Metabolic side effects of diuretics and β-adrenoceptorblockers

Abstract: A review is made of the metabolic side effects of diuretics and β-adrenoccptorblockers. The review is based on results from a population study. performed by the author, of women and on a survey of the literature. While diuretics give rise to hypokalemia, which may be of clinical importance, β-adrenoceptorblockers tend to increase the serum potassium levels. This does not, however seem to be of clinical significance. Both diuretics and β-adrenoceptorblockers increase serum uric acid levels, β-adrenoceptorblockers inciease serum tryglycerides. which is not observed when diuretics are used. Total cholesterol in serum is usually not changed either by diuretics or by β-adrenoceptorblockers. These drugs seem to have no influence on body weight when studied during long-term treatment. A further deterioration of glucose tolerance may be expected in subjects with an initially impaired glucose tolerance when diuretics are administered, while results from studies on glucose tolerance in subjects taking β-adrenoceptorblockers have been controversial. Diabetes miellitus seems to he more common umong subjects on diuretics as well as among subjects on β-adrenoceptorblockers, but as yet it cannot be stated whether this is an effect of the antihypertensive drugs or of the hypertension per se or of some other factor or factors.     

Sympatho-adrenal mechanisms and the antihypertensive response to thiazide diuretics

Abstract: Thazide diuretics lower the blood pressure during long-term treatment by reducing the peripheral vascular resistance. This seems to be related to the natriuresis rather than to a direct vasodilating effect of the thiazides. There is evidence that the volume depletion caused by thiazide treatment initially triggers an increase in sympathetic nerve activity, which may account for initial increases in vascular resistance. Although both responses subside during long-term treatment, there is no evidence showing a causal relationship between these changes. The long-term hemodynamic adaptation to thiazide treatment may be related to altered cardiovascular reflexes. Changes in sympathetic nerve activity and reduced vascular sensitivity to noradrenaline may contribute to the adaptation. An analysis of the relative importance of these mechanisms requires further studies comparing the time courses for various effects in respondcrs and non-responders to the treament.     

Changes in the lipoprotein profile during antihypertensive therapy

Abstract: In the Oslo study serum lipids have been studied during treatment with some of the most frequently used antihypertensive drugs. Hydrochlorothiazide induced no significant changes. However, those patients with the most marked increase in uric acid showed an increase of serum ti iglycerides. Total cholesterol was unchanged in these men. The β-adrenoceptorblocking drugs propranolol, aterolol and oxprenolol caused a reduction of HDL cholesterol and an increase of total triglycerides. Tolal cholesterol remained unchanged. Pindolol induced no significant lipoprotein changes. Prazosin reduced total cholesterol and total triglycerides. HDL. cholesterol remained unchanged. LDL + VLDL cholesterol was reduced.     

脂肪肝与高血脂、高血糖及高尿酸血症的关系

目的 探讨脂肪肝与高血脂、高血糖、高尿酸血症的关系。方法 对5000例来本院体检的不同职业的人员进行脂肪肝及相关因素调查，检测血清胆固醇（TC）、甘油三脂（TG）、空腹血糖（FBG）、血尿酸（UA）及肝功能等指标，并对相关资料进行统计学分析。结果 高TC、TG、FBG、UA人群中脂肪肝的发病率分别为38．8％、52．1％、35．2％和53．6％，明显高于正常TC、TG、FBG、UA人群中脂肪肝的发病率，分别为19．0％、11．7％、18．6％、15．0％。结论 高血脂、高血糖、高尿酸血症与脂肪肝的发生密切相关，并且相互影响。     

The effects of substituting frusemide for a thiazide diuretic in the drug regimens of patients with essential hypertension

Summary Eighteen patients with mild to moderate hypertension on a drug regimen which included a thiazide diuretic had the latter substituted by frusemide for twelve weeks after an initial two-week placebo wash-out period. Blood pressure and heart rate and a number of plasma and urinary biochemical indices were measured. Significant findings included a reduction in standing blood pressure and an elevation of plasma sodium, potassium, chloride, osmolarity, creatinine and alkaline phosphatase levels at the end of the twelve week frusemide phase relative to the values on the thiazide. However the means for all the biochemical indices remained within the normal laboratory reference limits. In the 24-hour urinary studies, no significant findings emerged, apart from an elevated calcium. The foregoing suggest that frusemide is an effective component of an anti-hypertensive drug regimen and that in a dose of 40 mg/day it produces no detectable perturbations of plasma electrolytes. The significance of the enhanced levels of urinary calcium excretion in conjunction with the augmented plasma alkaline phosphatase is unclear.     

