School of Pharmacy

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3D-QSAR and docking studies of pentacycloundecylamines at the sigma-1 (σ1) receptor
(Elsevier, 2013) Geldenhuys, Werner J.; Novotny, Nicholas; Malan, Sarel F.; Van der Schyf, Cornelis J.
Pentacycloundecylamine (PCU) derived compounds have been shown to be promising lead structures for the development of novel drug candidates aimed at a variety of neurodegenerative and psychiatric diseases. Here we show for the first time a 3D quantitative structure–activity relationship (3D-QSAR) for a series of aza-PCU-derived compounds with activity at the sigma-1 (r1) receptor. A comparative molecular field analysis (CoMFA) model was developed with a partial least squares cross validated (q2) regression value of 0.6, and a non-cross validatedr2 of 0.9. The CoMFA model was effective at predicting the sigma-1 activities of atest set with an r2 >0.7. We also describe here the docking of the PCU-derivedcompounds into a homology model of the sigma-1 (r1) receptor, which was developed to gain insight into binding of these cage compounds to the receptor. Based on docking studies we evaluated in a [3H]pentazocine binding assay anoxa-PCU, NGP1-01 (IC50 = 1.78 lM) and its phenethyl derivative (IC50 = 1.54 lM). Results from these studies can be used to develop new compounds with specific affinity for the sigma-1(r1)
4-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives as nmda receptor- And VGCC blockers with neuroprotective potential
(MPDI, 2020) Egunlusi, Ayodeji O.; Malan, Sarel F.; Omoruyi, Sylvester Ifeanyi
The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes. In the present study, we investigated novel 4-oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives for their cytotoxicity, neuroprotective effects via attenuation of MPP+-induced neurotoxicity and calcium influx inhibition abilities through the NMDA receptor and VGCC using neuroblastoma SH-SY5Y cells. All compounds, in general, showed low or no toxicity against neuroblastoma cells at 10-50 μM concentrations. At 10 μM, all compounds significantly attenuated MPP+-induced neurotoxicity as evident by the enhancement in cell viability between 23.05 ± 3.45% to 53.56 ± 9.29%.
4-Oxatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione Derivatives as NMDA Receptor- and VGCC Blockers with Neuroprotective Potential
(MDPI, 2020) Egunlusi, A; Malan, S; Omoruyi, S
The impact of excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptor overactivation and voltage gated calcium channel (VGCC) depolarization is prominent among the postulated processes involved in the development of neurodegenerative disorders. NGP1-01, a polycyclic amine, has been shown to be neuroprotective through modulation of the NMDA receptor and VGCC, and attenuation of MPP+-induced neurotoxicity. Recently, we reported on the calcium modulating effects of tricycloundecene derivatives, structurally similar to NGP1-01, on the NMDA receptor and VGCC of synaptoneurosomes.
A Community Pharmacy perspective on the epidemiology of antimicrobial drugs in the Kuilsriver urban area
(University of the Western Cape, 2017) Mhlanga, Miriam Rufaro; Obikeze, K
The epidemiology of drugs is 'defined as the manner in which drugs are used by doctors, nurses, pharmacists and patients. As such epidemiology of antimicrobial drugs is the manner in which this class of drugs is used by healthcare professional, patients or caregivers. Antimicrobial drugs have a pivotal role worldwide in preventing infections and treating infectious diseases. The challenge that lies in the health sector is to maintain antimicrobials' effectiveness by using them appropriately to avoid toxicity, adverse reactions and resistance among other problems. The world faces a future in which ten million people could die annually due to infections that are resistant to available antibiotics. Despite people already dying of drug-resistant infections in private and public hospitals, doctors are still prescribing antibiotics for viral infections, for which they have no effect. The aim of this research is to study the epidemiology of antimicrobial drugs and factors that lead to the inappropriate use of antimicrobials, which is resulting in a steep rise of antimicrobial resistance in the private sector from a community pharmacy perspective.
