18 research outputs found
Curcumin-related hybrid compounds as potential antimalarial agents : design, synthesis, mechanistic investigations, biological evaluation and pharmacokinetic studies
Includes bibliographical references.Malaria remains one of the most devastating tropical diseases, with staggering infection and mortality statistics. Over 200 million clinical cases of malaria (resulting in 1 - 3 million deaths) are reported annually. Africa bears the greatest burden of this disease. with the vast majority of malaria cases (>85%). and malaria-related deaths (>90%). being reported in sub-Saharan Africa. The main challenge to malaria control has been the development of clinically significant resistance Of the parasite to most known antimalarial drugs. This suggests that the development of new, highly efficadous drugs and/or treatment regimens for the management of malaria remains a key priority. This study applied molecular hybridization as a strategy in the development of novel potential antimalarial agents. The aim was to try and identify novel hybrid compounds containing scaffolds that are structurally related to the natural product curcumin, and which exhibit in vitro and in vivo antimalarial activity. Part of the study involved investigations into the pharmacokinetics and possible antimalarial mechanisms of action of selected target compounds
Prevalence and Antimicrobial Susceptibility of Bacteria Implicated in Neonatal Sepsis at Pumwani Maternity Hospital
Neonatal sepsis is one of the most common causes of morbidity and mortality among infants in developing countries. The etiology and antimicrobial sensitivity patterns of bacteria responsible vary in different hospitals. This study identified bacteria in blood cultures of neonates with clinically suspected septicemia and demonstrated their susceptibility patterns. A longitudinal design targeting all neonates at Pumwani maternity hospital with suspected sepsis was used. One hundred and fifty neonates were selected using consecutive sampling. Data was collected using a questionnaire. Out of 150 blood specimens cultured, the cases of confirmed bacterial sepsis were 48(32%). Gram-positive pathogens predominated with Staphylococcus aureus and Streptococcus viridans accounting for 70%. The only Gram-negative isolates were E. coli and Klebsiella spp. Gram-positive isolates showed high sensitivity (above 80%) to meropenem, gentamicin, ceftriaxone, ofloxacin, and amikacin. Gram- negative organisms were generally resistant to penicillins and absolutely sensitive to meropenem, ceftazidime and ciprofloxacin.
Keywords: Prevalence, Antimicrobial susceptibility, Neonatal sepsi
Prevention of Hyperglycemia
Hyperglycemia is the elevation of blood glucose concentrations above the normal range. Prolonged uncontrolled hyperglycemia is associated with serious life-threatening complications. Hyperglycemia arises from an imbalance between glucose production and glucose uptake and utilization by peripheral tissues. Disorders that compromise pancreatic function or affect the glucose counter-regulatory hormones cause hyperglycemia. Acute or serious illness or injury may also bring about hyperglycemia, as can many classes of drugs. Metformin lowers blood glucose levels by inhibiting the production of glucose by the liver whilst enhancing uptake of circulating glucose and its utilization in peripheral tissues such as muscle and adipose tissue. Metformin suppresses hepatic gluconeogenesis by inhibiting mitochondrial respiration and causing a reduction of cellular ATP levels. Metformin may also modulate the gut-brain-liver axis, resulting in suppression of hepatic glucose production. Metformin also opposes the hyperglycemic action of glucagon and may ameliorate pancreatic cell dysfunction associated with hyperglycemia. Metformin is therefore recommended for use in the prevention of hyperglycemia, including drug-induced hyperglycemia, in at risk patients. The benefits of metformin in the prevention of hyperglycemia are unmatched despite its contraindications
Clinical audit of Heparin use in Rift Valley General Hospital, Nakuru County, Kenya
Background: Heparin is a high risk medicine that may cause significant harm if not used properly. It is ranked among the top 5 “high alert” medications by the Institute of Safe Medication Practices because of its low therapeutic index and potential for serious adverse outcomes. Adherence to guidelines and protocols, as well as careful monitoring of heparin use, is important in maximizing benefits of its use and minimizing on harm. Objective: The aim of this study was to examine the processes and outcomes of heparin use in adult in- patients at the Rift Valley General Hospital through the conduct of a clinical audit. Methodology: A structured clinical audit tool was developed through consolidation of information from various sources. The structures supporting heparin use were physically assessed, including the availability of policies, guidelines or protocols, protamine and laboratory reagents. The processes and outcomes of its use were audited through the prospective observation of heparin dosing, administration and monitoring among eligible adult in-patients. Results: Clinical audit revealed there were no policies, protocols or guidelines to guide heparin use at Rift Valley General Hospital. Delayed or lack of heparin monitoring were observed. Heparin termination was done well by introduction of warfarin at least three days before stopping heparin in majority of the patients. The overall clinical audit score at Rift Valley General Hospital was 60.6% which showed minimal compliance to the performance threshold/standard of heparin use. Conclusions: Clinical audit for heparin use in RVGH concluded inadequate compliance to the set standards. There is need to avail guidelines, protocols or policies in the institution and conduct regular monitoring to ensure use of heparin is improved and maximum benefit is realized. Key words: Heparin, clinical audit, monitoring
Management of Type 2 Diabetes at Vihiga County referral hospital, Kenya: compliance with guidelines and prevalence of complications
