA in the indomethacin-induced small intestinal damage. Female Wistar rats were gavage with DHA (3 mg/kg) or omeprazole (3 mg/kg) for 10 days. Each rat received indomethacin (3 mg/kg, orally) daily to induce small intestinal damage. The total area of intestinal ulcers and histopathological analysis were performed. In DHA-treated rats, myeloperoxidase and superoxide dismutase activity, glutathione, malondialdehyde, leukotriene, and lipopolysaccharide (LPS) levels were measured. Furthermore, the relative abundance of selective bacteria was assessed. DHA administration (3 mg/kg, p.o.) caused a significant decrease in indomethacin-induced small intestinal injury in Wistar rats after 10 days of treatment. DHA's enteroprotection resulted from the prevention of an increase in myeloperoxidase activity, and lipoperoxidation, as well as an improvement in the antioxidant defenses, such as glutathione levels and superoxide dismutase activity in the small intestine. Furthermore, we showed that DHA's enteroprotective effect decreased significantly LPS levels in indomethacin-induced injury in small intestine. Our data suggest that DHA's enteroprotective might be attributed to the prevention of oxidative stress.

Causes of Acquired Methemoglobinemia – a Retrospective Study at a Large Academic Hospital

Methemoglobinemia is a potentially life-threatening condition caused by the formation of methemoglobin, a form of hemoglobin that cannot bind oxygen. While there are some rare congenital causes of methemoglobinemia, most cases are acquired from the effects of specific drugs or environmental exposures. In this retrospective study, we analyzed a large data set of whole blood samples analyzed for methemoglobin at an academic medical center in Midwestern United States that provides both pediatric and adult services. For a 14 year timeframe (May 2009- June 2023), we performed detailed chart analysis of all patients with a methemoglobin concentration of 3.1% or higher. For an earlier 13 year timeframe (January 1996-April 2009), we performed chart review for all patients with a methemoglobin concentration of 10.0% or higher. For the 2009-2023 data, dapsone was the most frequent cause of methemoglobinemia (methemoglobin 3.1% or higher) in both pediatric (73.3%, 115 clinical encounters, 105 unique patients) and adult (65.3%, 195 clinical encounters, 190 unique patients) populations. Inhaled nitric oxide as medical therapy was the next most frequent cause in both pediatric (18.1%) and adult (13.2%) populations. Causes associated with two or more unique episodes with methemoglobin concentrations of 10.0% and higher included the following: dapsone (n=40 episodes), benzocaine (n=10), recreational use of amyl or isobutyl nitrite (n=3), suicide attempt with sodium nitrite (n=3 with 1 fatality; all 3 cases within last 3 years), food contaminated with nitrates (n=2), and sepsis (n=2). A total of 18 patients received treatment with methylene blue including 5 cases associated with benzocaine and all of the cases associated with amyl nitrite, isobutyl nitrite, sodium nitrite, and contaminated food. Only 3 patients with dapsone-associated methemoglobinemia received methylene blue, reflecting primary management by dose reduction or discontinuation of drug. Overall, our data reinforce previous studies showing dapsone, inhaled nitric oxide, and nitrites as common agents causing methemoglobinemia in a patient population seen at a medical center. Our data also are consistent with recent epidemiology trends showing increase in suicide attempts using sodium nitrite.

A fluorescence-based sensor for calibrated measurement of protein kinase stability in live cells.

Oncogenic mutations can destabilize signaling proteins, resulting in increased or unregulated activity. Thus, there is considerable interest in mapping the relationship between mutations and the stability of signaling proteins, to better understand the consequences of oncogenic mutations and potentially inform the development of new therapeutics. Here, we develop a tool to study protein-kinase stability in live mammalian cells and the effects of the HSP90 chaperone system on the stability of these kinases. We determine the expression levels of protein kinases by monitoring the fluorescence of fluorescent proteins fused to those kinases, normalized to that of co-expressed reference fluorescent proteins. We used this tool to study the dependence of Src- and Raf-family kinases on the HSP90 system. We demonstrate that this sensor reports on destabilization induced by oncogenic mutations in these kinases. We also show that Src-homology 2 and Src-homology 3 domains, which are required for autoinhibition of Src-family kinases, stabilize these kinase domains in the cell. Our expression-calibrated sensor enables the facile characterization of the effects of mutations and small-molecule drugs on protein-kinase stability.

A Pharmacotherapeutic Approaches for Managing Labour Pain using Synthetic Drugs and Natural Therapies.

