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Efficacy of various antihypertensive drugs in the treatment of hypertension in the patients of end-stage renal disease leading to hemodialysis: a retrospective study

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Background: Cardiovascular complications are the leading cause of morbidity and mortality in the patients of end-stage renal disease leading to hemodialysis. Majority of these patients suffers from hypertension and adequate control of blood pressure is a challenge in these patients because of multifactorial etiology and complicated pharmacokinetic changes in these patients. The present study aims is to find out the best possible drug or combination of drugs that can provide better control of blood pressure and improve the quality of life of these patients.Methods: A retrospective study was carried out on the patients who attended the hemodialysis unit of Hakeem Abdul Hamid Centenary hospital from July 2015 to June 2016 (one year), data on antihypertensive drugs and blood pressure control (pre-dialysis and post-dialysis) were recorded and analyzed.Results: 68.75% patients on hemodialysis were suffering from hypertension and were on antihypertensive medication. A combination of Amlodipine and clonidine were the most frequently prescribed antihypertensive agents. Muscle cramps an acute rise in blood pressure and hypotension were the most frequently encountered intradialytic complications in these patients.Conclusions: Although a combination of amlodipine and clonidine was most frequently prescribed antihypertensive medication in these patients these drugs were associated with intradialytic complications like muscle cramps and hypotension. Amlodipine with beta-adrenoceptor blocker (metoprolol or bisoprolol) provided best control of blood pressure in these patients with least intradialytic complications.
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... Amlodipine (13.6%) is the type of antihypertensive drug that is most consumed by patients with chronic renal failure and hypertension before undergoing hemodialysis. This is consistent with research conducted at Hakeem Abdul Hamid Hospital Centenary, India which states that Calcium Channel Blocker drugs are most often given because they do not experience excretion during dialysis and are associated with lower mortality and cardiovascular events 14 . ...
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Gagal ginjal kronik ditandai dengan menurunnya fungsi ginjal secara ireversibel yang telah berlansung lebih dari tiga bulan dengan nilai laju filtrasi glomerulus kurang dari 15 ml/menit/1,73m2. Hemodialisis merupakan salah satu terapi pengganti ginjal yang paling sering dilakukan, namun hemodialisis memiliki komplikasi terhadap perubahan tekanan darah dan kadar gula darah. Penelitian ini bertujuan untuk mengetahui perbandingan tekanan darah dan kadar gula darah pada pasien gagal ginjal kronik sebelum dan sesudah hemodialisis di unit hemodialisis RSUP dr. Mohammad Hoesin Palembang. Penelitian ini merupakan penelitian observasional analitik dengan desain longitudinal menggunakan pengukuran berulang. Subjek penelitian adalah 74 pasien gagal ginjal kronik yang memenuhi kriteria inklusi dan eksklusi. Data penelitian diperoleh melalui data primer (pengukuran dan wawancara) dan dianalisis menggunakan Paired T-Test dan Wilcoxon. Rata-rata tekanan darah sebelum hemodialisis adalah 150,14 ± 30,045 mmHg (sistolik) dan 83,99 ± 16,469 mmHg (diastolik) serta sesudah hemodialisis adalah 159,66 ± 33,570 mmHg (sistolik) dan 86,35 ± 15,534 mmHg (diastolik). Rata-rata kadar gula darah sebelum hemodialisis adalah 161,61 ± 80,750 mg/dl serta sesudah hemodialisis adalah 131,51 ± 49,430 mg/dl. Hasil uji Paired T-Test menunjukkan perbandingan tekanan sistolik yang signifikan (p = 0,007), sedangkan hasil uji Wilcoxon menunjukkan perbandingan diastolik yang tidak signifikan (p = 0,193) dan perbandingan kadar gula darah yang signifikan (p = 0,000). Terdapat perbandingan tekanan darah sistolik yang signifikan, tekanan darah diastolik yang tidak signifikan, dan kadar gula darah yang signifikan sebelum dan setelah hemodialisis pada pasien gagal ginjal kronik di RSUP dr. Mohammad Hoesin Palembang.