Background: In 2013, 382 million people suffered from diabetes globally, with 19.8 million in Africa and a Kenyan prevalence of 4.2%. Poor diabetic related outcomes such as complications, high blood sugar levels have resulted due to inadequate management of the condition. To ensure effective diagnosis, management and monitoring of Type 2 diabetic patients, the healthcare team should adopt and adhere to standard treatment guidelines that are valid and up-to date Objective: To assess the management, monitoring and complications of Type 2 diabetes among adult outpatients at Vihiga County Referral Hospital, Kenya. Methodology: A retrospective cross sectional study design was used to obtain data from 212 patient files selected through a systematic random sampling. Using a pre-designed data collection form, data on patient demographics, blood pressure, blood sugar, weight and complications was collected. Descriptive statistics were used to summarize findings to determine the proportion of adult Type 2 diabetic cases diagnosed, managed and monitored as per the Institute of Clinical Systems Improvement (ICSI) guidelines. Inferential analysis using t-test and chi square test were also carried out to ascertain extent of adherence to the guidelines. Results: Majority of the participants (31.1%) were aged 50 – 59 years (31.1%), and most were female (70.3%). Most, 39.6% had had diabetes for 1 to 5 years. Random blood sugar test was the most used method of diagnosis (58.5%) whilst fasting blood glucose test was performed in 34%. A compliance rate of 72.2% was reported in ensuring metformin was part of first line therapy as recommended. The recommended blood pressure, weight and cholesterol monitoring at initiation of treatment was observed in 96.7, 1.4 and 6.1% of the patients, respectively. Of the 141 patients monitored using fasting blood sugar, 113 (80.1%) had uncontrolled blood sugar levels (median blood sugar = 8.9(IQR.7.4, 12.75) mmol/L; P=0.741). The prevalence of reported neuropathy, retinopathy and nephropathy were 41, 33 and 0.9% respectively. Discussion: The diagnosis, management and monitoring of most patients fell short of the ICSI treatment guideline recommendations especially to monitoring of blood sugar, lipid levels and weight. The presence of anomalies calls for sensitization of healthcare workers on the importance of adoption and adherence to evidence based, up to date treatment guidelines and optimize patient health outcomes. Key words: Type 2 diabetes, treatment guidelines, healthcare provider
Identification and characterization of potential drug interactions in hypertensive patients in a Kenyan tertiary hospital
Background: Hypertensive patients are particularly at risk of drug-drug interactions resulting from the concomitant use of multiple drugs to control their blood pressure. The presence of comorbidities and advancing age are also likely to contribute to the use of many drugs, further increasing this risk. Drug related problems such as drug interactions in the management of hypertension increase morbidity and mortality but there are limited published data to characterize them especially among the African population. Objective: To identify and characterize potential drug interactions among adult hypertensive patients attending Kenyatta National Hospital. Methods: This was a descriptive cross-sectional study done among 313 adult patients between May to July 2016 at Kenyatta National Hospital. Ethical approval was sought from the institutional review board. Data on patient demographics, clinical characteristics and current prescriptions were extracted from patient records into predesigned data collection forms. Potential drug interactions were identified using an online Drug Interactions Checker. Results: There was female predominance at 60.7% and the mean age of the study population was 55.2 years (SD 15.9). The mean number of drugs per prescription was 5.93 (SD 2.24). The prevalence of potential drug interactions was 92.7%. There was an average of 3.5 drug interactions per prescription. Majority (79.2%) of the potential drug interactions were categorized as moderate while major and minor interactions accounted for 4.1% and 16.8%, respectively. The most prevalent interacting drug pair was enalapril and furosemide (15.3 %). The most frequent major interaction found was between enalapril and spironolactone, which is associated with hyperkalaemia. Conclusions: There was a high prevalence of potential drug interactions. Prescribers should be encouraged to be vigilant during the management of hypertensive patients to avoid overt drug interactions which may compromise treatment outcomes and increase the health care costs. Keywords: Drug interactions, hypertension, prescriptions, Keny
Exploring a Tetrahydroquinoline Antimalarial Hit from the Medicines for Malaria Pathogen Box and Identification of its Mode of Resistance as PfeEF2
New antimalarial treatments with novel mechanism of action are needed to tackle Plasmodium falciparum infections that are resistant to first-line therapeutics. Here we report the exploration of MMV692140 ( 2 ) from the Pathogen Box, a collection of 400 compounds that was made available by Medicines for Malaria Venture (MMV) in 2015. Compound 2 was profiled in in vitro models of malaria and was found to be active against multiple life-cycle stages of Plasmodium parasites. The mode of resistance, and putatively its mode of action, was identified as Plasmodium falciparum translation elongation factor 2 ( Pf eEF2), which is responsible for the GTP-dependent translocation of the ribosome along mRNA. The compound maintains activity against a series of drug-resistant parasite strains. The structural motif of the tetrahydroquinoline ( 2 ) was explored in a chemistry program with its structure-activity relationships examined, resulting in the identification of an analog with 30-fold improvement of antimalarial asexual blood stage potency
How can natural products serve as a viable source of lead compounds for the development of new/novel anti-malarials?
