Thirtytwo patients with hypertension and nine patients with idiopathic renal hypouricemia five with and four without hypertension were enrolled for this study. Elizabeth ripley, ari hirschdivision of nephrology, virginia commonwealth university, richmond, virginia, usaabstract. Antihypertensive drugs and risk of incident gout among. To explore the effect of urate transporter 1 urat1 polymorphisms on the hypertensive patients with hyperuricemia and the uricosuric action of losartan therapy among hypertensive patients with. Renal effects of angiotensin ii receptor blockade in.
Swelling of your face, throat, eyes, legs, or other body parts. Uricosuric effects of angiotensin ii receptor antagonists. Methods losartan 50 mg was administered orally to 6 healthy males. Antihypertensives in people with gout or asymptomatic. Subsequently, the uricosuric effect of losartan was demonstrated in normotensive subjects studied on a high and a lowsodium diet 151.
Uricosuric medications drugs are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. Long term uricosuric therapy in gout university of michigan. Summarya substantial body of epidemiological and experimental evidence suggests that serum uric acid is an important, independent risk factor for cardiovascular and renal disease especially in patients with hypertension, heart failure, or diabetes. Highdose salicylate and indomethacin have both been studied uricosutic their uricosuric effects shin et effetc. Tell your doctor if any side effect gets worse or does not go away. If a clinically significant decrease in renal function. Mar 27, 2010 the heaal investigators nov 28, p 18401 show that highdose losartan, compared with lowdose losartan, can reduce mortality and readmission to hospital in patients with heart failure. Effects of combination treatment using antihyperuricaemic. Effect of the angiotensin ii receptor antagonist losartan on. Losartan, sold under the trade name cozaar among others, is a medication mainly used to treat high blood pressure.
Blood and urine samples for uric acid and oxypurine were collected before and up to 6 hours after losartan administration. Uricosuric effects of angiotensin ii receptor antagonists in. Effects of losartan and diltiazem on blood pressure, insulin. We hypothesize that the individual effect of both drugs on uricemia are counteracted in the combination of lh, whereas the capacity of amlodipine to lower serum uric acid levels was added to the uricosuric effects of losartan. Renal clearance of urate was increased 3fold in crf rats and 2fold in control rats after 7.
The uricosuric effect of losartan appears to be independent of the degree of activity of the raas as it was comparable with both types of sodium diet. Losartan also has a uricosuric effect not seen in other arbs and attenuates platelet aggregation, which is not seen or is seen to a lesser extent with the other arbs. Losartanhydrochlorothiazide is a prescription medication. The increase was found to be dose dependent and to persist after seven days of administration. Your voice becomes hoarse, or you have difficulty breathing or tightness in your throat. Effects of losartan and irbesartan on serum uric acid in hypertensive. The authors suggest that urate lowering antihypertensive drugs could help to reduce the high comorbidity burden of gout and hypertension in patients at high risk of developing gout. Therefore, the present study was designed to observe the effect of losartan on different biochemical parameters in essential hypertension. Twenty seven patients with gout were included in a fenofibrate plus antihyperuricaemic agents combination study, and 25 in a losartan plus antihyperuricaemic. Highdose versus lowdose losartan in patients with heart. Losartan inhibits the pressor effect of angiotensin ii as well as angiotensin i infusions. In contrast to irbesartan, losartan was uricosuric and decreased serum uric acid levels. Effect of losartan combined with amlodipine or with a.
Effects of losartan and candesartan on bp and renal. The angiotensin ii receptor antagonist losartan is an effective antihypertensive agent with unique uricosuric properties. Removal of the negative feedback of angiotensin ii causes a 2 to 3fold rise in plasma renin activity and. Effects of losartan and diltiazem on blood pressure. Urat1 is the central mediator in the transport of uric acid from the kidney into the blood. Pilot study of the uricosuric effect of dup753, a new. In general, uricosuric drugs act on the proximal tubules in the kidneyswhere they interfere with the absorption of uric acid from the kidney back into the blood. Losartan is the only arb that is uricosuric, which is independent of at 1 receptor blockade.
