Self-medication with chloroquine in a rural district of Tanzania: a therapeutic challenge for any future malaria treatment policy change in the country.

BACKGROUND: Malaria continues to be a leading cause of morbidity and mortality in children aged 5 years or younger in Tanzania. Children who develop mild disease can rapidly progress to severe malaria (cerebral malaria with convulsions) and even death, because of mismanagement, delays and inappropriate drug therapy in the remote areas where primary health care facilities are inaccessible or unavailable. The threat is particularly severe in those who are unable to take oral medications. OBJECTIVE: To identify treatment strategies adopted by mothers or guardians of children under five for malaria. METHOD: A cross-sectional descriptive study using a questionnaire and blood sampling was carried in Kibaha district primary health care facilities. Over 500 mothers/guardians of sick children aged up to 5 years who visited the public facilities seeking care were interviewed in order to assess what management they offered to their sick children in their homes prior to coming to the public health facilities. RESULTS: Seventy-four per cent of the mothers/guardians stated that they had given some medication to their children prior to visiting the public health facilities: mostly analgesics (asprin, paracetamol) and chloroquine. Eighty-five per cent of the sick children given chloroquine had whole blood chloroquine levels above 500 nmol/L and 33% of the sick children with whole blood chloroquine levels above 1,000 nmol/L had malaria parasites in their blood. Of the sick children given chloroquine at the health facilities, 63% had no malaria parasites in their blood. CONCLUSION: There is a need to educate both rural communities, and health care providers about rational prescribing, dispensing and use of antimalarials.

Comparative bioavailability of oral sugar-coated and plain formulation of chloroquine phosphate marketed in Tanzania.

The bioavailability of chloroquine from a single oral dose (10 mg/kg body weight) of a sugar-coated (Dawaquin) and a plain formulation (Shellyquine) of chloroquine phosphate were compared in two groups of 10 volunteers each, following an overnight fast. Whole blood chloroquine concentrations were measured using high-performance liquid chromatography (HPLC) and bioavailability was determined by measuring area under the blood chloroquine concentration curve (AUC ng mL(-1) h) and the peak blood chloroquine concentration (Cpmax ng/mL). The AUC and Cpmax for Shellyquine were 4396.3 +/- 833 ng mL(-1) h and 162 +/- 14 ng/mL, respectively. The AUC and Cpmax for Dawaquin were 2060 +/- 339 ng mL(-1) h and 56.6 +/- 5.2 ng/mL, respectively. Shellyquine was significantly more bioavailable than Dawaquin (P<0.001). Although the Cpmax for Dawaquin was higher than the required therapeutic level for sensitive Plasmodium falciparum of 30 ng/mL, its blood levels may not guarantee a rapid clearance of parasites. The differences between the two formulations point to a problem in the quality of pharmaceuticals marketed in this country, whose extent need to be ascertained further. Failure of chloroquine phosphate in this country has already been declared by the Ministry of Health, and the potential contribution of poorly formulated products remains a subject of debate.

The effect of Phyllanthus amarus aqueous extract on blood glucose in non-insulin dependent diabetic patients.

The glycaemic response to 124.5 +/- 9.3 (mean +/- SD) g of pancakes was monitored in 21 non-insulin dependent diabetic (NIDDM) patients while on oral hypoglycaemics, after a 1-week washout period and after a 1-week twice daily treatment with 100 mL of an aqueous extract from 12.5 g of powdered aerial parts of Phyllanthus amarus. After the 1-week washout period, the fasting blood glucose (FBG) and postprandial blood glucose increased significantly compared with treatment on oral hypoglycaemics ( p < 0.05). After a 1-week herbal treatment no hypoglycaemic activity was observed. Both FBG and postprandial blood glucose remained very similar to that recorded after the washout period ( p > 0.05). Both liver and renal functions based on alanine transaminase (ALAT) and serum creatinine, respectively, were not significantly affected by the use of the extract. Although the lymphocyte and monocyte levels were significantly decreased ( p < 0.05) and the granulocyte level was significantly increased after treatment ( p < 0.05) the overall total white blood cell (WBC) count and haemoglobin (Hb) were not significantly affected by the 1 week herbal treatment. We conclude that 1 week treatment with the aqueous extract of Phyllanthus amarus was incapable of lowering both FBG and postprandial blood glucose in untreated NIDDM patients.

