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Lege Artis Medicinae

OCTOBER 01, 2000

[Molecular mechanisms of cardiac hypertrophy and heart failure]

MIKALA Gábor, PETŐ Mónika, VÁLYI Nagy István, CSÁSZÁR Albert

[In this review, the most important molecular mechanisms leading to cardiac muscle hypertrophy and consequentially to heart failure are detailed. In numerous instances, understanding molecular mechanisms offers the possibility for pharmacotherapeutic intervention. First, trimeric G-proteins and their attached intracellular signaling pathways are introduced, with special emphasis on the pathways elucidated by transgenic animal models. In this area, there are several clinically effective drugs to influence cardiac hypertrophy, including ACE inhibitors, angiotensin receptor antagonists, as well as a- and B-adrenergic receptor blockers. Mitogen activated protein kinases participate later in the hypertrophic cascade. There are ongoing investigations on the potential therapeutic use of lipid-soluble statins these are indirect inhibitors of Ras-farnesylation. Altered cellular Ca2+-homeostasis is fundamental with respect to cardiac muscle hypertrophy and heart failure. The third part of this article investigates the role of the calcium/calmodulin dependent protein phosphatase called calcineurin in these processes. Administration of cyclosporin A or tacrolimus (both are inhibitors of calcineurin) may not be recommended in most forms of cardiac hypertrophy, however, in certain settings they may prove to be valuable therapeutic agents. One of the most serious, not yet properly addressed problem of late stage heart failure is the development of ventricular arrhythmias caused by repolarization abnormalities. Certain mechanisms of this phenomenon are highlighted with a special note on Nat-Cat exchange inhibitors as one of future therapeutic agents of much promise. ]

Lege Artis Medicinae

NOVEMBER 15, 2019

[Hypertension in the elderly ]

BARNA István

[Elevated isolated systolic pressure is the most common and greatest cardiovascular risk factor with age. The prevalence of hypertension increases with age and ex­ceeds 60% over 70 years. Proper treatment of hypertension in the elderly, even in very old age (> 80 years), increases life expectancy and reduces the risk of cardiovascular events. For patients over 65 years of age, the target blood pressure range is between 130-139 / 70-80 mmHg if the patient tolerates the treatment. In elderly patients with poorer conditions, systolic blood pressure may be <150 mmHg. White-coat hypertension is common, nondipper ratio is increased, autonomic nervous system dysregulation is more common, and orthostatic decrease of blood pressure. The renal function is decreased or already impaired, often resulting in poorer therapeutic cooperation due to impaired cognitive function. The blood pressure lowering effect of targeted lifestyle changes may be the same as medication monotherapy, with the main disadvantage of decreasing adherence over time, for which a proper physician-patient relationship is essential. First-line agents for the treatment of elderly hypertension include angiotensin converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), long-acting calcium channel blockers, and thiazide, thiazide-like diuretics. Beta-blockers should be used in the treatment of elderly hypertension if they have other indications (coronary heart disease, heart failure, arrhythmias). More than 70% of hypertensive patients should use combination therapy to achieve target blood pressure. Take advantage of fixed dose combination to improve compliance to optimize treatment. ]

Lege Artis Medicinae

OCTOBER 01, 2000

[Diabetes mellitus and hypertension - Facts, questions and thoughts]

KERÉNYI Zsuzsa, STELLA Péter, TAMÁS Gyula

[Using the new diagnostic criteria by WHO/ISH, the frequency of hypertension in type 1 diabetic patients is 15-61%, reaching 51-73% in type 2 cases. The combination of diabetes mellitus with hypertension increases the risks of stroke and cardiovascular diseases further compared to non-diabetic hypertensive patients. Authors review new recommendations concerning the diagnosis and treatment goals of hypertension in different types of diabetes mellitus. Most recent studies supporting these recommendations are also critically analysed. Theoretical advantages of new drugs and drug combinations in the therapy of hypertensive diabetics are reviewed. The strategy of treatment according to the cardiovascular riskprofile of diabetic patients is discussed in detail in the report. For the prevention of target-organ damage, the evidence based combination of ACE inhibitors and long-acting calcium channel blockers was strongly recommended. In about 70% of diabetic patients a combination of two drugs, in one-third of the cases a combination of three or four preparations seemed to be necessary, including low-dose diuretics and/or cardioselective beta-blockers. ]

