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Biomedical subjects

R F Moulds

Publications and source records attributed to R F Moulds.

At least 19 recordsLinked to original sources
PubMed1996

Hospitalisation for adverse events related to drug therapy: incidence, avoidability and costs.

OBJECTIVES: To determine the incidence of hospital admissions for adverse events related to drug therapy, and to assess whether these drug-related admissions (DRAs) could have been reasonably prevented. SETTING: A tertiary teaching hospital. DESIGN AND PATIENTS: Prospective assessment of all admissions through the emergency department and resulting in a stay of more than 24 hours during 30 consecutive days in November and December 1994 to determine if the admission was related to drug therapy. Cases of intentional overdose were excluded. MAIN OUTCOME MEASURES: The number, type, causality and avoidability of drug-related admissions. RESULTS: Of 965 admissions, 55 (5.7%) were assessed as being drug-related. Drug-related admissions (DRAs) were designated possibly (38%), probably (46%) or definitely (16%) drug-related; caused by prescribing factors (26%), patient noncompliance (27%) and adverse drug reactions (47%); and classified as definitely (5.5%), possibly (60.0%) and not (34.5%) avoidable. The estimated annual cost to the hospital for all DRAs was $3,496,956 and for unavoidable DRAs was $1,629,494. CONCLUSION: The DRA rate we found lies around the middle of the range of other published rates. Few DRAs were judged definitely avoidable and over one-third were unavoidable. Nevertheless, the largest proportion were judged possibly avoidable. As the drugs identified in this study are clearly needed in the community, efforts to reduce DRAs must concentrate on education, counselling and monitoring of drug therapy.

Adolescent↗
PubMed1995

Prescriber guidelines improve initiation of anticoagulation.

OBJECTIVES: To improve the initiation of anticoagulation in patients with thrombotic disorders. DESIGN AND SETTING: We carried out a preliminary audit in 1991, developed and implemented strategies to address identified problems, and followed up with another audit in 1993. Medical records of inpatients at The Royal Melbourne Hospital whose anticoagulation therapy was initiated with heparin (intravenous) in therapeutic doses and subsequently converted to warfarin were prospectively assessed over 19-day periods. INTERVENTION: Pocket-sized laminated prescriber guidelines for initiating anticoagulation were disseminated after publishing the results of the first audit, together with a single prominent display of two posters in series advocating the use of the guidelines. RESULTS: The audits identified 25 eligible patients in 1991 and 27 in 1993. The mean duration of intravenous heparin therapy was reduced from 150 hours in 1991 to 97 hours in 1993 (P < 0.002). The mean delay before initiating warfarin therapy after starting heparin therapy was reduced from 69 hours in 1991 to 21 hours in 1993 (P < 0.002). The mean percentage of time the activated partial thromboplastin time was within the therapeutic range increased from 30% in 1991 to 44% in 1993 (P < 0.05) and was above the therapeutic range increased from 13% in 1991 to 24% in 1993 (P < 0.01). Although the number of adverse events was too small to draw definitive conclusions, no difference in adverse haemorrhagic effects was noted between the 1991 and 1993 groups. CONCLUSION: There was an improvement in the initiation of anticoagulation and we hypothesise that this was most likely due to a broad acceptance of the guidelines into clinical practice.

Attitude of Health Personnel↗
PubMed1995

Increased sensitivity to inhibition by nifedipine of responses of the mesenteric artery bed of the SHRSP to noradrenaline is not dependent on alpha 1-adrenoceptor subtypes.

The effects of noradrenaline (NA) on the perfusion pressure of mesenteric vascular bed preparations from stroke-prone spontaneously hypertensive rats (SHRSP) or weight-matched normotensive Wistar-Kyoto (WKY) rats in the presence of chloroethylclonidine (CEC, alpha 1B-adrenoceptor antagonist) or WB4101 (WB, alpha 1A-adrenoceptor antagonist), with or without the addition of nifedipine, were studied. NA caused a greater maximum increase in the perfusion pressure of the SHRSP mesenteric bed than that of the WKY, and the EC50 for NA was lower in the SHRSP. There was no difference between the normotensive or hypertensive beds in the reduction of responses to NA produced by WB or CEC. Nifedipine, in the presence of either CEC or WB, further reduced responses to NA, but to a significantly greater extent in the SHRSP than in the WKY. There was no difference within either group between the additional inhibitory effect of nifedipine in combination with CEC or WB. These results confirm that following alpha 1-adrenoceptor subtype blockade, the response to NA by the mesenteric bed of the SHRSP is more sensitive to inhibition by nifedipine than its WKY counterpart. However, the increased sensitivity to the inhibitory effects of nifedipine on responses to NA is not a result of preferential linkage of Ca2+ entry mechanisms to one or other of the alpha 1-adrenoceptor subtypes.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1995

The difference in nifedipine sensitivity between hypertensive and normotensive rat aortae is dependent on age.

