Current Drug Safety - Volume 2, Issue 1, 2007

At first sight the question: "Is current drug safety an issue?" might appear to be unnecessary. On one hand, it might be argued that drug safety is straightforward: all the physician has to do is to consult his formulary and he will have all the information he requires to use drugs safely. On the other hand, the major clinical, medicolegal and financial aspects of drug safety, together with the ever-increasing store of knowledge and the burgeoning of scientific methods applied to the subject, might be taken to imply that there is no question about the fact that drug safety remains an enormous issue...

Erectile dysfunction occurs extensively among patients with arterial hypertension. We investigated the safety of sildenafil for patients with and without antihypertensive medication. Our study included data from 35 double-blind, placebo- controlled, and randomized investigations, with a total of 8115 patients. The term of therapy was between 6 weeks and 6 months, for both the sildenafil group (5-200 mg, n = 4819) as well as the placebo group (n = 3296). We studied the adverse events in the men who received 1 or more hypertensives (n = 2388), and in those who took no antihypertensive medication (n = 5727). Our findings disclosed equal frequency of adverse events in both groups, without influence by the number of different antihypertensives administered. The occurrence of AEs associated with blood pressure was slight, and was comparable between the individual groups. These results support the conclusion that sildenafil is also well tolerated by patients taking one or more antihypertensives. Patients being treated with alpha blockers should be stable on this therapy in order to minimize the possibility of orthostatic hypotension. An initial dose of 25 mg should furthermore be considered for these patients.

The range of diseases in which intravenous immunoglobulin (IVIG) is effective has expanded significantly since its initial use in primary antibody deficiency. This biological medicine must comply with three conditions: therapeutic efficacy, clinical tolerance and viral safety. Factors relevant to the viral safety of IVIG include: effective use of donor exclusion criteria, screening of donations in order to exclude potentially infectious donations, testing of plasma pools for evidence of viral infection, validated steps for removal and/or inactivation of potentially present infectious agents, equipment cleaning, traceability of lots, and post-marketing follow-up of patients. Variables potentially affecting the risk and intensity of adverse events associated with administration of IVIG include: patient age, underlying condition, dose, concentration, IgA content, stabilizing agent and rate of infusion. Mild adverse reactions (headache, flushing, low backache, nausea) are often associated with a fast infusion rate, and respond rapidly on slowing the infusion. Very rare serious and potentially fatal side effects include: anaphylactic reactions, aseptic meningitis, acute renal failure, and thrombotic complications. Many of these serious adverse reactions have occurred in patients who had significant risk factors or underlying disease states. Clinicians should pay close attention to patient selection and consider the potential risk/benefit ratio versus alternate therapies.

There is nothing new about supervision in primary health care service delivery. Supervision was even conducted by the Egyptian pyramid builders. Those supervising have often favoured ridicule and discipline to push individuals and communities to perform their duties. A traditional form of supervision, based on a top-down colonial model, was originally attempted as a tool to improve health service staff performance. This has recently been replaced by a more liberal "supportive supervision". While it is undoubtedly an improvement on the traditional model, we believe that even this version will not succeed to any great extent until there is a better understanding of the human interactions involved in supervision. Tremendous cultural differences exist over the globe regarding the acceptability of this form of management. While it is clear that health services in many countries have benefited from supervision of one sort or another, it is equally clear that in some countries, supervision is not carried out, or when carried out, is done inadequately. In some countries it may be culturally inappropriate, and may even be impossible to carry out supervision at all. We examine this issue with particular reference to immunization and other primary health care services in developing countries. Supported by field observations in Papua New Guinea, we conclude that supervision and its failure should be understood in a social and cultural context, being a far more complex activity than has so far been acknowledged. Social sciencebased research is needed to enable a third generation of culture-sensitive ideas to be developed that will improve staff performance in the field.

Formal retraction notice of article entitled Prevention of Emetic Episodes During Cesarean Delivery Performed Under Regional Anesthesia in Parturients (Curr Drug Saf. 2007 Jan;2(1):25-32) by Dr Y. Fujii. This article is being retracted as a result of: Failure of Dr. Fijii's institution as well as of himself to rationalize the legitimacy of the study and/or its data as stipulated in request by the Editors-in-Chief of the journals extended on April 9, 2012. Bentham Science Disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript, the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Attention-Deficit and Hyperactivity Disorder (ADHD) is a condition that presents with a variety of behavioral and social problems. The objective of this review was to examine the evidence concerning the controversies surrounding the diagnosis of ADHD and the safety of pharmacological and nonpharmacological treatment. A MEDLINE search was conducted using MeSH terms ADHD, children, treatments or behavioral therapy. The search was limited to January 1990 to present, randomized clinical trials, retrospective studies and English. Fifty-seven articles were selected for review. Controversies exist regarding the diagnosis: variations exist by gender, across countries and by method of diagnosis. These issues are currently unresolved. The interventions with the most data concerning their safety and efficacy in children were stimulant medications. Children with ADHD who took stimulant medications showed the greatest improvement in behavior when compared to other interventions such as behavior therapy or family counseling. Limitations of behavior therapy included that it is often a difficult process to continue on an ongoing basis and only a portion of the therapy stimulated the child's natural reward system. However, a combination of both stimulant medication and behavior therapy demonstrated synergistic efficacy. Care must be taken to insure that issues of gender and race, as well as the adverse effects of treatment options, are adequately taken into account by the treating clinician.

