Marketing of rural and remote pharmacy practice via the digital medium.

AIM: The shortage of community and hospital pharmacists is particularly acute in rural and remote areas of Australia. Pharmacy students, in particular, as those who may be able to alleviate this shortage, need to be made more aware of the challenges and rewards of rural pharmacy practice. A marketing tool was developed to promote rural and remote pharmacy practice as a career option. A DVD was produced from interviews with health professionals working in rural and remote areas of Australia. This DVD will complement current rural practical placements, which have been incorporated into the curriculum of Australian schools of pharmacy. METHODS: Interviews were conducted with healthcare professionals from areas in Tasmania, Northern Queensland and the Northern Territory. Interviewees included pharmacists, graduate pharmacists, pharmacy students, aboriginal health workers and a general practitioner. Each of the interviewees was able to provide personal accounts of experiences in rural and remote healthcare, and roles and opportunities for pharmacists. A final draft of the DVD was shown to University of Tasmania students to assess the impact and quality of the production. RESULTS: A number of common themes arose from interviewing and these were subsequently converted into five key chapters of the DVD - Lifestyle, Belonging, Diversity, Indigenous Health and 'Give it a go'. The final DVD, produced from over 15 h of footage, runs for 35 min. Students reported positive feedback on both the technical quality and the information contained within the DVD; 37% of students who viewed the DVD felt that it increased their awareness of what rural pharmacy has to offer. CONCLUSIONS: The rural pharmacy, 'Enjoy the Lifestyle' DVD can be used to increase awareness of rural and remote pharmacy practice to students and other pharmacists, and complements other pharmacy workforce strategies for rural and remote areas of Australia. It could also be a useful approach for adaptation in other countries.

Population pharmacokinetics of magnesium in preeclampsia.

OBJECTIVE: The purpose of this study was to determine the population pharmacokinetics of magnesium from sparse observational data in patients with preeclampsia. STUDY DESIGN: Serum magnesium concentrations (1-11 per patient) were obtained retrospectively from the records of 116 patients with preeclampsia who had a loading dose of magnesium sulfate (16 or 20 mmol), followed by a maintenance dose (1 mmol/h) over an average of 28 hours. Population clearance, volume of distribution, and the baseline magnesium concentration were estimated using the NONMEM program. RESULTS: The following population typical values, together with the interpatient variability (expressed as coefficient of variation) were obtained with the use of a 1-compartment model: systemic clearance, 4.28 L/h (37.3%); volume of distribution, 32.3 L (32.1%); baseline concentration, 0.811 mmol/L (18.5%). The average half-life was 5.2 hours. Clonus was not obtunded in 4 patients whose serum magnesium concentrations were similar to the average concentration of 1.7 mmol/L. The variability remaining unexplained after the population model was fitted to the data was 6.5% to 10.8%. CONCLUSION: This study extended knowledge of the pharmacokinetic disposition of magnesium in preeclampsia. The results are potentially useful for the calculation of loading and maintenance doses, particularly when the relationship between serum concentration and effect in preeclampsia is clarified.

Population pharmacokinetics of perhexiline from very sparse, routine monitoring data.

Using NONMEM, the population pharmacokinetics of perhexiline were studied in 88 patients (34 F, 54 M) who were being treated for refractory angina. Their mean +/- SD (range) age was 75 +/- 9.9 years (46-92), and the length of perhexiline treatment was 56 +/- 77 weeks (0.3-416). The sampling time after a dose was 14.1 +/- 21.4 hours (0.5-200), and the perhexiline plasma concentrations were 0.39 +/- 0.32 mg/L (0.03-1.56). A one-compartment model with first-order absorption was fitted to the data using the first-order (FO) approximation. The best model contained 2 subpopulations (obtained via the $MIXTURE subroutine) of 77 subjects (subgroup A) and 11 subjects (subgroup B) that had typical values for clearance (CL/F) of 21.8 L/h and 2.06 L/h, respectively. The volumes of distribution (V/F) were 1470 L and 260 L, respectively, which suggested a reduction in presystemic metabolism in subgroup B. The interindividual variability (CV%) was modeled logarithmically and for CL/F ranged from 69.1% (subgroup A) to 86.3% (subgroup B). The interindividual variability in V/F was 111%. The residual variability unexplained by the population model was 28.2%. These results confirm and extend the existing pharmacokinetic data on perhexiline, especially the bimodal distribution of CL/F manifested via an inherited deficiency in hepatic and extrahepatic CYP2D6 activity.

