Rezistentna arterijska hipertenzija Prkačin, Ingrid
Medicus (Zagreb, Croatia : 1992),
11/2016, Letnik:
25, Številka:
2 Kardiologija danas
Journal Article
Recenzirano
Odprti dostop
Prevalencija rezistentne hipertenzije (RH) iznosi između 10 – 30%, a povezana je s većim rizikom od oštećenja bubrega i kardiovaskularnog sustava. Patofiziologija RH povezana je s povišenom razinom ...aldosterona zbog čega važnu ulogu u terapiji imaju antagonisti mineralokortikoidnih receptora (MRA). Denervacija bubrežnih arterija (DBA) radiofrekvencijom jedna je od obećavajućih novih metoda liječenja rezistentne hipertenzije (RH), refraktorne na optimalno liječenje kombiniranom antihipertenzivnom terapijom koja uključuje 3 i više lijekova iz različitih antihipertenzivnih skupina, a od kojih jedan mora biti diuretik. Potrebno je prethodno isključiti sekundarne uzroke, neadekvatno mjerenje tlaka te nesuradljivost bolesnika.
Ascites happens in 50% of patients with liver cirrhosis, Some of them experienced permagna ascites (large ascites). Based on the European Association for the Study of the Liver (EASL) guidelines in ...2010, therapy of permagna ascites (large ascites) is paracentesis followed by restriction of sodium intake and diuretics. The use of diuretics can cause side effects such as hyperkalemia and hypokalemia. The aims of this study is to determine the effectiveness and safety of the combination of spironolactone and furosemide in patients with liver cirrhosis with permagna ascites.This study was an analytical observational study with retrospective cohort design. This study was done through a search of cirrhotic patients with permagna ascites’ medical record during January 2010-December 2014. This study was conducted at RSUP Dr. Sardjito. A total of 19 subjects categorized in the tense group and 39 subjects were in non-tense group. The effectiveness of diuretics seen by decreasing 1 cm/day of the patient's abdominal girth daily and the achievement of minimum of fluid balance -500 ml/day. Effectiveness data was analyzed by using independent t-test statistic. Side effects data was analyzed descriptively. There are no significantly different in reduction of abdominal girth and achieving fluid balance between cirrhotic patients with tense and non-tense ascites (p> 0.05); Adverse events of diuretics occurs in 5 patients, consist of hypokalemia 2 patients (3.45%), hyperkalemia 2 patients (3.45%) and hyponatraemia 1 patient (1.72%).
İlaça bağlı trombositopenide nadir olmasına rağmen, kanama gibi ölümcül sonuçlara neden olabileceği için önemlidir. Karaciğer sirozu olan hastalarda asite yönelik diüretik tedavisinde, çoğu zaman ...sprinolakton kullanılmaktadır. Tiazid grubu diüretiklerde trombositopeni rapor edilmiştir. Ancak Spironalaktona bağlı trombositopeni oldukça nadir görülmektedir. Karaciğer siroz tanısı konulan asitli hastamızda sprinolakton tedavisi başladıktan yaklaşık iki hafta sonra şiddetli trombositopeni gelişmesi üzerine sunduk.
Abstract Although it is rare, drug-induced thrombocytopenia is important since it may cause fatal results like bleeding. Mostly spironolactone is used for ascites palliation in the cirrhotic patients. Thrombocytopenia has been reported with thiazide group of diuretics. But thrombocytopenia caused by spironolactone is rarely seen. We presented our patient with ascites diagnosed as liver cirrhosis that developed severe thrombocytopenia after receiving two weeks of spironolactone treatment. Keyword: Liver cirrhosis, spironolactone, thrombocytopenia Özet İlaça bağlı trombositopenide nadir olmasına rağmen, kanama gibi ölümcül sonuçlara neden olabileceği için önemlidir. Karaciğer sirozu olan hastalarda asite yönelik diüretik tedavisinde, çoğu zaman sprinolakton kullanılmaktadır. Tiazid grubu diüretiklerde trombositopeni rapor edilmiştir. Ancak Spironalaktona bağlı trombositopeni oldukça nadir görülmektedir. Karaciğer siroz tanısı konulan asitli hastamızda sprinolakton tedavisi başladıktan yaklaşık iki hafta sonra şiddetli trombositopeni gelişmesi üzerine sunduk. Anahtar sözcükler: Karaciğer sirozu, spironolakton, trombositopeni
Stroke is one of the most frequent causes of death and disability worldwide, and has significant clinical and socioeconomic impact. Recombinant tissue plasminogen activator (rtPA) is currently the ...only drug approved for treatment of acute stroke. However, thrombolytic therapy with rtPA can be associated with a number of complications. Many of the rtPA related complications result from its thrombolytic action including bleeding (intracerebral and systemic haemorrhage), reperfusion injury with oedema, and angioedema. Beside all this complications is profound tissue inflammatory response following recanalization of occluded vessel. In our study, the administration of a low dose Spironolactone showed strong anti-inflammatory effects at the brain endothelial cells and whole brain tissue, blocking cytokine, chemokine, reactive oxygen species and adhesion molecule expression, after experimental model of stroke in in vivo and in vitro experiments. Animals treated with low dose Spironolactone during the onset of reperfusion exhibit less brain edema, smaller infarct volume and mortality rate, better neurological scores and better stroke recovery. This effect of Spironolactone was achieved by diminishing the activity of NF B transcription factor in brain endothelial cells, a master regulator of pro-inflammatory cytokine/chemokine/adhesion molecule expression during the ischemia-reperfusion injury. Anti-inflammatory effect of low dose- Spironolactone treatment on ischemia-reperfusion injury after stroke based on its effects in this study represents for the first time a potential of Mineralocorticoid receptor antagonist Spironolactone in prevention and stroke therapy.
