Lege Artis Medicinae

[Cardiovascular risk of non-steroidal antiinflammatory drugs]

FARSANG Csaba

APRIL 22, 2011

Lege Artis Medicinae - 2011;21(04)

[During the past decade, a number of original publications, reviews and metaanalyses were published on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). As this group of medicines is among the most frequently used ones and many preparations are available over the counter, it seems to be prudent to summarise the most important results on the safety of these drugs, and underline their potentially harmful cardiovascular side effects. Nevertheless, it can also be emphasized that there are substantial differences between different compounds, and the cardiovascular risk does not depend on the ratio of COX-1/COX-2 selectivity. Cardiovascular risk can be increased by all NSAIDs with the possible exception of naproxen.]

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[Among locally administered anti-inflammatory drugs used in dermatology, steroids are among the most commonly applied ones. In everyday practice, choosing the right local steroid preparation is not easy, since more than 50 different local steroid preparations with at least 30 different active ingredients are available. The choice of the local steroid preparation depends on a number of aspescts. It is recommended to apply local steroid preparations that, besides having a strong effect, also have favourable side effect profiles. Moreover, it is subservient to apply local steroids that penetrate deeply into the skin, but have minimal systemic absorption, therefore do not inhibit significantly the hypothalamicpituitary- adrenal axis if administered locally. These characteristics of local steroid preparations are determined by chemical modifications at various positions on the steroid-frame. In this study, we examined the different types of chemical modifications, and the relationship between halogen addition and the characteristics of steroid preparations. We compared the local steroid preparations using the data of previous clinical trials. Regarding the efficacy, safety, tolerability and the risk/benefit ratio, the halogenated steroid preparations were overall superior to nonhalogeneted ones. Among the halogenated preparations, the fluticasone propionate, the mometasone furoate and clobetasol propionate were proved to be the most suitable locally administered, very potent or super potent ones.]

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[IgG4-related disease]

ZEHER Margit

[IgG-4-related disease is a clinical entity characterised by significant elevation in serum IgG-4 levels, infiltration of IgG-4+ plasma cells into the involved tissues, enhanced fibrosis, and good therapeutic response to corticosteroids. The IgG-4 associated disease mostly affects two organs. The salivary and lacrimal gland enlargement and inflammation is known as Mikulicz’s disease, which had been previously known as a subtype of Sjögren’s syndrome for a long time. The other commonly involved organ is the pancreas, in which a special form of chronic pancreatitis, namely autoimmune pancreatitis develops. IgG-4 associated disease as a separate disease has been suggested by Japanese authors. Previously published data support the common pathogenesis of autoimmune pancreatitis and Mikulicz’s disease. Besides these two manifestations, similar histological lesions and elevated IgG-4 levels have been demonstrated in many other organs. At present, it is not clearly demonstrated whether IgG-4 syndrome is an autoimmune disorder, and we do not know the exact reason of the elevated IgG-4 levels in patients with this syndrome. IgG-4 is a regulatory immunoglobulin, the main function of which is to decelerate immune responses, thus its pathologic role in tissue destruction is difficult to explain. It is not clear either, whether IgG-4 syndrome is indeed a single disease, or only an example of overlapping symptoms of various diseases. On the basis of the characteristic histological lesions in various organs, IgG-4 syndrome is similar to multi-organ diseases, such as sarcoidosis or vasculitis.]

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[Diagnosis and therapy of cerebrovascular diseases - Retrospection to the efforts for managing patients with stroke in the last two decades in Hungary]

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[The first Hungarian guideline regarding management of stroke patients has been published in 1990 (LAM). In the past 21 years, clinical practice in stroke care has improved significantly in Hungary and is currently performed according to evidencebased protocols issued by international and national consensus meetings. Currently the EUSI guideline published in 2008 and the management protocol written in the same year by the board of the Hungarian Stroke Society are followed. The most important changes of the past 20 years in stroke management have been the following: the priority concept and lysis therapy have become common in daily practice, emergency examination has been performed in selected TIA cases and an up-to-date practice has been established in stroke prevention. The increasing number of lysis therapy each year demonstrates an improving organisation of stroke care and improving professional preparedness. In selected stroke centres, all the modern technical facilities are available, on the other hand, substantial development is needed in a number of stroke units. A national stroke registry and quality control are warranted for further professional development in Hungary.]