1. In order to investigate further whether the increased sensitivity to inhibition by nifedipine of the responses to noradrenaline of aortae from spontaneously hypertensive stroke-prone (SHRSP) rats is related to the development of the hypertension, we have compared the sensitivity to noradrenaline, potassium chloride (KCl) and nifedipine of aortae from SHRSP and control (Wistar-Kyoto) WKY rats of different age groups (young: 3-5 weeks, and adult: 13-16 weeks). 2. The sensitivity to KCl was found to be less in the aortae from the adult WKY group than in any of the other three groups. Responses to noradrenaline of the adult WKY aortae were also less sensitive to inhibition by nifedipine in comparison to each of the other three groups. 3. The changes in sensitivity were not due to the changes in the populations of alpha 1-adrenoceptor subtypes as responses of the adult SHRSP aortae to noradrenaline were more sensitive to nifedipine in the presence of either the alpha 1-adrenoceptor subtype antagonists chloroethylclonidine or WB4101 than were those of the adult WKY aortae, but aortae from the young SHRSP were not. 4. These results suggest that, rather than the SHRSP aorta becoming more sensitive to nifedipine and potassium depolarization as hypertension develops, it is the WKY aorta that becomes more resistant as it matures.

Adrenergic alpha-Antagonists↗
PubMed1994

Improving the quality of antibiotic prescription patterns in general practice. The role of educational intervention.

OBJECTIVE: To assess the quality of antibiotic prescribing by Victorian general practitioners, and the effectiveness of educational intervention techniques in improving prescribing. DESIGN: A randomised, controlled, parallel group trial. SETTING AND PARTICIPANTS: In rural and metropolitan Victoria, 182 general practitioners (78 control, 104 intervention) began and 103 (41 control, 62 intervention) completed the study. INTERVENTION: Participants recorded their antibiotic prescribing for tonsillitis. The intervention group received an educational mailing campaign. A project pharmacist visited each doctor to discuss campaign messages. MAIN OUTCOME MEASURE: The percentages of prescriptions of antibiotics for tonsillitis complying with those recommended in Antibiotic guidelines. RESULTS: In the intervention group, prescriptions consistent with recommendations in the guidelines increased from 60.5% before the campaign to 87.7% afterwards. Improvement also occurred in the control group, from 52.9% to 71.7% of prescriptions. The improvement within the intervention group was significantly greater than that within the control group. CONCLUSIONS: The educational campaign significantly improved the prescribing of appropriate antibiotics for tonsillitis by general practitioners.

Anti-Bacterial Agents↗
PubMed1994

Assessment of general practitioners' management of hyperlipidaemia. A study using personal visits and a scenario-based questionnaire.

In summary our study has looked at the current management practices of hyperlipidaemia by general practitioners in an innovative way. Our results suggest that most GPs are managing this condition appropriately. Where their management differs from current guidelines is mainly in introducing medication early. We obtained significantly lower participation rates in the metropolitan as compared with the regional and rural areas, but we found no significant differences in the overall assessment of appropriate management between the different geographical regions of Victoria.

Data Collection↗
PubMed1993

Effects of fentanyl on the rat aorta are mediated by alpha-adrenoceptors rather than by the endothelium.

We have assessed if fentanyl interacts with the endothelium to affect vessel tone. In the presence or absence of endothelium, fentanyl in concentrations greater than 10(-7) mol litre-1 decreased the sensitivity of the rat aortic rings to phenylephrine, but fentanyl in smaller concentrations had no significant effect. Rings, with or without endothelium, and pre-contracted by phenylephrine were relaxed by fentanyl, and this relaxation was not inhibited by the opioid receptor antagonist, naloxone. Pretreatment of the rings with either fentanyl or phentolamine protected alpha-adrenoceptors from block by the alpha-adrenoceptor antagonist, phenoxybenzamine. We conclude that, in the rat aorta, fentanyl-induced relaxation was mediated by alpha-adrenergic receptors, and that the endothelium modulated, but did not mediate, this relaxation.

Animals↗
PubMed1993

Sufentanil and alfentanil cause vasorelaxation by mechanisms independent of the endothelium.

