Drug-related problems and satisfaction among patients receiving pharmacist-led consultations at the initiation of cardiovascular drugs.

BACKGROUND: Drug-related problems (DRPs) lead to substantial morbidity and mortality and increase healthcare costs. Several interventions have been developed to reduce DRPs and improve the outcome of drug therapy. OBJECTIVE: To investigate DRPs identified through a pharmacist-led intervention and to assess patient satisfaction with the intervention. METHODS: Patients received two pharmacist consultations 1-2 weeks and 3-5 weeks after collecting a new cardiovascular medicine. Information about patient characteristics, beliefs about medicines (BMQ), DRPs, and patient evaluations were collected using questionnaires. RESULTS: Pharmacists identified DRPs among 52.4% and 43.1% of the 633 patients at consultation 1 and 2, respectively. Of the DRPs reported in consultation 1, 43.7% were solved at consultation 2. Among patients with side effects, patients who received advice on managing these in consultation 1 where more likely to have solved problems at consultation 2 (61.2% vs. 42.6%, p = 0.008). Female gender, high BMQ concern and the number of new medicines were associated with DRPs. Patients were highly satisfied with the intervention. Predictors of satisfaction were female gender, older age, higher BMQ necessity, face-to-face consultations, longer duration of consultation 1, and solved problems in consultation 2. CONCLUSIONS: The results indicate that the pharmacist-led follow-up intervention can aid early identification and solving of DRPs in patients prescribed new cardiovascular drugs. Knowledge of factors associated with DRPs and patients' satisfaction may allow further improvement of the intervention.

A novel series of piperazinyl-pyridine ureas as antagonists of the purinergic P2Y12 receptor.

A novel series of P2Y(12) antagonists for development of drugs within the antiplatelet area is presented. The synthesis of the piperazinyl-pyridine urea derivatives and their structure-activity relationships (SAR) are described. Several compounds showed P2Y(12) antagonistic activities in the sub-micromolar range.

Design of small molecule inhibitors of acetyl-CoA carboxylase 1 and 2 showing reduction of hepatic malonyl-CoA levels in vivo in obese Zucker rats.

Inhibition of acetyl-CoA carboxylases has the potential for modulating long chain fatty acid biosynthesis and mitochondrial fatty acid oxidation. Hybridization of weak inhibitors of ACC2 provided a novel, moderately potent but lipophilic series. Optimization led to compounds 33 and 37, which exhibit potent inhibition of human ACC2, 10-fold selectivity over inhibition of human ACC1, good physical and in vitro ADME properties and good bioavailability. X-ray crystallography has shown this series binding in the CT-domain of ACC2 and revealed two key hydrogen bonding interactions. Both 33 and 37 lower levels of hepatic malonyl-CoA in vivo in obese Zucker rats.

Effect of a pharmacist-led intervention on adherence among patients with a first-time prescription for a cardiovascular medicine: a randomized controlled trial in Norwegian pharmacies.

OBJECTIVE: To examine whether a pharmacist-led intervention improves medication adherence among patients who have filled a first-time prescription for a cardiovascular medicine. METHODS: Design: Unblinded randomized controlled trial. SETTING: 67 Norwegian pharmacies, October 2014-June 2015. PARTICIPANTS: 1480 adults with a first-time prescription for a cardiovascular medicine. INTERVENTION: Participants in the intervention group received two consultations with a pharmacist 1-2 and 3-5 weeks after filling the prescription. Participants in the control group received care according to usual practice. MAIN OUTCOME MEASURE: The primary outcome was self-reported adherence as measured by the 8-item Morisky Medication Adherence Scale (MMAS-8), at 7 and 18 weeks after filling the prescription. Adherence from baseline to week 52 was estimated using data from the Norwegian Prescription Database (NPD). KEY FINDINGS: Data from MMAS-8 showed that 91.3% of the patients in the intervention group were adherent after 7 weeks versus 86.8% in the control group (4.5% difference, 95% CI 0.8-8.2, P = 0.017). The corresponding proportions were 88.7% versus 83.7% after 18 weeks (5.0% difference, 95% CI 0.8-9.2, P = 0.021). NPD data (n = 1294) showed no significant difference in adherence after 52 weeks (95% CI -2.0 to 7.8, P = 0.24). However, adherence among statin users (n = 182) was 66.5% in the intervention group versus 57.4% among new statin users in the general population (n = 1500) (difference 9.1%, 95% CI 1.5-16.0, P = 0.019). CONCLUSION: The main outcome measure indicates that a short, structured pharmacist-led intervention may increase medication adherence for patients starting on chronic cardiovascular medication. However, these findings could not be confirmed by the NPD data analysis.

