Detection of drug-induced dyslipidaemia in HIV-positive patients treated with protease inhibitors in a South African district – A retrospective study

Purpose: To determine whether protease inhibitors (PIs) cause hypercholesterolaemia and hypertriglyceridaemia, and to assess the influence of sex and age on serum total cholesterol (TC) and triglycerides (TG), and the level of adherence to therapeutic laboratory monitoring guidelines in HIV positive patients in the Eastern Health District, South Africa.Methods: This was a retrospective study which compared baseline and follow-up TC and triglycerides serum levels in HIV-infected patients who received treatment, including PIs, between 2008 and 2012 in the Eastern Health District of the Cape Metropole Region (Cape Town, South Africa). Clinical and laboratory data were retrieved from patients’ folders and from a computerized database at National Health Laboratory Services (NHLS). The level of compliance with therapeutic laboratory monitoring protocols by health workers and patients was also assessed.Results: Out of 753 patients (491 females, 262 males), 176 were 0 - 17, 465 were 18 - 44 and 12 were > 44 years old. The proportion of patients who had test results at the various time points ranged from 16.33 to 25.90 %, 17.66 to 24.83 %, 25.10 to 47.41 % and 25.23 to 36.79 % for TC, triglycerides, CD4 count, and viral load (VL) tests, respectively. There was a significant time increase (p = 0.0137) for serum TC from baseline to 3 years. For serum triglycerides, the overall time effect was not significant (p = 0.4132). There was a significant increase from baseline in CD4 and a significant decrease in VL during the study period. Sex and age did not show any relationship with TC and triglyceride serum levels.Conclusion: This study demonstrated hypercholestrolaemia in HIV-infected patients receiving PIs. Age and sex did not have any effect on TC and triglycerides. Compliance with therapeutic laboratory monitoring guidelines was poor.Keywords: Hyperlipidaemia, Protease inhibitors, Therapeutic monitoring, HIV infection, Hypercholesterolaemia, Hypertriglyceridaemi

Effects of aqueous leaf extract of Asystasia gangetica on the blood pressure and heart rate in male spontaneously hypertensive Wistar rats

Background: Asystasia gangentica (A. gangetica) belongs to the family Acanthaceae. It is used to treat hypertension, rheumatism, asthma, diabetes mellitus, and as an anthelmintic in South Africa, India, Cameroun, Nigeria, and Kenya respectively. It has also been reported to inhibit the angiotensin I converting enzyme (ACE) in-vitro. Therefore, the aim of this study is to investigate the in-vivo effect of aqueous leaf extract (ALE) of A. gangetica on the blood pressure (BP) and heart rate (HR) in anaesthetized male spontaneously hypertensive rats (SHR); and to elucidate possible mechanism(s) by which it acts. Methods: The ALE of A. gangetica (10–400 mg/kg), angiotensin I human acetate salt hydrate (ANG I, 3.1–100 μg/kg) and angiotensin II human (ANG II, 3.1–50 μg/kg) were administered intravenously. The BP and HR were measured via a pressure transducer connecting the femoral artery to a Powerlab and a computer for recording. Results: A. gangetica significantly (p<0.05), and dose-dependently reduced the systolic, diastolic, and mean arterial BP. The significant (p<0.05) reductions in HR were not dose-dependent. Both ANG I and ANG II increased the BP dose-dependently. Co-infusion of A. gangetica (200 mg/kg) with either ANG I or ANG II significantly (p<0.05) suppressed the hypertensive effect of both ANG I and ANG II respectively, and was associated with reductions in HR. Conclusions: A. gangetica ALE reduced BP and HR in the SHR. The reduction in BP may be a result of actions of the ALE on the ACE, the ANG II receptors and the heart rate.Web of Scienc

Potential beneficial effects of Tulbaghia violacea William Henry Harvey (Alliaceae) on cardiovascular system - A review