The birth of a child is a critical and potentially traumatic experience for women, entailing multiple physiological and psychosocial changes. The psychological effects of childbirth pain can have both immediate and long-term effects on the mother's health and her bond with her child. Many studies investigated the different ranges of synthetic drugs available for pain control in labour, inclusive of neuraxial analgesics, inhaled analgesics, and various opioids. The inadequate efficacy and unfavourable side effects of these synthetic drugs prevent appropriate pharmacotherapy, resulting in a quest for natural therapies for reducing labour pain. Herbal therapies (aromatherapy) using several essential oils obtained from various natural plants are another alternative that calms and manages the mind and body through aromatic compounds that have neurological and physiological effects. The review discussed the safety profile of various synthetic drugs with their dosage information and also deliberated on the mechanism and safety profile of various natural plants that are used in aromatherapy. The review also briefly highlighted the other non-pharmacological miscellaneous techniques such as TENS, hypnosis, immersion in water, acupuncture, massage, and different other tactics that aim to assist women in coping with pain in labour.

DFT Study of Nanotubes as the Drug Delivery Vehicles for an Anticancer Drug

Abstract: Chemicals and poisons in the body interfere with the cell cycle and inhibit the growth of cancer cells. In this way, the function of chemicals in the body is controlled by taking anti-cancer drugs. Due to the degradability and compatibility of carbon nanotubes and boron nitride with the environment, they can act as suitable drug carriers for the transfer of anticancer drugs and deliver the drugs to the target cells. In the current work, the encapsulation of Formestane (FMS) anticancer drug into the carbon (CNT) and boron nitride (BNNT) (8,8) nanotubes was investigated for the first time using the density functional theory: B3LYP/3-21G* and the natural bond orbital analysis in the gas phase. Using natural bond orbital analysis, the charge transfer between FMS drug and CNT and BNNT nanotubes (8,8)/ FMS (BNNT/FMS) complexes were explored. Based on the results obtained from the calculation of encapsulation energy, it was found that the adsorption process was favorable. The interaction effects of FMS drug and CNT and BNNT (8,8) nanotubes on the natural bond orbital charge, the chemical shift parameters, and electronic properties were also evaluated. This study revealed that CNT and BNNT (8,8) nanotubes can be a suitable carrier for FMS drug delivery. The ultraviolet-visible spectra of the FMS drug, the CNT and BNNT (8,8), and the BNNT/FMS complexes were computed using time-dependent density functional theory (DFT: B3LYP) calculations.

Two-dimensional MXene-based nano-prodrug for synergistic chemo-photothermal therapy on cancer treatment

In cancer treatment, although prodrugs have been developed to overcome obstacles such as undesirable pharmacokinetic performance and serious off-target toxicity of most chemotherapeutics, the combination of prodrugs with nanotechnology could be used to overcome the shortcomings of conventional prodrug strategies and facilitate more efficient drug delivery and accumulation of anticancer prodrugs at specific sites/tissues. Phototherapy is a method that uses near-infrared (NIR) light to achieve local and non-invasive tumor therapy. The combination of chemotherapy and phototherapy has shown many therapeutic advantages, including synergistic therapeutic effects and the reduction of toxic and side effects of drugs through dose reduction. In this work, a hydrazone linkage was reported to conjugate Ti3C2Tx MXene nanosheets with doxorubicin hydrochloride (DOX) and methoxy poly(ethylene glycol) benzaldehyde (mPEG-CHO) through a chemical surface modification to form a two-dimensional (2D) nano-prodrug Ti3C2Tx-DOX/PEG (TDP) for synergistic chemo-photothermal therapy. First, hydrazide functionalized Ti3C2Tx was obtained. Then, the carbonyl group of DOX and the aldehyde group of mPEG-CHO can form a pH-responsive hydrazone bond with hydrazide-functionalized Ti3C2Tx. The high surface area of Ti3C2Tx could overcome the reduced drug loading caused by conjugation. Aqueous stability and biocompatibility were enhanced by the introduction of PEG, making the material capable of prolonged circulation in the body’s bloodstream. By achieving excellent antitumor results with this nano-prodrug, we have added another brick to the edifice of Ti3C2Tx MXene as an anticancer drug carrier, and given new vitality to the study of anticancer prodrugs combined with nanotechnology.

