Drug Interactions in Primary Health Care in the George Subdistrict; South Africa: a Cross-Sectional Study

Objectives: To investigate the prevalence of potential drug-drug interactions in primary healthcare clinics in the George subdistrict; to determine which drugs were involved; and to identify associated risk factors. Design: A cross-sectional retrospective folder review was performed.Setting and subjects: Four hundred randomly selected patient files from four primary care clinics in the George subdistrict. Outcome measures: The prevalence of potential drug-drug interactions in primary care; drugs involved in potential drug-drug interactions and associated risk factors. Results: The prevalence of scripts containing at least one moderate potential interaction was 42; severe potential interaction; 5.25; and contraindicated combinations; 0.5. The most common drugs involved were enalapril; aspirin; ibuprofen; furosemide and fluoxetine. The most common implicated drugs in potentially severe interactions were warfarin; aspirin; fluoxetine; tramadol and allopurinol. Two contraindicated combinations were found; namely verapamil plus simvastatin; and hyoscine butyl bromide plus oral potassium chloride. Advancing age and polypharmacy were associated with an increased risk of potential drug-drug interactions. Input from the regional hospital specialist departments greatly increased the risk of a patient being given a prescription that contained a potential drug-drug interaction. Eighty one per cent of severe interactions were from this group. Conclusion: The potential for drug-drug interactions occurring was common in primary healthcare clinics in the George subdistrict. Drug interactions are predictable and preventable. The risk factors identified in this study may assist in the design of interventions that reduce the risk

Influence of di-butyltin dilaurate on brain neurotransmitter systems and behavior in rats.

Exposure to DBTL (20, 40 or 80 mg/kg body weight) caused a decrease in levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) at all treatment levels. Hypothalamus and frontal cortex appeared to be most affected, since levels of all the three amines examined showed changes in these areas. Maximum decrease of DA was found in corpus striatum, NA in pons medulla and of 5-HT in frontal cortex. These animals also showed a decrease in spontaneous locomotor activity and learning at all the doses. The data indicates involvement of hypothalamus and frontal cortical regions of the brain in the neurotoxicity of DBTL.

Evidence for neuronal uptake and release of norfenefrine and evaluation of its alpha-agonistic effects in the rabbit pulmonary artery.

Rabbit pulmonary artery strips were used for the evaluation of the alpha 1-/alpha 2-agonistic activity of norfenefrine (active principle of the antihypotensive agent Novadral) and for the investigation of neuronal uptake and release mechanisms for norfenefrine in the vessel wall. At 0.1 and 1 mumol/l, norfenefrine caused contractions of the artery strips, while presynaptic inhibition of stimulation-evoked noradrenaline release could not be detected with certainty. Thus, in the range tested, alpha 1-agonistic activity was more pronounced. Uptake and release of 3H-norfenefrine was studied on noradrenaline-depleted arteries. Rabbits were pretreated either with alpha-methyl-p-tyrosine (metirosine, alpha-MT) to inhibit noradrenaline synthesis without affecting storage vesicle function or with reserpine to eliminate vesicular storage capacity. In arteries from animals pretreated with alpha-MT, more substance was retained after preincubation with 3H-norfenefrine, in comparison with reserpine pretreated arteries, and about 2% of the substance was released from Arteries from reserpine pretreated animals retained less 3H-norfenefrine after preincubation, in comparison with alpha-MT pretreated arteries, and less than 0.2% was released per stimulation period. After alpha-MT treatment, tension developed upon stimulation was enhanced after norfenefrine preincubation, while contractions of reserpine pretreated arteries were independent of norfenefrine preincubation. These results provide evidence for an uptake of norfenefrine in the noradrenaline storage vesiculation period. After alpha-MT treatment, tension developed upon stimulation was enhanced after norfenefrine preincubation, while contractions of reserpine pretreated arteries were independent of norfenefrine preincubation. These results provide evidence for an uptake of norfenefrine in the noradrenaline storage vesicles and a vesicular co-secretion of norfenefrine with noradrenaline upon stimulation. The impaired sympathetic transmission was thereby improved.

Stimulation of rabies vaccine in mice by low doses of polyadenylic:polyuridylic complex.

Addition of 100 mug of polyadenylic: polyuridylic (poly A:U) complex to each dose of inactivated rabies vaccine increased immunity to rabies challenge in mice. Stimulation was also observed after addition of 10 mug of poly A:U to the vaccines. Mixtures of rabies vaccine and poly A:U lost their stimulatory properties after storage at 37 or 4 C for 1 month. However, these data are encouraging for practical use of poly A:U as an adjuvant to viral vaccines.