Malaria continues to be an enormous global health challenge, with millions of new infections and deaths reported annually. This is partly due to the development of resistance by the malaria parasite to the majority of established anti-malarial drugs, a situation that continues to hamper attempts at controlling the disease. This has spurred intensive drug discovery endeavours geared towards identifying novel, highly active anti-malarial drugs, and the identification of quality leads from natural sources would greatly augment these efforts. The current reality is that other than compounds that have their foundation in historic natural products, there are no other compounds in drug discovery as part of lead optimization projects and preclinical development or further that have originated from a natural product start-point in recent years. This paper briefly presents both classical as well as some more modern, but underutilized, approaches that have been applied outside the field of malaria, and which could be considered in enhancing the potential of natural products to provide or inspire the development of anti-malarial lead compounds
Financing and Availability of Essential Medicines Before and After Introduction of the National Hospital Insurance Fund Civil Servants and Disciplined Services Medical Scheme At Webuye District Hospital, Kenya
Background: Financing is an important determinant of access to essential medicines. In Kenya, the National Hospital Insurance Fund Civil Servants and Disciplined Services Medical Scheme is a key contributor to financing the procurement of essential medicines. Main Objective: To compare availability and funding of essential medicines at Webuye District Hospital, Kenya before and after implementation of the new National Hospital Insurance Fund Medical Scheme. Methods: This was a longitudinal before-after study of four years (January 2010-December 2013); the latter two of which the scheme was in operation. Results: After introduction of the scheme, there was a higher allocation for the medicines budget from the Facility Improvement Fund, which hosts finances from the National Hospital Insurance Fund (p=0.008). The actual expenditure on essential medicines was also higher. Expenditure on essential medicines by the government, reduced (p<0.0001). The stock out rate decreased by 2.28% though this change was not statistically significant (p=0.099). The Facility Improvement Fund expenditure on essential medicines was a significant negative predictor of stock out rate. Conclusion: Although financing of medicines through the facility improvement fund increased after introduction of the new scheme, there was no change in the stock-out rate. Key words: financing, availability, essential medicines, insuranc
Examination of WHO/INRUD Core Drug Use Indicators at Public Primary Healthcare Centers in Kisii County, Kenya
Background. Irrational drug use is a global problem. However, the extent of the problem is higher in low-income countries. This study sets out to assess and characterize drug use at the public primary healthcare centers (PPHCCs) in a rural county in Kenya, using the World Health Organization/International Network for the Rational Use of Drugs (WHO/INRUD) core drug use indicators methodology. Methods. Ten PPHCCs were randomly selected. From each PPHCC, ninety prescriptions from October to December 2018 were sampled and data extracted. Three hundred (30 per PPHCC) patients and ten (1 per PPHCC) dispensers were also observed and interviewed. The WHO/INRUD core drug use indicators were used to assess the patterns of drug use. Results. The average number of drugs per prescription was 2.9 (SD 0.5) (recommended: 1.6–1.8), and the percentage of drugs prescribed by generic names was 27.7% (recommended: 100%); the percentage of prescriptions with an antibiotic was 84.8% (recommended: 20.0–26.8%), and with an injection prescribed was 24.9% (recommended: 13.4–24.1%). The percentage of prescribed drugs from the Kenya Essential Medicines List was 96.7% (recommended: 100%). The average consultation time was 4.1 min (SD 1.7) (recommended: ≥10 min), the average dispensing time was 131.5 sec (SD 41.5) (recommended: ≥90 sec), the percentage of drugs actually dispensed was 76.3% (recommended: 100%), the percentage of drugs adequately labeled was 22.6% (recommended: 100%), and the percentage of patients with correct knowledge of dispensed drugs was 54.7% (recommended: 100%). Only 20% of the PPHCCs had a copy of KEML available, and 80% of the selected essential drugs assessed were available. Conclusion. The survey shows irrational drug use practices, particularly polypharmacy, nongeneric prescribing, overuse of antibiotics, short consultation time, and inadequacy of drug labeling. Effective programs and activities promoting the rational use of drugs are the key interventions suggested at all the health facilities