Position of indapamide,a diuretic with vasorelaxant activities,in antihypertensive therapy

Opana^® ER (oxymorphone extended release [ER]) is a new oral long-acting formulation indicated for the treatment of moderate to severe chronic pain. Because the ER matrix slowly releases oxymorphone over 12 h, consistent plasma levels are produced with low peak-to-trough fluctuations. Oxymorphone ER is the only long-acting opioid that contains oxymorphone, which exhibits some distinct pharmacologic properties compared with most other opioids, including a longer half-life, higher affinity for the µ-opioid receptor, and lack of interaction with the CYPP450 drug-metabolizing system. With a safety and tolerability profile similar to other opioids and documented efficacy in several models of chronic pain (low back, cancer, and osteoarthritis), oxymorphone ER provides a new option for clinicians and patients in the treatment of chronic pain.     

Low doses of hydrochlorothiazide in hypertension

Summary The antihypertensive activity and side effects of three doses of hydrochlorothiazide combined with a potassium supplement (Esidrex^®-K novum, Ciba) were determined in 40 hypertensive subjects in a double-blind, cross-over study. The lowest daily dose (12.5 mg) gave almost the same blood pressure reduction as the doses in common use (25 mg and 50 mg) and as the adrenergic beta-blocking agents previously employed. Metabolic side effects in the form of decreased serum potassium and increased fasting blood sugar and serum uric acid were observed in patients on the lower dose and, with the exception of serum uric acid, were only slightly more pronounced with the higher doses. The frequency of subjective side effects, on the other hand, increased with increasing dose. No changes were noted in total body potassium at any dose level. It is suggested that hydrochlorothiazide in low dose, alone or in combination with other antihypertensive agents, is a useful therapeutic regimen in mild hypertension.     

2型糖尿病患者血清总胆红素、尿酸与冠脉病变的关系

目的:探讨2型糖尿病患者血清总胆红素、尿酸与冠脉病变程度之间的关系。方法:65例2型糖尿病及157例非糖尿病患者行冠状动脉造影检查,冠脉狭窄>50%者确诊为冠心病组,冠脉造影未见狭窄者为冠脉正常组。再按照病变血管严重程度分为单支、双支、三支3组。糖尿病患者按照上述条件分组,并检测血清总胆红素及尿酸、血糖、血脂等生化指标。结果:糖尿病患者冠脉造影阳性率为78.46%,冠脉复杂病变的比例为72.55%,均明显高于非糖尿病患者,差异有统计学意义(均P<0.01)。糖尿病合并冠心病患者血清总胆红素降低,尿酸升高,与单纯糖尿病组比较差异有统计学意义(P<0.01或P<0.05)。糖尿病合并冠心病患者,双支、三支病变组与单支病变组比较,血清总胆红素降低,尿酸升高,差异有统计学意义(P<0.01或P<0.05)。结论:糖尿病患者冠心病发病及冠脉病变严重程度明显高于非糖尿病患者。糖尿病合并冠心病患者血清胆红素降低、尿酸升高,且胆红素降低、尿酸升高程度与冠脉病变复杂程度一致。     

终末期肾病患者高血压的发生与血尿酸相关性的研究

目的:探讨末期肾病进行血液透析患者高血压的发生与血尿酸的关系,从而了解血尿酸对高血压的影响机制。方法:针对我院血液透析中心现有维持性血液透析患者80例,统计高血压的患病率、高尿酸血症发生率和控制情况。结果:在80例常规透析的患者中高血压的患病人数57例,占71%,这57例患者中血尿酸增高者23例,占40%,与血压正常组有明显差异(P<0.05),在尿酸降低的同时,血压有所降低(P<0.05),结论:通过本研究内容初步了解透析患者高血压的发生与血尿酸的关系,为透析高血压患者治疗提供新思路。     

高尿酸血症与脑梗死相关性的探讨

目的：研究血清尿酸水平与脑梗死的关系。方法：测定106例脑梗死患者和98例健康对照者血清尿酸水平,并根据神经功能缺损程度分析各血清尿酸水平的相关性。结果：急性脑梗死患者血清尿酸水平与健康对照者比较有显著性差异（P〈0.05）。轻型与中型尿酸比较有显著性差异（P〈0.05）,重型与轻型及中型比较有显著性差异（P〈0.05）。结论：血清尿酸水平增高与脑梗死的发生和严重程度有密切关系。     

Effect of oral diuretics on chronic warfarin therapy: a retrospective study

Background: Limited clinical documentation is suggestive of a drug interaction between warfarin and diuretics.