A Comprehensive Study on the Global Regulatory Requirements for the submission of a Post-Approval Change, specifically a Change in Manufacturing Site
(University of the Western Cape, 2017) Hoey, Barbara; Dube, Admire
Regulatory requirements for post-approval changes vary for different countries around the world. It is a challenging and costly process for pharmaceutical companies to manage changes to the approved regulatory dossier over the lifecycle of the product when it is registered in many countries. In practice the process can be complex, unpredictable and time consuming because of regional differences and frequent changes in regulatory procedures, requirements and timelines. The global regulatory requirements for the submission of a post-approval change, specifically a change in manufacturing site, were reviewed for six jurisdictions for this study. These include United States of America (US), Europe (EU), South Africa, Brazil, Russia and China. The study centred on the differences in the documentation required when submitting a post-approval change for a change in manufacturing site in these countries. The study compared and contrasted the differences and similarities between the jurisdictions. An analysis of the challenges for implementation of the change was performed. The study also examined what resources a company may need in order to meet the requirements. Some notable similarities but also many differences in the post-approval submission requirements between the countries were identified. Some of the similarities included classification of the type of variation, the submission application process, and the requirement to provide supportive stability data and updates to the common technical dossier (CTD). Differences highlighted were the types of application forms required, the amount of stability data required to support the change and the time lines for review of post-approval changes in each jurisdiction. The challenge for pharmaceutical companies arises in the effective management of these differences. Investment in a robust regulatory change management team is an essential resource requirement for pharmaceutical companies. Adoption of a QbD approach and careful consideration of the global requirements during the product development phase could potentially be of use in strategic planning within a company in order to ensure continued product access globally.
A Reductionistic Epistemology utilizing Brain Laterality which Investigates Pharmacists' Ideal Interactive Environment
(University of the Western Cape, 2018) Symon, Bernard Dennis; Butler, Nadine
The brain laterality of pharmacists may influence where the pharmacists are best suited to work. Brain laterality refers to the asymmetry of the hemispheres of the brain with regard to specific cognitive functions, such as objectivity and emotion. The left hemisphere functions objectively and rationally, whereas the right hemisphere is subjective and non-rational. Animal behaviour in the literature demonstrated an influence of brain laterality, thus selecting an ideal work environment may also be driven by brain laterality bias. Further support for the research included: amblyopia; hemiplegia; the WADA test. The research question investigated the matching of the brain laterality groups of pharmacists to their ideal work environments. The aims investigated: ear, eye, hand and foot dominance in determining brain laterality; influence of brain laterality and reductionistic variables on job choice; location of emotion generation and job choice. Five objectives investigated these aims: influence of brain laterality alone; influence of brain laterality and reductionistic variables; influence of a new brain laterality determining continuum; Propinquity Principle in achieving data; correctness of the Right Hemisphere Theory (RHT) or the Valence Theory (VT). The RHT suggests that the right hemisphere is dominant in processing all emotion. The VT argues that the left hemisphere is specialised in processing the positive emotions while the right hemisphere is specialised in processing the negative emotions. The resulting Null Hypothesis posits that there is no statistical difference between the different brain laterality groups enabling pharmacists to work competently in any placement. The Alternative Hypothesis was that there is a statistical difference between the brain laterality groups, thus brain laterality can be used to best place pharmacists into ideal placements.
Access to chronic medicines: patients’ preferences for a last kilometre medicine delivery service in Cape Town, South Africa
(Springer Nature, 2021) Adams, S; Mulubwa, M; van Huyssteen, M
: Chronic patients are required to access their chronic medicines on a regular basis, often only to refill their repeat prescriptions. Adherence to chronic medicines is challenging and has stimulated health care providers to devise differentiated service delivery models of care to decentralise chronic medicine distribution to decrease the frequency of medicine collection at health care facilities. One such option includes a last kilometre medicine delivery service. This study investigated chronic patients’ preferences for a last kilometre medicine delivery service model.