Helicobacter pylori (H. pylori) is a gram negative, spiral, microaerophylic bacterium that infects the stomach of more than 50% of the human population worldwide. H. pylori is well recognized as a critical factor in the majority of patients with peptic ulcer disease and successful treatment results in cure of the disease. On the other hand, H. pylori infection has been associated with several extra-intestinal diseases such as hepatic encephalopathy. In this study, a triple treatment was used in management and eradication of H. pylori infection. We hypothesized that H. pylori infection and/or eradication treatment increased the releasing of 28;“-glutathione S-transferase (28;“-GST). We also investigated whether 28;-GST is a more sensitive marker than aminotransferases (traditional liver function tests) for hepatocellular damage. However, we did not find any association between both H. pylori infection and eradication treatment and 28;“-GST levels. According to our data, eradication treatment did not cause hepatocellular damage.

The musculoskeletal system can be a target organ for adverse drug reactions (ADRs). Drug-induced muscle, bone or connective tissue injuries may be due to, i), primary direct drug action, or, ii), undirected consequence of generalized drug-induced disease. Musculoskeletal ADRs may be only temporarily disabling, such as muscle cramps, as well as in other cases may be serious and life-threatening, such as rhabdomyolysis. In the last few years there has been an increasing awareness of musculoskeletal ADRs. Some recent drug safety issues dealt with serious or uncommon musculoskeletal reactions like rhabdomyolysis associated to statins and tendon rupture associated to fluoroquinolones. In this review, we firstly selected those drug classes having a significantly high percentage of musculoskeletal disorder reports in the WHO adverse drug reaction database, maintained by the Uppsala Monitoring Centre. Secondly, the different musculoskeletal ADRs were closely analyzed through the data obtained from an Italian interregional ADRs spontaneous reporting database. The findings on drugs associated to different musculoskeletal disorders, have been integrated with a review of the epidemiological data available in the literature. For the most involved drugs (HMG-CoA reductase inhibitors, fluoroquinolones, corticosteroids, bisphosphonates, retinoids) the underlying musculoskeletal ADR mechanisms were also reviewed and discussed.

Pharmacovigilance is defined as "the detection, evaluation, understanding and prevention of adverse drug reactions (ADRs)". The ultimate aim of pharmacovigilance is the optimization of the risk-benefit ratio of marketed drugs at the individual level (i.e. the choice of the most suitable treatment for a given patient) and at the population level (i.e. maintenance or removal of a drug from the market, informing prescribers of its potential risks, etc.). Prevalence of drugrelated morbidity and mortality increase in correlation with the increase in drug use. Both physicians and patients prefer polypharmacy because of different reasons such as insufficient knowledge, lack of enough time for the patients, being misled by non-scientific newspaper / TV news, etc. Polypharmacy is among the major causes of drug-related morbidity and requires additional medication as treatment. On the other hand, adverse reactions might be minimized by adequate knowledge and rational prescribing, simply by reducing inappropriate polypharmacy. Therefore, physicians' prescribing habits based on rational pharmacotherapy processes which include choosing suitable drug(s), at an optimum dose and duration of use, among the effective and safe treatment alternatives, and informing patients about the diagnosis and treatment, can be a major contribution to optimize the risk-benefit ratio of drugs. As an essential step in the rational pharmacotherapy process, giving adequate information to the patients about their treatment (i.e. dosage, use instructions, warnings, effects, side effects, etc.) may prevent some of the drug-related problems. In addition, informed patients are more likely to seek advice from their physicians to seek advice for ADRs. In this review article, therefore, the influence of rational pharmacotherapy training on the pharmacovigilance of drugs will be discussed.

Spironolacotone and eplerenone are mineralocorticoid-blocking agents. These compounds block both the epithelial and non-epithelial actions of aldosterone with the latter assuming increasing clinical importance. Spironolactone and eplerenone both effectively reduce blood pressure either as mono- or add-on therapy; moreover, they each offer survival benefits in diverse circumstances of heart failure and the potential for renal protection in proteinuric chronic kidney disease. However, as the use of mineralocorticoid-blocking agents has increased the hazards inherent to use of such drugs has become more apparent. Whereas; the endocrine side-effects of spironolactone are in most cases little more than a cosmetic annoyance the potassium-sparing effects of both spironolactone and eplerenone can prove fatal if sufficient degrees of hyperkalemia develop. However, for most patients the risk of developing hyperkalemia in and of itself should not discourage the sensible clinician from bringing these compounds into play. Hyperkalemia should always be considered as a possibility in any patient receiving one or the other of these medications. As such, steps should be taken to lessen the likelihood of its occurring if therapy is being contemplated with agents in this class.

The serious nature of adverse drug reactions (ADRs) has been highlighted in a number of instances over the last forty years, the most recent of these being the occurrence of serious thrombotic events with the use of COX-2 inhibitors. ADRs are estimated to be between the 4th and 6th leading cause of death in the USA, with fatal ADRs occurring in 0.32% of patients. A recent UK study showed that 6.5% of hospital admissions were related to ADRs. ADRs can therefore be regarded as a significant public health and economic problem. There is an urgent need to develop better preventive strategies to reduce the burden of ADRs. Because ADRs can affect any bodily system, can have many different clinical presentations, and are of widely variable severity, prevention will not be easy and will have to be multifactorial in its approach. This paper reviews the epidemiology of ADRs in hospitals and evaluates the research that has been undertaken to date to prevent ADRs.