Slow release nifedipine and atenolol as initial treatment in blacks with malignant hypertension
01 Apr 1986-British Journal of Clinical Pharmacology (Br J Clin Pharmacol)-Vol. 21, Iss: 4, pp 377-383
TL;DR: Recommendations that most patients with malignant hypertension can be managed without recourse to parenteral therapy are supported.
Abstract: We have compared the efficacy and safety of slow release nifedipine and atenolol given orally as initial treatment for malignant hypertension. Twenty consecutive black patients with untreated malignant hypertension, whose diastolic pressure remained greater than 120 mm Hg after 3 h bed rest, were randomized to receive either slow release nifedipine 40 mg at 1 and 12 h, or atenolol 100 mg at 0 h only. Patients remained supine throughout the study. Blood pressure was measured using a semi-automatic recorder (Omega 1000) at 15 min intervals from -3 to 24 h. Baseline blood pressure was similar in the nifedipine (233/142 mm Hg) and atenolol (226/141 mm Hg) groups. The rate of fall of pressure was greater after nifedipine whose maximum hypotensive effect occurred 4-5 h after each dose. Blood pressure decreased more slowly and more enduringly after atenolol, although the extent of fall was the same (delta BP 5 h after first dose nifedipine = 67/41 mm Hg; delta BP 16 h after atenolol = 64/40 mm Hg). There were no precipitous falls in pressure. No patient developed focal neurological signs, nor was heart failure precipitated by either form of treatment. These results support recommendations that most patients with malignant hypertension can be managed without recourse to parenteral therapy.
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TL;DR: Preliminary findings indicate that sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud’s phenomenon.
Abstract: Nifedipine antagonises influx of calcium through cell membrane slow channels, and sustained release formulations of the calcium channel blocker have been shown to be effective in the treatment of mild to moderate hypertension and both stable and variant angina pectoris. Preliminary findings also indicate that these formulations are effective in the treatment of Raynaud's phenomenon and hypertension in pregnancy, and that they reduce the frequency of ischaemic episodes in some patients with silent myocardial ischaemia. The exact mechanism of action of nifedipine in all of these disorders has not been defined. However, its potent peripheral and coronary arterial dilator properties, together with improvements in oxygen supply/demand, are of particular importance. A major goal of sustained release therapy is to permit reductions in the frequency of nifedipine administration, preferably to once daily, and thus improve patient compliance. Two new once-daily formulations--the nifedipine gastrointestinal therapeutic system (GITS) and a fixed combination capsule comprising sustained release nifedipine 20 mg and atenolol 50 mg--have exhibited marked antihypertensive efficacy. The GITS preparation has also been used effectively in the treatment of stable angina pectoris, and both formulations appear to be well tolerated. Sustained release nifedipine formulations are generally better tolerated than their conventionally formulated counterparts, particularly with regard to reflex tachycardia. Adverse effects seem to be dose related, are mainly associated with the drug's potent vasodilatory action, and include headache, flushing and dizziness. Generally, these effects are mild to moderate in severity and transient, usually diminishing with continued treatment. Thus, sustained release nifedipine formulations are useful and established cardiovascular therapeutic agents which have demonstrable efficacy in various forms of angina, mild to moderate hypertension and Raynaud's phenomenon. Further, promising results shown by the nifedipine GITS formulation, with its advantage of once daily administration suggest that it is likely to become one of the preferred nifedipine formulations for the treatment of hypertension and the various forms of angina.
62 citations
01 Jan 2005
TL;DR: Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension: a report from Japan intended for the global renal protection in hypertensive patients (jlight study).
Abstract: s). Iino Y and Kawaguchi Y. Renoprotective effect of losartan in comparison to amlodipine in patients with chronic kidney disease and hypertension: a report from japanese losartan therapy intended for the global renal protection in hypertensive patients (jlight study). Nephrology Dialysis Transplantation 2003;18(Supplement
43 citations
TL;DR: There is important evidence in favor of the use of angiotensin-converting enzyme inhibitors for treating hypertensive urgencies, compared with calcium channel blockers, considering the better effectiveness and the lower frequency of adverse effects (like headache and flushing).