... 11,12 One study has shown that 50.64% of patients were prescribed with clonidine. 13 In another study, clonidine was prescribed in only 9.1% of hemodialysis patients. 14 The variation in prescribing frequency could be either due to its high rate of adverse event profile or the experience of the nephrologists. ...
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Background: Clonidine is less frequently used by nephrologists. Data on clonidine prescribing trends in hemodialysis patients is sparse. We assessed the clonidine utilization metrics from the case records of patients undergoing maintenance hemodialysis.Methods: In this retrospective chart review, we analysed the clinical records of hemodialysis patients using clonidine. We evaluated the frequency of clonidine use, mean dose of clonidine and percentage of patients receiving a particular dose. Additionally, we also correlated dose of clonidine with anti-hypertensive pill count.Results: A total of 70 hemodialysis patients case records were screened. All 70/70 (100%) of them were hypertensive. Only 25/70 (35.74%) of patients were prescribed clonidine as an anti-hypertensive agent. The mean clonidine dose was 352±171 µg. Majority of patients 9/25 (36%) received 400 µg of clonidine. The dose of clonidine was prescribed in the order 400 µg (36%)>200 µg (32%)>600 µg (16%)>100 µg (8%)>300 µg (4%)=700 µg (4%). There was a statistically significant correlation in the strength of clonidine prescribed with increasing anti-hypertensive drugs (p<0.05).Conclusions: In our study, we observed that 80% of our hemodialysis patients were non responders to either systolic blood pressure or diastolic blood pressure or both. Oral clonidine use was observed in 35.74% of our hemodialysis patients. There was a linear trend showing an increased dose of clonidine with an increase in the anti-hypertensive pill count.
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Background: The high rate of death and sickness perceived in patients with end-stage renal disease is principally ascribed to the inadequacy of haemodialysis (HD), and this may relate to inadequate analysis of the factors affecting the HD process, including drugs taken by these patients. Aims and Objective: To explore the potential association of a dihydropyridine calcium channel blocker (amlodipine) and a beta-blocker prototype (propranolol) separately with the dialysis efficiency in HD patients. Methods: This is a retrospective study which include 275 (112 females and 163 males, 83% of whom also suffered from hypertension) patients with end-stage renal failure on haemodialysis. Patients were categorized into three groups: 125 patients taking amlodipine, 81 patients taking propranolol, and 69 patients not taking any of the above medications (controls). The HD efficiency, and the percentage reduction in creatinine, uric acid, and urea levels were compared between groups. Results: Compared with patients who were not receiving amlodipine or propranolol, a significant increase in the major HD adequacy marker which is the Kt/V ratio, as well as in the percentage reduction in creatinine, uric acid, and urea levels, was observed in patients taking amlodipine, but a significant decrease in these markers was detected in patients taking propranolol. Conclusions: Taken together, these findings indicate that the haemodialysis efficiency may be significantly improved (diminished) by supplementation with amlodipine (propranolol).
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Background: The treatment of hypertension in dialysis patients is prevalent and poorly characterized. beta-Blockers and calcium channel blockers (CCBs) have been associated with reduced all-cause and cardiovascular mortality. This study describes the treatment of hypertension and assesses the association between mortality and class of anti hypertensive medication among a cohort of dialysis patients. Methods: The US Renal Data System (USRDS) Dialysis Morbidity and Mortality Study Wave II cohort was analyzed. A total of 2,877 patients initiating hemodialysis or peritoneal dialysis in 1996 or 1997 and treated with antihypertensives were included in this analysis. Vital status was followed until November 2000. Results: Calcium channel blockers were prescribed to 70.3% of patients. Only 31.5% and 27.0% of patients with cardiovascular disease were prescribed angiotensin-converting enzyme inhibitors and beta-blockers, respectively. Mono-, double-, triple-, and more than triple-therapy were reported in 48.0%, 36.1%, 13.2%, and 2.7% of the cohort, respectively. In multivariable, fully adjusted models, no individual class of antihypertensives was associated with changes in all-cause mortality. In all patients, nondihydropyridine CCBs (non-DHP CCBs) were associated with a reduced risk of cardiovascular death (hazard ratio, 0.78; 95% confidence interval, 0.62 to 0.97) and among end-stage renal disease patients with preexisting cardiovascular disease, dihydropyridine CCBs (DHP CCBs) and non-DHP CCBs were associated with reduced risk of all-cause and cardiovascular mortality. Conclusion: Calcium channel blocker use is widespread among hypertensive dialysis patients. Antihypertensive prescription patterns suggest a lack of consensus regarding treatment of hypertension. Multivariable analysis of associations between anti hypertensive class and mortality reveals results of uncertain clinical significance. Hypertension treatment trials in dialysis patients should be performed to appropriately inform treatment decisions. (C) 2003 by the National Kidney Foundation, Inc.