Objective: To evaluate the effect on international normalized ratio (INR) when a daily oral diuretic is started or increased in patients on chronic stable warfarin therapy.

Methods: The medical records of all active patients of two hospital-based anticoagulation clinics were retrospectively reviewed to identify patients who were started on or received a dose increase of a daily oral diuretic while on stable warfarin therapy. The primary endpoint was the mean difference between an INR recorded within 30 days prior to the diuretic initiation (pre-INR) and an INR recorded within 30 days after diuretic initiation (post-INR).

Results: A total of 1254 patient charts were screened and a total of 123 patients met the study criteria. The mean difference in pre-INR and post-INR was 0.09 (95% CI -0.03 to 0.21, p = 0.12). Post-INR values were outside of the patient's therapeutic range in 39 patients (32%), but no major bleeding or thromboembolic events were reported.

Conclusion: Based on this retrospective study, diuretics did not result in a significant change in the INR in patients on stable warfarin therapy.     

血尿酸水平与高血压病关系的探讨

目的 探讨高血压病患者血尿酸( Uric acid,UA)水平含量的变化与高血压病之间的内在联系.方法 分别测定150例高血压病患者(高血压病组)及150例正常体检者(对照组)UA水平含量,和高血压病不同临床分级、年龄患者高UA检出率比较.结果 两组UA含量水平和高尿酸血症检出率比较,有明显差异(P＜0.05、P＜0.01);高血压病不同临床分级患者UA水平含量比较,有明显差异(P＜0.05);高血压病不同临床分级、年龄患者高血尿酸检出率比较,有明显差异(P＜0.05).结论 血尿酸水平含量增高是高血压病的危险因素之一,高血压病患者UA水平含量升高,升高程度与高血压病临床分级呈正相关.     

高血压表观遗传药理学研究进展

伴随着遗传药理学的发展,人们逐渐认识到基因多态性不能完全解释降压药物疗效的个体差异。在分子水平上,高血压药物相关代谢酶、受体、转运体都受到基因表达调控的影响,并在降压疗效差异中起着重要的作用。因此,从表观遗传学的角度研究遗传因素与降压药物之间的关系,将有助于更好地解释临床上药物反应产生的个体差异。本文综述总结了DNA甲基化、组蛋白修饰和microRNAS等表观遗传调控方式对高血压相关药物编码基因的影响。     

老龄急性冠脉综合征患者血尿酸水平及相关因素分析

目的:探讨老龄急性冠脉综合征(ACS)患者血清尿酸(SUA)水平与ACS临床类型、冠状动脉病变程度的关系及其影响因素.方法:选择272例≥75岁的ACS患者,按照临床类型分为不稳定型心绞痛组151例,急性非ST段抬高型心肌梗死(NSTEMI)组25例、急性ST段抬高型心肌梗死(STEMI)组96例,比较3组的SUA水平;比较冠脉造影确定的单支病变、双支病变、三支病变组间的SUA水平;将SUA和血脂、空腹血糖(FPG)、血肌酐(Cr)、白细胞(WBC)水平行相关分析和多因素回归分析.结果:不稳定型心绞痛组、NSTEMI组及STEMI组SUA水平、不同冠状动脉病变组间SUA水平差异均无统计学意义(P＞0.05).SUA水平与三酰甘油(TG)、Cr、WBC呈正相关(P＜0.01),与高密度脂蛋白胆固醇(HDL-C)呈负相关(P＜0.01).Cr和WBC是影响血清SUA的因素.结论:老龄ACS患者SUA水平和ACS的临床类型及病变冠脉支数可能无关,血清Cr和WBC是SUA的影响因素.     

The effects of two different local anaesthetic solutions administered for oral surgery on plasma potassium levels in patients taking kaliuretic diuretics

Summary The effects of two different dental local anaesthetic solutions, administered for oral surgery, on the plasma potassium levels of patients taking non-potassium sparing diuretics has been investigated.There was a significant reduction in plasma potassium concentration in eight subjects who received 4.4 ml of 2% lignocaine with 1:80 000 adrenaline; the mean reduction from baseline being 0.30 mmol·l^–1 10 min following intra-oral extravascular injection of the local anaesthetic.There was no significant difference from the pre-treatment plasma potassium concentration 10 min following similar injections of 3% prilocaine with 0.03 IU·ml^–1 fely-pressin in 8 patients; the mean change in these subjects being –0.05 mmol·l^–1.It is suggested that the use of adrenaline-free local anaesthetics would seem to be appropriate in patients receiving kaliuretic diuretics.     