Statistical moments for placental transfer of solutes in man.

The placental transfer of red blood cells and solutes in man has been investigated by statistical moment analysis, using the impulse-response technique. Model compounds of different lipophilicity (sucrose, water, antipyrine, propranolol and labetalol) were injected with a vascular reference (labelled red blood cells) as boluses into either the foetal or maternal circulation of a single-pass perfused placental lobule. Maternal and foetal venous outflow fractions were collected at intervals ranging from 1 to 600 s. Perfusion was conducted at maternal flow rates of 4 and 6 mL min(-1) and foetal flow rates of 2 and 3 mL min(-1), respectively, to yield a constant materno-foetal flow ratio of 2. The outflow concentration-time profile curves were analysed by statistical moment analysis. The sum of foetal and maternal recovery was close to 100% for red blood cells, sucrose, water and antipyrine, but lower for propranolol and labetalol. The mean transit time (MTT) values ranged from 20 to 500 s. The normalized variance (CV2) for red blood cells in the foetal and maternal circulation of the placenta were in the ranges 2.31 to 3.86 and 2.00 to 2.03, respectively. The shape of the outflow concentration-time profiles after bolus input is consistent with that of vascular residence time models such as the dispersion model. The heterogeneity in red blood cell transit times, as defined by CV2, is greater than in either the perfused leg or perfused liver.

An isolated perfused human placental lobule model for multiple indicator dilution studies.

We describe a method for multiple indicator dilution studies in the isolated perfused human placental lobule developed to investigate the relationships between changes in pressure and flow and solute clearance. A peripheral lobule of a human placenta is perfused with a tissue culture-based medium and the perfusate oxygen tension, arterial and venous pressures, pH and perfusion temperature continuously monitored by a computerized system. Flow rates are readily changed. Bolus injections of vascular, extracellular and water space markers, and study compounds can be made into either maternal or fetal circulations, and precisely timed outflow fractions can be collected with computer-controlled fraction collectors, allowing simultaneous determination of concentration-time profiles of each marker.

Simplified sizing of low-density lipoprotein using polyacrylamide gradient gel electrophoresis of plasma.

Low-density lipoprotein (LDL) particles can be separated into subfractions according to size by non-denaturing polyacrylamide gradient gel electrophoresis. Established research methods require specialised equipment and are frequently unsuited to the clinical laboratory. In this study, we utilised a colour flat bed scanner in conjunction with shareware image analysis software to compare LDL particle diameters of isolated LDL with LDL in whole plasma. LDL was isolated by ultracentrifugation and electrophoresed on 3-13% gels (Gradipore; Sydney, Australia) for 2400 Volt-hours in parallel with plasma and molecular size standards. Coomassie Blue-stained gels were scanned in reflexive mode using a colour flat-bed scanner and Adobe Photoshop 3.0 software. Density traces of each lane were obtained using NIH Image software (public domain, USA). LDL particle diameters were determined from calibration curves of the log of molecular diameter of standards against migration distance. There was a good correlation between LDL particle diameters obtained using isolated LDL and whole plasma (r = 0.87, P < 0.001; n = 22). However, the group means (+/- S.D.) (24.7 +/- 0.6 and 24.8 +/- 0.5 nm respectively) were statistically different on the paired t-test (P < 0.05). It is unclear whether this numerically small difference is due to alterations in LDL during the longer preparative procedures for LDL, or to matrix effects during electrophoresis of plasma samples. In conclusion, plasma samples stained with Coomassie Blue and scanned with a colour flat bed scanner can conveniently be used for LDL particle sizing by non-denaturing polyacrylamide gradient gel electrophoresis.

