Recent advances on drug development and emerging therapeutic agents for Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative old age disease that is complex, multifactorial, unalterable, and progressive in nature. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and their combination therapy provides only temporary symptomatic relief. Sincere efforts have been made by the researchers globally to identify new targets, discover, and develop novel therapeutic agents for the treatment of AD. This brief review article is intended to cover the recent advances in drug development and emerging therapeutic agents for AD acting at different targets. The article is compiled using various scientific online databases and by referring to clinicaltrials.gov and ALZFORUM (alzforum.org) websites. The upcoming therapies act on one or more targets including amyloids (secretases, Aß42 production, amyloid deposition, and immunotherapy), tau proteins (tau phosphorylation/aggregation and immunotherapy) and neuroinflammation in addition to other miscellaneous targets. Despite the tremendous improvement in our understanding of the underlying pathophysiology of AD, only aducanumab was approved by FDA for the treatment of AD in 18 years i.e., since 2003. Hence, it is concluded that novel therapeutic strategies are required to discover and develop therapeutic agents to fight against the century old AD.

Combating COVID-19: The role of drug repurposing and medicinal plants.

BACKGROUND: A novel corona virus-2 disease has spread to 213 countries and territories across the globe. The corona pandemic has claimed more than 548,934 deaths worldwide till the evening of 8th of July 2020 and the number of confirmed cases is increasing at an alarming rate. Therefore, there is an urgent need to find a treatment or a vaccine for COVID-19 at the earliest. The aim of this mini-review is to give an overview of identified repurposed anti-COVID-19 drugs which are currently under clinical trials. METHODS: A thorough literature survey was done to retrieve relevant information using various web based search engines such as Google, Google scholar, and various other electronic research databases such as PubMed, Medline, MeSh etc. The findings of the recently published articles, clinical trials, COVID-19 update by World Health Organization etc., and the opinion of the authors is summarized in this brief review. The antiviral medicinal plants were identified based on their use in Chinese/Indian indigenous systems of medicine, traditional use, published scientific phytochemical studies and/or their effectiveness against upper respiratory infections, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). RESULTS: The disease is just over six months old and effective prophylactic or therapeutic agents are yet to be developed for COVID-19. Thus, in the absence of an effective therapy, scientific community has rationally considered the drug repurposing approach for the development of anti COVID-19 drugs. Various studies and clinical trials involving antimalarial drugs, anti-HIV drugs, anti-hepatitis drugs, anti-parasitic drug, anti-inflammatory drugs, the combination of antimalarial and macrolide antibiotic and few other molecules identified through drug repurposing are currently underway to combat COVID-19. Due emphasis is also given to develop novel corona vaccines for the prophylaxis and to identify drugs for adjunct/supportive therapy. Several medicinal plants along with their major phytochemicals exhibiting antiviral activity are identified for further exploration. It is anticipated that these natural products might also play an important role in combating COVID-19. CONCLUSIONS: Use of drug repurposing strategy to develop anti COVID-19 drugs and exploring antiviral medicinal plants as adjunct or supportive therapy appears to be a viable option. Therefore, it is the need of the hour to work in parallel on different strategies such as genetic engineering, in silico approach, herbal remedies and drug repositioning to achieve the common goal of finding a safe and effective treatment for COVID-19 at the earliest.

Patterns of prescription drugs use among pregnant women at Sultan Qaboos University Hospital and Sultan Qaboos University Hospital Family and Community Medicine Clinic, Oman.

OBJECTIVE: This study evaluates the patterns of prescription drugs use among women attending antenatal clinic at Sultan Qaboos University Hospital (SQUH) and SQUH Family and Community Medicine clinic (FAMCO), Oman. METHODS: The study was a descriptive retrospective cross-sectional study on pregnant women who attended the antenatal clinic at SQUH and FAMCO from February to April 2014 and received a prescription containing at least one drug. Patients' information was extracted from SQUH electronic records. RESULTS: A total of 105 pregnant women were included in the study. Among the recruited pregnant women, 35 (33.3%) had at least one chronic disease. The average number of drugs prescribed per patient per prescription during the period of pregnancy was 2.33 ± 1.43. Vitamins and minerals were the most frequently prescribed class of drugs (30.60%) followed by analgesics (11.19%) and antidiabetic drugs (10.13%). According to the Food and Drug Administration risk classification, most of the prescribed drugs were from category B (30.0%) and C (27.14%). No drug was prescribed from category X. There was a significant decrease in prescribing category A drugs over the three trimesters (20.7%, 12.7%, and 9.3%, respectively) (P < 0.047). CONCLUSION: The study gives an overview of the extent of drug prescription during pregnancy and increases the awareness of health-care providers and women about the potential risks of drug use during pregnancy.

Gum acacia mitigates genetic damage in adenine-induced chronic renal failure in rats.