Ishemični moždani udar predstavlja drugi uzrok smrtnosti i prvi uzrok trajnog invaliditeta u razvijenim zemljama. Visoka cena lečenja i rehabilitacije ovih pacijenata svrstava moždani udar u jedan od najvećih socioekonomskih problema današnjeg društva. Glavni nedostaci primene trombolitičke terapije, kao jedine odobrene terapije moždanog udara, su kratak prozor delovanja, reperfuziono oštećenje i hemoragija. U osnovi svih komplikacija trombolitičke terapije nalazi se jak inflamatorni odgovor tkiva nastao naglom rekanalizacijom krvnog suda. Upotreba malih doza spironolaktona nakon reperfuzije kod eksperimentalnog mišjeg modela ishemičnog moždanog udara pokazala je značajno smanjenje ekspresije inflamatornih medijatora (citokina, hemokina, slobodnih radikala i adhezionih molekula) endotelnih ćelija i celog tkiva mozga kao rezultat stabilizacije NF-κB-IκBα kompleksa i onemogućavanje relokalizacije transkripcionog faktora NF-κB u jedro što ima za posledicu smanjenje inflamacije, infarkta i edema mozga, blažih neuroloških oštećenja, brži oporavak i smanjenje smrtnosti. Rezultati ove studije otkrivaju do sada nepoznatu ulogu spironolaktona u modulisanju inflamatornog odgovora endotelnih ćelija mozga, kao i molekularni mehanizam ovog dejstva na ishemično reperfuziono oštećenje nakon eksperimentalnog mišjeg modela moždanog udara otvarajući mogućnost korišćenja ovog dobro poznatog leka u terapiji moždanog udara i drugih inflamatornih stanja endotela koja favorizuju nastanak moždanog udara.
Arteriální hypertenze a diabetes mellitus (DM) jsou dvě velmi časté klinické situace. Prevalence hypertenze je u osob s diabetes mellitus 2. typu 70–80 %. Cílový krevní tlak je asi 130/80 mm Hg. ...Základem farmakologické léčby hypertenze u diabetu jsou blokátory systému renin- angiotenzin (ACE inhibitory, AT1 blokátory), které snižují kardiovaskulární (KV) riziko a zpomalují progresi renálního poškození. Ve většině případů (asi 80–90 %) je však nutné u diabetiků s hypertenzí podávat kombinační terapii. Výhodná je dvojkombinace blokátorů RAS s blokátory kalciových kanálů (BKK). Diuretika jsou vhodná do trojkombinace. U těžších forem hypertenze se osvědčuje malá dávka spironolaktonu. Farmakologická léčba by měla být komplexní a měla by zahrnovat kromě hypertenze i intervenci všech dalších rizikových faktorů (RF) včetně redukce BMI u obezity. Zdá se, že TK mohou snižovat i některá nová antidiabetika (zejména glifloziny).
Hypertension and diabetes mellitus (DM) are common diseases. Prevalence of hypertension in DM type II is 70–80 %. Goal blood pressure (BP) is around 130/80 mm Hg. RAS blockers (ACE inhibitors or AT1 blockers) are considered as the drugs of choice because of the decrease of cardiovascular risk and prevention of nephropathy. Combination antihypertensive therapy is needed in 80–90 % of pts. Combination of RAS blocker and calcium channel blocker is clinically useful. Diuretics should be part of triple-combination. Low-dose spironolactone can be recommended in severe forms of hypertension. Pharmacological approach should involve also intervention of all other risk factors including BMI reduction in obese subjects. Some of new antidiabetic drugs may lead to significant BP decrease (gliflozines).