Active encapsulation of diclofenac sodium into liposomes for ophthalmic preparations
(University of the Western Cape, 2018) Alonjang, Evelyne Nguelweh; Ebrahim, Naushaad
Liposomes as a drug carrier in the pharmaceutical industry has gained currency since its discovery in 1965 by Bangham A. D. Liposomes have been shown to improve bioavailability as they can be delivered to target sites and possess sustained release properties which could be used to mitigate certain weaknesses associated with current diclofenac sodium eye drops. Diclofenac sodium (DNa) eye drop is a sterile Nonsteroidal Anti-inflammatory Drug (NSAID) with diclofenac sodium as its active ingredient. It is indicated for the lessening of ocular pain, prevention of miosis in eye operations, easing of postoperative inflammation and cystoids macular edema. The residence time of eye drops after application has been found to be 1-2 minutes as a result of continuous production of tears diluting the active ingredient, draining the eye drops into the nasolacrimal path, and eliminating it during blinking. As a result of the active ingredient not residing at the target site for the required duration, more frequent administration and medication is required and the risk of non-compliance is increased. Given the aforementioned potential of liposomes to redress the above weaknesses of current eye drops (dosage form) available for diclofenac sodium ophthalmic application, this study sought to encapsulate diclofenac sodium into liposomes for ophthalmic application. The main components of liposomes (cholesterol and phosphotidylcholine) and incubation time were set as the independent variables while percentage encapsulation, polydispersity index (PDI) and drug release profile constituted the dependent variable. Using analysis of variance (ANOVA) and t-test statistics, the interaction between the independent variables and their effect on the dependent variables were tested.
Active Principles of Tetradenia riparia; II. Antispasmodic Activity of 8(14), 15-Sandaracopimaradiene-7α, 18-diol
(Georg Thieme Verlag, 1987) Van Puyvelde, Luc; Lefebvre, Romain; Mugabo, Pierre; De Kimpe, Norbert; Schamp, Niceas
Tetradenia riparia is one of the most popular medicinal plants in Rwanda. Previously, several new substances have been isolated from the leaves, including a new diterpenediol, i.e. 8(14),15-sandaracopimaradiene-7α,18-diol. This new diterpenediol exhibits a papaverine-like antispasmodic activity on the contractions of the guinea pig ileum provoked by methacholine, histamine, and barium chloride and on the noradrenaline-induced contractions of the rabbit aorta.
Acute and chronic toxicity of the flavonoid-containing plant, Artemisia afra in rodents
(University of the Western Cape, 2005) Mukinda, James Tshikosa; Syce, James A.; School of Pharmacy; Faculty of Community and Health Sciences
The aim of this study was to investigate the possible toxicity of the flavonoid-containing plant, Artemisia afra and especially establish the safety of the aqueous extract of this plant after acute and chronic administration to mice and rats respectively.
Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV
(David Publishing, 2011) Mugabo, Pierre; Hassan, Mogamat Shafick; Slaughter, R.
The aim of this study was to compare the pharmacokinetics of antituberculosis drugs in patients with pulmonary tuberculosis (PTB) and in patients with PTB and HIV during the first 24 h of treatment. Designed as a case-control study, it compares the pharmacokinetics of first line antituberculous drugs, in HIV-positive (cases) and HIV-negative (control) patients both presenting with pulmonary tuberculosis. Blood samples were collected before and 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 8, 12 and 24 h after administration of drugs. Drugs plasma levels were tested using HPLC assays. Results: Fourteen HIV positive (7 males and 7 females) and 17 HIV negative (9 males and 8 females) enrolled. Rifafour, a combination tablet including rifampicin, isoniazid, pyrazinamide and ethambutol was used in HIV positive patients, CD4 counts were significantly lower, renal function mildly decreased in 85% patients and moderately decreased in 7% patients. Liver function was normal in both groups. None of these patients was on other drug therapy. In the HIV positive group isoniazid T1/2 and AUC were decreased and Cl increased whereas Tmax and Cmax were unchanged. Pyrazinamide Tmax and Cmax were significantly decreased in HIV positive patients and no significant changes were noticed in the T1/2, AUC and CL. Conclusion: The study suggest that ethambutol, pyrazinamide and rifampicin pharmacokinetics was not affected by HIV infection and that isoniazid disposition is affected by HIV.
