Masters Degrees (Pharmaceutical Sciences)

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Attitude and practices about the coronavirus disease and its’ impact on the mental well-being on university students: a cross-sectional study amongst pharmacy students in the University of KwaZulu-Natal.
(2023) Ebrahim, Nabeela.; Bangalee, Varsha.; Moudgil, Khayati.
Student mental health at a tertiary level of education has become a growing concern since the beginning of the COVID-19 pandemic. University students in South Africa face academic challenges as well as a cascade of socio-economic challenges making them more at risk for anxiety and depression. The restrictions, and challenges that COVID-19 brought has intensified these risks. The effect of the COVID-19 pandemic on the psychological well-being of South African university students has a major role to play in analyzing the future implications for the populations’ mental health. The steps that were taken to prevent the spread of COVID-19 including lockdown measures, social distancing and quarantine have introduced significant threats to the mental health of the public at large. The current study aims to determine the attitude, practices impact of COVID-19 on the mental health of Pharmacy students at University of KwaZulu-Natal (UKZN). Method This study was designed to be a cross-sectional quantitative study which was carried out as a survey questionnaire to fulfil the required objectives. Data was collected via a survey questionnaire; hard copies of the survey were distributed to third-and-fourth year pharmacy students at UKZN once on-site learning at the campus resumed after a period of remote learning as a result of COVID-19. The data was entered into Microsoft® Excel® and analyzed using Statistical Package for the Social Science® (SPSS®), version 28. Descriptive and inferential statistics were calculated, the results were discussed, and conclusions were drawn. Results A total of 190 participants completed the survey. There were no exclusions as all the participants were over the age of 18 and were studying in third- or fourth-year pharmacy at UKZN. Majority of the participants (72.5%) perceived the COVID-19 virus as a threat to their community and 83% of students felt scared towards the COVID-19 pandemic. Increased levels of anxiety, loneliness, depression, and substance abuse was also reported. Most students found trouble concentrating (75.9%), which impacts academic and daily functioning and 77.6% found that the lockdown had a negative impact on their academic experience. Conclusion The current study was able to provide a comprehensive assessment of the attitudes and practices about the Coronavirus Disease (COVID-19) and its’ impact on the mental well-being on university students amongst pharmacy students in the University of KwaZulu-Natal. The findings suggest that the Covid-19 outbreak has globally introduced many hurdles for tertiary education institutions and challenges for students’ mental health. A variety of factors that are linked to the pandemic such as financial difficulty, a weakened social circle, trouble sleeping, fear of contracting the virus, trouble concentrating, and loneliness have increased anxiety and stress among university students. The study also reports a thorough analysis of the students and their range of feelings during the pandemic and consequent lockdown to evaluate their energy levels, prepotent feelings and challenges faced as a result. Our findings highlight that most participants displayed negative feelings and experienced many challenges as a result of the lockdown. In light of these findings, it is imperative that proactive measures are implemented to address the mental health concerns of students. Such efforts should not only encompass addressing the immediate challenges posed by the pandemic but also address the pre-existing vulnerabilities that have been exacerbated. By recognizing the multifaceted nature of these challenges and the diverse emotional responses they elicit, institutions and governments can work in tandem to provide comprehensive support systems that aid students in navigating these unprecedented times.
Community pharmacists’ perceptions and experiences of medicine shortages in disruptive situations, in Durban, South Africa.
(2024) Bachoolall , Rivana.; Suleman, Fatima.
Background: Medicine shortages are a challenge in upper, lower and middle-income countries, including South Africa. In recent years, community pharmacists in Durban, South Africa, have experienced disruptions such as the COVID-19 pandemic, flooding, civil unrest and electricity disruptions. Little is known about the impact of these disruptive situations on medicine shortages in community pharmacies. Aim: Exploring the perceptions of community pharmacists and their experiences with medicine shortages during the COVID-19 pandemic and other disruptive situations. Method: A qualitative methodology was employed to explore the topic in-depth. Convenience and snowball sampling were used to recruit 15 community pharmacists in Durban, South Africa. Semi-structured interviews were conducted in person or via an online video conferencing platform. All interviews were audio-recorded and transcribed verbatim. The transcripts were coded deductively on NVivo 14 software, using the Framework Method of thematic analysis. Initial codes and themes were informed by a literature review and final themes were identified on review. Results: A total of fifteen community pharmacists were interviewed. Five major themes were identified from thematic analysis, viz. the perceptions of medicine shortages, the impact of disruptive situations, the consequences of medicine shortages, mitigation strategies; and further suggestions and resources. Perceptions were that shortages were exacerbated by the disruptive situations. Participants perceived a negative financial impact on patients and pharmacies, with out-of-pocket costs affecting the former and loss of income affecting the latter. The mitigation strategies used were contacting stakeholders, medicine substitution and stock management. Conclusion: Community pharmacists felt that medicine shortages required improved communication, collaboration, policies, notification systems and guidelines to mitigate the problem further. These should be investigated for possible implementation to create more transparency in the event of shortages.
Overview of proton pump inhibitor use: a medical scheme perspective.
(2023) Mohanlal, Kajal.; Bangalee, Varsha.; Oosthuizen, Frasia.