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[Nonsteroidal antiinflammatory drugs (NSAIDs) are among the most frequently used pharmaceuticals. Nevertheless, a number of studies emphasized that NSAIDs were damaging not only the gastrointestinal (GI), but also the cardiovascular (CV) system, could increase the blood pressure, the frequency of coronary events (angina, myocardial infarction) and stroke incidence, as well as they might deterio­rate renal functions. The National Institute for Health and Care Excellence (NICE) did not find evidence that administering NSAIDs could increase the risk of developing COVID-19 or worsened the condition of COVID-19 patients. However, unwanted effects of specific drugs differ substantially in their occurrence and seriousness as well. It seemed to be for a long time that the NSAIDs provoked higher GI-risk was closely related to the COX1/COX2 selectivity, like the cardiovascular (CV) risk to the COX2/COX1 selectivity, however, the recent data did not prove it clearly. Based on the available literature while pondering the gastrointestinal and cardiovascular adverse events, among all NSAIDs the aceclofenac profile seemed to be the most favourable.]

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[Familial hypercholesterolemia (FH) is an inherited defect of cholesterol metabolism characterized by high plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels and premature cardiovascular disease risk. Prevalence of hypertension in FH is not clarified, but its appearance is independent risk factor for the development of cardiovascular disease. Therefore, optimal treatment has a major priority in this high-risk population. We aimed to investigate the lipid parameters and evaluate the presence of hypertension and its treatment characteristics in 86 newly diagnosed, untreated heterozygous FH patients (27 males, 59 females, mean age 53.6±13.4 years). We diagnosed FH by using the Dutch Lipid Clinic Network criteria. The mean TC level was 8.49±1.7 mmol/l, the mean LDL-C level was 6.11±1.5 mmol/l, the mean high-density lipoprotein cholesterol (HDL-C) level was 1.62±0.5 mmol/l, while the median lipoprotein (a) level was 301 mg/l. We diagnosed 33 FH patients (38.4%) with hypertension. Beta blockers were used in 23, ACE-inhibitors in 13, ARBs in 12, calcium channel blockers in 9, and HCT in 11 cases. 11 patients was treated with monotherapy, for 10 patients double, for 11 patients triple, while for 1 patient quadruple combined antihypertensive therapy was administered. Based on our results, hypertension might be underdiagnosed in this specific patient population. Neither the types nor the combination patterns of blood pressure lowering agents are in line with current guidelines. Up to date screening and treatment of hypertension should be worth considering in this extremely high risk population with enhanced atherosclerosis.]

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[The reason of the unfavourable life expectancy of patients with chronic kidney disease (CKD) is not only the development of end-stage renal failure but the frequent appearance of cardiovascular diseases (CVD). Chronic kidney damage itself is a cardiovascular risk state and the occurrence of CVD/associated diseases is significantly higher in chronic kidney failure. Beside risk stratification and valid treatment of CVD (hypertension, diabetes mellitus, ischemic heart disease e.g.) we and the international nephrological community have left the cerebrovascular diseases of CKD patients out of consideration. However, up to 50% of patients suffering a stroke will die immediately, only 10% of stroke survivors can continue his/her profession, but the others will be permanently disabled. High blood pressure is a strong predictor of stroke and of other CVD in most of the patients. In stroke risk reduction it is particularly important to reach the target blood pressure values. The main object of the “Live under 140/90 mmHg” programme of the Hungarian Society of Hypertension is to familiarize with target blood pressure itself and how to reach target blood pressure. In 2010, prevention, early diagnosis and management of stroke are the most important challenges of this programme (The Brain Control Programme). We think it is advisable to prepare and publish a clinical practice guideline in collaboration with stroke societies which is similar to the guidelines of international societies and of the Hungarian Society of Stroke but specific for CKD patients. This guideline would help to give a uniform, up-to-date treatment for the cerebrovascular diseases of CKD patients.]