Captopril-associated agranulocytosis A .report of 3 cases

Three cases of captopril-associated neutropenia are described, which illustrate the clinical presentation, variable predisposing factors and outcome of this rare but potentially serious adverse event. Particular risk factors of renal failure and collagen vascular disease were present in only 1 patient, while a second patient had reversible mild renal impairment. The doses of captopril used ranged from 25 mg to 50 mg 3 times a day. Two patients recovered after withdrawal of the drug but the third died of septicaemia. Captopril-associated agranulocytosis is reviewed

Malignant hypertension and acute aortic dissection associated with caffeine-based ephedra-free dietary supplements: a case report

The use of weight loss dietary supplements is prevalent in the United States, and over the past decade, there has been tremendous growth of the use of these products. It is well documented that ephedra-based products are associated with various cardiovascular adverse effects. With new restrictions placed on such products, companies are now manufacturing caffeine-based ephedra-free herbal supplements. We present the case of 36-year old, previously healthy female who developed malignant hypertension and aortic dissection while taking various caffeine-based dietary supplements. Given the lack of research studies in regards to their safety and efficacy, judicious care should be taken with the use of dietary supplements, including those designated as ephedra-free

Allergic reaction related to ramipril use: a case report

<p>Abstract</p> <p>Background</p> <p>Angiotensin-converting enzyme (ACE) inhibitors are widely prescribed for patients with diabetes as a nephroprotector drug or to treat hypertension. Generally they are safe for clinical practice, but the relationship between these drugs and angioedema is known. The exact mechanism for ACE inhibitors-induced angioedema is not clear and it is still a matter of discussion.</p> <p>Case Report</p> <p>We reported a case of a 23-year-old black female with an 11 year history of type 1 diabetes, regularly monitored in the department of diabetes, in use of 0,98 UI/kg/day of human insulin, which presented an allergic reaction 24 h after ramipril use. The drug had been prescribed to treat diabetic nephropathy. There was no previous history of drug induced or alimentary allergy. The patient was instructed to discontinue the use of ramipril and oral antihistaminic drug and topical corticosteroid were prescribed. Skin biopsies were performed and confirmed the clinical hypothesis of pharmacodermy. The evaluation of ACE polymorphism identified <it>DD </it>genotype. Six months after the withdrawal of ramipril the patient was prescribed the angiotensin-II receptor blocker (ARB) losartan as nephroprotector. She remained well without adverse reactions.</p> <p>Conclusions</p> <p>ACE inhibitors-induced angioedema is uncommon and the clinical presentation is variable with lips, tongue, oropharinge, and larynge as the most common locations. The presence of angioedema during treatment requires the immediate cessation of treatment due to the risk of possible severe complications. The case reported presented moderate symptoms, with the development of early onset edema in uncommon regions. ACE <it>DD </it>genotype had been associated with angioedema-ACE inhibitors induced. In patients who have experienced ACE inhibitor-related angioedema, ARB should be used cautiously used. However in the case of our patient, the prescription of losartan as nefroprotector did not result in any recurrent adverse effect.</p

Community pharmacists’ knowledge and perspectives of reporting adverse drug reactions in Australia: a cross-sectional survey

Background Under-reporting of adverse drug reactions (ADRs) by healthcare professionals is prevalent worldwide. Community pharmacists are the most frequently visited healthcare professional and are well placed to document ADRs as a part of their routine practice. Objective To measure community pharmacists’ knowledge and perspectives towards ADR reporting and their reporting practices. Setting Community pharmacists in the New South Wales, Queensland, Victoria and Tasmania, Australia. Method A survey tool consisting of 28 items was developed, piloted and validated by a panel of expert reviewers. The final anonymised survey was distributed online to community pharmacists. Exploratory factor analysis and Cronbach’s alpha were used to measure the validity and reliability of the tool, respectively. Non-parametric statistical tests were used to analyse knowledge, perspectives and ADR reporting practices. Main outcome measures: Knowledge, perceived importance, enablers and barriers to reporting ADRs. Results The survey tool showed acceptable validity and reliability. A total of 232 respondents completed the survey. The median knowledge score was 5 out of 10 (interquartile range, 2). Less than a third of respondents (31.0%) reported sufficient knowledge and training on ADR reporting. Only 35.3% of pharmacists reported at least one ADR in the previous 12 months. Non-reporting pharmacists were more likely to report lack of time as a barrier (P < 0.001), conversely they were more likely to report if the practice was remunerated (P = 0.007). Conclusion Under-reporting of ADRs by community pharmacists is highly prevalent. Initiatives to educate and train them on ADR reporting and simplifying the reporting process may improve reporting practices