Background: Proton pump inhibitors (PPIs) are highly effective and safe drugs for the treatment of acid-related disorders. However, their easy availability over-the-counter (OTC) often results in the misuse of these drugs. Inappropriate prescribing practices also lead to overutilization, leading to potential long-term adverse effects and rising cost implications on medical schemes. This study aims to provide an overview of PPI misuse and the financial implications on medical schemes in South Africa. Method: Retrospectively, all acute and OTC PPI claims from four different medical schemes from January 2021 to December 2021 were extracted from an electronic database of a pharmaceutical benefit management organization. A total of 268 537 claims made by 81 566 patients were included in the study. The data obtained were recorded on Excel® and included patient age, sex, generic entity including strength and quantity claimed, prescriber and provider types, month claimed, benefit applicable and the cost reimbursed by the medical scheme per claim in South African Rands. Descriptive and analytical measures were used to evaluate the frequency and duration of PPI usage, provide an overview of the safe indications for use and determine the overall financial impact of PPI usage on medical schemes. Results: Five different PPI generic entities were analyzed (pantoprazole, omeprazole, lansoprazole, rabeprazole and esomeprazole). PPIs were claimed at an average of 8 times within the twelve-month period per patient. There was a significant correlation between the patient’s age and the duration of therapy (p < 0.001). Omeprazole (34%), pantoprazole (25%) and esomeprazole (24%) were the most frequently utilized generic entities. More than half of the PPIs claimed were prescribed by general practitioners. Lansoprazole 15 mg, omeprazole 10 mg and 20 mg and pantoprazole 20 mg are available for OTC usage. OTC pharmacy claims made up 13.99% of the total PPI claims submitted. The total cost to the medical schemes was R20 715 453,58, of which high-dose esomeprazole accounted for 30.08%. Two of the four medical schemes implemented an annual quantity limitation on PPIs of 90 tablets or capsules per year effective from 2023. Conclusion: Despite clear indications for safe use, PPIs are being overutilized on a long-term basis and for inappropriate indications. De-prescribing of PPIs in the elderly, especially high-dose esomeprazole, should be considered when re-evaluating patients to prevent overutilization. Authorized prescribers and pharmacists play an essential role in reducing PPI expenditure and discouraging PPI misuse by prescribing only according to national guidelines for appropriate indications and treatment duration, encouraging the use of cost-effective generics and alternative therapies, and educating patients on healthy lifestyle measures for the long-term management of acid-related disorders. The cost of PPIs to medical schemes in South Africa is currently very high and increasing steadily each year. The costs to medical schemes can be further reduced by implementing benefit design restrictions on PPI reimbursement.
pH-responsive gelatin nanoparticles for targeted delivery of ciprofloxacin against bacterial infections.
(2024) Hlabisa, Minenhle.; Govender, Thirumala.; Omolo, Calvin Andeve.
Background: Given the rise in antimicrobial resistance and challenges associated with traditional antibiotic dosage forms, there is an urgency to develop drug delivery systems that improve, safeguard, and augment the present antibiotics on the market. Further research is required to maximize extended and targeted drug release, which can be accomplished via stimuli-responsive approaches such as pH-responsive nano-drug delivery systems. Furthermore, these pH-responsive nanosystems may be employed as carriers for antimicrobial drugs, which could be beneficial against antimicrobial resistance. Aim: The aim of this study was to prepare novel pH-responsive gelatin nanoparticles to function as delivery agents of Ciprofloxacin (CIP) to enhance their antibacterial effectiveness against methicillin-resistant Staphylococcus aureus (MRSA). Methods: CIP-GNPs were prepared using a two-step desolvation method. The particle size, polydispersity index (PDI) and zeta potential (ZP) of CIP-GNPs were determined using the dynamic light scattering technique. Transmission electron microscopy analysis was conducted to confirm particle size and visualize the morphology of CIP-GNPs. The entrapment efficiency (EE %) of CIP-GNPs was determined using the ultrafiltration method and was quantified using High-Performance Liquid Chromatography (HPLC). In vitro drug release of CIP-GNPs was conducted using the dialysis bag technique and CIP released was quantified using HPLC. Drug release dissolution factors were analysed using the DDSolver program. Hemocompatibility of CIP-GNPs was performed using sheep blood. In vitro antibacterial activity of CIP-GNPs was determined using micro broth assay against Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), MRSA, and P. aeruginosa. Bacterial killing kinetics were performed against MRSA and P. aeruginosa using the plate colony counting method. MRSA and P. aeruginosa biofilm inhibition of CIP-GNPs was evaluated using the microtiter method. Results: CIP-GNPs had a particle size, polydispersity index, zeta potential, and entrapment efficiency of 212.3 ± 1.739, 0.259 ± 0.023, +4.58 ± 0.148 mV and 38.1 ± 3.85%, respectively. In vitro, biosafety testing identified CIP-GNPs as non-hemolytic. The CIP-GNPs demonstrated pH responsiveness with an increase in particle size from 204.1 ± 0.100 to 226.4 ± 0.451 nm and a charge switch on the zeta potential from -3.59 ± 0.428 to 1.06 ± 0.271 mV, followed by a significantly faster release of CIP at pH 6.0 compared to 7.4. The in vitro antibacterial activity of CIP-GNPs showed 2-fold lower minimum inhibitory concentration values compared to bare ciprofloxacin against Methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Pseudomonas aeruginosa (P. aeruginosa). Moreover, the bacterial-killing kinetic test showed 100% elimination of MRSA and P. aeruginosa within eight and one hour(s) of treatment with CIP-GNPs, respectively. In contrast, 100% elimination of MRSA and P. aeruginosa was observed within 24 and 12 hours of treatment with bare ciprofloxacin, respectively. CIP-GNPs eliminated 3,75-fold MRSA biofilm compared to bare ciprofloxacin, whereas 1.4-fold Pseudomonas aeruginosa biofilms were eliminated. Conclusion: CIP-GNPs could effectively treat MRSA infections at a faster rate as compared to bare CIP. Therefore, this novel pH-responsive CIP-GNPs may serve as a promising nanocarrier for enhancing antibiotic delivery and antibacterial activity
Formulation of nanostructured lipid carriers using eugenol and D-α-tocopherol succinate for the inhibition of bacterial efflux pumps to enhance delivery of ciprofloxacin.
(2023) Dlamini, Sbongumusa.; Govender, Thirumala.; Omolo, Calvin Andeve.