BACKGROUND: Subjects with chronic renal failure (CRF) exhibit oxidative genome damage, which may predispose to carcinogenesis, and Gum acacia (GumA) ameliorates this condition in humans and animals. We evaluated here renal DNA damage and urinary excretion of four nucleic acid oxidation adducts namely 8-oxoguanine (8-oxoGua), 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-oxoguanosine (8-oxoGuo) and 8-hydroxy-2-deoxyguanisone (8-OHdg) in rats with adenine (ADE)-induced CRF with and without GumA treatment. MATERIALS AND METHODS: Twenty-four rats were divided into four equal groups and treated for 4 weeks. The first group was given normal food and water (control). The second group was given normal food and GumA (15% w/v) in drinking water. The third group was fed powder diet containing adenine (ADE) (0·75% w/w in feed). The fourth group was fed like in the third group, plus GumA in drinking water (15%, w/v). RESULTS: ADE feeding induced CRF (as measured by several physiological, biochemical and histological indices) and also caused a significant genetic damage and significant decreases in urinary 8-oxo Gua and 8-oxoGuo, but not in the other nucleic acids. However, concomitant GumA treatment reduced the level of genetic damage in kidney cells as detected by Comet assay and significantly reversed the effect of adenine on urinary 8-oxoGuo. CONCLUSIONS: Treatment with GumA is able to mitigate genetic damage in renal tissues of rats with ADE-induced CRF.

Antimicrobial agent prescription patterns for chemotherapy-induced febrile neutropenia in patients with hematological malignancies at Sultan Qaboos University Hospital, Oman.

OBJECTIVES: The aim of this study was to describe the antimicrobial prescription patterns of patients with hematological malignancies who developed febrile neutropenia (FN) at Sultan Qaboos University Hospital (SQUH) in Oman. METHODS: This was a retrospective observational study covering a period of 3 years (January 2007-February 2010). FN episodes were studied in patients with hematological malignancies in three different wards at SQUH. RESULTS: A total of 176 FN episodes were analyzed. Overall, 64% of the 107 patients studied experienced at least 2 episodes during the analysis period. Approximately, 69% of the febrile neutropenia episodes had severe neutropenia. The duration of neutropenia was less than 1 week in the majority of the episodes (57%). The mean duration of treatment was approximately 7 days, with no significant difference between specialties or different types of malignancies. Only 34 (19%) episodes had positive cultures, and most of these were from blood samples (30 episodes, 88%). The majority of isolates were gram-negative organisms (63%). The initial empirical treatment included monotherapy (37%), dual therapy (60%) and triple therapy (3%). CONCLUSIONS: This study demonstrates that there is a large variation in the antimicrobial treatment of FN episodes in patients with hematological malignancies at SQUH. All chosen drugs were within international guideline recommendations.

Comparative efficacy of irbesartan/ hydrochlorothiazide and valsartan/hydrochlorothiazide combination in lowering blood pressure: a retrospective observational study in Oman.

OBJECTIVE: To compare blood pressure (BP) control in patients receiving irbesartan/hydrochlorothiazide (HCTZ) and valsartan/HCTZ at a tertiary care university hospital in Oman. SUBJECTS AND METHODS: This was a retrospective observational study, where 232 patients' medical records were reviewed during a 3-month period, July to September 2010, at Sultan Qaboos University Hospital in Oman. BP readings of the previous 6 months were also retrieved from the electronic medical records. Analyses were conducted using univariate statistical techniques. RESULTS: The mean age of the cohort was 58 ± 11 years (range: 21-88). Sixty-nine (30%) patients were on the irbesartan/HCTZ combination (150/12.5 mg) and 163 (70%) were on the valsartan/HCTZ combination. The patients on the valsartan/HCTZ combination were divided into two subgroups: 117 (72%) received 160/12.5 mg and 46 (28%) 80/12.5 mg. Diabetic patients (43/69, 62%, vs. 61/163, 37%, p < 0.001) and those with diabetic nephropathy (8/69, 12%, vs. 7/163, 4%, p = 0.039) were prescribed more often irbesartan/HCTZ than valsartan/HCTZ. In comparison to the valsartan/HCTZ cohort, the irbesartan/HCTZ group was associated with significant reductions in both systolic BP (SBP; -9 vs. -2 mm Hg; p = 0.021) and diastolic BP (DBP; -5 vs. 0 mm Hg; p = 0.022). BP reductions were noted more in diabetics than nondiabetics with the irbesartan/HCTZ patients associated with significant reductions in both SBP (-12 vs. 5.1 mm Hg; p < 0.001) and DBP (-6.4 vs. 1.9 mm Hg; p = 0.001). CONCLUSIONS: The irbesartan/HCTZ combination was associated with significant reductions in both SBP and DBP when compared with the valsartan/HCTZ combination. Specifically, the reductions were noted more in diabetics than nondiabetics.

Drug utilization pattern in an Omani pediatric population.

