[The effect of angiotensin receptor antagonists in diabetic nephropathy]
BÍBOK György
SEPTEMBER 20, 2002
Lege Artis Medicinae - 2002;12(09)
BÍBOK György
SEPTEMBER 20, 2002
Lege Artis Medicinae - 2002;12(09)
[Influencing the renin-angiotensin system through receptor blockade has become a new therapeutic approach toward the treatment of several morbidities, i.e. hypertension, cardiac failure and diabetic nephropathy. The current paper reviews the importance of diabetic nephropathy, the physiology of the renin-angiotensin system and specific effects of receptor blockade on different organs based on 3 new studies (published last year) using angiotensin-II receptor blockers. The paper gives a summary of the IRMA, IDNT and RENAAL studies, including their clinical and therapeutic significance in general practice as well as in specialized diabetes care. The new therapeutic approach (with an excellent safety profile, and infrequent side effects) could delay the progression or might even prevent the manifestation of diabetic nephropathy not only with lowering blood pressure but with its direct effects on target tissues as well. The angiotensin-II receptor blocking agents might be useful for the treatment of cardiac failure in hypertensive patients.]
Lege Artis Medicinae
[Alcoholic and drug induced liver diseases, nonalcoholic steatohepatitis, hepatitis C and B chronic hepatitis, autoimmune diseases (primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis) and metabolic disorders (hemochromatosis, Wilson's disease) are the main chronic liver diseases. Authors summarize, based on the latest literature data, the medications of chronic liver diseases, emphasizing the treatment of the everyday practice. Natural and synthetic antioxidants are approved for the treatment of chronic alcoholic liver diseases besides abstinence, with diet of adequate quality and quantity. Nucleoside analogues (lamivudin) are recommended for the first-line therapy of the treatment of chronic hepatitis B. Interferon is presently considered the optimal treatment for only certain patients. Interferon and ribavirin combined therapy is well-established in the treatment of chronic hepatitis C. Ursodeoxycholic acid is the beneficial treatment option for primary biliary cirrhosis and primary sclerosing cholangitis. Prednisolon and azathioprine constitute the basic therapy of autoimmune hepatitis. Presumably, in the future, new strategies based on immunosuppressive combinations will play a crucial role. The chelating deferoxamine has less important part in the treatment of hemochromatosis. D-penicillamine still plays principle role in the medication of Wilson's disease.]
Lege Artis Medicinae
[Reference pricing is one of the potential cost containment methods for pharmaceuticals. Authors describe its main types and the international examples of reference pricing together with technical details of its introduction. Consequences of the system are grouped into 5 categories: pharmaceutical expenditure, other health care expenditure, medical implications, consequences on patients and their health status, and political effects. They propose that reference pricing should be introduced only gradually based upon recommendations by multiprofessional teams. The system should be evidence based which includes clinical effectiveness, safety, compliance and cost-effectiveness. ”Real” active substance based reference pricing is justifiable for broad ranges of pharmaceuticals. General introduction of therapeutic reference pricing in Hungary, however, may result in serious negative consequences.]
Lege Artis Medicinae
[During the past decade numerous publications have reported the pathophysiological and clinical value of QT dispersion. Increased QT dispersion was observed to be associated with proarrhythmic drug effects, prediction of mortality in heart failure and risk assessment after acute myocardial infarction. Based on the results of the repolarization process research and other significant clinical studies, the meaning and the usefulness of QT dispersion seems to be challenged. The original concept of portraying QT dispersion as a direct measure of regional heterogeneity of myocardial refractoriness is seriously flawed. At the same time, disproving this concept is not a good reason for stating that QT dispersion does not exist. The measurement of QT dispersion seems to be an approximate expression of repolarization abnormalities and should not be taken as a gold standard for a noninvasive estimate of repolarization abnormalities. However, we presently have no decent and widely available alternative to address repolarization abnormalities in standard 12-lead ECG. The authors present the pathophysiological meaning of QT dispersion, the controversies of automatic and manual methodology and the possible clinical relevances based on the most recent studies.]