The continuously growing antibacterial resistance crisis is decreasing the availability of the antibiotics to treat bacterial infections. Bacteria develop additional mechanisms to survive lethal concentrations of antibiotics such as efflux pumps and biofilms. Novel drug delivery systems are urgently required to enhance antibiotic efficacy and overcome resistance. Furthermore, natural derivatives from medicinal plants have shown great potential as bacterial adjuvants to inhibit these mechanisms. Therefore, employing these compounds in the formulation of nanocarriers could restore antibiotic efficacy and overcome antibiotic resistance. Aim: The aim of this study was to explore the potential of ciprofloxacin-loaded nanostructured lipid carriers (CIP-NLCs) designed using D-α-tocopherol succinate (TS) and eugenol for enhancing antimicrobial activity and overcoming resistance mechanisms against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (P. aeruginosa). Methods: CIP-NLCs were prepared using hot homogenization/ultrasonication method. The particle size, polydispersity index (PDI) and zeta potential (ZP) of CIP-NLCs were determined using the dynamic light scattering technique. Transmission electron microscopy analysis was conducted to confirm particle size and visualize the morphology of CIP-NLCs. The entrapment efficiency (EE %) of CIP-NLCs was determined using the ultrafiltration method and was quantified using High-Performance Liquid Chromatography (HPLC). In vitro drug release of CIP-NLCs were conducted using the dialysis bag technique and CIP released was quantified using HPLC. Drug release kinetics were analysed using the DDSolver program. Haemocompatibility of CIP-NLCs was performed using sheep blood. The in vitro antibacterial activity of CIP-NLCs were determined using micro broth assay against Staphylococcus aureus (SA), Escherichia coli (E. coli), MRSA, and P. aeruginosa. Bacterial killing kinetics were performed against MRSA and P. aeruginosa using the plate colony counting method. MRSA and P. aeruginosa biofilm inhibition of CIP-NLCs was evaluated using microtiter method. DPPH scavenging was used to study the antioxidant activity of CIP-NLCs. In vivo antibacterial activity of MRSA was studied using the systemic MRSA infection on BALB/c mice. Results: CIP-NLCs had a particle size, PDI, ZP, and EE % of 147.4 ± 0.59 nm, 0.219 ± 0.009, -9.64 ± 2.22 mV, and 82.8 ± 0.39 %, respectively. The in vitro biosafety evaluation revealed CIP-NLCs as non- haemolytic. The in vitro drug release study showed a biphasic release of CIP from the CIP-LNCs for 48 hours at physiological pH (7.4). The in vitro antibacterial activity of CIP-NLCs (SA:0.195 μg/mL and MRSA:12.5 μg/mL) showed 2-fold lower minimum inhibitory concentration (MIC) values over bare ciprofloxacin (SA: 0.39 μg/mL and MRSA: 25 μg/mL) against MRSA, SA, whereas the MIC values of CIP-NLCs (E. coli: 0.048 μg/mL and P. aeruginosa: 0.097 μg/mL) were 4-fold lower CIP ( E. coli: 0.195 μg/mL and P. aeruginosa: 0.39 μg/mL) against E. coli, and P. aeruginosa. The bacterial-killing kinetic test showed 100% elimination of MRSA and P. aeruginosa within eight and one hour(s) of treatment with CIP-NLCs, respectively. Conversely, 100% elimination of MRSA and P. aeruginosa was shown within 24 and 12 hours of treatment with bare ciprofloxacin, respectively. CIP-NLCs eliminated 3-fold MRSA biofilm compared to bare ciprofloxacin, whereas 1.25-fold P. aeruginosa biofilms were eliminated. The efflux pump inhibition potential of CIP-NLCs was confirmed using cartwheel assay, which showed high fluorescence intensity on bacteria treated with CIP-NLCs. The DPPH scavenging assay of CIP-NLCs proved antioxidant activity equivalent to Vitamin C (ascorbic acid), which is reported to be a potent antioxidant. The in vivo systematic infection in BALB/c mice reduced MRSA infection in kidney, liver, and blood by 12.27-fold, 4.47-fold, and 1613-fold, respectively. Conclusion: CIP-NLCs designed using TS and eugenol could enhance the antimicrobial activity against MRSA and P. aeruginosa infections and inhibit efflux pumps associated with these bacteria. Therefore, the CIP-NLCs may serve as a promising tool for enhanced delivery of ciprofloxacin and treatment of bacterial infections.
Nanoencapsulation of novel pyrazolone-based compounds to enhance solubility and biological activity.
(2022) Igbokwe, Nkeiruka Nkeonyere.; Faya, Andile Kennedy Mbuso.; Karpoormath, Rajshekhar.
The biological activity of pyrazolone-based derivatives has been thoroughly documented; nonetheless, low stability and water solubility are their main drawbacks, preventing effective translation to clinical application. Based on this, two previously reported weakly soluble pyrazolone-based compounds, PBC-301 and PBC-302, were encapsulated using PLGA: poloxamer complex to improve their solubility and further examine the influence of solubility augmentation on their biological activities. We first developed and validated a simple, accurate RP HPLC-PDA method for detecting, measuring, and standardising the compounds in nanoformulations to achieve this wide goal. Efficient separation and quantification were carried out using Shim-pack GIST C18 (5 𝜇m 150 × 4.6 mm) column, maintained at 25 ℃ with isocratic elution using acetonitrile and acidified water (0.1% Trifluoracetic acid) (75:25 v/v) at 0.5 mL/min flow rate. The injection volume was 20 𝜇L, and eluents were detected at 333 nm at a retention time of 4.82 mins. Method validation was done following ICH guidelines. Results demonstrated that the method is specific, precise, and accurate within the recommended limits. The method showed good linearity with a 0.9994 correlation coefficient over a concentration range of 2.5-50 𝜇g/ml. The method efficiently detected and quantified the novel pyrazolone compound in the nanosuspension. The obtained nanoformulations PBC-PLGA 301 and PBC-PLGA 302 were characterised using various in vitro techniques. Size, PDI and ZP of the optimised nanoformulations were 166.6 ± 7.12 nm, 0.129 ± 0.042, -14.14 ± 2.90 mV for PBC-PLGA 301 and 192.5 ± 1.08 nm, 0.132 ± 0.025, -10.77 ± 1.515 mV for PBC-PLGA 302 with the encapsulation efficiency being 84.20 ± 0.930 and 81.5 ± 2.051, respectively. The compound release from the nanovesicles followed a sustained release pattern, with PBC-PLGA 301 and PBC-PLGA 302 attaining a cumulative release of approximately 37% and 53% in 48 hours. The biological activity assays showed a better-enhanced activity with the nanoformulations compared to the non-encapsulated PBC 301 and PBC-302. In vitro antibacterial activity revealed that the compound-loaded nanovesicles have better activity against the two gram-positive bacteria S. aureus and Methicillin-resistant S. aureus compared to the standard drug vancomycin and the non-encapsulated compound. On the other, the cell penetration assay further revealed that the compound-loaded nanovesicles achieved greater than 90% propidium iodide penetration (translating to cell death) at the reported MIC well for S. aureus while showing 86% and 89% cell penetration for Methicillin-resistant S. aureus. Also, the nanoformulations showed improved radical scavenging activity in a concentration-dependent manner, with PBC-PLGA 301 exhibiting the best antioxidant activity against DPPH, FRAP and nitric oxide compared to the standard antioxidant-gallic acid and the non-encapsulated compounds. In conclusion, the aqueous solubility of the two pyrazolone compounds, PBC-301 and PBC-302, was greatly enhanced by their encapsulation into a nanosystem, resulting in improved biological activities. Therefore, the nanoformulations of the pyrazolone-based derivatives can be exploited as potential pharmaceutical agents to fight bacterial infections and other diseases triggered by oxidative stress, cancer, and hepatic and vascular diseases. The data from this study has resulted in two first-authored research publications.