Jiří Widimský Jr
Aldosterone blocker Spironolactone has antiinflammatory, antiproliferative and antioxidative effects, that is why pathogenetically it is expedient to use it in complex therapy of rheumatoid ...arthritis. Material and methods: 46 patients with RA took 2550 mg/day of Spironolactone during 12 months as an addition to standard therapy, the comparison group consisted of 47 patients that got only standard therapy, all the patients were fully examined prior and post the treatment. Results: complex RA therapy leads to improved VAS, HAQ, the antioxidative potential index F; decreased blood concentrations of TNFα, ICAM1, FGF and VEGF in contrast to standard therapy. Complex therapy made reduced the DAS 28 more > 0.6. Conclusions: applying of Spironolactone in complex therapy of rheumatoid arthritis contributes to more pronounced improvement in indices of articular syndrome and patients life quality, reduce of antiinflammatory, antiproliferative and angiogenic cytokines, and more effectively reduces the activity of the disease comparing to standard therapy.
Elena Komarova, Borys Rebrov
Literatura
Studie PATHWAY-2, financována Britskou nadací pro srdce (British Heart Foundation), randomizovala 335 pacientů s rezistentní hypertenzí (léčených již podle současných guidelines léčbou A + C + D na ...12týdenní léčbu spironolaktonem (25–50 mg), bisoprololem (5–10 mg), doxazosinem (4–8 mg s modifikovaným uvolňováním) a placebem. Plán studie dovoloval porovnání léků u každého pacienta, 230 pacientů dokončilo všechny cykly. Výsledky ukázaly, že podávání spironolaktonu snížilo domácí systolický tlak o 8,70 mm Hg více než placebo (< 0,001), o více než 4,26 mm Hg než bisoprolol/doxazosin (< 0,001), o 4,03 mm Hg více než doxazosin (< 0,001) a o 4,48 mm Hg více než bisoprolol (< 0,001). Na konci studie bylo zjištěno jen 15 pacientů vhodných k zařazení do studie o renální denervaci u nekontrolované hypertenze. Studie PATHWAY-2 bude mít velký dopad pro nábor pacientů do studií sledujících význam renální denervace.
The PATHWAY-2 study, funded by the British Heart Foundation, randomised 335 patients with resistant hypertension (already treated according to guidelines) to sequentially receive 12 weeks of spironolactone (25–50 mg), bisoprolol (5–10 mg), doxazosin (4–8 mg modified release) and placebo. The study design allowed drug comparisons in each patient, with 230 patients completing all cycles. Results showed that spironolactone reduced home systolic BP by 8.70 mm Hg more than placebo (< 0.001), 4.26 mmHg more than bisoprolol/doxazosin (< 0.001), 4.03 mm Hg more than doxazosin (< 0.001), and by 4.48 mm Hg more than bisoprolol. By the end of the trial, there would only be 15 patients considered eligible for renal denervation trials in uncontrolled hypertension. PATHWAY-2 will have significant implications for patient recruitment in to other trials.
Jiří Widimský
Studie TOPCAT byla studií sledující vliv spironolaktonu u chronického srdečního selhání se zachovalou ejekční frakcí levé komory. Studie nezjistila ovlivnění primárního cíle studie, tj. kombinace ...kardiovaskulární mortality, zvládnuté srdeční zástavy nebo hospitalizace pro léčbu srdečního selhání. Jediným nálezem studie byl pokles hospitalizací pro srdeční selhání. Post-hoc analýza však zjistila nápadný rozdíl mezi pacienty z Amerik (USA, Kanada, Argentina, Brazílie) a pacienty z Ruska/Gruzínska. Rozdíly byly veskrze nápadné. Zatímco u pacientů z Amerik došlo k významnému snížení výskytu primárního cíle, kardiovaskulární mortality a hospitalizace pro srdeční selhání léčbou spironolaktonem, výskyt všech klinických příhod byl výrazně nižší v Rusku/Gruzii, a u pacientů z Ruska/Gruzie nebyl zjistitelný žádný zjistitelný dopad spironolaktonu na jakýkoliv cíl. Tato post-hoc analýza tedy ukázala na možný léčebný účinek spironolaktonu v Amerikách, jakož i v populacích vykazujících obdobné vlastnosti jako populace v Amerikách. Většina prací se spokojuje s definicí opírající se jen o srdeční selhání se zachovalou ejekční frakcí levé komory. Práce upozorňuje na nutnost zpřesnění této definice, která se musí také opírat o změny diastolické funkce levé komory při definici diastolického srdečního selhání.
