Helen O. Kwanashie

Antinociceptive and smooth muscle contracting activities of the methanolic extract of Cassia tora leaf.

The leaves of Cassia tora Linn. (Family: Caesalpiniaceae) were soxhlet extracted with methanol. The spasmogenic effects of the extract were evaluated on guinea pig ileum, rabbit jejunum and mice intestinal transit. Antinociceptive activity of the extract was also evaluated in the mice. The LD(50) values of the extract in mice were >2000 mg/kg i.p. and p.o. The extract contracted smooth muscles of guinea pig ileum and rabbit jejunum in a concentration-dependent manner. Atropine reversibly blocked this activity. Mepyramine also reduced the contractile amplitude due to the extract in a concentration-dependent manner. The extract increased intestinal transit in mice dose dependently. C. tora extract significantly (P<0.05) reduced the number of acetic acid induced abdominal constrictions in mice and the effect was comparable to that of aspirin (150 mg/kg i.p.). The extract also significantly (P<0.05) reduced the nociceptive response of mice to increased force (g). The effects were dose-dependent. The studies suggest that the use of C. tora, traditionally, as a purgative and in the treatment of other ailments is justifiable.

Central Inhibitory Effects of the Methanol Extract of Neorautanenia mitis Root in Rats and Mice

ABSTRACT Decoctions of the root of the plant Neorautanenia mitis. (A. Rich) Verde (Papilonaceae) are commonly employed ethnomedicinally in the treatment of neuropsychiatric disorders and some other conditions. The central inhibitory effects of the methanol extract of N. mitis. (5–20 mg/kg) were therefore investigated in mice and rats to provide scientific evidence for some of these claims. Activities of the extract were studied on pentobarbital hypnosis in rats, and spontaneous motor activity (SMA), exploratory activity, rota-rod performance (motor coordination), and amphetamine-induced as well as apomorphine-induced hyperactivity, all in mice. The extract at doses of 5, 10, and 20 mg/kg (i.p.) produced significant (p < 0.05) prolongation of pentobarbital hypnosis and significantly (p < 0.05) reduced both SMA and exploratory behavior at the same doses. The extract attenuated both amphetamine- and apomorphine-induced hyperactivity in mice at the higher doses (10 and 20 mg/kg) but had no effect on motor coordination. The results suggest that the extract possesses biologically active principles with central effects that are sedative in nature and may partly be mediated through activity on dopamine (D2)-receptors.

Some Pregnancy-Related Effects of Artemether in Laboratory Animals

Artemether, highly effective in multi-drug-resistant malaria is not routinely available for use in pregnancy due to the lack of adequate research data in animals and man. This study was therefore aimed at investigating some pregnancy-related effects of artemether. Artemether (1.5, 7.5 and 15 mg/kg i.p. daily for 7 days) did not produce changes in rat oestrous cycle. The drug did not prevent or prolong the rate of conception or parturition, cause pre-term delivery and affect litter size. Birth weight and growth rate of pups from artemether-pretreated dams were within the normal range. Artemether (48–480 µg/ml) had no agonist effect on the isolated uterine smooth muscles of both non-pregnant and pregnant rats and guinea pigs. However, the drug (24– 240 µg/ml) reduced oxytocin-induced contraction of uterine tissues concentration-dependently, particularly in pregnant uteri.

Effects of acute bovine trypanosomosis (Trypanosoma vivax) on plasma kinetics of intravenously administered lactose

Four calves infected with Trypanosoma vivax and four uninfected control calves were each injected intravenously with repeated doses of 0.5 g lactose kg-1 body weight, thrice daily at intervals of 4 h. Plasma samples were collected at specified time intervals and analysed for lactose. Pharmacokinetic parameters were calculated from the data. T. vivax infection delayed excretion of lactose from the body, thus leading to significantly (P < 0.001) increased biological half life (t1/2) and a significantly (P < 0.001) reduced elimination rate constant for lactose in the body. The apparent volume of distribution and total clearance of lactose were not affected by the infection. T. vivax infection also appeared to cause accumulation of lactose in the plasma after repeated intravenous administration.