Erythromycin, Roxithromycin, Azithromycin and Clarithromycin targeting the SARS-COV-2 spike protein: a molecular dynamics study.
(2022) Naidoo, Eustacia.; Faya, Andile Kennedy Mbuso.
The Covid-19 global pandemic has taken the lives of many people and has left the health sector in ruins. There is a desperate need for the scientific and medical community to pose new strategies to combat this virus. One way is repurposing of already existing drugs for the safe treatment of Covid-19. In view of the above facts, the present research project work was planned and aimed to identify the mechanism of inhibition of macrolides by evaluating them in silico against the SARS-CoV-2 spike protein. We performed molecular dynamics and molecular docking studies on the following macrolide antibiotics: azithromycin, erythromycin, clarithromycin and roxithromycin, and we compared these with the results achieved from our controls (Ivermectin and Remdesivir). Our ligands were prepared using chemdraw and chimera software. Protein data bank was used to retrieve the four receptors: 3CLpro (6LU7), native human ACE2 (1R42), RdRp (6M71) and spike RBD-ACE2 (6LZG)). AutoDock Vina software was used to perform all docking experiments. Fitting analyses were performed using PyMOL and Biovia Discovery Studio. GROMACS was used for molecular dynamics studies to determine RMSD (Root Mean Square Deviation) and RMSF (Root Mean Square Fluctuation) values. We then went on to determine the intermolecular hydrogen bonding present, as well as the distances of the ligand whilst inside the pocket. Our findings revealed that all the macrolide antibiotics portrayed similar results with each other, as well as with each of our controls (Ivermectin and Remdesivir). Each of the macrolide antibiotics showed strong binding with each of the four receptors. However, azithromycin showed the greatest binding potential (-7.9 kcal/mol) relative to the two controls (Ivermectin (-10.4 kcal/mol) and Remdesivir (-8.5 kcal/mol)). Azithromycin-ACE2 complex showed the least deviation to the ACE2 protein and is therefore the most similar. The average RMSF values shows that there are potential interactions of azithromycin with the receptor protein (ACE2). Covid-19 emerged in 2019, and to this date, 2022, there is no known cures. There have been vaccines like Johnson and Johnson and Pfizer which have been tried and tested and has shown to reduce severity of disease and minimize fatality. However, due to the new emerging strains, there is a continuous need for new therapeutic interventions. Azithromycin has also showed similar results to both Ivermectin and Remdesivir (controls), showing great binding affinity for the ACE-2 receptor. Our analysis based on molecular dynamics simulation and MM-PBSA binding free energy calculation suggests that azithromycin, erythromycin, clarithromycin and roxithromycin could serve as SARS-CoV-2 inhibitors, hence an alternative solution to treat COVID-19 upon further clinical validation.
O-alkylated/acylated coumarin analogues: synthesis, anti-diabetic evaluation and docking studies.
(2016) Ngcoya, Nomandla Innocentia.; Singh, Parvesh.
Diabetes mellitus (DM) represents a group of chronic disorders with diverse multiple etiology. It is characterized by high blood glucose (hyperglycemia) resulting from the malfunctioning in insulin secretion and/or insulin action, leading to impaired metabolism of carbohydrates, lipids and proteins in the body. According to 2013 WHO report, approximately 4.9 million people have died thus far and around 415 million are currently suffering from DM worldwide. Different approaches such as anti-diabetic drugs, insulin injection, and lifestyle modification are currently being used to control/treat diabetes. However, these techniques are not so effective and suffer a number of limitations which is why the development of novel potent anti-diabetic drugs is highly anticipated. Recent literature review revealed that the coumarins have potential to act as anti-diabetic agents with excellent pharmacological profile. Hence, the aim of this project was to synthesize variedly substituted coumarin analogues and to test their anti-diabetic potential under in vitro conditions. Accordingly, three 4-methylcoumarins bearing hydroxyl moiety were synthesized using substituted phenols and a β-ketoester using the Pechmann reaction. The hydroxyl group of synthesized coumarins was then engaged in further transformations by its alkylation and acylation using a variety of alkyl/acyl halides under basic conditions. The synthesized compounds were structurally characterized using different spectroscopic techniques viz. proton nuclear magnetic resonance spectroscopy (1H NMR, FT-IR and HR-MS). 2D NMR such as heteronuclear multiple bond correlation (HMBC), heteronuclear single quantum coherence spectroscopy (HSQC) and correlation spectroscopy (COSY) were also conducted to assign each proton and carbon resonances of the compounds synthesized. All the synthesized compounds were tested in vitro for their anti-diabetic activity using the standard drug (acarbose) as a control. Some of the coumarin derivatives exhibited excellent anti-diabetic activity, even better than the standard drug, based on the IC50 data. The effect of alkyl chain length and electronic nature (electron-donating/withdrawing) of substituents attached to coumarin ring on the anti-diabetic activity was monitored, and a detailed structure activity relationship (SAR) was established. The in vitro anti-oxidant activity of compounds further revealed the importance of hydroxyl (-OH) groups in coumarins for their antioxidant activity. The alkylation or acylation of coumarins significantly reduced their antioxidant activity. On the other hand, the attachment of nitro (-NO2) group to the aromatic ring of coumarin, impressively increased the antioxidant activity. Molecular docking simulations were finally conducted to predict the binding propensities of the compounds in the binding site of -glucosidase, an enzyme that regulates the sugar level in the body. Since, the X-ray data for this protein is not available in protein data bank, its 3D model was generated using homology modelling technique. The predicted free binding energies predicted these compounds to be good inhibitors for the protein. Docking data suggested the importance of both the hydrogen bonding and hydrophobic forces in their host-guest relationship.