The TOPCAT study followed the effect of spironolactone on a chronic heart failure with a preserved left ventricular ejection fraction. The study did not find any impact on the primary goal of the study, i.e. a combination of cardiovascular mortality, managed cardiac arrest or hospitalization rate for heart failure treatment. The only finding of the study was the decrease in hospitalization rates for a heart failure. A post hoc analysis, however, identified a significant difference between patients from the Americas (USA, Canada, Argentina, Brazil) on the one hand and those from Russia/Georgia on the other. The differences were rather striking. Whereas the former manifested a significant reduction in the incidence of the primary goal, i.e. cardiovascular mortality and hospitalization with heart failure through treatment with spironolactone, the incidence of all clinical events was considerably lower in Russia/Georgia and no impact of spironolactone at all on any of the goals was identified regarding the patients from Russia/Georgia. This post hoc analysis therefore suggested a possible therapeutic effect of spironolactone in the Americas, as well as in the populations of similar characteristics. Most studies accept a definition only based on the heart failure with a preserved left ventricular ejection fraction. The study points to the need to further elaborate this definition which also has to consider changes of the left ventricular diastolic function when defining a diastolic heart failure.
Jiří Widimský Sr
Amaç:Siproteron asetat (CPA) ve spironolaktonun (SP) kıl büyümesi üzerine olan etkileri 138 hirsutizimli kadından oluşan randomize prospektif bir çalışmada karşılaştırıldı.
Çalışmanın Yapıldığı Yer: ...Süleyman Demirel Üniversitesi Tıp Fakültesi Kadın Hast. ve Doğum Anabilim Dalı
Materyal ve metod: Diane (siproteron asetat 2 mg+ethinil estradiol 0.05 mg) ile 78 kadın, 6 ay süreyle ve 60 kadın 100 mg/gün dozunda SP ile 6 ay süreyle tedavi edildiler.
Bulgular: CPA ile toplam kıl çapı, yüz bölgesinde %38.6 ve alt karın bölgesinde %23.9 azaldı (p<0.0001, p<0.001). SP ile yüz bölgesinde %29.8 ve alt karın bölgesinde %16.4 azaldı(p<0.001, p<0.001). CPA ve SP meduller çapı toplam kıl çapından daha fazla azalttı. İki ilaç arasında toplam ve medullar kıl çapı üzerine olan etkileri yönünden anlamlı bir fark mevcuttu (p<0.05, p<0.001). Tedavi etkinliğini subjektif değerlendirdiğimizde tedavi öncesi ve sonrasında üç kıl parametresi(kıl büyümesinin azalması, yeni kıl oluşumu, yumuşak kıla dönüşüm) kullanıldı ve CPA ve SP tedavi gruplarının her ikisinde de kıl parametrelerinde anlamlı ilerlemeler gözlendi(sırasıyla %72 ve %50 ). CPA tedavisi alan 4 vakada ve SP alan 2 vakada yan etkiler nedeniyle tedavi kesilmesi görüldü. CPA tedavi grubunda 4 kadın ve SP tedavi grubunda 1 kadın hirsutism üzerine istenilen etki olmadığından tedaviyi tamamlamadılar.
Sonuç: Bizim çalışmamız hirsutism tedavisinde hem CPA' nın hem de SP' nin her ikisinin de hirsutism tedavisinde etkili olduklarını doğrulamasına karşın, CPA kıl parametreleri ve kıl çapları üzerine daha iyi klinik etkilere sahiptir.
Objective: The effects of cyproterone acetate (CPA) and spironolactone(SP) on hair growth were compared in a randomized prospective study consisting 138 women with hirsutism.
Institution: Department of Obstetrics and Gynecology, University of Süleyman Demirel.
Material and Method: Seventy eight women have completed 6 months therapy with Diane® (cyproterone acetate 2 mg+ethinyl estradiol 0,05 mg) and 60 women have completed 6 months therapy with SP in a dose of 100 mg/day.
Findings: Total hair diameter fell by 38.6% with CPA for the face and by 23.9% for the lower abdominal region(p<0.0001, p<0.001). It was reduced 29.8% with SP for the face and 16.4% for the lower abdominal region(p<0.001, p<0.001). CPA and SP reduced medullary diameter much less than total hair diameter. There was a significant difference between the two drugs with respect to their effects on total and medullary hair diameter(p<0.05, p<0.001). When we consider the subjective assessment of treatment success, three hair parameters (reduced hair growth, formation of new hair and a change to softer hair) were used before and after treatment and significant improvements in the hair parameters were observed both in the CPA and SP treatment groups(72% and 50%, respectively). Cessation of treatment in 4 subjects taking CPA and 2 subjects taking SP was seen because of side effects. Four women in the CPA treatment group and one woman in the SP treatment group discontinued treatment because lack of any desired effectiveness on hirsutism.
Results: Our study confirms that both CPA and SP are effective agents in the treatment of hirsutism but CPA has better clinical effects on the hair parameters and hair diameters.