The cardiovascular and central nervous system effects in the human of U-62066E. A selective opioid receptor agonist.

The cardiovascular and central nervous system effects of the kappa opioid receptor agonist U-62066E were investigated in ten normal male subjects who received U-62066E or placebo with low or high dose naloxone in a randomized, double blind study. Blood pressure and heart rate in the supine and standing position, plasma adrenaline and noradrenaline, regional Doppler blood velocity indices and psychometric assessments were recorded for 1.25 h before and 6 h following injection. U-62066E caused sedation and dysphoria but no euphoria. Plasma noradrenaline was increased by U62066E when compared with basal levels. This action of U62066E was prevented by high but not low dose naloxone. U-62066E had no significant effect on blood pressure, heart rate or regional blood flow indices in the vessels studied and no effect on plasma adrenaline levels. Since U62066E at a dose known to have marked kappa effects was not found to influence cardiovascular indices our results do not support a major role for kappa opioids in the control of the circulation. However, U62066E may influence noradrenaline release or clearance and cause sedation and psychotomimetic effects.

Mechanism of diuretic action of spiradoline (U-62066E)--a kappa opioid receptor agonist in the human.

1. The mechanism of the diuretic effect of the kappa opioid receptor agonist spiradoline was investigated in 10 healthy male subjects in a placebo-controlled, double-blind cross-over study. 2. Urine volume and osmolality, plasma vasopressin and Doppler renal blood velocity indices were recorded for 1.25 h before and 6 h following injection. 3. Spiradoline caused a significant increase in urine output which was antagonized by high but not low dose naloxone. The urine increase was accompanied by a significant decrease in osmolality which was also antagonised by high but not low dose naloxone. 4. Spiradoline had no effect on plasma vasopressin concentration or on renal blood velocity indices. 5. We conclude that kappa agonists induce diuresis in humans by a mechanism not involving suppression of vasopressin or changes in renal blood velocity indices.

Reproducibility of Doppler blood flow velocity waveform measurements: study on variability within and between day and during haemodynamic intervention in normal subjects.

Reproducibility of Doppler blood velocity waveform measurements in external and internal carotid, middle cerebral, and brachial arteries and ascending aorta was determined in 8 normal male volunteers twice daily on three occasions each separated by two or more weeks. Measurements were made in supine and standing positions at rest and after taking glyceryl trinitrate and in the supine position after performing a standardized exercise test. The Doppler blood flow waveform indices showed a between days coefficient of variation of less than 15% both for baseline measurements and during haemodynamic change induced by exercise or glyceryl trinitrate. We conclude that Doppler blood velocity waveform measurement in different vascular beds is reproducible at baseline and when the cardiovascular system is interrupted pharmacologically or physiologically.

The influence of food on the pharmacokinetics of 'biphasic' nifedipine at steady state in normal subjects.

Previous studies following single dose administration have suggested that the pharmacokinetics of various nifedipine formulations could be influenced by the timing of associated food consumption. In order more closely to reflect the clinical situation we have carried out a study at steady state using a 'biphasic' formulation comprising 'rapid' and 'retarded' drug release components. Fifteen normal subjects took 20 mg 'biphasic' nifedipine 12 hourly for 10 days. Studies were carried out on days 4, 7 and 10. On these days the nifedipine was taken 2 h or 1 h before or immediately following a light breakfast. A light breakfast influenced neither the rate nor the extent of nifedipine absorption nor the rate or extent of major metabolite appearance. We conclude that at steady state the timing of a light meal is unlikely to alter in any clinically important manner the pharmacokinetics of nifedipine released from 'biphasic' tablets.