The pharmacological management of Autism Spectrum Disorder in children.
(2022) Maniram, Jennal.; Oosthuizen, Frasia.; Karrim, Saira Banu.
Background Autism Spectrum Disorder (ASD) is a developmental disorder that affects individuals from early childhood. The pharmacological management of ASD in children remains a challenge due to limited effective management options and the absence of approved drugs to manage the core symptoms. This study aimed to review pharmacological treatment options used in the management of ASD in children at a public hospital in KwaZulu-Natal by identifying pharmacological agents prescribed and determining the role and impact on treatment outcomes. Additionally, the study aimed to review effective pharmacological management options employed in managing the core symptoms and comorbidities of ASD on an international scale by conducting a systematic review. Method A quantitative retrospective study was conducted by reviewing patient files of children diagnosed with ASD, meeting the inclusion criteria. A descriptive analysis was done to identify prescribing trends and therapeutic outcomes. A systematic review was also conducted to identify pharmacotherapeutic options for the management of ASD in children and adolescents. A systematic search for studies from January 2012 to January 2022 was performed using four databases, which included: PubMed, Scopus, Science Direct, and PsycInfo. A narrative synthesis was used for data analysis. Results A total of 181 children met the inclusion criteria for the study. Risperidone was the most frequently prescribed drug (88%) for the management of comorbidities and/or core symptoms of ASD. Attention deficit hyperactivity disorder (54%), irritability or aggression (25%), and sleep dysregulation (22%) were frequent ASD comorbidities that warranted pharmacotherapy. Drugs prescribed to manage ASD comorbidities included methylphenidate, melatonin, sodium valproate, risperidone, oxybutynin, carbamazepine, and others. Risperidone and non-pharmacological therapies played a prominent role in targeting the core symptoms of ASD. In 41% of patients, there was a positive response to treatment and 20% of patients experienced improvements in the core symptoms of ASD. The systematic review provides a comprehensive list of effective management options for ASD comorbidities and core symptoms from 33 included studies. Risperidone, aripiprazole, methylphenidate, guanfacine, levetiracetam, and atomoxetine are examples of effective pharmacological drugs against ASD comorbidities. Effective drugs for the management of ASD core symptoms include but are not limited to, bumetanide, fluoxetine, intranasal oxytocin, intranasal vasopressin, and prednisolone. Conclusion Pharmacotherapy plays an important role in managing the comorbidities of ASD, however, the use of drugs in the management of ASD core symptoms is limited at the public hospital in KwaZulu-Natal. The systematic review successfully summarised the pharmacological advancements made in the past decade and includes promising therapeutic options that manage the core symptoms and comorbidities of ASD.
Drug utilization review of analgesics in the management of pain in accordance with the South African Standard Treatment Guidelines at a hospital level in Limpopo, South Africa.
(2022) Rikhotso, Muhluri Alvinah.; Bangalee, Varsha.; Suleman, Fatima.
Background One of the aims of the National Drug Policy (NDP) of South Africa was to promote the rational use of medicines and to achieve this goal, the Essential Medicines Programme (formerly EMP), which included an Essential Medicines List (EML) and Standard Treatment Guidelines (STGs), was developed. The STGs offer guidance on the rational use of medicines for the most common conditions including pain management. A perceived marked increase in the use of tramadol for pain management requires that research be undertaken to confirm if there is use of tramadol outside of prescribed guidelines, and to determine the contributing factors for this. Study aim The overall aim of the research was to review the use of analgesics in the management of pain in terms of compliance with STGs by prescribers and to determine the cost implication of failure to follow STGs in pain management for the district hospital. Prescriber awareness and use of the guidelines for pain management and the associated cost implications of nonadherence to guidelines was also assessed. Finally the study sought to ascertain prescriber experience on the misuse of tramadol when treating patients for pain. Methods This was a quantitative study in which the records of patients admitted and being treated for chronic mild to moderate pain at a district hospital in Limpopo from the 1st of April to the 30th of September 2021 were reviewed to determine whether the Hospital Level Adults STG/EML (2019) was followed when patients commenced with treatment. An Excel spreadsheet was used to record patient demographics; diagnosis; pain medication prescribed; dosage regimen; prescriber post and prescriber compliance with recommended STG. The treatment regimens for pain that were captured included paracetamol; ibuprofen; and tramadol as single prescribed therapies as well as combinations of paracetamol and ibuprofen; paracetamol and tramadol; and a combination of all three, viz. paracetamol, ibuprofen and tramadol. The recorded prescriptions were assessed for compliance in terms of the stepwise process of pain management as outlined in the Hospital Level Adults STG/EML (2019). Descriptive statistics and Excel were used for data analysis. The cost of analgesics was obtained from the Limpopo Province Pharmaceutical Depot (LPPD). A questionnaire was used to determine prescribers’ awareness of STGs, compliance with guidelines for the management of chronic mild to moderate pain, and awareness of the cost implications of non-compliance among prescribers assigned to the general ward for the period of data collection. Full ethical approval was obtained before commencement with the study. Results A total of 224 prescriptions were recorded for the 6-month period. Patients initiated on paracetamol as first-line treatment for pain were 129 (57.5 %). Nineteen patients (8.5%) were initiated on tramadol and 54 patients (24 %) on paracetamol and tramadol. Patients initiated on paracetamol and ibuprofen were 12 (5.4%); those on ibuprofen were 3 (1.3%) and 7 (3%) were switched between pain regimens. The prescription compliance rate in terms of the stepwise process of pain management as outlined in the STGs/EML was 90.6% and 9.4% were noncompliant. The total cost for both compliant and non-compliant prescriptions was R1128,10. Compliance to STGs when prescribing analgesics as reported by prescribers was 33%. Half of the prescribers (50%) stated that they only follow guidelines occasionally. Only 33% followed STGs when prescribing tramadol although 83% stated that they prescribe paracetamol for pain. All prescribers had encountered tramadol misuse by patients but only 50% monitored patients after the medicine was prescribed. The study found that 67% of prescribers had poor knowledge of the cost implication associated with non-compliance to STG. Conclusion This study has identified that there is a prescription compliance rate of 90.6% among prescribers in prescribing analgesics according to the STG/EML. There is however still room for improvement because non-compliance to guidelines has cost implications. In the South African setting where there are resource constraints, compliance is critical for the purpose of efficient use of health care resources. There is also a need for educating prescribers on the importance of compliance to guidelines.