OBJECTIVE: Evidence suggests that medication errors have a higher incidence in children and infants than in adults. At present, there is limited local data that investigates the drug prescription trends in pediatric populations. This study aims at understanding drug utilization patterns in pediatric patients at Sultan Qaboos University Hospital (SQUH), Oman. MATERIALS AND METHODS: A retrospective cross-sectional study was conducted in the outpatient pediatric clinics and inpatient pediatric wards at SQUH, a tertiary care hospital attached to the Sultan Qaboos University Medical College, Oman. RESULTS: The average number of drugs per prescription was 2.3 ± 1.5, and it was almost similar in all age groups and in both males and females. About 16% of the study group received antibiotics. Paracetamol was the most prescribed drug in the patients (13%). Respiratory system drugs were the most prescribed class of drugs (22%) and salbutamol was the most prescribed drug in this class. CONCLUSIONS: This study will help in assessing rational usage and cost control of various medications used in the pediatric setting.

Drug utilization patterns in the emergency department: A retrospective study.

OBJECTIVES: The aim of this study was to assess the prescribing trends and costs of drugs in the emergency department (ED) at Sultan Qaboos University Hospital (SQUH), a tertiary care hospital, in Muscat, the Sultanate of Oman. MATERIALS AND METHODS: This was a retrospective cross-sectional study of all patients (n = 300) who attended the ED at SQUH in May 2012. Analyses were performed using descriptive and univariate statistics. RESULTS: The average age of patients was 34 ± 19 years. The average number of drugs prescribed per patients was 3.2 ± 1.9 and the majority of the patients (n = 78; 26%) received two drugs. The most common route of drug administration was the oral route (n = 481; 51%) followed by parenterally (n = 357; 38%). Non-steroidal anti-inflammatory drugs (NSAIDs) were the most commonly prescribed class of drugs (38%) followed by the gastro-intestinal tract drugs (19%) and central nervous system drugs (13%). The average cost per prescription was 242 ± 632 US$. Morphine had the highest cost (1885 US$) followed by cefuroxime (1404 US$) and filgrastim (939 US$) over the 1-month period. There was a significant positive correlation between hospital cost and age (P < 0.001), duration of stay at the ED (P = 0.008) and emergency types (P < 0.001). CONCLUSION: NSAIDs were the most frequent class of drugs administered to patients. Highest number of drugs was prescribed for cardiovascular diseases followed by respiratory and gastrointestinal diseases. Anti-infective drugs cost was the highest among all other classes. The results of the present study are attempts to highlight the importance of strategies that have to be implemented to optimize medication use at the ED.

Genetic variations related to hypertension: a review.

Hypertension is a complex multifactorial disorder with genetic, environmental and demographic factors contributing to its prevalence. The genetic element contribution to blood pressure variation ranges from 30 to 50%. Therefore, identifying hypertension susceptibility genes will help understanding the pathophysiology of the disease. In addition to the potential impact of genomic information in selecting antihypertensive drug therapy, it may also help in recognizing those at risk of developing the disease, which may lead to new preventive approaches. Several strategies and methods have been used to identify hypertension susceptibility genes. Currently, genetic analysis of such data produced complex results, which makes it difficult to draw final conclusion on the use of genomic data in management of hypertension. This review attempts to summarize present known genetic variations that may be implicated in the pathogenesis of hypertension and to discuss various research strategies used to identify them. It also highlights some of the opportunities and challenges, which may be encountered in interpreting the value of these genetic variations to improve management of hypertension.

Drug utilization pattern of anti-epileptic drugs: a pharmacoepidemiologic study in Oman.

PURPOSE: To get an insight into the type and aetiology of epileptic seizures; to describe the drug utilization pattern of anti-epileptic drugs (AEDs) for the treatment of various forms of epileptic seizures in this tertiary referral centre in Oman; and to compare our drug utilization pattern with that from other countries. In addition, the tolerability of AEDs and the use of therapeutic drug monitoring (TDM) were evaluated. METHODS: In a 6-month study, all epileptic patients aged 14 and above who were prescribed an AED were considered for analysis. Demographic data, type and aetiology of epileptic seizures, AED data, tests performed and adverse drug reaction (ADR) data were collected. RESULTS: A total of 1039 prescriptions originated from 488 epileptic patients. The age ranged from 14 to 77 years (median, 24 years). Generalized tonic-clonic seizures (51%) of idiopathic/cryptogenic origin (83%) were the most common type and aetiology of epileptic seizures, respectively. An average of 1.34 AEDs per patient was prescribed with 78% of patients being on monotherapy. Sodium valproate (49%) was the most frequently prescribed AED, followed by carbamazepine (44%), phenytoin (12%) and lamotrigine (11%). Ten patients suffered an ADR and phenobarbital followed by carbamazepine were most commonly the subject of TDM. CONCLUSIONS: Unlike the results in most other studies, generalized seizures represented the majority of epileptic seizures. The selection of the AEDs corresponded well with their known efficacy profiles for specific epileptic seizure types. Monotherapy was the type of therapy most frequently used, and sodium valproate and carbamazepine were the most commonly used AEDs.