Evaluation of a structured pharmacist-led inhalation technique assessment service for patients with asthma and COPD in Norwegian pharmacies.

OBJECTIVE: To investigate whether the inhalation technique improved among patients with asthma and chronic obstructive pulmonary disease after an Inhalation Technique Assessment Service (ITAS), and to assess the patients' and pharmacists' perceptions of ITAS. METHODS: This uncontrolled, pre-post study included 405 patients recruited from 42 Norwegian pharmacies. Inhalation technique was assessed by trained pharmacists before ITAS (baseline), directly after (follow-up 1) and three months after ITAS (follow-up 2), and analyzed statistically using SPSS. Perceptions of ITAS were assessed using a questionnaire. RESULTS: 488 ITAS were performed. At baseline, 8% of the inhalation technique demonstrations were rated as optimal and 31% as acceptable. Following ITAS, this increased to 72% (optimal) and 86% (acceptable). At follow-up 2 inhalation technique remained significantly higher than baseline (optimal: 52%, acceptable: 75%). The median rate of wrong steps decreased from 25% (baseline) to 0% (follow-ups). The usefulness of ITAS was rated 4 on a 5-point Likert scale. CONCLUSION: Inhalation technique improved significantly after ITAS for both new and experienced users and all assessed devices. The technique remained significantly improved at follow-up 2. ITAS was well accepted by pharmacists and patients. PRACTICE IMPLICATIONS: ITAS can contribute to significant improvements in inhalation technique among patients using inhaler devices.

Liposomes as carriers of amphiphilic gadolinium chelates: the effect of membrane composition on incorporation efficacy and in vitro relaxivity.

The effects of membrane composition (phospholipid type and amount of cholesterol), liposome size, drug/lipid ratio (loading) and nature of the amphiphilic gadolinium (Gd) chelate on the incorporation efficacy and magnetic resonance (MR) contrast efficacy (longitudinal (T1) relaxivity) were investigated using a fractional factorial design. A highly lipophilic Gd-chelate was required to ensure complete liposome incorporation. High T1-relaxivity was obtained by using liposomes composed of cholesterol and phospholipids with short acyl chain lengths (dimyristoyl phosphatidyl choline (DMPC) and dimyristoyl phosphatidyl glycerol (DMPG). Two key factors, the loading of Gd-chelate and the amount of cholesterol in small-sized DMPC/DMPG liposomes, were studied further in a central composite optimising design. A robust high relaxivity region was identified, comprising high loading of cholesterol and Gd-chelate. However, the highest T1-relaxivity (52 mM(-1) s(-1)) was found in an area containing no cholesterol and low content of Gd-chelate. Nuclear magnetic resonance dispersion (NMRD) profiles were obtained for five of the liposome compositions from the optimising design, and high relaxivity peaks in the 20 MHz region confirmed the presence of Gd-chelates with a long tau(R). A liposome formulation was selected for surface modification with polyethylene glycol (PEG), without having any effect on the T1-relaxivity.

Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687).

A new series of pyrazinecarboxamide DGAT1 inhibitors was designed to address the need for a candidate drug with good potency, selectivity, and physical and DMPK properties combined with a low predicted dose in man. Rational design and optimization of this series led to the discovery of compound 30 (AZD7687), which met the project objectives for potency, selectivity, in particular over ACAT1, solubility, and preclinical PK profiles. This compound showed the anticipated excellent pharmacokinetic properties in human volunteers.

Preparation and in vitro evaluation of GdDOTA-(BOM)4; a novel angiographic MRI contrast agent.

A novel Gd(III) complex, GdDOTA-(BOM)4, has been prepared by a simple three-step procedure. The complex showed high T1-relaxivity values in serum albumin solutions, blood and plasma, resulting from high affinity for serum albumin. The T1-relaxivity in plasma, 67.4 s-1 mM-1 (20 MHz, 37 degrees C), makes it a promising candidate for angiographic applications of MRI.

Preparation and in vitro evaluation of a novel amphiphilic GdPCTA-[12] derivative; a micellar MRI contrast agent.

A novel amphiphilic GdPCTA-[12] derivative has been prepared. The complex formed micelles in aqueous solution with a relatively low CMC, 0.15 mM (25 degrees C). The concentration dependent T1-relaxivity (r1) of the system has been described. The maximum T1-relaxivity, 29.2 s-1 mM-1 (20 MHz, 25 degrees C), was higher than for previously described micellar MRI contrast agents. This high T1-relaxivity is a consequence of the favourable water residence time (tau M) and the fact that the complex is heptadentate allowing two water molecules to coordinate to the gadolinium ion (q = 2).