Propofol attenuates the myogenic response of vascular smooth muscle.

The myogenic response is the tendency of certain vessels, most notably small arteries and arterioles, to constrict in response to an increase in intravascular pressure. The effects of propofol on the myogenic response of the isolated pressurized rabbit ear artery were studied in segments preconstricted either with norepinephrine or 5-hydroxytryptamine and subjected to pressure increases from 60 to 100 mm Hg applied either rapidly (jumps over 500 ms) or slowly (ramps over 120 s). In the control experiments the preconstricted vessels initially dilated, then rapidly returned toward their initial diameter. In response to pressure ramps, vessels slowly dilated, but closely retained their resting diameter. Administration of propofol (1.6 x 10(-4) to 1.6 x 10(-3) M) resulted in dilation of the constricted vessels. With pressure jumps vessels had a reduced capacity to recover their initial diameters, and with pressure ramps vessels dilated to greater diameters. When the concentration of vasoconstrictor was increased to antagonize the propofol-induced dilation the myogenicity was not restored. This attenuation of myogenicity, distinct from the drug's vasodilator effect may represent a further mechanism by which anesthetic agents can affect cardiovascular function.

Intraarterial propofol is not directly toxic to vascular endothelium.

To determine if accidental intraarterial injection of propofol results in vascular damage, the effect of bolus administration of propofol on vascular smooth muscle and the endothelium was investigated using the isolated rabbit ear artery. Ear artery segments, removed from urethane anesthetized rabbits, were perfused with Krebs solution (1 ml.min-1) and pressurized to 60 mmHg before being constricted with extraluminal norepinephrine (1.8-4.2 x 10(-6) M). The external diameter of the vessel was measured by an array of light-dependent diodes. Functional responsiveness was determined by the degree of constriction to norepinephrine and the subsequent dilatation of the artery to intraluminal acetylcholine (2 x 10(-6) M) and glyceryl trinitrate (2 x 10(-6) M), and by the myogenic reactivity to a pressure increase from 60 to 100 mmHg. These responses were measured before and after perfusion with 1% propofol for 120 s. Administration of propofol did not result in any vasoactivity nor did it increase the sensitivity to norepinephrine. Vessels maintained their capacity to dilate to both agents, while the myogenic activity was unaffected. Histologic examination of the propofol exposed vessels showed no changes to smooth muscle structure, and the endothelial layer remained intact.

Myogenic response of isolated pressurized rabbit ear artery is independent of endothelium.

Central ear artery segments, removed from urethan-anesthetized rabbits, were used to assess whether distention activation was dependent on intact and functional endothelium (ENDO). Changes in external arterial diameter were measured with light-dependent diode array mounted above the vessel. After constriction with norepinephrine, slow increases in pressure from 60 to 80 or 100 mmHg performed over 120 s (pressure ramps) failed to initiate distention, but initial diameter was maintained. Rapidly applied (500 ms) pressure increases (pressure jumps) across same pressure ranges gave rise to initial distention and a myogenic response resulting in a return to almost initial diameter while new pressure was maintained for 120 s. Myogenic activity was measured from extent of recovery of vessel to its initial diameter during maintenance of pressure jumps or ramps. Rapid jumps and slow ramps were performed in presence of an intact ENDO and again after ENDO was removed by passage of intraluminal gas. With pressure jumps 60 to 80 mmHg, degree of recovery in ENDO-denuded vessels was 91.9% compared with 89.5% in ENDO intact vessels. For pressure jumps 60 to 100 mmHg, extent of recovery was 87.4 and 89.6%. During application of pressure ramps of 20 or 40 mmHg, vessel diameter did not increase by greater than 5%. There are no significant differences in these data, and we conclude that myogenic response in rabbit ear artery is mediated independently of endothelial-derived factors, irrespective of whether myogenic activation is induced by pressure jumps or ramps.