Abstract: CONTEXT AND OBJECTIVE: Hypertensive urgencies are defined as severe elevations in blood pressure without evidence of acute or progressive target-organ damage. The need for treatment is considered urgent but allows for slow control using oral or sublingual drugs. If the increase in blood pressure is not associated with risk to life or acute target-organ damage, blood pressure control must be implemented slowly over 24 hours. For hypertensive urgencies, it is not known which class of antihypertensive drug provides the best results and there is controversy regarding when to use antihypertensive drugs and which ones to use in these situations. The aim of this review was to assess the effectiveness and safety of oral drugs for hypertensive urgencies. METHODS: This systematic review of the literature was developed at the Brazilian Cochrane Center, and in the Discipline of Emergency Medicine and Evidence-Based Medicine at the Universidade Federal de Sao Paulo — Escola Paulista de Medicina (Unifesp-EPM), in accordance with the methodology of the Cochrane Collaboration.RESULTS: Sixteen randomized clinical trials including 769 participants were selected. They showed that angiotensin-converting enzyme inhibitors had a superior effect in treating hypertensive urgencies, evaluated among 223 participants. The commonest adverse event for calcium channel blockers were headache (35/206), flushing (17/172) and palpitations (14/189). For angiotensin-converting enzyme inhibitors, the principal side effect was bad taste (25/38). CONCLUSIONS: There is important evidence in favor of the use of angiotensin-converting enzyme inhibitors for treating hypertensive urgencies, compared with calcium channel blockers, considering the better effectiveness and the lower frequency of adverse effects (like headache and flushing).
31 citations
TL;DR: The variation in properties of beta adrenoceptor blocking drugs can be used as a basis for classification and beta1 selective drugs have been previously termed ‘cardioselective’ reflecting their preferential effect on the heart in contrast to certain other tissues, such as bronchial smooth muscle.
Abstract: The variation in properties of beta adrenoceptor blocking drugs can be used as a basis for classification. There are those which are non-selective, those which have a selective action on the beta1receptors, and then those drugs which in addition possess vasodilator or alpha receptor blocking properties. They may be further sub-divided into various groups according to the presence or absence of intrinsic sympathomimetic activity (I.S.A) or partial agonist activity and membrance stabilising activity (M.S.A) [1, 2, 3] (Table 1). Beta1 selective drugs have been previously termed ‘cardioselective’ reflecting their preferential effect on the heart in contrast to certain other tissues, such as bronchial smooth muscle, however as beta1 and beta2 receptors are found in the heart the term ‘cardioselective’ is inaccurate.
26 citations
TL;DR: The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system.
Abstract: The major antihypertensive mechanism of calcium antagonists is by decreasing the systemic vascular resistance, modified by the counter-regulatory responses of the baroreflexes and the renin-angiotensin-aldosterone system. In severe hypertension, the concept that calcium overload of the vascular myocyte could precipitate or aggravate peripheral vasoconstriction provides a logical basis for the use of these agents as first choice therapy; nifedipine, especially, has been well tested. As monotherapy for mild to moderate hypertension each of the three first-generation agents compares well with β-blockers. Calcium antagonists may have a special role in the therapy of certain patient groups (elderly, black) or in those subjects whose life style involves intense physical or mental exertion (hemodynamics better maintained than with β-blockade) or in patients with early end-organ damage such as left ventricular hypertrophy or renal insufficiency. However, the goal blood pressure may not be reached during monotherapy so that drug combinations may be required. Further indications for these compounds are as follows. Verapamil and diltiazem are frequently used in supraventricular tachycardias including acute and chronic atrial fibrillation. In the arrhythmias of the Wolff-Parkinson-White syndrome, there is the potential danger of provocation of anterograde conduction. Further indications for calcium antagonists, still under evaluation, include congestive heart failure (controversial), hypertrophic cardiomyopathy (verapamil), primary pulmonary hypertension (high doses required), Raynaud's phenomenon (nifedipine and diltiazem effective), peripheral vascular disease (proof not yet documented), cerebral insufficiency and subarachnoid hemorrhage (nimodipine promising), migraine, exertional bronchospasm, renal disease, atherosclerosis (experimental), and primary aldosteronism (nifedipine inhibits aldosterone release). Second-generation agents include dihydropyridines, such as nitrendipine, nicardipine, felodipine, amlodipine, nisoldipine, nimodipine, and isradipine. From these will be selected agents that are longer acting and provide higher vascular selectivity. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. Minor side effects include those caused by vasodilation (flushing and headaches), constipation (verapamil), and ankle edema. Serious side effects are rare and result from improper use of these agents, as when intravenous verapamil is given to patients with sinus or atrioventricular nodal depression from drugs or disease, or nifedipine to patients with aortic stenosis. The potential of a marked negative inotropic effect is usually offset by afterload reduction, especially in the case of nifedipine. Yet caution is required when calcium antagonists, especially verapamil, are given to patients with myocardial failure unless caused by hypertensive heart disease. Drug interactions of calcium antagonists occur with other cardiovascular agents such as α-adrenergic blockers, β-adrenergic blockers, digoxin, quinidine, and disopyramide. Combination therapy of calcium antagonists with β-blockers is increasingly common, and is probably safest in the case of the dihydropyridines. Other combinations being explored are with angiotensin-converting enzyme inhibitors and diuretics. With the correct selection of drug and patient, the calcium antagonists as a group can be remarkably effective at relatively low cost of serious side effects.