Losartan, the first at1 receptor blocker arb, was fda approved 15 years ago. To determine if this effect can increase the risk of acute urate nephropathy. Wilcoxons test was used to assess the effect of losartan on hypouricemic patients. Drugs that reduce blood uric acid are not all uricosurics. The effects of the addition of losartan on uric acid. Uricosuric action of losartan via the inhibition of urate transporter 1. As a specific inhibitor of the urate transporter 1 slc22a12, urat1, losartan blocks the uptake of uric acid into cells, thus leaving more available in the bloodstream to be filtered and excreted by the kidneys. The heaal investigators nov 28, p 18401 show that highdose losartan, compared with lowdose losartan, can reduce mortality and readmission to hospital in patients with heart failure. Dailymed losartan potassium and hydrochlorothiazide tablet. The active metabolite is 10 to 40 times more potent by weight than. This study evaluates the uricosuric effects of losartan in 10 hypertensive heart transplant patients with hyperuricemia. Participants all incident cases of gout n24 768 among adults aged 2079 and a random sample of 50 000 matched controls.
The uricosuric effect of losartan appears to decrease with time when a new steady state of lower serum uric acid is reached. The angiotensin ii receptor blocker losartan lowers serum concentration of urate sur in hypertensive subjects through a significant uricosuric action. The clinical response to losartan potassium and hydrochlorothiazide tablets 50 mg12. Main outcome measure relative risk of incident gout. Materials and methods the present work was an open prospective study conducted in an opd of medicine department of 50. The 2012 acr guidelines endorse the use of additional uricosuric agents such as fenofibrate and losartan in combination with xanthine oxidase.
Effects of losartan and irbesartan on serum uric acid in. Angiotensin is known to lower uric acid renal clearance, but the uricosuric effect of losartan did not appear to be mediated by angiotensin inhibition. Effect of a reduction in uric acid on renal outcomes. To determine if this effect can increase the risk of acute urate nephropathy, 63 hypertensive patients with.
Oct 14, 2019 the clinical response to losartan potassium and hydrochlorothiazide tablets 50 mg12. Losartan is a prescription drug used to treat hypertension high blood pressure. Comparative effects of losartan and irbesartan on serum. Uricosuric medications are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. Nov 10, 2005 losartan, an angiotensin ii receptor antagonist, is an effective antihypertensive drug that also has a uricosuric effect due to its molecular disposition or physical property. Pdf the hypotensive and uricosuric effect of valsartan compared. Hyperuricaemia has been shown to be a strong, independent. In some persons with lossoffunction mutations of urat1, the uricosurics benzbromarone and losartan had no effect, suggesting these drugs act on urat1 in vivo. To determine if this effect can increase the risk of acute urate nephropathy, 63 hypertensive patients with thiazideinduced asymptomatic hyperuricemia serum uric acid 7.
Losartan is an angiotensin ii receptor blocker arb that has uricosuric effects via inhibition of the urat1 and glucose transporter glut9. Safety of losartan in hypertensive patients with thiazide. Conclusions losartan, which has a high affinity for the urateanion exchanger, has a transient uricosuric effect. Effect of a reduction in uric acid on renal outcomes during.
The effect of angiotensin ii receptor blockers on hyperuricemia. Hyperuricaemia has been shown to be a strong, independent marker of. Repeated dosing with losartan resulted in a gradual waning of uricosuric and ph effects. Comparative effects of losartan and irbesartan on serum uric. Elevated serum uric acid is highly predictive of mortality in patients with heart failure or coronary artery disease and of cardiovascular events. To assess the effect of a combination treatment using antihyperuricaemic agents with fenofibrate andor losartan on uric acid metabolism in hypertriglyceridaemic andor hypertensive patients with gout. Uricosuric action of losartan via the inhibition of urate. Objective the acute effects of the angiotensin ii receptor antagonist losartan on uric acid and oxypurine metabolism were evaluated. When one compares the baseline values with those on the various drugs, one sees that with each drug employed, the majority of patients experienced an increase in. Effect of losartan on different biochemical parameters in. A dose of 100 mg inhibits the pressor effect by about 85% at peak with 2540% inhibition persisting for 24 hours. Losartan is an orally active agent that undergoes substantial firstpass metabolism by cytochrome p450 enzymes. Our data indicate that losartan induces a significant decrease in the urinary excretion of hypoxanthine without changes in xanthine.
In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the at1 receptor. This agent promotes uric acid excretion via effects on the organic anion transport the aiia losartan also produces a uricosuric effect in healthy volunteers. Effect of the angiotensin ii receptor antagonist losartan. Its also used to treat diabetic nephropathy, and to reduce stroke risk. Treatment with the antihypertensive drug losartan lowers sua. Mean systolic and diastolic bp were reduced in the candesartan group, from 156 mm hg at baseline to 2 mm hg at 24 weeks, and from 90. Uricosuric effect of losartan in patients with renal transplants. However, it is still unknown whether the inhibitory effect of losartan on urat1 contributes to its uricosuric action in humans.
