Improving rational drug use in Africa: the example of Sudan.

The aim of this review is to determine the extent of irrational drug use and contributing factors in Sudan and to identify the interventions that need to be strengthened to promote the rational use of drugs in the country and to evaluate the impact of different types of intervention. We present an overview of studies describing patterns of drug prescribing, dispensing and self-medication. Rates for inappropriate prescribing and dispensing practices and prevalence of self-medication with antimicrobials and herbal products were alarmingly high. Indicators of rational drug use have worsened over the past decade despite the implementation of managerial, regulatory and training interventions. Multifaceted interventions have proved effective in changing suboptimal prescribing practices. Educational interventions are needed to address self-medication and adherence.

Improving rational drug use in Africa: the example of Sudan

The aim of this review is to determine the extent of irrational drug use and contributing factors in Sudan and to identify the interventions that need to be strengthened to promote the rational use of drugs in the country and to evaluate the impact of different types of intervention. We present an overview of studies describing patterns of drug prescribing, dispensing and self-medication. Rates for inappropriate prescribing and dispensing practices and prevalence of self-medication with antimicrobials and herbal products were alarmingly high. Indicators of rational drug use have worsened over the past decade despite the implementation of managerial, regulatory and training interventions. Multifaceted interventions have proved effective in changing suboptimal prescribing practices. Educational interventions are needed to address self-medication and adherence

Changing antibiotics prescribing practices in health centers of Khartoum State, Sudan.

OBJECTIVE: A major problem with inappropriate use of antibiotics is the emergence of resistance. Thus, cost-effective interventional strategies are required to improve their use. This study aimed to evaluate the effect of multifaceted interventions on prescribing practices of antibiotics in health centers of Khartoum State, Sudan. METHODS: Twenty health centers were randomly assigned to receive: (1) no intervention; (2) audit and feedback; (3) audit and feedback + seminar; or (4) audit and feedback + academic detailing. A total of 1,800 patient encounters, 30 from each health center, were randomly collected. The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice, dose and duration of therapy before the study and at 1 and 3 months post-intervention. RESULTS: In comparison to the control group, the prescriber targeted interventions involving audit and feedback, together with academic detailing (4), reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 (p<0.001) at 1 and 3 months post-intervention, respectively. In addition, the mean number of encounters with an inappropriate antibiotic with respect to diagnosis, doses and/ or duration of therapy was reduced by 5.3 and 5.9 (p<0.001) at 1 and 3 months post-intervention, respectively. For audit and feedback together with seminars (3) and for audit and feedback alone (2), the corresponding reductions were 5.3, 7.1, 4.4 and 5.1 (p<0.001) and 1.4, 2.8, 1.8 and 1.9 (p>0.05), respectively. CONCLUSION: Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State, Sudan, are alarmingly high. Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practices of antibiotics than audit and feedback alone.

Changing the prescribing patterns of sexually transmitted infections in the White Nile Region of Sudan.

BACKGROUND: The number of inappropriate prescriptions for sexually transmitted infections (STIs) in Sudan is suspected to be high. Simple multifaceted interventions directed at prescribers may improve prescribing patterns in the Sudan. OBJECTIVE: To evaluate the effect of multifaceted interventions on prescribing for STIs in the White Nile State, Sudan. METHODS: The study involved 20 health centres randomly assigned to four different multifaceted interventions to improve prescribing. RESULTS: Prescriber targeted interventions involving audit and feedback together with academic detailing and practice guidelines reduced the number of inappropriate prescriptions by 50% (p < 0.001). Audit and feedback together with seminars and practice guidelines reduced inappropriate prescriptions by 43% (p < 0.001). Audit and feedback alone reduced inappropriate prescriptions by 16% (p = 0.127). CONCLUSION: Prescribing for STIs in the White Nile State of Sudan needs improving. Multifaceted interventions appear effective in improving prescribing.

Pharmacokinetics of artesunate following oral and rectal administration in healthy Sudanese volunteers.

