Adverse drug reactions reporting at a referral hospital in Zimbabwe.

OBJECTIVES: To establish factors influencing voluntary reporting of adverse drug reactions among health workers. A second objective was to establish the level of awareness on adverse drug reaction reporting and attitudes towards the voluntary adverse drug reaction reporting scheme. DESIGN: Cross sectional descriptive study. SETTING: Parirenyatwa Hospital, a major referral and teaching hospital in Harare, Zimbabwe. SUBJECTS: 200 health professionals randomly selected from various departments. MAIN OUTCOME MEASURES: Number of health workers reporting adverse drug reactions; awareness of the adverse drug reaction reporting scheme. RESULTS: 144 (72%) questionnaires were completed. About half (47.2%) of the respondents did not know how to report an adverse drug reaction and 47.1% were unaware of the existence of a formal adverse drug reaction reporting scheme in Zimbabwe. One fifth (20.1%) of the respondents had reported an adverse drug reaction at some point. Two main factors contributing to under-reporting cited by respondents were the poor feedback from the national reporting centre (59%) and inaccessibility of reporting facilities (45.8%). Beliefs that one should only report an adverse drug reaction if certain of causality (46.5%) and that really serious adverse drug reactions are well documented before a drug is marketed (35.4%) could also account for under reporting. However, 75.7%, viewed adverse drug reaction reporting as a professional obligation. CONCLUSION: Lack of awareness of healthcare professionals to the national (Medicines Control Authority of Zimbabwe) adverse drug reaction voluntary reporting scheme, poor feedback and inaccessibility of reporting facilities are the main factors contributing towards underreporting.

Effects of DDT on paracetamol half-life in highly exposed mothers in Zimbabwe.

After assessment of the levels of DDT residues in the milk samples, 1 g paracetamol was administered p.o. to 28 breastfeeding mothers selected from a population of 116, according to DDT residues in their milk (the 14 with the highest values and the 14 least exposed). Post dose blood samples were taken from the basilic veins of the mothers at time intervals up to 4 h, post dose. The paracetamol blood concentrations were determined. A significantly shorter paracetamol half-life was found in mothers with higher DDT body burden, who also exhibited lower paracetamol concentrations in blood. The results highlighted concern for the highly exposed mothers taking paracetamol (NSAID) as an analgesic, or as an antipyretic.

Assessment of environmental pollution by PCBs, DDT and its metabolites using human milk of mothers in Zimbabwe.

The milk samples were collected from mothers who had lived in the area for at least 5 years, healthy and breast feeding their first, second or third child. Of the 175 mothers' milk samples analysed, the organochlorine pesticide residues were detected in the following order of frequency: pp-DDE, 100%, pp-DDT 98%; and sum PCB, 53%. Of all the seven areas analysed the Kariba area and the highest mean level of sum DDT--25,259 ng/g milk fat and the lowest mean level of sum DDT of 1607 ng/G milk fat was found in Esigodini which is a rural area. The major DDT metabolite was pp-DDE. The ratio of pp-DDT/pp-DDE was highest in Kariba (0.6) suggesting recent pollution by DDT in that area. The results show that the vector control programmes (extensive pesticide spraying of disease-carrying pests, such as mosquitoes and tsetse flies), agricultural activities and dietary habits were the main contributing factors towards the high levels of pesticides in most of the areas. Kadoma area had the highest mean level of sum-PCB (60 ng/g milk fat).

GABAergic and dopaminergic systems may be involved in seizures induced by pyrimethamine in mice.

1. The effects of some GABAergic and dopaminergic agents on pyrimethamine-induced tonic seizures were investigated in mice. 2. Pyrimethamine dose dependently induced seizures in mice. 3. Muscimol, AOAA and DABA significantly protected mice against pyrimethamine-induced seizures. 4. Bicuculline and picrotoxin effectively potentiated seizures elicited by pyrimethamine and significantly antagonized the protective effect of muscimol against the seizures. 5. Diazepam and phenobarbitone effectively protected mice against seizures elicited by pyrimethamine. 6. L-Dopa significantly potentiated pyrimethamine-induced seizures. 7. Apomorphine and pargyline significantly reduced the latency of seizures induced by pyrimethamine. 8. Haloperidol and pimozide effectively protected mice against pyrimethamine-elicited seizures and also significantly antagonized the potentiating effects of apomorphine and L-dopa on the seizures. 9. Disulfiram significantly potentiated seizures induced by pyrimethamine and also significantly enhanced the seizure-potentiating effect of L-dopa. 10. alpha-Methyl-p-tyrosine effectively protected against seizures induced by pyrimethamine. However, L-dopa significantly potentiated the seizures in alpha-methyl-p-tyrosine-pretreated animals. 11. Muscimol significantly attenuated the potentiating effect of L-dopa on pyrimethamine-induced seizures while bicuculline significantly enhanced the effect of L-dopa. Furthermore, haloperidol significantly potentiated the protective effect of muscimol against pyrimethamine-induced seizures. 12. These results suggest that both GABA and dopamine might be involved in the mechanism(s) of pyrimethamine seizures in mice.

gamma Aminobutyric acid mediation of the anticonvulsant effect of clonidine on pentylenetetrazol-induced seizures in mice.