Additional regulatory review pathways can facilitate faster dossier approvals in South Africa
(University of the Western Cape, 2019) Mattew, Ilona; Joubert, Jacques
The objective of the study was to perform a comparative review of pathways, timelines and improvements of countries with markets that the South African Health Products Authority (SAHPRA) benchmark themselves against. Furthermore, this study intends to identify the factors that improved and accelerated submissions and approval process in investigated countries and potential introduction of these strategies into the South African market.
Adverse effects experienced by patients on first line antiretroviral drugs used at Keetmanshoop Hospital (Namibia).
(University of the Western Cape, 2015) Mutenda, Nicholus Mbangu; Mugabo, Pierre
Adverse effects are a significant factor that determine how long patients will tolerate a given antiretroviral drug regimen. They also influence treatment options, and play an important role in the much needed adherence to treatment by patients on Highly Active Antiretroviral Therapy (HAART). This study is aimed at understanding adverse effects experienced by patients on the first line antiretroviral therapy at Keetmanshoop Hospital in Namibia. Methods : A retrospective quantitative method was used to review records of patients on first line antiretroviral treatment who started treatment between November 1st 2007 and December 1st, 2008 and followed up until they reached 36 – 48 months on treatment. Records of 94 patients were found eligible to be included in the study. Data was analysed using Stata 12 data analysis software. Results : The most reported adverse effect was musculoskeletal disorders (25%) whereas headache (16%) was the least reported. Low haemoglobin (78%) was the most common recorded hematologic adverse effect whereas low red cell distribution width and low mean platelet volume were the least recorded adverse effects (0%). A Male patient was more likely to experience a low haemoglobin levels compared to a female patient (adjusted OR: 3.29, 95% CI: 1.3 – 8.3). A male patient was found to be 64% times less likely to experience a higher mean cell haemoglobin compared to a female patient (adjusted OR. 0.31, 95% CI: 0.11 – 0.87). A patient on nevirapine was more likely to experience an elevated creatinine level compared to a patient on efavirenz (adjusted OR; 36.0, 95%CI: 2.02 – 62.5). At baseline, a patient who had prior exposure to ART had an 81 times (adjusted OR: 81.4, 95%CI: 5.3 – 119, p-value=0.00) increased odds of experiencing a high mean cell volume (MCV) compared to a patient with no ART exposure. A patient with a higher CD4 count was also less likely to experience a low hemoglobin compared to a patient with low CD4 count (adjusted OR; 0.31, 95% CI: 0.12 – 0.77). The author recommends further studies with higher sample size to confirm whether higher creatinine levels are more prevalent in patients on nevirapine compared to patients on efavirenz; this will have clinical implications especially in patients with impaired renal system. Antiretroviral treatment increases chances of developing macrocytosis anaemia; clinical implication of this condition may need to be investigated.
