Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new moduretic research articles will be listed here shortly after becoming available to us.
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Medical research on moduretic
Niger Postgrad Med J. 2008 Mar; 15(1): 58-60
Puepet FH, Agaba EI, Chuhwak EK, Ugoya SO
OBJECTIVE: To draw attention to primary hyperparathyroidism as a cause of severe hypertension. RESULTS: A 47 year old Nigerian male presented with headache, occasional blurring of vision and dyspnoea on mild exertion of 2/12 duration. He had been troubled by painful osteoarthritis of the knees for 2 years for which he was taking NSAIDs. He was found to be severely hypertensive, BP 210/130mmHg and had bilateral knee crepitus. BP was resistant to control on Nifedipine R and Moduretic. Serum urea, creatinine, uric acid were normal but there was hyperacalcaemia and hyperchloraemia. Haematological indices, urinalysis, microscopy and culture of urine were normal. Parathyroid hormone level was raised. A parathyroid MIBI scan study showed an extensive area of significance towards the inferior pole of the right lobe of thyroid medially with a second area of very low significance medial to the left pole. These findings indicated the presence of a right inferior parathyroid adenoma. He had parathyroid surgery and a large adenoma in the right inferior gland and a smaller left inferior gland were removed and confirmed histologically. Corrected calcium and parathyroid hormone levels dropped to normal, and the BP was easily controlled with Lisinopril 5mg daily subsequently. He is not currently on antihypertensive medication two years post surgery. CONCLUSION: This case highlights the need for thorough investigation of cases of hypertension to exclude specifically secondary causes, which in some cases may be endocrine in origin and may easily be corrected.
Drugs. 2006; 66 Spec No 1: 13-5
Matsuoka H
Treatment with antihypertensive drugs improves prognosis in patients with hypertension. The single-blind STONE (Shanghai Trial of Nifedipine in the Elderly) study conducted in elderly Chinese patients with hypertension proved that treatment with a Ca2+ channel antagonist led to improvement of prognosis. Compared with placebo, treatment with twice-daily nifedipine significantly decreased the relative risk of cardiovascular events, especially stroke. The randomised, double-blind INSIGHT (International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment) study compared nifedipine GITS with the diuretic combination of amiloride plus hydrochlorothiazide (co-amilozide) in hypertensive patients. The investigators found a similar cardiovascular event rate with nifedipine GITS and co-amilozide, but nifedipine prevented new-onset of diabetes and hyperlipidaemia. Besides, inhibition of carotid artery thickening and slowing of coronary artery calcification was also confirmed with nifedipine GITS in a side-arm study of the INSIGHT study. From these data it is evident that treatment with long-acting nifedipine improves prognosis in patients with hypertension.
Hong Kong Med J. 2007 Dec; 13(6): 471-4
Yip KK, Yeung WT
We report a case of lithium overdose in a patient who presented in non-convulsive status epilepticus. The lithium toxicity was probably due to interaction with Moduretic. The diagnosis was not suspected until electroencephalography was performed. This case underscores the importance of therapeutic drug level monitoring of lithium, especially where toxicity is suspected, and the indispensable role electroencephalography plays by allowing a correct diagnosis to be made promptly.
J Pharm Pharm Sci. 2005; 8(2): 235-42
Yusuff KB, Balogun O
PURPOSE: To evaluate physicians' prescribing of anti-hypertensive drug combinations in a tertiary care setting in southwestern Nigeria, determine the degree of usage of Angiotensin Converting Enzyme (ACE) inhibitor-based combinations and identify specific points of intervention to improve outcomes of anti-hypertensive combination therapy. METHODS: A cross-sectional retrospective drug use review was conducted between June 1st and August 31st 2002 using randomly selected 200 case notes of patients attending the Hypertension Clinic at a 900-bed tertiary care facility in southwestern Nigeria. 11 case notes were not used due to incompleteness. RESULTS: 73% (138) of the patients were on anti-hypertensive drug combinations, comprising 71.7% (99), 24.4% (34) and 3.6% (5) on combinations of two, three and four drugs respectively. Overall, Thiazide diuretic consisting mainly of fixed dose combination of Amiloride and Hydorchlorothiazide (Moduretic(r)) was the most frequently prescribed drug class in anti-hypertensive combination therapy (83.3%). ACE inhibitor, Lisinopril (Zestril(r)), was prescribed in combination with Moduretic(r), Calcium channel blocker and beta-blocker in 6.5%, 8.5% and 0.7% respectively. Blood pressure control was adequate in only 29% (40) of patients, though adherence with therapy was documented as adequate in 77.5% (107). Type-2 diabetes mellitus (32.7%) and osteoarthritis (21.8%) were the most frequent co-morbidities. Potentially harmful drug-drug interactions in the study sample were identified in 17.5% (46) of patients. Physician documentation of adverse drug reactions among patients was done in only 10.9% of cases. There appear to be no institutionalised system in place to monitor, detect and document adverse drug reactions among patients on anti-hypertensive drug therapy. CONCLUSION: Physicians' prescribing of anti-hypertensive drug combinations in a tertiary care setting in southwestern Nigeria is considerable. However, this practice does not appear to have positively impacted on blood pressure control among hypertensive patients nor being modulated by an Institutionalised standard guide.