The effect of consignment on the price of pharmaceuticals and liquidity in a private hospital in Mombasa, Kenya.
(2022) Ganiwalla, Shaheed Imtiaz.; Bangalee, Varsha.
Background A well-structured procurement system will enable the acquisition of quality products in the correct quantity, at the right time, and the right cost. There are several procurement methods available for organizations’ to choose from, and each method will alter the organizations financial position in its unique way. Bomu Hospital transitioned from a tenderbased procurement system to a consignment model in 2020. Aim and Objectives This study aims to assess the impact of consignment on the financial health of Bomu Hospital. Specific objectives include: i) to determine the effect of consignment on the cost price of pharmaceuticals, ii) to assess the effect of consignment on the liquidity ratio, iii) to evaluate the effect of combining a tender and consignment system on the cost price of pharmaceuticals, and iv) to compare the mean adjusted cost price of pharmaceuticals with the Management Sciences for Health International Medical Products Price Guide 2015. Methodology The study used a retrospective pre-post observational design. Medicine purchase price data was collected from the 2019 tender document, 2020 consignment supplier invoices, and the 2022 tenders-for-consignment document. Liquidity was assessed by comparing the institution's cash flow statements from 2019 and 2020. Descriptive and inferential statistics were used to determine the effect of the two procurement systems on the purchase price of pharmaceuticals and its effect on the liquidity. Results The dataset included 65 products listed by proprietary name. Quantitative analysis of the purchase price obtained through tenders in 2019 and consignment in 2020 shows that the price increased by a median of 4.78% [IQR = -5.66% - 12.71%] (p=0.48). However, when tenders-for-consignment were introduced, the price reduced by a median of 7.71% [IQR = -11.72% - 1.935%] (p=0.65). Consignment resulted in a direct cash savings of KES 4,427,266.10 in one year. The median price ratio was 4.4319 [IQR = 0.8496-12.6193]. Conclusion Consignment offers substantial savings through reduced capital expenditure. However, eliminating competition results in higher purchase prices that can harm the affordability of medicines. Comparatively, tenders provide the best prices because of competition between suppliers. Combining both results in substantial savings for the institution without negatively impacting the cost of medicines.
Assessment of factors affecting adherence to chronic medicines among stable patients registered onto the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme: the case of eThekwini Metropolitan Health District, South Africa.
(2018) Naidoo, Mary-Anne.; Nlooto, Manimbulu.
Background Globally more deaths are due to chronic disease compared to infectious disease. In South Africa, the number of patients has been increasing over the years for those who have been diagnosed with chronic diseases and thus requiring chronic treatment. The Centralized Chronic Medicine Dispensing and Distribution (CCMDD) programme is a national programme with the aim to improve patients access to medicines in the public health sector. To establish the implications of factors that affect patient adherence to chronic medication on the CCMDD programme in eThekwini Metropolitan Health district. Methods A descriptive cross-sectional study was conducted among stable chronic patients on the CCMDD programme in five public health facilities in eThekwini Metropolitan Health District South Africa between May and August 2017. The researcher administered face-to-face interviews were carried out using a semi-structured questionnaire with open and closed-ended questions. Results Most patients reported never experiencing out of stock of medicines at PUPs (365/417, 87 .5%, 95%CI [84.1-90.5]) and never received an incomplete parcel (324/417, 77.7%, 95%CI [73.7-81.7]). Many respondents rated their relationship with CCMDD as good (221/417, 53.0%, 95%CI [48.12-57.79]); they were satisfied to collect their medicines without counselling at PUPs (411/417, 98.6%, 95%CI [97.47-99.73]) and rarely experienced challenges with the CCMDD programme (345/417, 82.7%, 95%CI [79.07-86.33]). Majority ofrespondents reported a waiting time less than 30 minutes (411/417, 98.6%, 95%CI [97.47-99.3]) after CCMDD programme implementation compared to two hours (398/417, 95.4%, 95%CI [93.39-97.41]) before CCMDD program implementation. Most respondents (370/417, 88.7%, 95%CI [85.66-91.74]) reported not missing their appointment for collection of their medicines. Conclusion Most respondents reported neither experiencing medicine stock-outs nor receiving incomplete medicine parcels, they had a good relationship with the CCMDD programme, were satisfied with no counselling at the PUPs and rarely experienced challenges. Majority respondents reported a significant decrease in the waiting time for the collection of their medicines after CCMDD programme implementation. Missed appointments for collection of medicine parcels were significantly low among study participants. These findings can suggest high levels of adherence to such a programme.
Evaluating the impact of Single Exit Pricing (SEP) on medicine product withdrawal from the private health care market in South Africa.
(2019) Naidoo, Kasturie.; Fatima, Suleman.