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Background. Information concerning medication use in Asian haemodialysis patients is sparse. We surveyed prescribed medications and examined the relation between the number of medications and mortality and clinical characteristics in chronic haemodialysis patients, in Okinawa, Japan. Methods. We conducted a cross‐sectional multicentre survey in August 1999 and patients were observed during 13 months of follow up. Results. The clinical demographics of 850 chronic haemodialysis patients in seven dialysis units were obtained. Compared with the mean number of medications prescribed in ambulatory patients treated in general practice reported from Ministry of Health and Welfare of Japan (2.7 (n=20 716)), the mean number medications in haemodialysis patients was larger (7.2 (n=850)). The three most prescribed drug types in haemodialysis patients were those related to calcium and phosphate metabolism (88%), antihypertensive agents (71%), and erythropoietin (60%). Among the 850 patients, 38 died during the 13‐month follow‐up period. The number of medications was positively associated with mortality after adjusting for age, sex, and other clinical factors: the hazard ratio was 1.14 (95% confidence interval 1.03–1.26, P=0.007). A multiple linear regression analysis using the number of medications as a dependent factor and sex and other clinical characteristics as independent factors revealed that male sex (P=0.04), diabetes mellitus (P<0.0001), and duplication of drugs (P<0.0001) were positively correlated with the number of medications. Conclusions. Multiple drug use was observed in haemodialysis patients. The number of prescribed drugs was a significant predictor of short‐term mortality. Male sex, diabetes mellitus, and duplication of drugs were correlated with increases in the number of medications.
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Hypertension affects most hemodialysis patients and is often poorly controlled. Adequate control of blood pressure is difficult with conventional hemodialysis alone but is important to improve cardiovascular outcomes. Nonpharmacologic interventions to improve blood pressure include educating patients about limiting sodium intake, ensuring adequate sodium solute removal during hemodialysis, and achieving target "dry weight." However, most patients require a number of antihypertensive medications to achieve an appropriate blood pressure. First-line antihypertensive agents include angiotensin converting enzyme inhibitors and angiotensin receptor blockers given their safety profile and demonstrated benefit on cardiovascular outcomes in clinical trials. beta-blockers and combined alpha- and beta-blockers should also be used in patients with cardiovascular disease or congestive heart failure and may improve outcomes in these populations. Calcium channel blockers and direct vasodilators are also effective for controlling blood pressure. Many blood pressure agents can be dosed once daily and should preferentially be administered at night to control nocturnal blood pressure and minimize intradialytic hypotension. In patients who are noncompliant with therapy, renally eliminated agents (such as lisinopril and atenolol) can be given thrice weekly following hemodialysis. Older antihypertensive agents which require thrice daily dosing ought to be avoided given the high pill burden with these regimens and the concern for noncompliance resulting in rebound hypertension. Newer antihypertensive agents, such as direct renin inhibitors, may provide alternative options to improve blood pressure but require testing for efficacy and safety in hemodialysis patients.