Blood Press. 2004; 13(5): 310-5
Mancia G, Ruilope L, Palmer C, Brown M, Castaigne A, De Leeuw P, Rosental T, Wagener G
AIMS: This study tested the effects on cardiovascular outcomes of treatments based on nifedipine gastrointestinal therapeutic system (GITS) compared with the diuretic combination co-amilozide in a pre-specified subset of patients with isolated systolic hypertension (ISH) enrolled in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) study. MAJOR FINDINGS: Of 6321 randomized patients, 1498 (23.7%) had ISH with a baseline mean BP of 173/88 mmHg in both treatment groups. Mean BP fell by 29/10 mmHg in the nifedipine and 30/10 mmHg in the diuretic group to a mean BP of 144/78 mmHg and 143/79 mmHg, respectively, at endpoint. The percentage of primary outcomes in patients with ISH was not significantly different between the two treatment groups (nifedipine GITS 6.0%, co-amilozide 6.6%). The number of ISH patients with composite secondary outcomes was 90 (12.2%) in the nifedipine GITS group and 110 (14.5%) in the co-amilozide group (not significant). The incidence rates of primary and secondary outcomes were similar in patients without ISH. CONCLUSION: In patients with ISH, nifedipine GITS and co-amilozide had similar effects on clinical outcomes and BP lowering. They lend support to international guidelines for the treatment of hypertension recommending the use of long-acting dihydropyridine calcium-channel blockers as one treatment option for patients with ISH.
Low-renin status in therapy-resistant hypertension: a clue to efficient treatment.
J Hypertens. 2004 Nov; 22(11): 2217-26
Eide IK, Torjesen PA, Drolsum A, Babovic A, Lilledahl NP
OBJECTIVE: Therapy resistance is an enduring problem in clinical hypertension. Our aims were to estimate: (1) the contribution of a low-renin status in therapy resistance; (2) whether such status could give a clue to more successful treatment; and (3) the contribution by adrenal cortical adenomas and by primary aldosteronism. SETTING: Patients were referred from general and internal medicine practices following written invitations and included consecutively. Participants were examined and followed-up on an outpatient basis. DESIGN AND INTERVENTIONS: Patients were divided according to renin status. Low-renin patients were treated with an aldosterone inhibitor in a prospective, randomized, placebo-controlled, double-blind, cross-over study. MAIN OUTCOME MEASURES: Prevalence of low-renin status in therapy resistance. Blood pressure and hormonal responses to specific treatment. Numbers of adrenocortical adenomas and primary aldosteronism. RESULTS: In 90 treatment-resistant hypertensive, 67% had plasma renin activity (PRA) below 0.5 nmol/l per hour. Of the 60 low-renin patients, 38 were studied on a fixed combination of amiloride and hydrochlorothiazide. Three weeks' treatment reduced blood pressure by 31/15 mmHg compared to placebo (P < or = 0.0001). Serum aldosterone and plasma renin activity increased substantially during active treatment. Through the subsequent 6-12 months of open treatment, seven patients (18%) showing an escape phenomenon had their high blood pressure effectively treated by extra amiloride. Of the 60 low-renin patients, eight had adrenal adenoma. CONCLUSION: A low-renin status characterized two-thirds of patients with treatment-resistant hypertension, who could be treated efficiently by aldosterone inhibition. Patients with an escape phenomenon (18%) could effectively be treated by increasing the aldosterone inhibitor. Low-renin hypertensives had high prevalence of adrenocortical adenomas and primary aldosteronism.
Calcium antagonists and atherosclerosis protection in hypertension.