Hypertension and nephrology

APRIL 29, 2021

[When should antihypertensive be taken: in the morning and/or evening? Chronopharmacotherapy of hypertension in practice]

SZAUDER Ipoly

[The circadian (24-hour) variability of blood pressure (BP) is influenced by constant and variable (external and internal) factors. With this in mind and by determining the type of hypertension with a 24-hour blood pressure monitoring (ABPM), individual chronopharmacological (chronopharmacotherapy) treatment can be planned. There are significant differences in the chronokinetics of antihypertensive drugs administered at different times. Their therapeutic range and efficacy depend significantly on their circadian timing. Although the most modern antihypertensives have a 24-hour effect, they are not able to lower blood pressure at all times. Morning intake of ACE inhibitors, ARB-s, alpha-blockers mainly affect the afternoon and early evening rise, while evening intake reduces nocturnal and morning rise. Calcium channel blockers, beta-blockers (except carvedilol and labetolol), do not affect the circadian blood pressure profile. Therefore, in nondipper hypertension or in the case of morning rise, the twice daily morning and evening administration is more effective than the single morning administration. (Usually a lower dose is sufficient in the evening.) Adequate control of nocturnal or morning blood pressure elevations can be achieved with medication taken in the evening. According to the relevant studies the conclusion is that there is no convincing evidence that the administration of BP-lowering drugs in the evening provides any significant advantage in terms of quality of BP control, prevention of target organ damage or reduction of cardiovascular events, so evening intake only is not recommended. In particular the administration of antihypertensive drugs at bedtime, especially in the case of elderly patients may cause excessive BP fall at night with increased risk of silent cerebral infarct and the myocardial ischemia in patients with coronary heart disease.]

Lege Artis Medicinae

APRIL 23, 2021

[Benefits of SGLT-2 inhibitors: beyond glycemic control]

BALOGH Zoltán, SIRA Lívia

[In the recent years, according to international and Hungarian guidelines, in addition to lifestyle modification, metformin is the preferred initial glucose-lowering drug for most people with type 2 diabetes, if not contraindicated. Sodium glucose co­transporter-2 inhibitors have been shown to reduce progression of chronic kidney disease, or kidney failure, as well as the risk of hospitalizations for congestive heart failure and (mainly in secondary prevention) cardiovascular death in patients with type 2 diabetes. For major adverse cardiovascular events and for the renoprotection, there seems to be no class effect. On the other hand, a class effect of sodium glucose co­transporter-2 inhibitors is evident for hospitalization for heart failure. In this review the authors summarize novel data about sodium glucose cotransporter-2 inhibitors, and about their new perspectives in the near future.]

Clinical Neuroscience

MARCH 20, 1996

Clinical perspectives of the new, reversible and selective MAO-A inhibitors

VOLZ H P, GLEITER C H, MÖLLER H J

The classical monoamine oxidase inhibitors are used with great care due to their potency to induce severe side effects caused by tyramine interactions from food. With the advent of reversible and selective inhibitors of monoamine oxidase type A their interaction potential was considerably reduced. The first compounds are brofaromine and moclobemide, the latter already, registered for five years in Europe. The paper reviews the essential pharmacological properties of both compounds and gives a survey of the relevant clinical trials. Their efficacy in major depression is established. Regarding therapy resistant depressions, a certain advantage of brofaromine seems to exist. Promising trials in social phobia and panic attacks have been performed with both drugs.

Lege Artis Medicinae

APRIL 18, 2020

[Interrelations between antidepressants and diabetes]

HARGITTAY Csenge, GONDA Xénia, MÁRKUS Bernadett, VÖRÖS Krisztián, TABÁK Gy. Ádám, KALABAY László, RIHMER Zoltán, TORZSA Péter