Thus, uricosuric drugs may be candidates for management in a personalized medicine model. Pdf the hypotensive and uricosuric effect of valsartan. Uricosuric effect of the angiotensin ii receptor antagonist. Losartan uricosuric effect pdf wonderful australia. Uricosuric definition of uricosuric by medical dictionary.
Objective to determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension. The effect of uricosuric drugs on urate excretion as measured by the urate a1earance. Urat1 gene polymorphisms influence uricosuric action of. Possible mechanisms for the hypouricemic effects of the angiotensin ii receptor antagonist losartan were examined using rats with experimental chronic renal failure crf and control animals. Effects of the specific angiotensin ii receptor antagonist. To investigate the effect of losartan versus diltiazem on blood pressure, albuminuria, insulin sensitivity and lipid profile in a randomised, open study. The dosedependent sideeffects of losartan such as renal impairment, hypotension, and hyperkalaemia were more common in the highdose group. Losartan was first reported to decrease sua in a dosedependent manner with single doses ranging from 25200 mg.
In general, this effect is achieved by action on the proximal tubule of the kidney. Effect of losartan versus candesartan on uric acid, renal. A literature search of medline 1946 to june 2015 and embase 1947 to june 2015 was conducted. Fenofibrate and losartan annals of the rheumatic diseases. Losartan metabolites have been identified in human plasma and urine. Jan 12, 2012 objective to determine the independent associations of antihypertensive drugs with the risk of incident gout among people with hypertension.
It is also used for diabetic kidney disease, heart failure, and left ventricular enlargement. Longterm comparison of losartan and enalapril on kidney. Effects of losartan on a background of hydrochlorothiazide. Whereas some studies demonstrated a significant uricosuria with losartan,5,10,11 others failed to do so.
Materials and methods the present work was an open prospective study conducted in an opd of medicine department of 50 bed multispecialty private hospital in western maharashtra. Comparative effects of chronic ace inhibition and at1. Both losartan and enalapril administered alone or in combination with other agents induced significant reductions in sitting clinic p effect of losartan on urat1 contributes to its uricosuric action in humans. A total of 59 patients were entered into the study 30 in the losartan and 29 in the candesartan group. Further suggestions of an effect independent of angiotensin ii receptor blockade came from the observation that the uricosuric effect did. Abstract the purpose of this multicenter trial was to compare the antihypertensive efficacy and safety of losartan potassium losartan, a selective angiotensin ii receptor antagonist, when added to hydrochlorothiazide in hypertensive patients whose blood pressure was not adequately controlled by 25 mg hydrochlorothiazide monotherapy.
Patient information for losartan potassium liconsa 50 mg filmcoated tablets including dosage instructions and possible side effects. The result is the significant reduction in uricemia that we observed. Twenty seven patients with gout were included in a fenofibrate plus antihyperuricaemic agents combination study, and 25 in a losartan plus antihyperuricaemic agents. The same examinations were performed later using enalapril 5 mg. Data sources include ibm watson micromedex updated 10 apr 2020, cerner multum updated 6 apr 2020, wolters kluwer updated.
It is converted, in part, to an active carboxylic acid metabolite that is responsible for most of the angiotensin ii receptor antagonism that follows losartan treatment. This drug is available as the brandname drug hyzaar and as a generic drug. Early studies in the healthy population demonstrated that the peak uricosuric effect was already observed 2 to 4 hours after administration. Losartan, an angiotensin ii receptor antagonist, is an effective antihypertensive drug that also has a uricosuric effect due to its molecular.
Up to six weeks may be required for the full effects to occur. Serum urate response to uricosuric theravu average serum urate before therapy on therapy no. Losartan, an angiotensin ii receptor antagonist, is an effective antihypertensive drug that also has a uricosuric effect due to its molecular disposition or physical property. During those years, researchers and clinicians have developed a growing base of. Safety of losartan in hypertensive patients with thiazideinduced. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Losartan showed a slightly higher hypotensive effect. Jan 12, 2012 the authors suggest that urate lowering antihypertensive drugs could help to reduce the high comorbidity burden of gout and hypertension in patients at high risk of developing gout. The uricosuric response to losartan was comparable with both types of sodium diet, suggesting that the uricosuric effect of this compound is independent of the blockade of the reninangiotensin. It may be used alone or in addition to other blood pressure medication. Losartanhydrochlorothiazide is a prescription drug thats used to treat high blood pressure hypertension. Indicated for diabetic nephropathy with an elevated serum creatinine and proteinuria urinary albumin to creatinine ratio. The results show that losartan has a uricosuric effect in rats with normal or decreased renal function.
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