Ibrahim A Oreagba

Toxicological evaluation of the aqueous leaf extract of Moringa oleifera Lam. (Moringaceae).

ETHNOPHARMACOLOGICAL RELEVANCE The rapid increase in consumption of herbal remedies worldwide has been stimulated by several factors, including the notion that all herbal products are safe and effective. However, over the past decade, several news-catching episodes in developed communities indicated adverse effects, sometimes life-threatening, allegedly arising as a consequence to taking herbal products or traditional medicines from various ethnic groups. Despite the popular use of Moringa oleifera for treating various disorders, there is limited or no scientific data available regarding safety aspects of this remedy, nor are there any documented toxicological studies that can be used to ascertain the safety index of its herbal preparation. Therefore, this present study aimed to carry out extensive toxicological evaluation of the aqueous leaf extract of Moringa oleifera. MATERIALS AND METHODS In an acute toxicity test, male Wistar albino mice were orally administered an aqueous extract up to 6400 mg/kg and intraperitoneally up to 2000 mg/kg. A sub-chronic toxicity test was performed by daily administration with the extract at 250, 500 and 1500 mg/kg orally for 60 days. Control rats received distilled water. Sperm quality was analyzed, haematological and biochemical (liver enzymes, urea and creatinine) parameters were determined and a histopathological examination was carried out. RESULTS The LD(50) was estimated to be 1585 mg/kg. The extract did not elicit any significant difference (P≥0.05) in sperm quality, haematological and biochemical parameters in the treated rats compared to the control. Moreover, there was no significant difference in weight gain of the control and treated animals although there was a dose-dependent reduction in food consumption of the animals treated with 250 to 1500 mg/kg extract. CONCLUSIONS Results obtained in this study suggest that the aqueous leaf extract of Moringa oleifera is relatively safe when administered orally.

The antiplasmodial effect of the extracts and formulated capsules of Phyllanthus amarus on Plasmodium yoelii infection in mice

OBJECTIVE To investigate the antiplasmodial activity of the extracts of Phyllanthus amarus (P. amarus) on Plasmodium yoelii (P. yoelii) (a resistant malaria parasite strain used in animal studies) infection in mice. METHODS The aqueous and ethanol extracts of the whole plant of Phyllanthus amarus was administered to Swiss albino mice at doses of 200 mg/kg/day, 400 mg/kg/day, 800 mg/kg/day and 1600 mg/kg/day and the prophylactic and chemotherapeutic effect of the extracts against P. yoelii infection in mice was investigated and compared with those of standard antimalaria drugs used in the treatment of malaria parasite infection. Acute toxicity test was carried out in mice to determine the safety of the plant extract when administered orally. RESULTS The results showed that the extracts demonstrated a dose-dependent prophylactic and chemotherapeutic activity with the aqueous extracts showing slightly higher effect than the ethanol extract. The antiplasmodial effects of the extracts were comparable to the standard prophylactic and chemotherapeutic drugs used in chloroquine resistant Plasmodium infection although the activity depended on the dose of the extract administered. The extracts showed prophylactic effect by significantly delaying the onset of infection with the suppression of 79% at a dose of 1600 mg/kg/day. CONCLUSIONS The results obtained indicate that the extracts of the whole plant of P. amarus possess repository and chemotherapeutic effects against resistant strains of P. yoelii in Swiss albino mice. The findings justify the use of the extract of P. amarus in traditional medicine practice, for the treatment of malaria infections.

Clinically significant interactions between antiretroviral and co-prescribed drugs for HIV-infected children: profiling and comparison of two drug databases

Background Drug–drug interactions are an important therapeutic challenge among human immunodeficiency virus-infected patients. Early recognition of drug–drug interactions is important, but conflicts do exist among drug compendia on drug interaction information. We aimed to evaluate the consistencies of two drug information resources with regards to the severity rating and categorization of the potential interactions between antiretroviral and co-prescribed drugs. Methods We reviewed the case files of human immunodeficiency virus-infected children who were receiving treatment at the human immunodeficiency virus (HIV) clinic of the Lagos University Teaching Hospital, Idi Araba, between January 2005 and December 2010. All of the co-prescribed and antiretroviral drug pairs were screened for potential interactions using the Medscape Drug Interaction Checker and the Monthly Index of Medical Specialties Interaction Checker. Drug–drug interaction (DDI) severity and categorization were rated on a scale of A (no known interaction); B (minor/no action needed); C (moderate/monitor therapy); D (major/therapy modification); and X (contraindicated/avoid combination). Results A total of 280 patients were at risk of 596 potential DDIs. The databases showed discrepancies, with Medscape database identifying 504 (84.6%) and USA MIMS database identifying 302 (50.7%) potential DDIs. Simultaneous identification of DDIs by both databases occurred for only 275 (46.1%) listed interactions. Both databases have a weak correlation on the severity rating (rs = 0.45; P < 0.001). The most common DDIs identified by the databases were nevirapine and artemisinin-based combination therapy (170; 28.5%), nevirapine and fluconazole (58; 9.7%), and zidovudine and fluconazole (55; 9.2%). There were 272 (45.6%) interaction severity agreements between the databases. Conclusion Discrepancies occurred in DDI listings between Medscape and USA MIMS databases. Health care professionals may need to consult more than one DDI information database to ensure safe concomitant prescribing for HIV patients.