Adverse Foetal Outcomes in Gestational Diabetes: A Systematic Review and Meta-analysis
(University of the Western Cape, 2020) Chukwuemeka, Scholarstica Chinwe; Obikeze, Kenechukwu
Gestational diabetes mellitus (GDM) is a condition that affects pregnant women and is one of the most common complications related to pregnancy. According to the World health organisation (WHO), the usual window for diagnosing GDM is between 24 and 28 weeks of gestation and the primary aim of diagnosing gestational diabetes is to identify women and infants at risk of short- or longer-term adverse outcomes. Recent results from the hyperglycaemia and adverse pregnancy outcome (HAPO) study have suggested that even mild levels of hyperglycaemia can have adverse effects on foetal outcomes but there are uncertainties about the prevalence of these outcomes in GDM diagnosed according to the latest WHO 2013 guideline and/or IADPSG 2010 criteria in diverse populations. GDM prevalence has been studied by different researchers, but the prevalence of adverse foetal outcomes in GDM diagnosed based on the latest WHO 2013 guideline and/or IADPSG 2010 criteria have not yet been explored except for the data published by the HAPO study. Due to the lack of sufficient knowledge on foetal outcomes in GDM, this study was conducted to review the evidence on the prevalence of adverse foetal outcomes in GDM diagnosed according to WHO 2013 guideline and/or the IADPSG 2010 criteria. Different databases including PubMed, Science Direct, Google Scholar and CINAHL as well as bibliographic citations were searched using a well-formulated search strategy to find the relevant observational studies (prospective/retrospective cohort and case-control) using explicit inclusion and exclusion criteria. The following search terms were used, “gestational diabetes”, “pregnancy”, “adverse fetal outcomes” and “adverse foetal outcomes”. The findings of this study were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and the obtained data analysed using MetaXL ® version 5.3. This review was registered online on PROSPERO, the International prospective register of systematic reviews (registration number: CRD42020155061). Fifteen studies with 88,831 pregnant women (range: 83-25,543 participants) from 12 countries around the world were identified, with a wide variation in the prevalence of foetal outcomes in GDM using the stipulated criteria. These studies were unevenly distributed geographically as six of them were conducted in Asia, four in Europe, four in North America, one in Australia and none in Africa, Antarctica and South America. A meta-analysis found that the overall prevalence of foetal outcomes ranged from 1% (perinatal mortality) to 11% ( large for gestational age). The finding is limited due to the paucity of data on the prevalence of foetal outcomes in GDM. However, more studies using these criteria in low- and middle- income countries (LMICs) are needed by health care providers, to inform practice and allocate resources for control of GDM and its adverse foetal outcomes in diverse settings and ethnic groups, especially in LMICs.
Adverse pregnancy outcomes among HIV-positive pregnant women treated with efavirenz-containing antiretroviral drugs: a retrospective cohort study in the Cape Flats
(University of the Western Cape, 2017) Mohammednur, Mohammedmekin Mohammedseid; Mugabo, Pierre
The use of efavirenz (EFV) in the first trimester of pregnancy remains controversial. In South Africa, the use of EFV-containing antiretroviral therapy (ART) as part of a Fixed Dose Combination (FDC) during the first trimester of pregnancy started in April, 2013. Literature to date has reported conflicting outcomes following the use of EFV-containing ART during the first trimester of pregnancy. The objectives of the study were to determine the prevalence of adverse pregnancy outcomes among HIV-positive pregnant women treated with EFV-containing ART and compare these results with those of pregnant women treated with NVP-containing ART and HIV-negative pregnant women in resource-limited settings. In addition, the study also aimed to determine the effect of the time of initiation of ART on the prevalence of adverse pregnancy outcomes.
Allergic rhinitis: To sneeze or to wheeze. Pollen is the question, what is the answer?
(Medpharm Publications, 2018) Martin, Bjorn; Wehmeyer, Alexander; Upton, Edward
Allergic rhinitis, also known colloquially as hay fever, is the most common among the allergic diseases. Recent literature reports that it affects up to a tenth of the world population. Atopic diseases have a particularly high prevalence in young children which is often attributed to their immature immune systems. Traditionally, atopic diseases have plagued industrialised countries, but the burden has recently extended its reach to developing countries. Over the past few decades, there has been a marked increase in all allergy-related diseases. Supported by the advent of the Atopic March, research has been primarily directed at understanding the aetiology and pathophysiology associated with diseases stemming from atopy. In this article, we review current treatments available in South Africa and explain the pathophysiology of allergic rhinitis.