Corrections to “Spectroscopic Analysis of Candida Species, Viability, and Antifungal Drug Effects with a Microwave Flow Cytometer”

Corrections to “Spectroscopic Analysis of Candida Species, Viability, and Antifungal Drug Effects with a Microwave Flow Cytometer”

A review study on Agni karma and Ksha akarma in the management of Garbha Saya Grivamukhagata Vrana (cervical erosion)

Purpose: To review the effectiveness of Agni karma and Ksha akarma in the management of Garbha Saya grivamukhagata vrana (Cervical Erosion). Material and Methods: All the research studies from 2002 to 2024 related to concerned topic collected from electronic data base and journals both online and offline. The procured data were studied in details and scientific review was done. Results: On reviewing the previous works it is found that maximum studies were done on Agnikarma by shalaka having vrana shodhana, ropana andprasadana properties. Though Ksharakarma also yielded good results but comparatively fewer studies were found. Discussion: Cervical erosion warrants urgent attention of the gynecologists as it affects the patient’s reproductive health and psychology. Modern treatment for cervical erosion is cauterization and cryosurgery which have many complications such as bleeding per vagina, cervical incompetence, secondary infertility etc. So Agnikarma and Ksharakarma can be better alternative for effective treatment of cervical erosion Conclusion: All the research works mainly were targeted for finding a best Shodhana and Ropana drugs for cervical erosion. All works were carried out on Bahya parimarjana (external application). This facilitates drugs effect for early and uncomplicated wound healing.

Shenqi Fuzheng injection hinders non-small cell lung cancer cell growth by regulating the Bax/Bcl-2 signaling pathway.

Lung cancer (LC) is the most common solid tumor and is currently considered the primary cause of cancer-related deaths worldwide. In clinical efficacy studies, it was not difficult to find that the combination of SFI and chemotherapy could improve the general condition of patients, reduce the side effects of chemotherapy drugs, and have a cooperative antitumor effect in NSCLC patients. However, whether SFI can be used as a novel antitumor drug is still unknown. First, meta-analysis aimed to explore the efficacy of SFI in NSCLC patients, and SFI was identified by ultra-performance liquid chromatography‒mass spectrometry (UPLC‒MS). Cell proliferation, migration, and invasion were explored by Cell Counting Kit-8 (CCK-8), scratch healing, and Transwell assays, respectively. Cell cycle and apoptosis assays were performed by flow cytometry. Transcriptome sequencing analysis was performed in four NSCLC cell lines. Differential expression analysis was used to identify potential targets. Apoptosis-related protein levels were detected by Western blotting assays. The effects of SFI in NSCLC were further investigated by mouse xenografts. SFI could markedly improve the chemotherapy efficacy of NSCLC patients. The main active ingredients include flavonoids and terpenoids, which can effectively exert antitumor effects. SFI could not only inhibit tumor cell proliferation and cell migration/invasion but also regulate the cell cycle and promote tumor cell apoptosis. In NSCLC, SFI could enhance the transcription level of the CHOP gene, thereby upregulating the expression of the proapoptotic proteins Bax and caspase 3, and inhibiting the expression of the antiapoptotic protein Bcl-2. SFI hindered the growth of mouse NSCLC xenografts in vivo. SFI hindered tumor progression and might promote apoptosis by increasing the expression of Bax, caspase 3 and decreasing the level of Bcl-2 in NSCLC.

Understanding the impact of ABCG2 Polymorphisms on Drug Pharmacokinetics:Focus on rosuvastatin and allopurinol.

In addition to the well-established understanding of the pharmacogenetics of drug metabolizing enzymes, there is growing data on the effects of genetic variation in drug transporters, particularly ATP-binding cassette (ABC) transporters. However, the evidence that these genetic variants can be used to predict drug effects and to adjust individual dosing to avoid adverse events is still limited. This review presents a summary of the current literature from the PubMed database as of February 2024 regarding the impact of genetic variants on ABCG2 function and their relevance to the clinical use of the HMG-CoA reductase inhibitor rosuvastatin and the xanthine oxidase inhibitor allopurinol. Although there are pharmacogenetic guidelines for the ABCG2 missense variant Q141K, there is still some conflicting data regarding the clinical benefits of these recommendations. Some caution appears to be warranted in homozygous ABCG2 Q141K carriers when rosuvastatin is administered at higher doses and such information is already included in the drug label. The benefit of dose adaption to lower possible side effects needs to be evaluated in prospective clinical studies.