20 citations
References
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TL;DR: It is concluded that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.
Abstract: We enrolled 125 neurologically normal patients with intracranial aneurysms in a multi-institution, prospective, double-blind, randomized, placebo-controlled trial within 96 hours of their subarachnoid hemorrhage, to determine whether treatment with the calcium blocker nimodipine would prevent or reduce the severity of ischemic neurologic deficits from arterial spasm. A deficit from cerebral arterial spasm that persisted and was severe or caused death by the end of the 21-day treatment period occurred in 8 of 60 patients given placebo and in 1 of 56 given nimodipine (P = 0.03, Fisher's exact test). Analysis of the amount of basal subarachnoid blood on pre-entry CAT scans in patients with deficits from spasm showed that an increase in subarachnoid blood was not associated with a worse neurologic outcome among patients who received nimodipine, unlike the situation in patients given a placebo. There were no side effects from nimodipine. We conclude that nimodipine should be given to patients who are neurologically normal after subarachnoid hemorrhage in order to reduce the occurrence of severe neurologic deficits due to cerebral arterial spasm.
1,021 citations
TL;DR: The observations in effectively treated hypertensive patients strongly suggested a readaptation of CBF autoregulation toward normal in some cases, and it was found that 8–12 months of antihypertensive treatment on average did not influence the lower limit of CBf autoreGulation.
Abstract: Autoregulation of cerebral blood flow (CBF) was studied by the arteriovenous oxygen difference method in 13 patients with untreated or ineffectively treated severe hypertension, nine patients with effectively treated, formerly severe hypertension, and ten normotensive controls. Resting mean blood pressure in these three groups was 145 +/- 17 (1 SD) mm Hg, 116 +/- 18 mm Hg, and 98 +/- 10 mm Hg, respectively. Blood pressure was decreased by trimethaphan infusion combined with head-up tilt. The lower limit of CBF autoregulation in the three groups was 113 +/- 17 mm Hg, 96 +/- 17 mm Hg, and 73 +/- 9 mm Hg, and the lowest tolerated blood pressure where mild symptoms of brain hypoperfusion were encountered was 65 +/- 10 mm Hg, 53 +/- 18 mm Hg, and 43 +/- 8 mm Hg. These pressures were all significantly higher (P less than 0.01) in the group of untreated or ineffectively treated hypertensive patients than in the normotensive group demonstrating a shift of CBF autoregulation in the former. The observations in effectively treated hypertensive patients strongly suggested a readaptation of CBF autoregulation toward normal in some cases. In four hypertensive patients studied twice it was found that 8-12 months of antihypertensive treatment on average did not influence the lower limit of CBF autoregulation.
542 citations
TL;DR: Methods for the quantitative detection of unchanged nifedipine in the presence of the pyridine analog in plasma (HPLC) and of the main metabolites in plasma and urine (GLC) have been developed and a simple semiquantitative method for detecting metabolites in urine (HPTLC) can be used to monitor patient compliance.