The effects of muscimol, amino-oxyacetic acid (AOAA), diamino-N-butyric acid (DABA), bicuculline, picrotoxin, diazepam and phenobarbitone on the protective effect of clonidine against pentylenetetrazol-induced seizures were studied in mice. Muscimol, AOAA, DABA, phenobarbitone and diazepam significantly protected mice against pentylenetetrazol-induced seizures and also significantly potentiated the protective effect of clonidine against the seizures. Bicuculline and picrotoxin significantly potentiated seizures induced by pentylenetetrazol and significantly attenuated both the protective effects of muscimol and clonidine against the seizures. These data suggest that activation of gamma-aminobutyric acid systems may underlie the protective effect of clonidine against seizures induced by pentylenetetrazol in mice.

Cimetidine-induced seizures in mice. Antagonism by some GABAergic agents.

The effects of muscimol, aminooxyacetic acid (AOAA), diamino-n-butyric acid (DABA), baclofen, bicuculline, picrotoxin, strychnine, diazepam, phenobarbitone and phenytoin on cimetidine-induced seizures were studied in mice. Cimetidine (400-1000 mg/kg, i.p.) induced dose-dependent tonic convulsion. Muscimol, AOAA and DABA effectively protected mice against cimetidine-induced seizures. Bicuculline and picrotoxin significantly potentiated the seizures induced by cimetidine and effectively antagonized the protective effects of muscimol, AOAA and DABA against the seizures. Diazepam and phenobarbitone significantly protected the mice against cimetidine-induced seizures while phenytoin and strychnine did not significantly alter the seizures. These results indicate that the attenuation of central gamma-aminobutyric acid neurotransmission may underlie cimetidine-induced seizures in mice.

Chloroquine-induced seizures in mice: the role of monoaminergic mechanisms.

The influence of some dopaminergic and noradrenergic agents on seizures induced by chloroquine (45-100 mg/kg, i.p.) was investigated in mice. Apomorphine (0.2-0.8 mg/kg, s.c.). L-dopa (25-50 mg/kg, s.c.) benserazide (5 mg/kg, i.p.) plus L-dopa (50 mg/kg, s.c.), pargyline (100 mg/kg, i.p.), FLA-63 (10-20 mg/kg, s.c.) and FLA-63 (10 mg/kg, s.c.) plus L-dopa (50 mg/kg, s.c.) profoundly shortened the latency of seizures induced by chloroquine (65 mg/kg, i.p.). L-Dopa (50 mg/kg, s.c.) weakly reduced the latency and weakly increased the incidence of chloroquine (50 mg/kg, i.p.)-induced seizures. alpha-Methyl-p-tyrosine (25-100 mg/kg, i.p.) dose-dependently and significantly reduced the incidence and significantly prolonged the latency of chloroquine (65 mg/kg, i.p.)-induced seizures. However, L-dopa (50 mg/kg, s.c.) effectively increased the proportion of animals convulsing and effectively reduced the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in alpha-methyl-p-tyrosine-pretreated mice. Haloperidol (0.25-1.0 mg/kg, i.p.) and pimozide (2-4 mg/kg, i.p.) markedly reduced the incidence and markedly prolonged the latency of seizures induced by chloroquine (65 mg/kg, i.p.) in a dose-related manner. However, apomorphine (0.4-0.8 mg/kg, s.c.) and L-dopa (25-50 mg/kg, s.c.) profoundly attenuated the protective effects of haloperidol (0.5 mg/kg, i.p.) and pimozide (4 mg/kg, i.p.) against chloroquine (65 mg/kg, i.p.)-induced seizures.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetic interaction of single doses of quinine and carbamazepine, phenobarbitone and phenytoin in healthy volunteers.

Effects of single doses of quinine on plasma and urine concentrations of carbamazepine, phenobarbitone and phenytoin were studied in healthy volunteers. Quinine (600mg, p.o.) markedly augmented the peak plasma concentrations and area under the curve (AUC [0-24]) values of carbamazepine (200mg,p.o.) and phenobarbitone (120mg,p.o.) but did not affect those of phenytoin (200mg,p.o.). Mean urinary recoveries of carbamazepine, phenobarbitone and phenytoin over 24 hours also profoundly increased with concomitant administration of quinine. These results indicate possible interaction between quinine and carbamazepine or phenobarbitone.