Introduction: The introduction of medicine pricing policies in South Africa in the form of Single Exit Pricing (SEP), provided a mechanism to improve medicine price transparency and reduce both medicine price and inflation. However regulating medicine prices may have had further unforeseen effects on the availability of medicine. This research presents the impact of medicine price controls in the form of SEP on medicine product discontinuations from the private health care market in South Africa Aim The aim of this study is to evaluate the impact of SEP legislation on the availability of medicines in the private health sector market in South Africa, in terms of withdrawal of medicines from the market and rationale for withdrawal. Methods A descriptive, quantitative analysis of all registered medicines on the South African market by Stock Keeping Units (SKUs) to establish medicine products withdrawn from the market by SKU during a 14 year period from 2001 to 2014. Results A total number of 152 manufacturers discontinued 3691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (sd= 58.11), while innovator manufacturers discontinued a mean of 27.61 (sd= 41.89). The 2002 saw the largest number of SKUs being commercially withdrawn n=603, followed by 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase; with a Pearson’s correlation coefficient (r) = -0.414 (p=0.14). Discussion Medicine pricing policies may have a dual impact in the market. Policies are typically aimed to make medicines more affordable to the patient; however pricing policies may have a negative effect on medicine availability. The results show that the SEP and transparent pricing policy may have had an impact on SKU withdrawal from the market. Lower prices and control of annual increases on medicines may have led to SKUs exiting the market. Conclusion The result of reduced product availability in the market and its impact to the cost and quality of healthcare to the patient needs to be regularly monitored and evaluated to ascertain if direct price regulations are achieving the intended outcomes as well as evaluate other intended or unintended effects in pharmaceutical market dynamics.
Assessment of factors affecting adherence to chronic medicines among stable patients registered onto the Centralized Chronic Medicines Dispensing and Distribution (CCMDD) programme: the case of eThekwini Metropolitan Health District, South Africa.
(2018) Naidoo Pillay, Mary-Anne.; Nlooto, Manimbulu.
Abstract Background Globally more deaths are due to chronic disease compared to infectious disease. In South Africa, the number of patients has been increasing over the years for those who have been diagnosed with chronic diseases and thus requiring chronic treatment. The Centralized Chronic Medicine Dispensing and Distribution (CCMDD) programme is a national programme with the aim to improve patients access to medicines in the public health sector. To establish the implications of factors that affect patient adherence to chronic medication on the CCMDD programme in eThekwini Metropolitan Health district. Methods A descriptive cross-sectional study was conducted among stable chronic patients on the CCMDD programme in five public health facilities in eThekwini Metropolitan Health District South Africa between May and August 2017. The researcher administered face-to-face interviews were carried out using a semi-structured questionnaire with open and closed-ended questions. Results Most patients reported never experiencing out of stock of medicines at PUPs (365/417, 87 .5%, 95%CI [84.1-90.5]) and never received an incomplete parcel (324/417, 77.7%, 95%CI [73.7-81.7]). Many respondents rated their relationship with CCMDD as good (221/417, 53.0%, 95%CI [48.12-57.79]); they were satisfied to collect their medicines without counselling at PUPs (411/417, 98.6%, 95%CI [97.47-99.73]) and rarely experienced challenges with the CCMDD programme (345/417, 82.7%, 95%CI [79.07-86.33]). Majority ofrespondents reported a waiting time less than 30 minutes (411/417, 98.6%, 95%CI [97.47-99.3]) after CCMDD programme implementation compared to two hours (398/417, 95.4%, 95%CI [93.39-97.41]) before CCMDD program implementation. Most respondents (370/417, 88.7%, 95%CI [85.66-91.74]) reported not missing their appointment for collection of their medicines. Conclusion Most respondents reported neither experiencing medicine stock-outs nor receiving incomplete medicine parcels, they had a good relationship with the CCMDD programme, were satisfied with no counselling at the PUPs and rarely experienced challenges. Majority respondents reported a significant decrease in the waiting time for the collection of their medicines after CCMDD programme implementation. Missed appointments for collection of medicine parcels were significantly low among study participants. These findings can suggest high levels of adherence to such a programme.
A case study on the impact of international benchmarking on the price of medicines in South Africa using immunosuppressive medicines for transplant recipients for comparison.
(2019) Cassar, Kerry-Louise.; Suleman, Fatima.
No abstract available.
Potential hepatoprotective effects of naringenin in nucleoside reverse transcriptase inhibitor-induced oxidative stress and apoptosis in hepatocytes in vitro.
(2019) Govender, Khmera.; Owira, Peter Mark Oroma.
Abstract available in PDF.
Evaluating the impact of Single Exit Pricing (SEP) on medicine product withdrawal from the private health care market in South Africa.
(2019) Naidoo, Kasturie.; Suleman, Fatima.
ABSTRACT / SUMMARY Introduction The introduction of medicine pricing policies in South Africa in the form of Single Exit Pricing (SEP), provided a mechanism to improve medicine price transparency and reduce both medicine price and inflation. However regulating medicine prices may have had further unforeseen effects on the availability of medicine. This research presents the impact of medicine price controls in the form of SEP on medicine product discontinuations from the private health care market in South Africa Aim The aim of this study is to evaluate the impact of SEP legislation on the availability of medicines in the private health sector market in South Africa, in terms of withdrawal of medicines from the market and rationale for withdrawal. Methods A descriptive, quantitative analysis of all registered medicines on the South African market by Stock Keeping Units (SKUs) to establish medicine products withdrawn from the market by SKU during a 14 year period from 2001 to 2014. Results A total number of 152 manufacturers discontinued 3691 SKUs between 2001 and 2014. The mean number of discontinuations per generic manufacturer was 22.34 (sd= 58.11), while innovator manufacturers discontinued a mean of 27.61 (sd= 41.89). The 2002 saw the largest number of SKUs being commercially withdrawn n=603, ` 2 followed by 2003 (n=463) and 2004 (n=407). There was a negative correlation between number of discontinued SKUs per year and SEP increase; with a Pearson’s correlation coefficient (r) = -0.414 (p=0.14). Discussion Medicine pricing policies may have a dual impact in the market. Policies are typically aimed to make medicines more affordable to the patient; however pricing policies may have a negative effect on medicine availability. The results show that the SEP and transparent pricing policy may have had an impact on SKU withdrawal from the market. Lower prices and control of annual increases on medicines may have led to SKUs exiting the market. Conclusion The result of reduced product availability in the market and its impact to the cost and quality of healthcare to the patient needs to be regularly monitored and evaluated to ascertain if direct price regulations are achieving the intended outcomes as well as evaluate other intended or unintended effects in pharmaceutical market dynamics.