血尿酸检测在妊娠期高血压疾病中的意义

目的探讨妊娠高血压患者血清尿酸(UA)水平测定的意义及临床价值。方法随机抽取2010年1月至2011年4月在我院产检和分娩的妊娠高血压孕妇80例作为观察组,其中轻度32例,中度27例,重度21例;另抽取同期我院正常妊娠妇女50例作为对照组;分别对两组血清尿酸(UA)水平进行测定。结果观察组UA水平为(364.7±96.5)μmol/L,对照组为(230.6±53.8)μmol/L,两组比较,差异有统计学意义(P<0.01);轻度妊娠高血压患者UA水平为(296.5±59.2)μmol/L,中度妊娠高血压为(356.0±69.9)μmol/L,重度妊娠高血压为(473.8±93.3)μmol/L。中度妊娠高血压患者UA水平明显高于轻度妊娠高血压,差异有统计学意义(P<0.01);重度妊娠高血压UA水平明显高于中度及轻度妊娠高血压,差异有统计学意义(P<0.01)。结论妊娠高血压病情严重程度与UA水平密切相关,动态监测血清UA水平的变化,对妊娠高血压的诊断和预后有十分重要的临床意义。     

Reversal of an unfavorable effect of hydrochlorothiazide compared to angiotensin converting enzyme inhibitor on serum uric acid and oxypurine levels by estrogen–progestin therapy in hypertensive postmenopausal women

Background: The aim was to assess the effect of estrogen–progestin therapy (EPT) on serum levels of uric acid (SUA) and its precursors xanthine (X) and hypoxanthine (HX), and on uric acid (UA) renal excretion in hypertensive postmenopausal women treated with an angiotensin-converting enzyme inhibitor (ACEI) or thiazide diuretic (HCTZ) (ClinicalTrials.gov identifier: NCT03921736, registered 19 April 2019).

Methods: Postmenopausal women with untreated essential hypertension were recruited to the study. The control group consisted of 40 postmenopausal women with normal blood pressure. Hypertensive women were randomized to two groups: hydrochlorothiazide (n?=?50) or perindopril (n?=?50) and to a group receiving or not receiving EPT (EPT+/EPT?) due to vasomotor symptoms. The follow-up period was one year. Blood pressure measurements as well as blood tests for SUA and its precursors X and HX were performed at baseline and after 12?months.

Results: In hypertensive women, baseline serum X and HX were significantly higher when compared to the group of normotensive women. Treatment with HCTZ led to a statistically significant increase in SUA in the subgroup of EPT- women. In this group concentrations of X and HX increased significantly after 12?months. UA/X significantly decreased after treatment with HCTZ. Lack of EPT resulted in a decrease of renal plasma flow in the HCTZ group. However, in the HCTZ and EPT?+?group, SUA decreased significantly when compared to baseline. None of these unfavorable effects was observed in the ACEI group regardless of EPT.

Conclusions: 1) EPT prevents the development of hyperuricemia during antihypertensive treatment with thiazide diuretics. 2) Arterial hypertension and menopause cause impairment of UA excretion and increase the levels of SUA and its precursors X and HX. 3) EPT reduces the risk of hyperuricemia in postmenopausal women.     

Effect of Repeated Doses of Hydroflumethiazide on Renal Excretion of Electrolytes and Uric Acid in Healthy Subjects

Abstract: Urinary excretion of electrolytes and uric acid was investigated in six healthy subjects during repeated oral administration of 100 mg hydroflumethiazide (HFT) daily for seven days, and related to urinary thiazide excretion. Mean 24 hr-urinary excretion of sodium and chloride increased 100% (P<0.02) after the first HFT-dose, whereas 24 hr-excretion values were at control level after the fourth and seventh doses. Mean 24 hr-urinary excretion of potassium was increased by 31% after the first HFT-dose (P<0.05) and by 47% after the fourth dose (P <0.05). After HFT was discontinued, mean urinary excretion rates of sodium and chloride dropped to 30% and that of potassium to 70% of control. In the state of fluid deficiency and elevated aldosterone concentration, there was a significant positive correlation between log excretion rate of HFT and excretion rate of sodium (r=0.68, P<0.002) calculated from excretion data 0–6, 6–12, and 12–14 hrs after the seventh dose. After the first dose of HFT, sodium excretion was also significantly correlated to log excretion rate of HFT (r=0.86, P<0.001) but was probably influenced by other factors as well. Mean serum concentration of uric acid increased significantly, but mean 24 hr-urinary excretion of uric acid was constant during HFT-treatment.