A High Throughput Screen Identifies Nefopam as Targeting Cell Proliferation in β-Catenin Driven Neoplastic and Reactive Fibroproliferative Disorders

Fibroproliferative disorders include neoplastic and reactive processes (e.g. desmoid tumor and hypertrophic scars). They are characterized by activation of β-catenin signaling, and effective pharmacologic approaches are lacking. Here we undertook a high throughput screen using human desmoid tumor cell cultures to identify agents that would inhibit cell viability in tumor cells but not normal fibroblasts. Agents were then tested in additional cell cultures for an effect on cell proliferation, apoptosis, and β-catenin protein level. Ultimately they were tested in Apc1638N mice, which develop desmoid tumors, as well as in wild type mice subjected to full thickness skin wounds. The screen identified Neofopam, as an agent that inhibited cell numbers to 42% of baseline in cell cultures from β-catenin driven fibroproliferative disorders. Nefopam decreased cell proliferation and β-catenin protein level to 50% of baseline in these same cell cultures. The half maximal effective concentration in-vitro was 0.5 uM and there was a plateau in the effect after 48 hours of treatment. Nefopam caused a 45% decline in tumor number, 33% decline in tumor volume, and a 40% decline in scar size when tested in mice. There was also a 50% decline in β-catenin level in-vivo. Nefopam targets β-catenin protein level in mesenchymal cells in-vitro and in-vivo, and may be an effective therapy for neoplastic and reactive processes driven by β-catenin mediated signaling

Fetal cyclophosphamide exposure induces testicular cancer and reduced spermatogenesis and ovarian follicle numbers in mice

<div><p>Exposure to radiation during fetal development induces testicular germ cell tumors (TGCT) and reduces spermatogenesis in mice. However, whether DNA damaging chemotherapeutic agents elicit these effects in mice remains unclear. Among such agents, cyclophosphamide (CP) is currently used to treat breast cancer in pregnant women, and the effects of fetal exposure to this drug manifested in the offspring must be better understood to offer such patients suitable counseling. The present study was designed to determine whether fetal exposure to CP induces testicular cancer and/or gonadal toxicity in 129 and in 129.MOLF congenic (L1) mice. Exposure to CP on embryonic days 10.5 and 11.5 dramatically increased TGCT incidence to 28% in offspring of 129 mice (control value, 2%) and to 80% in the male offspring of L1 (control value 33%). These increases are similar to those observed in both lines of mice by radiation. <i>In utero</i> exposure to CP also significantly reduced testis weights at 4 weeks of age to ∼70% of control and induced atrophic seminiferous tubules in ∼30% of the testes. When the <i>in utero</i> CP-exposed 129 mice reached adulthood, there were significant reductions in testicular and epididymal sperm counts to 62% and 70%, respectively, of controls. In female offspring, CP caused the loss of 77% of primordial follicles and increased follicle growth activation. The results indicate that i) DNA damage is a common mechanism leading to induction of testicular cancer, ii) increased induction of testis cancer by external agents is proportional to the spontaneous incidence due to inherent genetic susceptibility, and iii) children exposed to radiation or DNA damaging chemotherapeutic agents <i>in utero</i> may have increased risks of developing testis cancer and having reduced spermatogenic potential or diminished reproductive lifespan.</p></div