Cerebrovascular and neurological perspectives on adrenoceptor and calcium channel modulating pharmacotherapies

Adrenoceptor and calcium channel modulating medications are widely used in clinical practice for acute neurological and systemic conditions. It is generally assumed that the cerebrovascular effects of these drugs mirror that of their systemic effects – and this is reflected in how these medications are currently used in clinical practice. However, recent research suggests that there are distinct cerebrovascular-specific effects of these medications that are related to the unique characteristics of the cerebrovascular anatomy including the regional heterogeneity in density and distribution of adrenoceptor subtypes and calcium channels along the cerebrovasculature. In this review, we critically evaluate existing basic science and clinical research to discuss known and putative interactions between adrenoceptor and calcium channel modulating pharmacotherapies, the neurovascular unit, and cerebrovascular anatomy. In doing so, we provide a rationale for selecting vasoactive medications based on lesion location and lay a foundation for future investigations that will define neuroprotective paradigms of adrenoceptor and calcium channel modulating therapies to improve neurological outcomes in acute neurological and systemic disorders.     

The prevalence of premenstrual symptoms in Wellington women

A survey of 1826 women in the Wellington region was carried out. Participants were asked about their general and gynaecological health and their menstrual, contraceptive and obstetric history. Detailed questions were asked about the menstruating women's last menstrual cycle. Subjects were premenopausal women attending a random sample of general practice surgeries for any reason. The achieved sample is not intended as a cross-section of the Wellington community, but is nevertheless reasonably representative of the general adult female population aged 20 to 45. Most women volunteered one or more premenstrual symptoms; and about half of the women said these symptoms were such that they affected their lives.     

An exploration of the role of the nurses'' uniform through a period of non-uniform wear on an acute medical ward

The nursing staff on an acute medical hospital ward elected to wear their own clothes to work for a period of 2 months. The trial was evaluated using a variety of research methods and it raised a number of issues about the role of uniform, about patients' perceptions of nurses and nurses' perceptions of their role. The study has led to questions being raised about the assumptions that are made if uniform is worn and the appropriateness of a uniform dress.     

Prednisolone versus dexamethasone in croup: a randomised equivalence trial.

BACKGROUND: Croup remains a common respiratory problem presenting to emergency departments. A single oral treatment of oral dexamethasone results in improved outcome. Prednisolone has similar pharmacokinetic properties and has a significant advantage in that it is commercially available in liquid preparations. OBJECTIVE: To ascertain whether a single oral dose of prednisolone was equivalent to a single oral dose of dexamethasone (matched for potency) in children with mild to moderate croup. DESIGN: A double blind, randomised, controlled equivalence trial. SETTING: Tertiary paediatric emergency department. Patients: 133 children aged 3 to 142 months presenting with mild to moderate croup. INTERVENTIONS: Children received either a single oral dose of dexamethasone 0.15 mg/kg or single oral dose of prednisolone 1 mg/kg. Outcome: The main outcome measure was unscheduled re-presentation to medical care as determined by telephone follow up at 7 to 10 days. Croup score, adrenaline (epinephrine) use, time spent in the emergency department, and duration of croup and viral symptoms were secondary outcome measures. RESULTS: Children treated with prednisolone were more likely to re-present: 19 of 65 children (29%) reattended medical care compared with 5 of 68 (7%) from the dexamethasone group. The confidence intervals around this 22% difference in outcome were 8% to 35%, outside the 0% to 7.5% range of equivalence. There were no significant differences in other outcome measures. CONCLUSION: A single oral dose of prednisolone is less effective than a single oral dose of dexamethasone in reducing unscheduled re-presentation to medical care in children with mild to moderate croup.     

New developments in sustained-release antihypertensive therapy: formulation and pharmacokinetic considerations.

In order to achieve a consistently absorbed form of nifedipine over 24 hours, a novel formulation approach, INDAS, was used to develop a once-daily, sustained-release (SR) form of nifedipine that could provide effective control of blood pressure at a low total daily dose. The pharmacokinetic characteristics of this new formulation of nifedipine-SR were compared with those of divided doses of conventional nifedipine. The SR formulation was shown to achieve a lower peak plasma nifedipine level but with a prolonged plasma profile characterized by an extended time to peak plasma levels (Tmax), a higher trough plasma level, a longer apparent half-life, and a markedly lower peak-to-trough fluctuation in plasma nifedipine concentrations. In a separate study, the gastrointestinal transit parameters and physical characteristics of the SR tablet were evaluated. This study established that the large intestine is the major site of residence and absorption for this dosage form. The physical erosion and disintegration characteristics of the SR formulation are such that a well-maintained absorption of nifedipine is consistently achieved over the 24 hour dosing interval.     

A study comparing biopharmaceutic characteristics of four once daily controlled release diltiazem preparations

Summary— In the present study we have compared the steady state biopharmaceutic characteristics of four diltiazem once daily controlled release capsules: Mono-Tildiem LP 300® (300 mg), Adizem® XL (300 mg)¹, Cardizem® (300 mg) and Dilacor® (240 mg). Sixteen healthy male volunteers (aged 22.9 ± 3.3 years, range 19–31 years) completed an open label, multiple oral dose, randomized, four-period crossover study without a washout period in between. The volunteers received each diltiazem formulation once daily for four days. Trough diltiazem and metabolites plasma concentrations were determined on days 3 and 4. The 24-h plasma concentration-time profiles were assessed after the dose on day 4 of each period. The following steady state pharmacokinetic parameters for diltiazem were calculated: the minimum plasma concentration (c_min), the maximum plasma concentration (c_max), the time to reach that concentration (t_max), the time interval during which the plasma concentration exceeds 50% of c_max (t₅₀), the area under the plasma concentration-time curve (AUC_72–96) and the peak-to-trough fluctuation (PTF). For the metabolites of diltiazem, N-mono-desmethyl-diltiazem (NDM) and desacetyldiltiazem (DAD), AUC_72–96 (AUC_NDM and AUC_DAD) and the ratio metabolite/parent compound were calculated. Steady state was achieved on day 3. Except one, all controlled release formulations have satisfactory controlled release properties allowing once daily administration. However, significant (P < 0.05) differences were found between the pharmacokinetic characteristics which do not allow exchange of the various formulations. Concentrations well below 50 ng·mL^-1 in the morning hours were observed for Dilacor® (240 mg) and Adizem® XL (300 mg), which could be a disadvantage of these formulations as it is well-known that ischaemic events occur at a higher rate during that part of the day. The plasma concentration profiles of NDM and DAD, the major circulating metabolites, parallel the plasma concentration profiles for the parent compound. From a clinical point of view, all treatments were well tolerated.