Medication errors among health professionals in Nigeria: A national survey

BACKGROUND Medication errors are preventable causes of patient harm with significant contributions to adverse drug events but they remain understudied in Nigeria. OBJECTIVES To estimate the prevalence of self-reported medication errors among health professionals and examine their knowledge of medication errors with the hope of identifying appropriate measures to promote medication safety. METHODS A cross sectional survey among doctors, pharmacists and nurses in 10 tertiary hospitals. Information was obtained using a self-administered structured questionnaire. Correct responses evaluating the knowledge of prescription, dispensing and administration errors were scored one mark each and the composite scores computed. Appropriate statistics were applied to summarize and establish the relationship between variables at 5% level of significance using SPSS 17.0. RESULTS A total of 2,386 professionals participated in the study (46.3% nurses, 44.9% doctors, 8.8% pharmacists).The prevalence of self-reported medication errors was 47%.The professional groups differ in their knowledge of all the aspects of medication errors with professional cadres influencing knowledge.Overwork was the most reason for being error prone (59.2%) and only 35.5% had ever reported medication error. 33.4% did not think reporting was necessary. CONCLUSIONS The prevalence of medication errors is high among health care professionals in Nigeria. Knowledge gaps and practice deficiencies were identified requiring interventions.

Adverse reactions to fluoroquinolones in the Nigerian population: an audit of reports submitted to the National Pharmacovigilance Centre from 2004 to 2016

Adverse drug reactions (ADRs) recorded in national pharmacovigilance databases in developed countries have been analyzed. However, adverse reactions to fluoroquinolones were observed globally despite their wide use and safety concerns. We provided information on the pattern of adverse reactions to fluoroquinolones reported spontaneously to the National Pharmacovigilance Centre (NPC), Nigeria. ADRs to fluoroquinolones reported to the NPC, over a period of 12 years, were analyzed. Evaluation was done for annual reports, age and gender of patients, type of reporter, suspected fluoroquinolones and adverse reactions, onset and outcome of ADRs, and causality. A total of 18527 ADR reports were received by the NPC. Antibiotics accounted for 1371(7.4%) of the total reports and fluoroquinolones accounted for 256 (18.7%) cases. A total of 540 ADRs due to fluoroquinolones was experienced by the patients. Multiple ADRs were experienced by 165 (65%) patients. Norfloxacin (2; 0.8%), moxifloxacin (3; 1.2%), ofloxacin (10; 3.9%), ciprofloxacin (112; 43.8%), and levofloxacin (129; 50.4%) were responsible for the ADRs. Neurological disorders (121; 22.4%), gastrointestinal disorders (118; 21.9%), and skin‐appendage disorders (116; 21.5%) were the most reported ADRs, while pruritus (41; 7.6%), abdominal pain (34; 6.3%), vomiting (34; 6.3%), and skin rash (27; 5.0%) were the most frequently reported specific ADRs. Thirty‐four (6.4%) patients experienced serious ADRs. Fluoroquinolones accounted for a small but significant proportion of ADRs spontaneously reported to the NPC in Nigeria. Ciprofloxacin and levofloxacin were the two most culpable fluoroquinolones due to their inappropriate use or increased use in multi‐drug resistant tuberculosis (MDR‐TB) treatment.

Use of complementary medicines among HIV-infected children in Lagos, Nigeria

BACKGROUND Complementary medicine (CM) use is common among children with chronic illnesses such as epilepsy and asthma. Lack of data on the profile of CM use among children with human immunodeficiency virus (HIV) infection necessitated this study. METHODS Parents or caregivers of HIV-infected children attending the paediatric HIV-clinic in a teaching hospital in Lagos, Nigeria, were randomly selected and interviewed with a semi-structured (open- and close-ended) questionnaire. Clinical details of the patients were extracted from their case files. RESULTS A total of 187 parents/caregivers were interviewed. Most of the parents/caregivers (181; 96.8%) have used CMs for their children. Mind-body interventions (181; 36.6%) and biological products (179; 36.2%) were frequently used. Relatives, friends and neighbours influenced CM use in 37.1% of the children. CMs were used mostly to treat weight loss (79; 43.7%), cold (40; 22.1%), and fever (39; 21.6%). CONCLUSION CM use is common among HIV-infected children in Lagos.

