Changes of electrocardiogram and hemodynamics in response to dipyridamole: In vivo comparative analyses using anesthetized beagle dogs and microminipigs

Microminipigs are expected as a novel animal model for cardiovascular pharmacological experiments. Since inherent vulnerability of coronary circulation of microminipigs has not been characterized, we performed dipyridamole-stress test to both microminipigs and beagle dogs, and compared the results. Dipyridamole in doses of 0.056 and 0.56 mg/kg were intravenously infused over 10 min (n = 4 for each animal). Dipyridamole decreased the systolic/diastolic blood pressures and double product in dogs as well as in microminipigs; but it did not significantly alter the heart rate or the global balance between the myocardial oxygen demand and supply in either animal. While organic coronary arterial stenosis was not detected in either animal, dogs have well-developed epicardial intracoronary networks unlike microminipigs. Like in humans, dipyridamole did not affect the ST segment of microminipigs, whereas it substantially depressed that in dogs. The results indicate the onset of subendocardial ischemia by dipyridamole in dogs may be partly associated with their well-developed native coronary collateral channels. Microminipigs would be more useful to evaluate the drugs which may affect the coronary circulation in the pre-clinical study than dogs.     

Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.     

The development of biological therapies for neurological diseases: moving on from previous failures

Introduction: Although years of research have expanded the use of biologics for several clinical conditions, such development has not yet occurred in the treatment of neurological diseases. With the advancement of biologic technologies, there is promise for these therapeutics as novel therapeutic approaches for neurological diseases.

Areas covered: In this article, the authors review the therapeutic potential of different types of biologics for the treatment of neurological diseases. Preclinical and clinical studies that investigate the efficacy and safety of biologics in the treatment of neurological diseases, namely Alzheimer’s disease, amyotrophic lateral sclerosis, Parkinson disease, multiple sclerosis, and stroke, were reviewed. Moreover, the authors describe the key challenges in the development of therapeutically safe and effective biologics for the treatment of neurological diseases.

Expert opinion: Several biologics have shown promise in the treatment of neurological diseases. However, the complexity of the CNS, as well as a limited understanding of disease progression, and restricted access of biologics to the CNS has limited successful development. Therefore, more research needs to be conducted to overcome these hurdles before developing effective and safe biologics for neurological diseases. The emergence of new technologies for the design, production and delivery of biologics will accelerate translating biologics to the clinic.     

Comparison of Local-Only Anesthesia Versus Sedation in Patients Undergoing Staged Bilateral Carpal Tunnel Release: A Randomized Trial

Purpose: Carpal tunnel syndrome is a common disease treated operatively. During the operation, the patient may be wide-awake or sedated. The current literature has only compared separate cohorts. We sought to compare patient experience with both local-only anesthesia and sedation. Methods: Staged bilateral carpal tunnel release utilizing open or endoscopic technique was scheduled and followed through to completion of per-protocol analysis in 31 patients. Patients chose initial hand laterality and were randomized regarding initial anesthesia method: local-only or sedation. Data collection via questionnaires began at consent and continued to 6 weeks postoperatively from second procedure. Primary outcome measures included patient satisfaction and patient anesthesia preference. Results: At final follow-up, 6 weeks postoperatively, high satisfaction (30 of 31 patients per method) was reported with both types of anesthesia. Among these patients, 17 (54%) preferred local-only anesthesia, 10 (34%) preferred sedation, 2 had no preference, and 2 opted out of response. Although anesthesia fees were approximately $390 lower with local-only anesthesia, total costs for carpal tunnel release were not significantly different with respect to the anesthesia cohorts. Total time in surgical facility was approximately 26 minutes quicker with local-only anesthesia, largely due to shorter time in the post-anesthesia care unit. Scaled comparison of worst postoperative pain following the 2 procedures revealed no difference between local-only anesthesia and sedation. Conclusions: Patients reported equal satisfaction scores with carpal tunnel release whether performed under local-only anesthesia or with sedation. In addition, local-only anesthesia was indicated as the preference of patients in 59% of cases.     

Cardiac metastasis of great saphenous vein leiomyosarcoma

We present a case with cardiac metastasis of the great saphenous vein leiomyosarcoma (LMS) that presented to the emergency department with dyspnea and palpitations 2 months ago. In this patient, hemodynamic instability was caused by an extensive right ventricular cavity and outflow tract invasion of the LMS. Treatment of the patient included incomplete mass resection, adjuvant chemotherapy, and permanent pacemaker implantation (due to postoperative complete atrio-ventricular block).     