Medication compliance behavior in psychiatric out-patients with psychoactive substance use comorbidity in a Nigerian tertiary hospital

BACKGROUND Psychotropic medication adherence is a major challenge in psychiatric patients with comorbidity. OBJECTIVE The objective was to determine medication adherence behavior among psychiatric out-patients with psychoactive substance use comorbidity in a Nigerian Tertiary Hospital. SETTINGS AND DESIGN A cross-sectional study of a tertiary hospital in Northern Nigeria. METHODS Adult patients who have been attending the out-patient clinic for at least 1 year were included. From the routine clinic, each consecutive fourth patient completed a socio-demographic and drug use questionnaire, a self-administered medication adherence scale, and a semi-structured proforma which sought reasons for poor adherence, information on supervision and who keeps patient medications at home; until a calculated sample of 208 was attained. STATISTICAL ANALYSIS Done by means of descriptive statistics using the Statistical Package for Social Sciences version 16. The level of significance was set at P < 0.05. RESULTS Totally, 208 patients participated in the study. 61 (29.3%) of them were substance users, out of which 59% never reported missing their medications. No statistically significant relationship was found between substance use and medication adherence. A significant proportion of substance users were compliant with medication use when the drugs were in their possession. For substance users and nonusers, the major reason for poor drug adherence was the unavailability of the medications, while nonsubstance users were more likely to complain about being tired of the medications. No report of side effects in supervised patients. CONCLUSION The use of psychoactive substances in patients with other mental disorders influences their medication adherence behavior.

Prevalence and socio-demographic risk factors associated with psychoactive substance use in psychiatric out-patients of a tertiary hospital in Nigeria

Background: The co-morbidity of psychoactive substance use and other mental disorders is a major challenge to the management of both conditions in several parts of the world. There is relative dearth of information on co-morbidity and its predictors in Nigeria. This study determined the prevalence and socio-demographic risk factors associated with psychoactive substance use in the psychiatric out-patients of a tertiary hospital in Nigeria. Study Design: A cross-sectional study. Materials and Methods: From routine clinic visits over a 4-month period, each consecutive 4th adult patients (>18 years) who had previously attended the clinic at least for 1 year, completed a socio-demographic and semi-structured drug use questionnaires and interview with the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) to generate substance use diagnosis. Data was analysed using the statistical package for social sciences (SPSS), version 16. Level of significance was set at P < 0.05. Results: The lifetime prevalence for the use of substance was 29.3%, while that for multiple substances was 17.7%. The most commonly used substances were alcohol, cannabis and tobacco and they were also the ones mostly used in combination with one or the other. A total of 10.1% of the patients had a psychoactive substance use disorder. Being male, married with at least primary education and unemployed were significant risk factors for substance use. Conclusion: Psychoactive substance is common among the psychiatric outpatients of the hospital with males, those with formal education, the married and unemployed being at high risk of substance use.

Drug use pattern in out-patient children: A comparison between primary and secondary health care facilities in Northern Nigeria

Children are more vulnerable to adverse events related to use of drugs. It is therefore important to study drug use in children in order to optimize pharmacotherapy. The aim of this study was to compare drug utilization in paediatric outpatient departments of primary and secondary health care facilities. The patient and drug information of 600 patients was analyzed for World Health Organization (WHO) recommended prescribing indicators. The average number of drugs per prescription was significantly (p < 0.0005) lower in secondary (2.97) compared to primary (3.62) facilities, while average consultation time was shorter (p < 0.0005) in primary than secondary facilities. Percentages of drugs prescribed from Nigerian Essential Drug List (EDL, primary {89.78%}; secondary {91.79%}) and by generic name (primary {55.04%}; secondary {57.88%}) were insignificantly different between the facilities. The use of injectables was low (8.32% in primary versus 3.74% in secondary facilities) while antibiotic use was high (54.14% in primary to 60.28% in secondary facilities). Analysis of the dispensing indicators showed that the secondary facilities were significantly (p < 0.05) better than the primary facilities, even though not a single drug was adequately labeled in both the primary and secondary facilities. Prescription from EDL was found to be fair in the study area while use of injections was low. There is a need for improvement in case of medicines prescribed by generic name.

