Sex-specific responses to mineralocorticoid receptor antagonism in hypertensive African American males and females.

BACKGROUND: African Americans (AA) develop hypertension (HTN) at an earlier age, have a greater frequency and severity of HTN, and greater prevalence of uncontrolled HTN as compared to the white population. Mineralocorticoid antagonists have been shown to be very effective in treating uncontrolled HTN in both AA and white patients, but sex-specific responses are unclear. METHODS: We evaluated the sex-specific impact of mineralocorticoid antagonism in an AA population. An AA cohort (n = 1483) from the Genetic Epidemiology Network of Arteriopathy study was stratified based on sex and whether they were taking spironolactone, a mineralocorticoid antagonist, in their antihypertensive regimen. RESULTS: As compared to AA women not prescribed a mineralocorticoid antagonist, AA women taking spironolactone (n = 9) had lower systolic and diastolic blood pressure despite having a similar number of antihypertensive medications. The proportion of AA women with uncontrolled HTN was significantly less for patients taking spironolactone than for patients not prescribed spironolactone. Interestingly, none of these associations were found in the AA males or in white females. CONCLUSIONS: Our data suggests that spironolactone is particularly effective in reducing blood pressure and controlling HTN in AA women. Further research into the impact of this therapy in this underserved and understudied minority is warranted.

Mixing medication into foodstuffs: identifying the issues for paediatric nurses.

Medication is often mixed into soft foods to aid swallowing in children. However, this can alter the physical/chemical properties of the active drug. This study reports on the prevalence of the modification procedure, the nature of foodstuffs routinely used and factors which influence how the procedure is performed by nurses working in the National Health Service in Scotland. Mixed methods were employed encompassing an online self-administered questionnaire and semi-structured interviews. One hundred and eleven nurses participated, of whom 87% had modified medication prior to administration. Fruit juice (diluted and concentrated) and yoghurts were most commonly used. The interviews (i) identified the limitations of the procedure; (ii) explored the decision-making process; and (iii) confirmed the procedure was a last resort. This study intends to address some of the uncertainty surrounding the medicine modification procedure within the paediatric population.

Discovery of AZD3199, An Inhaled Ultralong Acting ß2 Receptor Agonist with Rapid Onset of Action.

A series of dibasic des-hydroxy ß2 receptor agonists has been prepared and evaluated for potential as inhaled ultralong acting bronchodilators. Determination of activities at the human ß-adrenoreceptors demonstrated a series of highly potent and selective ß2 receptor agonists that were progressed to further study in a guinea pig histamine-induced bronchoconstriction model. Following further assessment by onset studies in guinea pig tracheal rings and human bronchial rings contracted with methacholine (guinea pigs) or carbachol (humans), duration of action studies in guinea pigs after intratracheal (i.t.) administration and further selectivity and safety profiling AZD3199 was shown to have an excellent over all profile and was progressed into clinical evaluation as a new ultralong acting inhaled ß2 receptor agonist with rapid onset of action.

Design driven HtL: The discovery and synthesis of new high efficacy ß2-agonists.

The design and synthesis of a new series of high efficacy ß(2)-agonists devoid of the key benzylic alcohol present in previously described highly efficacious ß(2)-agonists is reported. A hypothesis for the unprecedented level of efficacy is proposed based on considerations of ß(2)-adrenoceptor crystal structure, other biophysical data and modeling studies.