Antinociceptive, anti-inflammatory and antiulcerogenic activities of ethanol root extract of Strophanthus hispidus DC (Apocynaceae)

Abstract Background: Strophanthus hispidus DC (Apocynaceae) is a medicinal plant widely used in traditional African medicine in the treatment of rheumatic afflictions, ulcer, conjunctivitis, leprosy and skin diseases. This study sought to investigate the antinociceptive, anti-inflammatory and antiulcer properties of the ethanol root extract of S. hispidus. Methods: Antinociceptive activity was evaluated using acetic acid-induced writhing and formalin tests in mice. The carrageenan- and egg albumin-induced rat paw edema tests were used to investigate the anti-inflammatory actions, whereas the antiulcer activity was investigated using ethanol-, HCl- and pyloric ligation-induced gastric ulcer models in rats. Results: S. hispidus [100–800 mg/kg orally (po)] produced significant (p<0.05) inhibition of writhing reflex with peak effect of 74.13% inhibition observed at 800 mg/kg. Similarly, S. hispidus significantly (p<0.05) attenuated formalin-induced early and late phase of nociception with peak effect of 61.84% and 89.43%, respectively, at 200 mg/kg. S. hispidus (25–800 mg/kg po) caused significant (p<0.05) inhibition of edema development in the carrageenan and egg albumin models with peak effect (93.40% and 90.10% inhibition of edema formation) observed at 50 mg/kg. With respect to antiulcer activity, S. hispidus (100–800 mg/kg) showed potent antiulcer activity with respective peak effects of 96% (ethanol-induced), 99% (HCl-induced) and 70.60% inhibition of ulcer. Conclusions: The findings in this study suggest that the ethanol root extract of S. hispidus possesses antinociceptive, anti-inflammatory and antiulcerogenic activities. This justifies the use of the extract in folklore medicine for the treatment of ulcer and inflammatory disorders.

Antimalaria Action of Antiretroviral Drugs on Plasmodium berghei in Mice

Malaria parasitemia enhances replication of human immunodeficiency virus. Antiretroviral drugs that possess antiplasmodial activity may reverse such an effect. Activity of the antiretroviral drugs lamivudine (L), zidovudine (Z), nevirapine (N), and stavudine (S) against Plasmodium berghei inoculated into 70 adult albino mice was investigated. Eight groups of five animals each were treated with different drugs as either curative or prophylactic regimens. These regimens were also given to four groups as L/Z/N or L/S/N. Z therapy alone and L/Z/N eliminated malaria parasites as follows: curative and prophylactic Z groups, mean ± SEM = 62,132.87 ± 22,816.1 parasites/μL and 62,474.85 ± 14,639.1 parasites/μL, respectively on day 4 and 0 parasites/μL on day 26; curative L/Z/N group, 31,583.53 ± 6,361.67 parasites/μL, and 0 parasites/μL (days 4 and 18, respectively); prophylactic L/Z/N group, 41,138.1 ± 3,528.03 parasites/μL, and 0 parasites/μL (days 4, and 20 respectively). Peters four-day suppressive values were 67-82.2%. Zidovudine or L/Z/N therapy may modify the epidemiology of malaria and therefore the pandemic of human immunodeficiency virus infection.

Protective but Non-Synergistic Effects of Nigella Sativa and Vitamin E against Cisplatin-Induced Renal Toxicity and Oxidative Stress in Wistar Rats

BACKGROUND Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress. METHODS 48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis. RESULTS Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects. CONCLUSION These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative.

Off-label prescribing for children with chronic diseases in Nigeria: findings and implications

ABSTRACT Background: Prescribing medicines in an off-label manner for children with chronic conditions is sparsely documented, even more so among developing countries. This needs addressing. The objective of this research was to investigate the extent of off-label prescribing among children with epilepsy, asthma, and sickle cell anaemia in Nigeria. Methods: Prescriptions for children ≤16 years documented in their case files that attended paediatric clinics in Lagos, Nigeria, for these three conditions between January and October 2015, were reviewed retrospectively to extract data on the medicines prescribed. British National Formulary for children and American Hospital Formulary Service Drug information were used as references. Results: 477 patients received 1746 prescriptions. Off-label prescriptions were seen in 7.7% of prescriptions, related to dose (93; 68.9%), indication (22; 16.3%), and age (20; 14.8%). Nervous system (525; 30.1%) and anti-infective (441; 25.2%) medicines were the most prescribed but only 9.5% and 8.2% of the respective prescriptions were off-label. Children with epilepsy received the most number (94; 69.6%) of off-label prescriptions. The three chronic conditions did not associate significantly with the category of off-label medicine prescribed (p = 0.925). Conclusion: Off-label prescribing for children with epilepsy, asthma and sickle cell anaemia occurs. Encouragingly, the overall rate appears low in Nigeria.