Direct treatment costs of invasive candidiasis in Haematology patients at a South African private hospital.
(2019) Cruickshank, Rozlyn.; Suleman, Fatima.
ABSTRACT Background: Haematology patients are at a high risk of developing invasive candidiasis (IC). Fluconazole has been the mainstay of prophylaxis and treatment but recently a newer class of therapeutic options, the echinocandins, has seen a considerable improvement in treatment success. However, these agents are associated with substantial acquisition costs when compared to fluconazole. Objective: This study analysed the direct treatment costs of invasive candidiasis in haematology patients. Methods: This is a retrospective, single-centre economic analysis of haematology patients with IC, at a private hospital in Durban, KwaZulu-Natal province, South Africa.. The direct medical costs related to managing IC were analysed. These included antifungal administration costs, hospital ward costs, haematologist consultation costs and laboratory costs for blood cultures. Adult patients (≥18 years old) diagnosed with a haematology disorder and a positive blood culture for Candida who were prescribed fluconazole and/or an echinocandin as treatment were included in the study, patients in the three groups were analysed separately and compared. Results: There was a statistically significant difference for duration of antifungal treatment (p = 0.013) and antifungal administration costs (p = 0.003) between the three groups. Median overall direct treatment costs per patient were, ZAR110 365 for patients treated with fluconazole, ZAR219 915 for patients receiving an echinocandin and ZAR181 502 (for patients treated with both the antifungals. Overall hospital stay was the biggest cost contributor to the overall cost of treatment. Conclusion: The results of this cost analysis found that treatment with fluconazole only is considerably less expensive, almost half of the mean daily treatment cost, when compared to an echinocandin only and treatment using both agents is still less expensive than an echinocandin as first line therapy. 1
Comparative chemistry of COA® herbal medicine and herbal extracts of azadirachta indica and carica papaya.
(2019) Nwabuife, Joshua Chukwufumnanya.; Manimbulu, Nlooto.; Karpoormath, Rajshekhar.
Natural products have indeed endowed man with a variety of efficacious benefit combinations which can be dated to origin of the universe. The essence of herbs in the mitigation of human indisposition cannot be overstressed. The plant kingdom is believed to be a dockyard of never-ending genesis of active compounds paramount for the prophylaxis and mitigation of countless communicable and non-communicable disease conditions of mankind. Orthodox therapeutic substances used for basic medical care necessity, in recent times, have caught the attention of researchers; the rationale for this may be explained by the increased use of chemically derived therapeutic agents having adverse effects and negative clinical outcomes. This has seen the good turn of people to natural products such as COA® herbal medicine produced in Ghana and used by people in South Africa. However, the phytochemistry of COA® herbal medicine may not be well known. This study was aimed to establish the differences and similarities of phytochemical compounds found in COA® herbal medicine and two of its constituent plants (Azadirachta indica and Carica papaya Linn.) collected in Cape Coast (Ghana), Durban and Port Shepstone (South Africa). Method An experimental study was conducted in the pharmaceutical chemistry laboratory, discipline of pharmaceutical sciences, School of Health Sciences and in the chemistry laboratory, School of Chemistry and Physics, University of KwaZulu – Natal. A phytochemical screening and Gas Chromatography–Mass Spectrometry (GC-MS) were carried out using hexane, ethanol, ethyl acetate and dichloromethane extracts to establish the similarities and disparities between the COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. The mass spectra of the compounds found in the analyzed extracts were matched with the National Institute of Standards and Technology (NIST) library. Results The results of the phytochemical screening revealed the presence of alkaloids, anthraquinones, flavonoids, saponins, tannins, terpenoids and steroids, cardiac glucosides. GC–MS results revealed the presence of common phytochemical compounds such as Phyto acetate, Octadecanoic acid, Pentadecanoic acid, Stigmast-5-en-3-ol, Stigmast-5,22-dien-3-ol, in COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. However, this study confirmed the differences in phytochemical compounds from leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa. Conclusion This study found that there were similarities between COA® herbal medicine and leaf extracts of Azadirachta indica and Carica papaya Linn. However, differences in phytochemical compounds were observed between leaf extracts of Azadirachta indica and Carica papaya Linn. collected in Ghana and South Africa.
Cytochrome p450 monooxygenase cyp139 family involved in the synthesis of secondary metabolites in mycobacterial species.
(2019) Syed, Puleng Rosinah.; Karpoormath, Rajshekhar.
Tuberculosis (TB) is one of the top infectious diseases causing numerous human deaths in the world. Despite enormous efforts, the physiology of the causative agent, Mycobacterium tuberculosis, is still poorly understood. To contribute to better understanding the physiological capacity of these microbes, we have carried out extensive in silico analyses of the 1111 mycobacterial species genomes focusing on revealing the role of the orphan cytochrome P450 monooxygenase (CYP) CYP139 family. We have found that CYP139 members are present in 894 species belonging to three mycobacterial groups: M. tuberculosis complex (850-species), Mycobacterium avium complex (34-species), and non-tuberculosis mycobacteria (10-species), with all CYP139 members belonging to the subfamily “A”. CYP139 members have unique amino acid patterns at the CXG motif. Amino acid conservation analysis placed this family in the 8th among CYP families belonging to different biological domains and kingdoms. Biosynthetic gene cluster analyses have revealed that 92% of CYP139As might be associated with producing different secondary metabolites. Such enhanced secondary metabolic potentials with the involvement of CYP139A members might have provided mycobacterial species with advantageous traits in diverse niches competing with other microbial or viral agents, and might help these microbes infect hosts by interfering with the hosts’ metabolism and immune system.

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