1. The aim of these experiments was to determine if the vasorelaxation of the rat isolated aorta induced by sufentanil or alfentanil is mediated by the endothelium, and, if not, by alpha-adrenoceptor blockade, or a direct effect on the smooth muscle. 2. Both sufentanil (from 10(-7) mol/L to 10(-4) mol/L) and alfentanil (from 10(-7) mol/L to 3 x 10(-4) mol/L) relaxed rings, where endothelium was intact and precontracted with 40 mmol/L KCl, in a concentration-related manner. Similarly, sufentanil and alfentanil relaxed rings, in the presence or absence of endothelium, which had been precontracted with phenylephrine. 3. Naloxone (10(-4) mol/L) had no significant effect on the relaxation induced by either sufentanil or alfentanil. 4. In a similar manner as phentolamine, pretreatment with sufentanil protected alpha-adrenoceptors from blockade by phenoxybenzamine (PBZ) in both endothelium intact and denuded rings, but the estimated potency of sufentanil was approximately 100-fold less than that of phentolamine in alpha-adrenoceptor protection. Treatment with alfentanil did not produce any receptor protection. 5. We concluded that, in the rat aorta, vascular relaxation induced by sufentanil is mediated by both alpha-adrenoceptor blockade and a direct effect on smooth muscle, whilst the relaxant effect of alfentanil is caused by direct effects alone. We also concluded that the endothelium has little role in relaxation produced by either drug.

Adrenergic alpha-Antagonists↗
PubMed1991

Anticonvulsants in pregnancy.

OBJECTIVE: To review the potential problems and their management associated with the use of anticonvulsant drugs during pregnancy. DATA SOURCES: Studies published between 1968 and 1990 assessing the effect of pregnancy on the pharmacokinetics of anticonvulsant drugs, the teratogenicity of anticonvulsants, breast feeding and anticonvulsants and use of the oral contraceptive pill in patients taking anticonvulsant medication, were reviewed. RESULTS OF DATA SYNTHESIS: In general, plasma levels fall during pregnancy and rise during the puerperium. A number of factors including possible reduced absorption, increased volume of distribution, reduced protein binding, increased clearance and noncompliance, contribute to this fall in plasma concentration. All anticonvulsants are potentially teratogenic. The incidence of fetal malformations is higher in patients treated with multiple anticonvulsant drugs and on higher dosages with higher plasma levels. Anticonvulsants are excreted in low concentrations in breast milk. All anticonvulsants except valproic acid have been associated with failure of the oral contraceptive pill. This is due to liver enzyme induction of these drugs. CONCLUSION: As plasma levels of anticonvulsants fall during pregnancy, concentrations should be monitored regularly. Due to the fall in protein binding, marginally low total plasma levels of highly protein bound drugs may not reflect reduced unbound levels, and hence an increase in dosage may not be required. In order to reduce teratogenicity, one should aim to use a single anticonvulsant drug and the lowest dosage able to achieve seizure control. In general, breast feeding is not contraindicated.

Abnormalities, Drug-Induced↗
PubMed1991

Differences between rat and guinea pig aorta in postreceptor mechanisms of alpha 1-adrenoceptors.

The relative importance of different postreceptor mechanisms associated with alpha 1-adrenoceptor activation in guinea pig aorta and rat aorta was compared. In both tissues, a concentration-dependent correlation was observed between contractile responses produced by high concentrations of norepinephrine (NE) and inositol-1-phosphate (IP1) accumulation. Blockade of Ca2+ entry through voltage-dependent membrane channels by nifedipine had no inhibitory action on NE-induced contractile responses in guinea pig aorta, but significantly inhibited NE-induced contractile responses in rat aorta. Nifedipine had no major effect on NE-induced IP1 accumulation in either tissue. A medium with no Ca2+ inhibited NE-induced contractile responses and IP1 accumulation in guinea pig aorta, but had a more marked effect on contractile responses and IP1 accumulation in rat aorta. The combination of a high concentration of nifedipine and a medium with no Ca2+ almost completely inhibited NE-induced contractile responses and IP1 accumulation in both tissues. Exposure to EGTA also virtually completely inhibited NE-induced contractile response and IP1 accumulation in both tissues. Significant 45Ca2+ entry was stimulated in rat aorta by NE, and this entry was completely blocked by nifedipine. No significant 45Ca2+ entry was stimulated by NE in guinea pig aorta. We conclude that the most important postreceptor event linked to alpha 1-adrenoceptor stimulation in guinea pig aorta is activation of the phosphatidylinositol pathway, whereas in rat aorta Ca2+ entry through voltage-dependent membrane channels is as important as activation of the phosphatidylinositol pathway. We also conclude that activation of the phosphatidylinositol pathway in both tissues is critically dependent on the presence of a small amount of Ca2+, which may enter from the external medium.