Abstract: Nifedipine is almost completely absorbed from the gastrointestinal tract as shown by plasma levels after sublingual, oral, and rectal administration. Because of presystemic metabolism, the bioavailability is about 56% to 77%. After oral administration of 10 mg, the mean plasma concentration of nifedipine reaches maximum values of 160 +/- 49 micrograms/liter after 30 to 60 minutes. After 8 hours, the mean concentration drops to 3.4 +/- 1.2 micrograms/liter. After intravenous administration (0.015 mg/kg) biphasic elimination occurs, the half-life of the alpha-phase being about 13 minutes and of the beta-phase 1.26 +/- 0.55 hours in healthy volunteers. After oral administration of higher doses (40 mg) and after continuous infusion over 24 hours, a third phase with a half-life of about 8 hours can be seen. The apparent volume of distribution of the central compartment (Vce) is 0.294 +/- 0.1 l/kg, and the total body clearance amounts to 0.45 +/- 0.1 liter/hr . kg. Nifedipine is eliminated from the body by hepatic metabolism to the major metabolites 2,6-dimethyl-4-(2-nitrophenyl)-5-methoxycarbonyl-pyridine-3-carboxylic acid (M I) and the corresponding 2-hydroxymethyl-pyridinecarboxylic acid (M II). Methods for the quantitative detection of unchanged nifedipine in the presence of the pyridine analog in plasma (HPLC) and of the main metabolites in plasma and urine (GLC) have been developed. A simple semiquantitative method for detecting metabolites in urine (HPTLC) can be used to monitor patient compliance.
221 citations
TL;DR: Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.
Abstract: The effects and safety of using oral nifedipine 10-20 mg as acute antihypertensive treatment were studied in a single-blind placebo-controlled study of 25 consecutive patients with very high blood pressure requiring emergency reduction. In addition the effect of this treatment on cerebral blood flow was investigated using xenon-133 in 10 patients randomly allocated to receive oral nifedipine or intravenous clonidine. Whereas placebo did not alter the blood pressure, oral nifedipine significantly reduced the systolic and diastolic blood pressures in all 25 patients (from 221 +/- 22/126 +/- 14 mm Hg to 152 +/- 20/89 +/- 12 mm Hg after 30 minutes, p less than 0.001). Heart rate increased from 74 +/- 11 to 84 +/- 11 beats/minute (p less than 0.01); this effect was inversely related to age (r = -0.65, p less than 0.01). The falls in systolic and diastolic blood pressures were closely related to the blood pressures before treatment ) r = 0.67, p less than 0.001 for systolic, and r = -0.58, p less than 0.01 for diastolic values). No serious unwanted effects were observed. Measurement of cerebral blood flow after nifedipine showed an increase in flow in four out of five patients. Clonidine, by contrast, reduced cerebral blood flow in all patients by up to 28%. Nifedipine is a simple, effective, and safe alternative drug for managing hypertensive emergencies, especially when continuous monitoring of the patient cannot be guaranteed.
210 citations
TL;DR: It is suggested that the blood pressure in patients with accelerated hypertension should be lowered gently over a period of several hours or even days in order to allow time for the cerebrovascular autoregulatory mechanisms to recover.
Abstract: The malignant phase of hypertension is invariably fatal unless treated, and rapid reduction of arterial pressure is thought to be the treatment of choice. Ten patients with accelerated hypertension are described in whom abnormal neurological signs developed following the rapid reduction of arterial pressure. Three patients died without recovering from the neurological damage. A fourth died of an unrelated cause a month later. Areas of ischaemic damage were found in the brains of three of these cases. Of the six survivors, four were left with some permanent neurological disability. It is likely that these changes resulted from the inability of the cerebral circulation in patients with severe hypertension to autoregulate blood flow to the brain, so that a rapid reduction in arterial pressure led to ischaemia, especially of the watershed areas of the brain. Cerebrovascular autoregulation is likely to be compromized in patients with cerebral oedema, stenosis of major cranial vessels or in those patients with long-standing severe hypertension. It is suggested that the blood pressure in patients with accelerated hypertension should be lowered gently over a period of several hours or even days in order to allow time for the cerebrovascular autoregulatory mechanisms to recover.
148 citations