A Comprehensive Investigation of Stimulatory Agents on MAIT and Vα7.2+/CD161− T Cell Response and Effects of Immunomodulatory Drugs

Mucosal-associated invariant T (MAIT) cells, a subset of Vα7.2+ T cells, are a crucial link between innate and adaptive immunity, responding to various stimuli through TCR-dependent and independent pathways. We investigated the responses of MAIT cells and Vα7.2+/CD161− T cells to different stimuli and evaluated the effects of Cyclosporin A (CsA) and Vitamin D3 (VitD). Peripheral blood mononuclear cells (PBMCs) from healthy donors were stimulated with various agents (PMA/Ionomycin, 5-OP-RU, 5-OP-RU/IL-12/IL-33) with or without CsA and VitD. Flow cytometric analysis assessed surface markers and intracellular cytokine production. Under steady-state conditions, MAIT cells displayed elevated expression of CCR6 and IL-13. They showed upregulated activation and exhaustion markers after activation, producing IFNγ, TNFα, and TNFα/GzB. CsA significantly inhibited MAIT cell activation and cytokine production. Conversely, Vα7.2+/CD161− T cells exhibited distinct responses, showing negligible responses to 5-OP-RU ligand but increased cytokine production upon PMA stimulation. Our study underscores the distinct nature of MAIT cells compared to Vα7.2+/CD161− T cells, which resemble conventional T cells. CsA emerges as a potent immunosuppressive agent, inhibiting proinflammatory cytokine production in MAIT cells. At the same time, VitD supports MAIT cell activation and IL-13 production, shedding light on potential therapeutic avenues for immune modulation.

The Incorporated Drug Affects the Properties of Hydrophilic Nanofibers

Hydrophilic nanofibers offer promising potential for the delivery of drugs with diverse characteristics. Yet, the effects of different drugs incorporated into these nanofibers on their properties remain poorly understood. In this study, we systematically explored how model drugs, namely ibuprofen, carvedilol, paracetamol, and metformin (hydrochloride), affect hydrophilic nanofibers composed of polyethylene oxide and poloxamer 188 in a 1:1 weight ratio. Our findings reveal that the drug affects the conductivity and viscosity of the polymer solution for electrospinning, leading to distinct changes in the morphology of electrospun products. Specifically, drugs with low solubility in ethanol, the chosen solvent for polymer solution preparation, led to the formation of continuous nanofibers with uniform diameters. Additionally, the lower solubility of metformin in ethanol resulted in particle appearance on the nanofiber surface. Furthermore, the incorporation of more hydrophilic drugs increased the surface hydrophilicity of nanofiber mats. However, variations in the physicochemical properties of the drugs did not affect the drug loading and drug entrapment efficiency. Our research also shows that drug properties do not notably affect the immediate release of drugs from nanofibers, highlighting the dominant role of the hydrophilic polymers used. This study emphasizes the importance of considering specific drug properties, such as solubility, hydrophilicity, and compatibility with the solvent used for electrospinning, when designing hydrophilic nanofibers for drug delivery. Such considerations are crucial for optimizing the properties of the drug delivery system, which is essential for achieving therapeutic efficacy and safety.

Poly(2-(dimethylamino)ethyl methacrylate)-Grafted Amphiphilic Block Copolymer Micelles Co-Loaded with Quercetin and DNA

The synergistic effect of drug and gene delivery is expected to significantly improve cancer therapy. However, it is still challenging to design suitable nanocarriers that are able to load simultaneously anticancer drugs and nucleic acids due to their different physico-chemical properties. In the present work, an amphiphilic block copolymer comprising a biocompatible poly(ethylene glycol) (PEG) block and a multi-alkyne-functional biodegradable polycarbonate (PC) block was modified with a number of poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) side chains applying the highly efficient azide–alkyne “click” chemistry reaction. The resulting cationic amphiphilic copolymer with block and graft architecture (MPEG-b-(PC-g-PDMAEMA)) self-associated in aqueous media into nanosized micelles which were loaded with the antioxidant, anti-inflammatory, and anticancer drug quercetin. The drug-loaded nanoparticles were further used to form micelleplexes in aqueous media through electrostatic interactions with DNA. The obtained nanoaggregates—empty and drug-loaded micelles as well as the micelleplexes intended for simultaneous DNA and drug codelivery—were physico-chemically characterized. Additionally, initial in vitro evaluations were performed, indicating the potential application of the novel polymer nanocarriers as drug delivery systems.