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Patients undergoing dialysis have a substantially increased risk of cardiovascular mortality and morbidity. Although several trials have shown the cardiovascular benefits of lowering blood pressure in the general population, there is uncertainty about the efficacy and tolerability of reducing blood pressure in patients on dialysis. We did a systematic review and meta-analysis to assess the effect of blood pressure lowering in patients on dialysis. We systematically searched Medline, Embase, and the Cochrane Library database for trials reported between 1950 and November, 2008, without language restriction. We extracted a standardised dataset from randomised controlled trials of blood pressure lowering in patients on dialysis that reported cardiovascular outcomes. Meta-analysis was done with a random effects model. We identified eight relevant trials, which provided data for 1679 patients and 495 cardiovascular events. Weighted mean systolic blood pressure was 4.5 mm Hg lower and diastolic blood pressure 2.3 mm Hg lower in actively treated patients than in controls. Blood pressure lowering treatment was associated with lower risks of cardiovascular events (RR 0.71, 95% CI 0.55-0.92; p=0.009), all-cause mortality (RR 0.80, 0.66-0.96; p=0.014), and cardiovascular mortality (RR 0.71, 0.50-0.99; p=0.044) than control regimens. The effects seem to be consistent across a range of patient groups included in the studies. Treatment with agents that lower blood pressure should routinely be considered for individuals undergoing dialysis to reduce the very high cardiovascular morbidity and mortality rate in this population.
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The aim of this study was to evaluate the effect of treatment with subcutaneous injections of recombinant human erythropoietin (rhEpo), 20-40 IU kg-1 body weight, 3 times a week, on resting blood pressure, blood pressure response during submaximal exercise, some haematological parameters, and subjective side-effects in 15 healthy male subjects. RhEpo increased both haemoglobin (Hb) concentration and haematocrit (Hct) significantly, the values for Hb being 152 +/- 4.2 g l-1 before treatment and 169 +/- 9.3 g l-1 (mean values +/- SD) after 6 weeks of rhEpo treatment (P less than 0.001). The corresponding values for Hct were 44.5 +/- 1.5% and 49.7 +/- 1.9% (P less than 0.001), respectively. The systolic and diastolic blood pressure values at rest were unchanged after rhEpo treatment. A marked increase in systolic blood pressure was observed during submaximal exercise at 200 W, the initial and final values being 177 +/- 14.2 mmHg and 191 +/- 19.5 mmHg (P less than 0.01), respectively. Heart rate during exercise at 200 W was significantly lower after rhEpo treatment than before it: 144 +/- 15 beats min-1 compared to 136 +/- 8 beats min-1 (P less than 0.001). The leucocyte count remained unchanged after rhEpo treatment, but there was a significant decrease (P less than 0.05) in the number of lymphocytes. Reticulocyte and platelet counts were unchanged. Serum (S) ferritin decreased from 87.3 +/- 41.8 mmol l-1 to 59.3 +/- 27.8 mmol l-1 after rhEpo treatment (P less than 0.001). Serum-Na, S-K, S-Ca, S-creatinine, S-bilirubin, S-aspartate aminotransferase (ASAT), S-alanine aminotransferase (ALAT), and S-lactate dehydrogenase (LD) were unchanged after rhEpo treatment. No subjective side-effects were reported. In conclusion, low doses of rhEpo increased Hb levels and Hct by more than 10% after 6 weeks. Blood pressure at rest was unchanged, but rhEpo induced a markedly accentuated blood pressure reaction during exercise. A minor decrease in the lymphocyte count was observed, but electrolyte and creatinine levels remained unchanged after rhEpo treatment.
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The pharmacokinetics of verapamil were studied in patients with renal failure who were undergoing maintenance hemodialysis and in normal subjects after an IV infusion of 10 mg and a single oral dose of 120 mg. Plasma levels of verapamil and its active metabolite, norverapamil, were analyzed by a sensitive and specific HPLC procedure. Severe renal failure requiring hemodialysis did not change the time course of verapamil and norverapamil plasma concentrations after either the IV or oral dose. The terminal elimination rate constant, clearance, volume of distribution, and bioavailability of verapamil were not significantly different between the two groups of subjects. In addition, the apparent maximal plasma concentration, terminal elimination rate constant, and area under the curve for norverapamil were similar in patients with renal failure and normal subjects. The study showed that the plasma disposition of verapamil and norverapamil was not affected in patients with impaired renal function. Furthermore, this study does not indicate that any change in dosage is necessary when single doses of verapamil are administered to patients with renal failure.