The aims of this study were to determine the pharmacokinetic parameters of a single dose of 200 mg oral and rectal artesunate in healthy volunteers, and to suggest a rational dosage regimen for rectal administration. The study design was a randomized open cross-over study of 12 healthy volunteers; the analytical method used was a reversed phase high performance liquid chromatography with post column derivatization and subsequent ultraviolet detection. Pharmacokinetic parameters were derived from the main metabolite alpha-dihydroartemisinin data due to the rapid disappearance of artesunate from the plasma. Dihydroartemisinin following oral administration of artesunate had a significantly higher AUC(0-infinity) (P<0.05 95% confidence interval (CI) -1168.73, -667.61 ng x h/mL(-1)) and Cmax (P<0.05; 95% CI -419.73, -171.44 ng/mL(-1)), and had shorter tmax (P<0.05; 95% CI -0.97, -0.10 h) than that following rectal artesunate. There was no statistically significant difference in the elimination half-life between both routes of administration (P>0.05; 95% CI -0.14, 0.53 h). The relative bioavailability of rectal artesunate was [mean (coefficient of variation %) 54.9 (24.8%) %]. On the basis of these data an 8 hourly dosing regimen per day with rectal artesunate is proposed.

Descriptive study on the efficacy and safety of artesunate suppository in combination with other antimalarials in the treatment of severe malaria in Sudan.

Documentation on the efficacy of artesunate in Africa is limited, and no experience of artesunate use in Sudan is documented. Severe malaria in rural areas of Sudan, where facilities for the safe and effective use of parenteral quinine are lacking, is a frequent problem. Early treatment with artesunate suppositories would provide a simple method for use by unskilled staff and would be an alternative approach to treat malaria in settings with poor resources. We describe a hospital-based study of rectal artesunate in 100 adult patients with severe falciparum malaria with a dose derived from pharmacokinetic data (200 mg every 8 hours) over 3 days, which halted progression of severe disease and had a low fatality rate. The dosage schedule led to a rapid clinical response and reduced parasite clearance and fever subsidence times of (31.5 +/- 10.1 hours) and (31.4 +/- 11.1 hours). The sequential treatment of rectal artesunate with either doxycycline or pyrimethamine/sulfadoxine or mefloquine resulted in similar clinical cure rates of around 100%, and the combination of artesunate with either doxycycline or pyrimethamine/sulfadoxine was equally effective as mefloquine in preventing recrudescence. There were no significant adverse effects or signs of toxicity related to the treatment observed during the 28-day follow-up. The combination regimens could be used in areas where there is limited access to parenteral therapy for malaria.

Efficacy of Sulphadoxine and Pyrimethamine, Doxycycline and their combination in the treatment of chloroquine resistant Falciparum Malaria.

OBJECTIVE: The present in vivo study evaluates the efficacy of sulphadoxine/pyrimethamine, doxycycline and their combination in the treatment of Sudanese patients infected by chloroquine resistant falciparum malaria. METHODS: Febrile patients with positive blood smears of Plasmodium falciparum were given chloroquine 25mg-base/kg body weight and followed up for 3 days. Patients with recrudescence due to chloroquine resistance were readmitted for test treatment. Using simple number randomization patients were divided into groups, A, B and C. These were treated with doxycycline, sulphadoxine/ pyrimethamine and a combination therapy of sulphadoxine/pyrimethamine plus doxycycline. Doxycycline was initially administered as a single dose of 200mg followed by 100mg daily for 6 days whereas sulphadoxine/pyrimethamine was given as a single dose of sulphadoxine 1500mg and pyrimethamine 75mg. Patients of group C received the combination therapy of sulphadoxine/pyrimethamine and doxycycline. Clinical observations and examination of blood films were carried out for each patient daily for 6 days and thereafter weekly for 4 weeks. RESULTS: A high level of chloroquine resistance (75%) was documented amongst 280 patients (age 15-53 years) visiting Omdurman Hospital of Endemic Diseases during 1996-1998. The study demonstrated that only 46% and 78% of the patients were cured after 4 days of treatment by doxycycline and sulphadoxine/pyrimethamine. Patients treated with sulphadoxine/pyrimethamine in combination with doxycycline had a cure rate of 90% and 100% after 3-4 days of treatment, a single recrudescent case was detected on day 6. No relapses occurred during the follow up period. All patients were successfully treated by all regimens with the exception of one case treated by doxycycline. All treatments were well tolerated but a few cases had complaints of nausea. CONCLUSION: The combination therapy of doxycycline/sulphadoxine/pyrimethamine appeared to be significantly effective in the treatment of patients with chloroquine resistant falciparum malaria without causing any serious side effects. Such a combination regimen has the advantages of being available at a reasonable cost and less prone to development of resistance.