Three-Dimensional Hepatocyte Spheroids: Model for Assessing Chemotherapy in Hepatocellular Carcinoma

BACKGROUND: Three-dimensional cellular models provide a more comprehensive representation of in vivo cell properties, encompassing physiological characteristics and drug susceptibility. METHODS: Primary hepatocytes were seeded in ultra-low attachment plates to form spheroids, with or without tumoral cells. Spheroid structure, cell proliferation, and apoptosis were analyzed using histological staining techniques. In addition, extracellular vesicles were isolated from conditioned media by differential ultracentrifugation. Spheroids were exposed to cytotoxic drugs, and both spheroid growth and cell death were measured by microscopic imaging and flow cytometry with vital staining, respectively. RESULTS: Concerning spheroid structure, an active outer layer forms a boundary with the media, while the inner core comprises a mass of cell debris. Hepatocyte-formed spheroids release vesicles into the extracellular media, and a decrease in the concentration of vesicles in the culture media can be observed over time. When co-cultured with tumoral cells, a distinct distribution pattern emerges over the primary hepatocytes, resulting in different spheroid conformations. Tumoral cell growth was compromised upon antitumoral drug challenges. CONCLUSION: Treatment of mixed spheroids with different cytotoxic drugs enables the characterization of drug effects on both hepatocytes and tumoral cells, determining drug specificity effects on these cell types.

Neutropenia induced by ceftriaxone and meropenem

Neutropenia by non-chemotherapy drugs is an extremely rare idiosyncratic life-threatening drug reaction. Ceftriaxone and meropenem are widely used broad-spectrum antibiotics and are generally safe and well tolerated. The authors present a case of neutropenia induced by ceftriaxone and meropenem in an adult patient. The resolution of neutropenia occurred within 48 hours of ceftriaxone and meropenem being discontinued. Although antibiotic-induced neutropenia is uncommon, clinicians should be mindful of this adverse drug effect because of its potential development of severe neutropenia, septicaemia, septic shock, deep-seated infections and even death. Therefore, neutropenic sepsis treatment should be initiated without delay, particularly if the patient becomes septic and febrile. Granulocyte-colony stimulation factor (G-CSF) may be administered to facilitate the recovery process with daily monitoring of neutrophil count. Mortalities from antibiotic-induced neutropenia remain rare, with a range of 2.5–5%.

The Advent of Molecular Targeted Therapies Against Cancer. Toward Multi‐Targeting Drugs Through Materials Engineering: A Possible Future Scenario

The authors, actively engaged in the development of mesoporous silica‐based solutions, initially for modified drug release, later for the smart administration of conventional chemotherapeutic cytotoxic drugs, present the evolution of the concept of targeted therapy across different disciplines. They also discuss the diverse therapeutic needs and related challenges (adverse drug effects) that have unfolded over the last 30 years. Nanomedicine potentialities, mainly against cancers, that have emerged globally during the intense research activity of the last few decades, are critically discussed. The authors glimpse the growing potential of immune‐based therapeutic solutions, including those assisted by nanotechnology, as well as molecular targeted therapies (MTT) on which they focus. The advantages offered by targeted molecular therapies, despite the limits of monotargeted therapies, suggest the engineering of multi‐targeted therapies. Nanomedicine solutions such as ligand‐specific internalization and pH‐sensitive drug release that they have extensively tested and recently presented in open literature, still remain available instruments. According to the authors, MTT can offer shining perspectives in the near future that will depend on a thorough comprehension of nanostructures synthesis and tumor physiology. This article gives an interdisciplinary point of view tailored for non‐specialist readers imagining possible future scenarios in the field.

