Registration of amiloride in South Africa: Cutting the Gordian knot.

Amiloride is an antagonist of the renal tubular epithelial sodium channel (ENaC). As such, it is a diuretic that is both potassium and magnesium sparing. It is used for the treatment of potassium depletion and hypertension, and is the specific therapy for hypertension due to overactivity of the ENaC (Liddle syndrome and several additional genetic causes of the Liddle phenotype - low renin and low aldosterone). It is listed as a World Health Organization essential drug, but has never been registered in South Africa (SA) and can therefore only be prescribed under a Section 21 application to the SA Health Products Regulatory Authority (SAHPRA) on a case-by-case basis. In SA, >50% of patients treated for hypertension are not controlled. In the USA, the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study reported that African Americans are more likely to be diagnosed with hypertension, more likely to be treated, more likely to be treated intensively, and less likely to achieve blood pressure (BP) control. Although the reasons are complex, studies show that 10 - 20% of blacks may carry the Liddle phenotype. Observational data and a controlled clinical trial done in three African countries have shown that these patients respond to amiloride and not to conventional guideline-based antihypertensive treatment. The former is likely to result in a significant reduction in cardiovascular, stroke and kidney morbidity and mortality, because of improved BP control. Amiloride is very unlikely to ever be registered in SA, as it was first developed >50 years ago, and SAHPRA regulations prevent widespread prescription of this essential drug. This is a classic Gordian knot that requires a novel approach from authorities to sever the knot and improve the health of many South Africans.

International Cooperative Ataxia Rating Scale for pharmacological assessment of the cerebellar syndrome. The Ataxia Neuropharmacology Committee of the World Federation of Neurology.

Despite the involvement of cerebellar ataxia in a large variety of conditions and its frequent association with other neurological symptoms, the quantification of the specific core of the cerebellar syndrome is possible and useful in Neurology. Recent studies have shown that cerebellar ataxia might be sensitive to various types of pharmacological agents, but the scales used for assessment were all different. With the long-term goal of double-blind controlled trials-multicentric and international-an ad hoc Committee of the World Federation of Neurology has worked to propose a one-hundred-point semi-quantitative International Cooperative Ataxia Rating Scale (ICARS). The scale proposed involves a compartimentalized quantification of postural and stance disorders, limb ataxia, dysarthria and oculomotor disorders, in order that a subscore concerning these symptoms may be separately studied. The weight of each symptomatologic compartment has been carefully designed. The members of the Committee agreed upon precise definitions of the tests, to minimize interobserver variations. The validation of this scale is in progress.