Lege Artis Medicinae
Lege Artis Medicinae
[1600 mg/d oral clodronate has been shown to reduce the incidence of skeletal complications significantly in advanced breast cancer cases with lytic bone metastases. Analysis of clinical trials revealed that the adjuvant, prophylactic administration of clodronate possibly decreases the number of non-skeletal metastases and might prolong survival.]
Lege Artis Medicinae
[The authors review the pathomechanism of severe COVID-19 leading to systemic uncontrollable inflammation, thrombotic events and other complications. The review includes the extremely complex interactions between the infecting coronavirus and the in loco cellular-tissue contact system, the kinin-kallikrein and the renin-angiotensin systems. Authors critically evaluate some potential therapeutic interventions aiming at the mitigation of the dominant bradykinin-cytokine storm in the background of severe COVID-19 by inhibiting bradykinin formation, facilitating its degradation, or blocking either the B2 receptor or the bradykinin induced cytokine response.]
Hypertension and nephrology
[For the first time, we demonstrated the fenestration in the endothelium of the distal portion of renal afferent arteriole (AA), which is unusual among high pressure vessels. The fenestrae are co-localized with renin producing granular epithelioid cells; this arrangement makes it likely that the relatively large renin molecules may use this path to enter into the plasma. We also demonstrated that the length and area of this fenestrated segment 1) correlates with the activity of the renin-angiotensin system (RAS), 2) may change by age, in response to some stimuli such as thirst and in some diseases, 3) allows filtration of fluid prior to the glomerular filtration, which can be as high as about 30% of GFR. This morphology and the high filtration volume in AA is one of the most striking observations of renal microcirculation, and question several basic renal physiological issues.]
Hypertension and nephrology
[Angiotensin II (Ang II) by activating angiotensin type 1 receptors (AT1R) is one of the most potent vasoconstrictors in the regulation of vasomotor tone and thus systemic blood pressure. In this study, we hypothesized that aging alters Ang II - induced vasomotor responses and expression of vascular mRNA and protein angiotensin type 1 receptor (AT1R). Thus, carotid arteries were isolated from newborn, young, middle age, old and senescent rats and their vasomotor responses were measured in a myograph (DMT-600) to repeated administrations of Ang II. Vascular relative AT1R mRNA level was determined by qRT-PCR and the AT1R protein density was measured by Western blot. Contractions of vessels to the first administration of Ang II increased from newborn to young and middle age rats then they decreased to senescent rats. In general, second administration of Ang II elicited reduced contractions, but they also first increased and then they decreased to old age. Similarly, the AT1R mRNA level and the AT1R protein density increased from newborn to young and middle age rats then they decreased to senescent rats. The pattern of these changes correlated with functional vasomotor data. We conclude that aging (newborn to senescence) has substantial effects on Ang II-induced vasomotor responses and AT1R signaling suggesting that it is - and thus regulation of systemic blood pressure is - determined primarily by genetic programs.]
Lege Artis Medicinae
[Dyslipidaemia is one of the known main risk factors of atherosclerosis by causing endothelial dysfunction that initiates and promotes vascular remodelling. Recent data from experimental and clinical studies suggest the existence of lipoprotein- neurohormonal interactions that may adversely affect vascular structure and function. Elevated lipid levels enhance the activation of the renin-angiotensin system, and, on the other hand, activation of the renin-angiotensin system leads to increased LDL cholesterol biosynthesis and oxidized-LDL uptake. These findings may explain the synergistic effect on cardiovascular risk observed in patients with coexisting hypertension and dyslipidaemia. The combined use of cholesterol-lowering drugs and inhibition of the tissue renin-angiotensin system may be more efficient in reducing cardiovascular risk.]
Lege Artis Medicinae
[The role of the renin-angiotensin system in the regulation of blood pressure is outlined. The mechanism of action as well as the role of angiotensin converting enzyme inhibitors (ACEI) in the treatment of various forms (primary, secondary, uncomplicated, complicated) of hypertension is discussed. The individualized , stepped care" approach is detailed, therefore the advantages of the therapeutic combinations of ACEi-s are emphasized. Interactions with other antihypertensive agents and with other drugs are also described, and side effects are also briefly addressed]
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