Quality of life of patients with uterine fibroids

BACKGROUND: Currently, there is an elevation in the incidence of uterine fibroids in increasingly younger women of reproductive age. Taking into account the current trend of late motherhood, this cohort of patients is interested in using reliable reversible contraception. Combined hormonal contraceptives meet these criteria and are able to neutralize the clinical manifestations of uterine fibroids, thereby improving the quality of life of patients. At the same time, some combined hormonal contraceptives users may experience a decrease in libido and a change in their psycho-emotional state as a manifestation of the side effects of these drugs. AIM: The aim of this study was to assess the effect of combined hormonal contraceptives on the quality of life in patients with uterine fibroids. MATERIALS AND METHODS: This study involved 100 patients with uterine fibroids (F3–F6 according to classification of the International Federation of Gynecology and Obstetrics, without indications for surgical treatment) and 30 healthy women aged 18 to 49 years. For contraceptive purposes, 40 participants with uterine fibroids used combined hormonal contraceptives containing ethinyl estradiol (group I) and 60 patients with uterine fibroids did not use any medications (group II). The following validated questionnaires were used for patients with uterine fibroids — at the beginning and after 6 months, and for healthy women in the control group (group III) — once upon entry into the study: Short Form-36, Female Sexual Function Index, and Beck Depression Inventory. A comparative statistical analysis of the studied parameters over time was carried out. RESULTS: At baseline, a lower quality of life was noted in patients with uterine fibroids compared to the control group (Short Form-36): 94 ± 6 vs 102 ± 11 points, respectively (p 0.05). After 6 months, patients in group I showed positive dynamics with increasing in the total Short Form-36 from 95 ± 4 to 98 ± 5 points (p 0.05) compared to patients in group II: 94 ± 6 and 93 ± 5 points (p 0.05). We revealed no changes in the Female Sexual Function Index in the study groups — at baseline: 24.8 ± 8.9 (group I), 23.9 ± 9.5 (group II), and 27.8 ± 4.7 (group III); and after 6 months: 26.4 ± 9.2 (group I) and 23.9 ± 10.0 (group II) (p 0.05 for all comparisons). When comparing the results of a questionnaire on the Beck scale, no dynamics were determined in patients with uterine fibroids, including those who used combined hormonal contraceptives. CONCLUSIONS: The study demonstrated a lower quality of life in patients with uterine fibroids compared to healthy women and an improved quality of life in patients with uterine fibroids using combined hormonal contraceptives. We showed no negative effects of contraceptive drugs on libido and emotional state in women with uterine fibroids who used combined hormonal contraceptives for 6 months.

HMG-CoA reductase is a potential therapeutic target for migraine: a mendelian randomization study

Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10−7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

Value of Assessing 1-Hydroxymidazolam in Drug-Drug Interaction Studies with Midazolam as a Substrate of Cytochrome P450 3A.

The purpose of this overview was to perform an exploratory analysis of in-house drug-drug interaction (DDI) studies conducted with investigational drugs and oral midazolam to assess the value of measuring 1-OH-midazolam (1-OHM) in such studies. The perpetrator effect of the investigational drugs on cytochrome P450 3A (CYP3A) was assessed by analyzing both midazolam and 1-OHM in plasma and evaluating their pharmacokinetic parameters. Given the almost exclusive metabolism of the parent drug by CYP3A to the main metabolite 1-OHM, an increase in midazolam and a decrease in 1-OHM exposure in the case of CYP3A inhibition caused by a perpetrator drug would be expected. The opposite would be anticipated in the case of CYP3A induction. For this analysis, the perpetrator potential of eight different investigational drugs was incorporated. Among the 10 studies included, the identified CYP3A inhibitors (n = 4) and inducers (n = 1) were classified based on the data generated with midazolam per se, with 1-OHM levels not contributing to the interpretation of the data as they did not corroborate the findings of the parent compound. Therefore, it was concluded that continued analysis of 1-OHM in plasma may be questionable as it does not add value to the interpretation of the results when performing CYP3A DDI studies with an investigational drug as a perpetrator.

An assessment of pharmacist counselling on the patients’ knowledge of ophthalmic medications

Background: Pharmacist counselling helps patients achieve their treatment goals by improving their medication knowledge, including ocular drugs. The visual system transmits 80% of sensory information; hence, eye health is crucial. Routine pharmacist counselling has been carried out to gain ophthalmic medication knowledge for every patient dispensed with a prescription in the outpatient pharmacy Surabaya eye clinic. However, the result of this counselling on patients’ knowledge has not been evaluated. Objective: The aim of this study is to measure the level of patients’ knowledge of ophthalmic medications. Methods: A cross-sectional study was carried out for one month by interviewing patients. A well-structured questionnaire of 15 questions was developed to assess the patient’s knowledge. The level of knowledge was classified as high, moderate, or low. Results: This study involved a total of 80 patients. The study showed that patients with a high, moderate, or low level of knowledge were represented by 33(41.25%), 45(56.25%), and 2(2.5%) patients, respectively. Demographic characteristics (gender and educational level) did not affect patients’ knowledge of ophthalmic medication (p > 0.05). The knowledge of potential side effects of ophthalmic drugs was least understood. Conclusion: There is a need for improvement in the performance of pharmacist counselling since most patients have moderate to low knowledge of ophthalmic medications.