Animals↗
PubMed1991

Differing calcium sensitivities of human cerebral and digital arteries, human metatarsal veins, and rat aorta.

1. The effects of the voltage dependent calcium channel blocking agent nifedipine, and of a calcium free bathing medium, on the responses of human blood vessels obtained postmortem to various agonists have been compared with those of the rat aorta. The human vessels studied were digital arteries, basilar arteries and metatarsal veins. 2. Responses to potassium chloride (5-80 mM), noradrenaline (10(-9)-10(-4) M), 5-hydroxytryptamine (10(-8)-10(-4) M) and U46619 (10(-11)-10(-6) M), in the presence and absence of nifedipine (1, 10, and 100 nM) or in a calcium-free bathing medium, were assessed using an area-under-curve analysis. 3. In general, the order of sensitivity of the vessels to inhibition of agonist induced contractures by nifedipine was basilar arteries greater than metatarsal veins = digital arteries = rat aorta. 4. For all the vessels, the order of sensitivity for antagonism of responses to the agonists by nifedipine was potassium chloride greater than 5-hydroxytryptamine = noradrenaline greater than U46619. 5. A calcium free bath inhibited responses of digital arteries to potassium chloride more than noradrenaline, 5-hydroxytryptamine or U46619, and responses of rat aorta to a greater extent than responses of the digital arteries. 6. In the rat aorta, a calcium-free bath inhibited responses to all agonists (except KCl) to a greater degree than did nifedipine. 7. We conclude that inhibition of extracellular calcium entry through voltage dependent calcium channels affects contractile responses of different blood vessels to different extents, and, within the same blood vessel, responses to different contractile agonists to different extents.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1991

Ponalrestat does not cause a protein binding interaction with warfarin in diabetic patients.

Ponalrestat (Statil, ICI; Prodiax, Merck Sharp and Dohme) is an aldose reductase inhibitor which is highly protein bound. Ponalrestat markedly displaced warfarin from its protein binding in vitro at a concentration of 500 micrograms ml-1, but not at a concentration of 50 or 100 micrograms ml-1. Twelve diabetic patients (six males), age range 38-65 years, in receipt of chronic stable warfarin therapy, were given ponalrestat (600 mg daily) for 2 weeks in an open trial. A matching placebo tablet was administered for 1 week before and after the active treatment period. Patients were seen ten times (four times during the ponalrestat phase), and during the ponalrestat phase, plasma samples were also taken before and at 3 h after the daily dose of ponalrestat. At none of the visits was there any significant change in prothrombin ratio (INR), plasma total or unbound warfarin concentrations, or percentage protein binding of warfarin. No clinical complications of combination treatment were detected. The maximum ponalrestat concentration observed in the patients was approximately 100 micrograms ml-1. We conclude that no significant interaction between these drugs occurs at the doses of ponalrestat studied.

Adult↗
PubMed1990

Measurement of cost-effectiveness of drug therapy: a review of the treatment of hypertension.

There is good quantitative epidemiological evidence on the risk of cardiovascular disease posed by hypertension and, from large clinical trials, on the actual benefits gained from treatment of hypertension. Thus, hypertension presents a good model for the performance of cost-effectiveness analysis. From the Framingham study, it can be calculated that hypertensive men (blood pressure, greater than 160/95 mmHg) have a 2.8-fold higher cardiovascular mortality than normotensive men (blood pressure, less than 140/90 mmHg), and hypertensive women have a 2.3-fold higher incidence of cardiovascular mortality than normotensive women. Hypertension presents an equal relative risk to both men and women, but the absolute risk to men is greater. The largest absolute risk from hypertension is of coronary heart disease (144 events per 10,000 men per year); however, the largest relative risk from hypertension is of stroke (approximately 700%). From the Framingham data, it can be calculated that the complete reversal of hypertension for 18 years across a community could reduce the incidence of coronary heart disease by approximately 63%, and of strokes by 87%. Meta-analysis of the large clinical trials on the treatment of hypertension shows that mortality from stroke was reduced as a result of treatment by 38%, and that from coronary heart disease by 8%. Therefore the actual benefits of treatment, while significant, have not matched the theoretical benefits that could have been achieved. One of the reasons for this is that treatment may have adverse effects on other risk factors for coronary artery disease. All these factors, including the incidence of side effects interfering with quality of life, need to be taken into consideration when performing a cost-effectiveness analysis of the treatment of hypertension.

Aged↗