Effect of dehydration on the pharmacokinetics of oxytetracycline hydrochloride administered intravenously in goats (Capra hircus).

1. The effects of various levels of dehydration induced by water deprivation were studied in six Nubian goats on the pharmacokinetics of oxytetracycline after intravenous administration (5 mg/kg). 2. In goats that had lost an average of 7.6% body weight after 2 days of water deprivation, the elimination rate constant of the drug was significantly decreased (P<0.01) and the total body clearance was significantly slower (P<0.001). No statistically significant changes were observed in the pharmacokinetic parameters describing the distribution of the drug at this dehydration level. 3. Water deprivation for 3 or 4 days resulted in a level of dehydration at which the goats lost an average of 10.3% or 12.7% of their body weight, respectively; significant changes were observed in the pharmacokinetic distribution and elimination parameters of oxytetracycline. The volume of distribution at steady state was significantly decreased (P<0.01). Significantly slower total body clearance (P<0.001) and subsequent prolongation of the elimination half-life were found at these dehydration levels. 4. The alterations caused by dehydration on the disposition kinetics of the drug should be considered for better definition of dosage regimens for sick, dehydrated animals.

Hyperpyrexic interaction between debrisoquine and pethidine in rabbits.

Pethidine injection into rabbits treated with debrisoquine either acutely or chronically resulted in severe interaction and fatal hyperpyrexia. Pretreatment of rabbits with p-chlorophenylalanine, chlorpromazine, or crypoheptadine protected them against the interaction, while alpha-methyl-p-tyrosine was ineffective. In addition the administration of debrisoquine into 5-HTP pretreated rabbits produced a severe interaction and hyperpyrexia. The hepatic N-demethylation of pethidine was significantly inhibited by debrisoquine pretreatment both in vivo and in vitro. The debrisoquine-pethidine interaction could be due to 5-HT potentiation or prevention of uptake. Alternatively it could be due to inhibition of biotransformation of pethidine by debrisoquine. However, neither mechanism by itself alone could be held responsible as the sole explanation of the interaction.

Furazolidone-pethidine interaction in rabbits.

1 The intravenous injection of pethidine in rabbits pretreated with furazolidone administered orally but not systemically resulted in severe interaction and fatal hyperpyrexia. 2 Treatment with rho-chlorophenylalanine, chloropromazine of cyproheptadine protected the rabbits against the furazolidone-pethidine interaction, while alpha-methyl-rho-tyrosine was ineffective. 3 5-Hydroxytryptophan produced a fatal hyperpyrexia in furazolidone pretreated rabbits. 4 Pretreatment of rabbits with 1,1,1-trichloro-2, 2-bis(rho-chlorophenyl)ethane (DDT) accelerated and enhanced the furazolidone-pethidine interaction, while oxytetracycline pretreatment completely prevented the interaction. 5 It is concluded that furazolidone-pethidine interaction might depend mainly on potentiation of the effects of 5-hydroxytryptamine in the CNS and that the transformation of furazolidone into an active monoamine oxidase inhibitor metabolite might occur mainly in the gut microflora in the gut lumen.