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The chronic use of propranolol is characterized by 10%-20% decrements of renal plasma flow (RPF) and glomerular filtration rate (GFR). The results of most investigations, however, suggest that the use of nadolol, a long-acting nonselective agent, spares renal function. Similarly, intrinsic sympathomimetic activity (ISA)-positive and cardioselective beta-adrenergic inhibitors and the combined alpha-beta blocker, labetalol, appear to preserve renal hemodynamics. The reason(s) for the apparent disparate effects of various beta blockers is uncertain. The pathophysiological mechanisms are probably multifactorial and relate to either diminished cardiac output or increased renal vascular resistance, or both. It is possible that inhibition of renal vasodilator mechanisms plays a role. The explanation for the relative absence of adverse effects with a given medication probably varies from agent to agent. The clinical implications of beta-blocker-induced renal changes are presently unknown. The alterations are probably not clinically important in patients with normal renal function. In patients with underlying renal insufficiency, there is no reason to avoid the use of beta-adrenoceptor blockers. In some patients, however, one may wish to prescribe those beta blockers that tend to spare RPF and GFR.
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Treatment of hypertension with beta-adrenergic blockers may impair renal perfusion, perhaps because of beta 2-blockade in the renal vascular bed. We evaluated the effects of the cardioselective (beta 1 selective) beta-blocker metoprolol upon renal hemodynamics, intravascular volume, and renal electrolyte handling in nine essential hypertensive men. Metoprolol normalized systemic BP without significant acute or chronic changes in glomerular filtration rate, renal plasma flow, or renal blood flow. Overall renal sodium excretion and fractional sodium excretion increased on chronic metoprolol, without changes in intravascular volume or renal excretion of other electrolytes. Thus, cardioselective beta-blockade with metoprolol normalizes BP without renal hemodynamic impairment.
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The kinetics of tritiated metoprolol and its metabolites have been determined after intravenous and oral administration in dialysis patients. The kinetic behaviour of metoprolol in these patients does not differ from that in healthy volunteers, since its elimination depends on hepatic metabolism. The pharmacologically less active metabolite alpha-hydroxymetoprolol is formed to an individually varying degree and its half-life is prolonged. The concentration of the total radioactivity, which represents the sum of all metabolites, does not decline in the dialysis interval. During haemodialysis, however, its concentration decreases with a half-life of 5h. It might be assumed, that dialysis of these polar compounds is rather nonspecific and that it depends essentially on the dialysis technique.
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The effects on renal function and urinary albumin excretion of 7 years of antihypertensive treatment compared to the effects of normal aging were studied in a random sample of 40 men with newly diagnosed primary hypertension and in 17 normotensive men of the same age, respectively. The hypertensives were treated with metoprolol either as monotherapy (n = 21) or combined with hydrochlorothiazide or hydralazine. Glomerular filtration rate (GFR; inulin clearance), renal blood flow (RBF; para-aminohippurate clearance), renal vascular resistance (RVR), and the 24 h urinary albumin excretion were determined. GFR was significantly reduced from 104 +/- 15 mL/min (mean +/- SD) to 86 +/- 20 mL/min (P < .001) in the hypertensive group, but the reduction was not significantly greater than in the normotensive group. As judged from the study of a subgroup of the hypertensives, most of the decrease in GFR occurred early as an immediate drug-induced, functionally explained decrease. The changes in RBF and RVR after 7 years of treatment did not differ significantly from those due to normal aging. RVR remained higher and RBF remained lower in the hypertensives than in the normotensives. The urinary albumin excretion in the hypertensives was significantly reduced after 7 years but remained higher than in the normotensives. In conclusion, the changes in renal function and hemodynamics seen after long-term treatment with metoprolol in primary hypertension were not significantly different from the changes caused by normal aging in normotensives.