Effects of some GABAergic agents on quinine-induced seizures in mice.

The effects of some GABAergic agents on seizures induced by quinine were studied in mice. Muscimol, AOAA, DABA and baclofen significantly protected mice against quinine-induced convulsions. Bicuculline effectively enhanced quinine-induced convulsions, and significantly attenuated the protective effects of muscimol, AOAA and DABA against convulsions induced by quinine. Diazepam and phenobarbitone significantly protected mice against convulsions induced by quinine. However, phenytoin did not affect quinine-induced seizures to any significant degree. These results indicate that the convulsant effect of quinine may be due to a disturbance in the status of the GABAergic system.

Residues of organochlorine pesticides in human milk from mothers living in the greater Harare area of Zimbabwe.

Residue levels of the chlorinated hydrocarbons p,p -DDT, p,p, -DDE, p,p TDE, p,p -DDT, alpha-beta-gamma-hexachlorocyclohexane (HCH), heptachlor epoxide, dieldrin and polychlorinated biphenyls (PCBs) were determined in human milk of 40 Zimbabwean mothers living in the greater Harare area. Three municipal clinics and one main hospital were randomly selected as collecting points. The main organochlorine contaminants found in all the samples analysed were p,p -DDT and p,p -DDE and the mean levels of sum DDT and DDT/DDE ratio were 6 mg/kg milk fat and 0.74 respectively. In general, relatively low residue levels of alpha-beta-,gamma-HCH, heptachlorepoxide and dieldrin were detected in 58,100,63,13 and 65pc, respectively of all the milk samples analysed. Trace of the PCB congener 2,2,4,5,5'-pentachlorobiphenyl (PCB 101) were found in 15 samples and only one sample contained traces of 2,3',4,4',5-pentachlorobiphenyl (PCB 118). The results were examined with regard to health ad living condition of the mothers. From the small population observed around the greater Harare area--social status, educational background an living conditions could be described as important demographic variables influencing the frequency distribution of residual levels of sum DDT in the mother's milk.

PIP: Researchers analyzed data from interviews with 40 mothers living in suburban Harare, Zimbabwe and analyses of their breast milk to study contamination levels of organochlorine pesticides in breast milk. The 14 mothers living in the low-density suburbs of Milton Park, Queensdale, Avondale, and Borrowdale had a higher socioeconomic status and a higher educational status than the other mothers. These 14 mothers also had a nutritious diet and adequate knowledge of pesticides and their use (group 1). The high-density suburbs included Mbare, Mufakose-Kambuzuma, Dzivaresekwa, and Epworth. The 26 mothers living in these areas tended to be of a low socioeconomic status and have only primary education, poor diet, and limited pesticide knowledge (group 2). Breast milk of Group 2 mothers contained a higher mean level of total DDT (as expressed in ppm mg/kg of fat weight) and DDT/DDE ratio than group 1 breast milk, but the differences were insignificant (7.39 vs. 3.44 and 0.93 vs 0.37). The total DDT intake surpassed the acceptable daily intake (ADI) for infants based on the FAO/WHO ADI for adults. Yet no evidence existed that this amount was harmful to infants. The only metabolite found in the breast milk of all mothers was p,p'-DDE (the major metabolite of p,p'-DDT). Its mean was highest in group 2 breast milk (2.72 vs. 2.18). These results reflected the continued use of DDT in agriculture and effects of the malaria control program in Zimbabwe. The persistent levels of p,p'-DDE also indicated that the women ate meat from animals in which p,p'-DDE had accumulated. Residues of 3 lindane isomers were present in 58-100% of the breast milk samples with beta-HCH being the most persistent. Dieldrin and heptachlor epoxide levels were quite low (mean 0.05 and 0.01 respectively) indicating minimal use Zimbabwe. The researchers reiterated a commitment to breast feeding, but further research about the effects of pesticide residues is needed.

A comparative study of the hepatotoxicity of 1-fluoropentane and 1-fluorohexane.

Phenobarbitone pretreatment potentiated hepatocyte lesions in male rats 24 hr after treatment with 1-fluoropentane (3.5 mg/kg body weight) and 1-fluorohexane (0.17 mg/kg body weight). Serum levels of the enzymes ornithine carbamyltransferase, glutamic-pyruvic transaminase and gamma-glutamyltranspeptidase were significantly elevated by the test compounds with the peak effect occurring 24-72 hr after a single ip administration. Significant elevation of hepatocyte triglyceride content and mitochondrial calcium and citrate levels were demonstrated 24 and 48 hr after a single ip injection of 1-fluoropentane or 1-fluorohexane, respectively.