Am J Ther. 2003 Nov-Dec; 10(6): 409-14
Hernández RH, Armas-Hernández MJ, Velasco M, Israili ZH, Armas-Padilla MC
Calcium antagonists are effective in hypertensive patients of all ethnic groups, irrespective of age, dietary salt intake, salt-sensitivity status or plasma renin activity profile. Some prospective studies show that the calcium antagonists, nifedipine GITS and nitrendipine, reduce cardiovascular morbidity and mortality at least to the same extent as the diuretics. Other prospective studies are in progress to evaluate the effect of calcium antagonists on cardiovascular morbidity and mortality, and the progression of atherosclerosis in hypertensive patients. Calcium antagonists, especially the highly lipophilic amlodipine, lacidipine and nisoldipine, are shown to possess antioxidant properties. These drugs reduce the oxidation of LDL and its influx into the arterial wall, and reduce atherosclerotic lesions in animals. Platelet production of malondialdehyde, a marker of oxygen free radical formation, is suppressed by amlodipine, lacidipine or nifedipine in hypertensive patients. New evidence from long-term clinical trials of calcium antagonists indicates that these drugs can reduce the rate of progression of atherosclerosis in hypertensive and coronary heart disease patients. In the Regression Growth Evaluation Statin Study (REGRESS), co-administration of calcium antagonist, amlodipine or nifedipine with pravasatin caused a significant reduction in the appearance of new angiographic lesions. In the Verapamil in Hypertension and Atherosclerosis Study (VHAS), verapamil was more effective than chlorthalidone in promoting regression of thicker carotid lesions in parallel with a reduction in the incidence of cardiovascular events. In the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT), amlodipine slowed the progression of early coronary atherosclerosis in patients with coronary artery disease. In a subprotocol of the Intervention as a Goal in the Hypertension Treatment (INSIGHT) study, nifedipine GITS significantly decreased intima-media thickness as compared to co-amilozide (hydrochlorothiazide + amiloride). Preliminary results of the European Lacidipine Study on Atherosclerosis (ELSA) show that lacidipine reduced the intima-media thickness progression rate as compared to atenolol. Thus, selective calcium antagonists are potential antiatherosclerotic agents.
Recessive type of nephrogenic diabetes insipidus.
Am J Kidney Dis. 2003 Oct; 42(4): A41, E1
Vandermarliere A, Maes B, Vanrenterghem Y
Current treatment of patients with hypertension: therapeutic implications of INSIGHT.
Drugs. 2003; 63(14): 1435-44
Taddei S, Ghiadoni L, Salvetti A
When planning treatment for patients with hypertension, current guidelines emphasise the importance of risk stratification, based on blood pressure, the presence of end-organ damage and other cardiovascular risk factors. Because the beneficial effect of antihypertensive therapy seems to be linked to the degree of blood pressure reduction, guidelines recommend reducing blood pressure below 140/90mm Hg, with a lower target in patients who are young or who have diabetes mellitus (with or without nephropathy) or non-diabetic nephropathy. Blood pressure reduction can be achieved with several classes of drugs, including diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists and calcium channel antagonists. Calcium channel antagonists have been shown to reduce the risk of stroke and major cardiovascular events. However, it is still controversial whether different treatment regimens based on different drug classes can offer advantages beyond similar degrees of blood pressure control in preventing cardiovascular morbidity and mortality. The International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) was a controlled clinical trial aimed at comparing the efficacy of a long-acting calcium channel antagonist, nifedipine gastrointestinal-transport-system (GITS), versus co-amilozide, a combination of the diuretics hydrochlorothiazide (HCTZ) and amiloride, on morbidity and mortality in high-risk hypertensive patients. Nifedipine GITS and HCTZ/amiloride were equally effective at reducing blood pressure and the risk of primary outcomes (a composite of death from any cardiovascular or cerebrovascular cause, non-fatal stroke, myocardial infarction and heart failure). Results from other studies indicate that there may be greater benefits for stroke and smaller benefits for coronary artery disease with calcium channel antagonist-based regimens than with diuretic or beta-blocker-based regimens. However, there is at present insufficient evidence to recommend a specific drug choice based on patient risk profile. Thus, the choice of antihypertensive drug(s) should be according to efficacy and tolerability. In addition to the reductions in cardiovascular risk, two substudies of INSIGHT showed that nifedipine GITS was able to prevent the progression of intima media thickness in the common carotid artery and slow the progression of coronary calcification. The clinical significance of this effect in the prevention of cardiovascular events still remains to be established.
Hypertension. 2003 Mar; 41(3): 431-6
Mancia G, Brown M, Castaigne A, de Leeuw P, Palmer CR, Rosenthal T, Wagener G, Ruilope LM,
To investigate the impact of treatment on cardiovascular mortality and morbidity, we assessed outcomes in patients with hypertension and diabetes who received co-amilozide or nifedipine in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension. Participants had to be 55 to 80 years of age, with hypertension (> or =150/95 or > or =160 mm Hg) and at least one additional cardiovascular risk factor. Patients received 30 mg nifedipine once daily or co-amilozide (25 mg hydrochlorothiazide and 2.5 mg amiloride) daily. Doses were doubled if target blood pressures (