[Diabetes and depression are frequent comorbidities. They are a heavy burden by themselves, however, as comorbidities increase additionally the number of diabetes-related complications, morbidity, and mortality. In the background of interrelations, there are both well-known and hypothetical mechanisms. The aim of the present review is to outline these interrelations between antidepressants and diabetes and to discuss the effect of medications on carbohydrate metabolism respectively. Anti­depressant treatment on the one hand may improve mood, cognitive function and medication adherence leading to an improved glucose metabolism, on the other hand through their metabolic side effects, they may worsen carbohydrate metabolism. Concerning metabolic side effects, selec­tive serotonin reuptake inhibitors are the sa­fest, while tricyclic antidepressants and mo­noamine oxidase inhibitors should be administered under close monitoring. Se­rotonin and noradrenaline reuptake inhibitors may deteriorate gly­cae­mic control via increased noradre­nergic activation. Novel antidepressants, how­ever, have a neutral or positive impact on gly­caemic measures. Screening for and temporally adjusted treatment of depres­sion may decrease the risk of comorbidities ge­nerated complications. While caring for diabetic patients with depression, one should consider metabolic side effects of antidepressants and close monitoring of carbohydrate metabolism.]

Clinical Oncology

APRIL 10, 2019

[CDK 4/6 Inhibitors in Breast Cancer: Current Controversies and Future Directions]

SPRING M. Laura, WANDER A. Seth, ZANGARDI Mark, BARDIA Aditya

[Purpose of review: To describe the clinical role of CDK 4/6 inhibitors in hormone receptor-positive (HR+) metastatic breast cancer (HR+MBC) as well as current controversies and evolving areas of research. Recent fi ndings: Palbociclib, ribociclib, and abemaciclib are each approved in combination with an aromatase inhibitor or fulvestrant for HR+MBC. Abemaciclib is also approved as monotherapy for pre-treated patients. Key questions in the fi eld include whether all patients with HR+MBC should receive a CDK 4/6 inhibitor up front versus later line, impact on overall survival, role of continued CDK 4/6 blockade, mechanism of clinical resistance, and treatment sequencing. Summary: The development of CDK 4/6 inhibitors has changed the therapeutic management of HR+MBC. Additional research is needed to determine optimal treatment sequencing, understand mechanisms governing resistance, and develop novel therapeutic strategies to circumvent or overcome clinical resistance and further improve the outcomes of patients with MBC.]

Hypertension and nephrology

SEPTEMBER 12, 2018

[Treatment of hypertension in kidney transplant patients]

KOVÁCS Tibor, WAGNER László

[Most of the renal transplant recipients suffer from hypertension. Hypertension substantially contributes to the high cardiovascular mortality in this population. The recommendation of the Hungarian Society of Hypertension and the international guidelines suggest to achieve less than 130/80 mmHg as target blood pressure in these patients. Several factors may be in the background of hypertension after kidney transplantation, which can be summarized as factors from the recipient-side, the donorside and factors provoked by transplantation itself. In most of the cases early after transplantation high doses of immunosuppressive drugs (especially calcineurin inhibitors and steroids) are responsible for the increased blood pressure. There are some further special methods apart from the general recommendations which are needed during the examination of hypertension of kidney transplant patients: e.g. measurement of blood trough-level of immunosuppressive drugs, investigation of bone-mineral disorder, screening for the level and causes of anaemia, check-up of the renal graft circulation. Kidney transplant patients suffering from hypertension usually need more than two antihypertensive drugs beyond the use of non-pharmaceutical antihypertensive methods. In the early posttransplantation period calcium channel blockers are preferred antihypertensive medications, because they counterbalance the vasoconstrictive effect of calcineurin inhibitors. The administration of renin-angiotensin-aldosterone inhibitors are rather suggested after the stabilization of renal function (from the 1-3 months posttransplantation). When designing antihypertensive strategy, comorbidities and special factors should be regarded as well, especially volume overload, proteinuria, allograft function (GFR), diabetes, other cardiovascular risk factors, previous cardiovascular events. The setup of an individual therapeutical strategy is advised in view of all these factors, which is different according to the timing after transplantation: the perioperative, the early postoperative phases and from 1-3 months after transplantation have special focuses.]

Hypertension and nephrology

FEBRUARY 24, 2021

[Prevalence and treatment of hypertension in patients with newly diagnosed familial hypercholesterolemia]

NÁDRÓ Bíborka, DIÓSZEGI Ágnes, KOVÁCS Beáta, PARAGH György, PÁLL Dénes, HARANGI Mariann

[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.]