Alternative mechanisms for delivery of medication in South Africa: A scoping review
(AOSIS, 2021) Mash, Robert; Christian, Carmen; Chigwanda, Ruvimbo V
Background: The number of people in South Africa with chronic conditions is a challenge to the health system. In response to the coronavirus infection, health services in Cape Town introduced home delivery of medication by community health workers. In planning for the future, they requested a scoping review of alternative mechanisms for delivery of medication to patients in primary health care in South Africa. Methods: Databases were systematically searched using a comprehensive search strategy to identify studies from the last 10 years. A methodological guideline for conducting scoping reviews was followed. A standardised template was used to extract data and compare study characteristics and findings. Data was analysed both quantitatively and qualitatively. Results: A total of 4253 publications were identified and 26 included. Most publications were from the last 5 years (n = 21), research (n = 24), Western Cape (n = 15) and focused on adherence clubs (n = 17), alternative pick-up-points (n = 14), home delivery (n = 5) and HIV (n = 17). The majority of alternative mechanisms were supported by a centralised dispensing and packaging system. New technology such as smart lockers and automated pharmacy dispensing units have been piloted. Patients benefited from these alternatives and had improved adherence. Available evidence suggests alternative mechanisms were cheaper and more beneficial than attending the facility to collect medication. Conclusion: A mix of options tailored to the local context and patient choice that can be adequately managed by the system would be ideal. More economic evaluations are required of the alternatives, particularly before going to scale and for newer technology.
Amitriptyline prescribing in public sector healthcare facilities in the Western Cape, South Africa
(Public Library of Science, 2020) Coetzee, Renier; Johnson, Yasmina; van Niekerk, Johan
Inappropriate medication use is a major patient safety concern, especially for the elderly population. Amitriptyline is widely used in primary care in South Africa and a cross-sectional study found that amitriptyline was prescribed potentially inappropriately in 6.5% of elderly patients. An analysis of prescriptions from the Chronic Dispensing Unit in the Western Cape revealed that amitriptyline was one of the most common medicines prescribed without a suitable diagnosis listed on the prescription.
Amount of cycloserine emanating from terizidone metabolism and relationship with hepatic function in patients with drug resistant tuberculosis
(Springer, 2019) Mulubwa, Mwila; Mugabo, Pierre
The dosing of cycloserine and terizidone is the same, as both drugs are considered equivalent or used interchangeably. Nevertheless, it is not certain from the literature that these drugs are interchangeable. Therefore, the amount of cycloserine resulting from the metabolism of terizidone and the relationship with hepatic function were determined. This prospective clinical study involved 39 patients with drug-resistant tuberculosis admitted for an intensive phase of treatment. Cycloserine pharmacokinetic parameters for individual patients, like area under the curve (AUC), clearance (CLm/F), peak concentration (Cmax) and trough concentration (Cmin), were calculated from a previously validated joint population pharmacokinetic model of terizidone and cycloserine. Correlation and regression analyses were performed for pharmacokinetic parameters and unconjugated bilirubin (UB), conjugated bilirubin (CB), albumin, the ratio of aspartate transaminase to alanine aminotransferase (AST/ALT), or binding afnity of UB to albumin (Kaf), using R statistical software version 3.5.3.
Anaemia – a pale ale?
(Cogent OA, 2017) Muntingh, G. L.; Viljoen, M.
Despite some modest improvements described recently, anaemia remains a significant global public health concern affecting both developed and developing countries. It affects a quarter of the global population, including 293 million (47%) children who are younger than five years of age. A prevalence of 42% and 30% has been described in pregnant and non-pregnant women, respectively. Children and women of reproductive age are at high risk, partly because of physiological vulnerability, followed by the elderly. Africa and Asia are the most heavily affected regions, accounting for 85% of the absolute anaemia burden in highrisk groups. According to the World Health Organization global database on anaemia (1993–2005), this disorder was considered to be a moderate public health problem in South African preschool children, pregnant women and non-pregnant women of reproductive age.

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