Tulbaghia violacea William Henry Harvey (Harv. Alliaceae) is a small bulbous herb belonging to the family Alliaceae. It is used in South Africa to treat fever, colds, asthma, paralysis, and hypertension. Meanwhile, cardiovascular disease accounts for about 30 % of total global death, with most of these deaths occurring in low and middle-income countries. Furthermore, people in low-income countries are still largely dependent on plants in their surroundings for both prophylaxis and treatment of diseases, partly due to limited access to and cost of pharmaceuticals, and folkloric evidence of the potency of medicinal plants and/or local belief systems. Therefore, the present review aims to proffer possible ways by which T. violacea may improve cardiovascular outcomes. An extensive and systematic review of the literature was carried out, and relevant findings presented in this review. There is evidence that T. violacea may modulate the renin-angiotensin system, the autonomic nervous system, oxidative stress and haemostasis, with resultant protection of the cardiovascular system in both health and disease.Web of Scienc

Acute pharmacokinetics of first line anti-tuberculosis drugs in patients with Pulmonary Tuberculosis and in patients with Pulmonary Tuberculosis co-infected with HIV

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.Web of Scienc

Comparison of the acute effects of Tulbaghia violacea William Henry Harvey (Alliaceae) on blood pressure and heart rate of ageing male normotensive Wistar kyoto rats and adult male spontaneously hypertensive rats

Purpose: To assess the effect of the crude methanol leaf extracts of Tulbaghia violacea William Henry Harvey (Alliaceae) on blood pressure (BP) and heart rate in ageing normotensive Wistar Kyoto rats (WKY), and compare the results obtained with those for adult spontaneously hypertensive rats (SHR).Methods: T. violacea (5 – 150 mg/kg) and/or vehicle (dimethylsulfoxide and normal saline) were respectively and randomly administered intravenously to groups of ageing (15 months) WKY and adult (&lt; 5 months) SHR, weighing 380 - 470 and 280 - 320 g, respectively. BP and heart rate (HR) were measured via a pressure transducer connecting the femoral artery and Powerlab equipment.Results: T. violacea significantly and dose-dependently reduced systolic BP, diastolic BP, mean arterial pressure (MAP) and HR in both strains of rats. No statistically significant differences were however observed when the changes in BP and HR in the two rats strains were compared.Conclusion: T. violacea was effective in reducing BP and HR in both age-induced and spontaneously hypertensive rats.Keywords: Age, Wistar Kyoto rats, blood pressure, heart rate, Tulbaghia violace

Amount of cycloserine emanating from terizidone metabolism and relationship with hepatic function in patients with drug resistant tuberculosis

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

Steady‐state population pharmacokinetics of terizidone and itsmetabolite cycloserine in patients with drug‐resistanttuberculosis

Despite terizidone being part of the second‐line recommended drugs fortreatment of drug‐resistant tuberculosis (DR‐TB), information on its pharmacokineticsis scarce. The aim of this study was to describe the steady‐state population pharma-cokinetics (PPK) of terizidone and its primary metabolite cycloserine in patients withDR‐TB and determine the effect of patient characteristics. This clinical study involved 39 adult DR‐TB patients admitted toBrewelskloof Hospital in Cape Town, South Africa for intensive treatment phase.Blood samples were collected at predose and 0.5, 1, 2, 3, 3.5, 4, 8, 16 and 24 hoursafter drug administration. The estimation of PPK parameters was performed usingnonlinear mixed‐effects modelling software Monolix 2018R1. Free‐fat mass was usedto perform allometric scaling on disposition parameters

Characterization and Cradiovascular Effects of (13S)-9α,13α-epoxylabda-6β(19),15(14)diol dilactone, a Diterpenoid Isolated from Leonotis leonurus

A new diterpenoid, (13S)-9 ,13 -epoxylabda-6 (19),15(14)diol dilactone (1), was isolated from Leonotis leonurus and the structure determined via NMR analysis. The compound causes significant changes in blood pressure of anaesthetized normotensive rats and exhibits a negative chronotropic effect.Web of Scienc

Active Principles of Tetradenia riparia; II. Antispasmodic Activity of 8(14), 15-Sandaracopimaradiene-7α, 18-diol

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.Web of Scienc

Assessment of Vancomycin Pharmacokinetics and Dose Regimen Optimisation in Preterm Neonates

The pharmacokinetics of vancomycin, a drug used for the treatment of methicillin-resistant Staphylococcus aureus (MRSA), varies between paediatric and adult patients. The objective of this study was to assess the pharmacokinetics of vancomycin in preterm neonates and determine the optimum dose regimen