Community pharmacists’ knowledge,behaviors and experiences about adverse drug reaction reporting in Saudi Arabia

Objective

To assess community pharmacists’ knowledge, behaviors and experiences relating to Adverse Drug Reaction (ADR) reporting in Saudi Arabia.

Methods

A cross-sectional study was conducted using a validated self-administered questionnaire. A convenience sample of 147 community pharmacists working in community pharmacies in Riyadh, Saudi Arabia.

Results

The questionnaire was distributed to 147 pharmacists, of whom 104 responded to the survey, a 70.7% response rate. The mean age of participants was 29 years. The majority (n = 101, 98.1%) had graduated with a bachelorette degree and worked in chain pharmacies (n = 68, 66.7%). Only 23 (22.1%) said they were familiar with the ADR reporting process, and only 21 (20.2%) knew that pharmacists can submit ADR reports online. The majority of the participants (n = 90, 86.5%) had never reported ADRs. Reasons for not reporting ADRs most importantly included lack of awareness about the method of reporting (n = 22, 45.9%), misconception that reporting ADRs is the duty of physician and hospital pharmacist (n = 8, 16.6%) and ADRs in community pharmacies are simple and should not be reported (n = 8, 16.6%). The most common approach perceived by community pharmacists for managing patients suffering from ADRs was to refer him/her to a physician (n = 80, 76.9%).

Conclusion

The majority of community pharmacists in Riyadh have poor knowledge of the ADR reporting process. Pharmacovigilance authorities should take necessary steps to urgently design interventional programs in order to increase the knowledge and awareness of pharmacists regarding the ADR reporting process.     

Annatto Tocotrienol Improves Indices of Bone Static Histomorphometry in Osteoporosis Due to Testosterone Deficiency in Rats

This study aimed to evaluate the effects of annatto tocotrienol on indices of bone static histomorphometry in orchidectomized rats. Forty male rats were randomized into baseline (BL), sham (SH), orchidectomized (ORX), annatto tocotrienol-treated (AnTT) and testosterone enanthate-treated (TE) groups. The BL group was sacrificed upon receipt. All rats except the SH group underwent bilateral orchidectomy. Annatto tocotrienol at 60 mg/kg body weight was administered orally daily to the AnTT group for eight weeks. Testosterone enanthate at 7 mg/kg body weight was administered intramuscularly once weekly for eight weeks to the TE group. The rat femurs were collected for static histomorphometric analysis upon necropsy. The results indicated that the ORX group had significantly higher osteoclast surface and eroded surface, and significantly lower osteoblast surface, osteoid surface and osteoid volume compared to the SH group (p < 0.05). Annatto tocotrienol and testosterone enanthate intervention prevented all these changes (p < 0.05). The efficacy of annatto tocotrienol was on par with testosterone enanthate. In conclusion, annatto tocotrienol at 60 mg/kg can prevent the imbalance in bone remodeling caused by increased osteoclast and bone resorption, and decreased osteoblast and bone formation. This serves as a basis for the application of annatto tocotrienol in hypogonadal men as an antiosteoporotic agent.     

A systematic review of hospitalization resulting from medicine-related problems in adult patients

Aims

Medicine-related problems (MRPs) represent a major issue leading to hospitalization, especially in adult and elderly patients. The aims of this review are to investigate the prevalence, causes and major risk factors for MRPs leading to hospitalization in adult patients and to identify the main medicine classes involved.

Methods

Studies were identified through electronic searches of Medline, Embase, Scopus and International Pharmaceutical Abstracts between January 2000 and May 2013. A systematic review was conducted of both retrospective and prospective studies. Studies included were those involving hospitalization resulting from MRPs in adults (≥18 years old), whereas studies excluded were those investigating drug misuse and abuse and studies investigating MRPs in hospitalized patients. Data analysis was performed using SPSS version 20.

Results

Forty-five studies were identified, including 21 that investigated hospitalization resulting from adverse drug reactions, six studies that investigated hospitalization due to adverse drug events and 18 studies that investigated hospitalization due to MRPs. The median prevalence rates of hospitalization resulting from adverse drug reactions, adverse drug events and MRPs were 7% (interquartile range, 2.4–14.9%), 4.6% (interquartile range, 2.85–16.6%) and 12.1% (interquartile range, 6.43–22.2%), respectively. The major causes contributing to MRPs were adverse drug reactions and noncompliance. In addition, the major risk factors associated with MRPs were old age, polypharmacy and comorbidities. Moreover, the main classes of medicines implicated were medicines used to treat cardiovascular diseases and diabetes.

Conclusions

Hospitalization due to MRPs had a high prevalence, in the range of 4.6–12.1%. Most MRPs encountered were prevalent among adult patients taking medicines for cardiovascular diseases and diabetes.