Histopathological effects of sub-chronic lamivudine-artesunate co-administration on the liver of diseased adult Wistar rats

Background: Lamivudine and artesunate are sometimes co administered in HIV-malaria co morbidity. Both drugs are used concurrently in presumptive malaria treatment and simultaneous HIV post exposure prophylaxis. Aim: The aim of this study was to investigate the effect of lamivudine-artesunate co administration on the histology of the liver of diseased adult Wistar rats. Materials and Methods: Five groups of rats of both sexes were used for the study and placed on feed and water ad libitum. Disease state consisted of immunosuppression with cyclophosphamide, and infection with Plasmodium berghei. Group 1 animals served as vehicle control, while group 2 were the diseased controls. Group 3 animals received 20 mg/kg lamivudine for three weeks, while group 4 similarly received 20 mg/kg Lamivudine but also received 10 mg/kg artesunate from day 12. Animals in group 5 received 10 mg/kg artesunate from day 12. All drugs were administered intraperitoneally. The animals were treated for twenty-one days, at the end of which they were sacrificed and their livers fixed in 10% formalin for histological studies. Result: Results from the study show the presence of regions of focal necrosis and perivascular cuffing with animals that received artesunate. Hemosiderosis was a common feature in all the parasitized groups, while fatty degeneration was observed in the group that received artesunate alone. Conclusion: Concurrent lamivudine-artesunate administration resulted in some histopathological changes in the liver. This study suggests there may be considerable histological changes with repeated occurrence of malaria and immunosuppression that may warrant intermittent lamivudine-artesunate administration, and may require evaluation as well as monitoring of liver function during such therapeutic interventions.

Histopathological effects of artemether on selected organs in rat

Dose and treatment-duration neurotoxic effects are reported for artemisinin drugs of mostly the liposoluble derivatives; and yet artemether, the only parenteral formulation of the artemisinin series available in Nigeria is fat-soluble and also has a treatment-duration of 5–7 days (in an attempt to delay recrudescence). Since parenteral drugs are usually resorted to in severe/complicated or multidrug-resistant malaria against the oral artemisinin co-formulated therapies (ACT), this study is aimed to investigate the pathological changes on selected tissues (if any), in rats, of the normal 7-days artemether-injections when used both in the normal and higher doses. Artemether was administered i.p., at three dose levels, equivalent to therapeutic dose (1.5 mg kg−1) as well as 5 and 10 times higher (7.5 and 15 mg kg−1). A three percentage v/v Tween 80 vehicle was used for the control experiment. The pathological changes in the kidney, heart, liver, and lungs evaluated using percentage mean organ:body-weight ratio showed no changes in the organs. No histopathological effect was observed in the organs of rats treated with 1.5 mg kg−1. However, rats treated with 7.5 and 15 mg kg−1 revealed necrositic lesions with mononuclear cellular-infiltration in the liver and brain. The liver had focal area necrosis, while the brain had liquefactive necrosis, neuronal degeneration, congested blood vessels, hemorrhage, and vacuolations. The interstitial spaces of the glomerulus and renal tubules of one kidney from rats that received 15 mg kg−1 had focal area fibrositic-necrosis.

Dose-Related and Other Effects of Maternal Cimetidine Pretreatment during Lactation on Drug Metabolism in Mouse Dams and Pups

The effects of maternal cimetidine pretreatment at different dose levels during lactation, on drug metabolism, were investigated in mouse dams and recently weaned pups. Aminopyrine N-demethylase, aniline hydroxylase and pentobarbitone metabolism were inhibited in both dams and pups in a dose-dependent manner (15, 25 and 50 mg/kg/day, i.p.). Pretreatment at a dose level of 50 mg/kg/day resulted in comparable levels of inhibition of drug metabolism in dams and female pups while male pups were less affected. Of the three indices studied, aniline hydroxylase was the least influenced by cimetidine pretreatment. Thus, the effects of maternal cimetidine pretreatment on drug metabolism in the nursing pair varied with the dose, sex and substrate. The possible implications of these results for man are discussed.