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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The dihydropyridine derivatives constitute a distinct subcategory of calcium channel blockers that have marked peripheral vascular effects with minimal or no electrophysiologic actions when administered to intact animals or humans. These dihydropyridine derivatives are structurally similar to nifedipine, the most widely studied dihydropyridine. The derivatives have varying affinities for different regional circulations, and there may be an important relationship between structure and activity of these compounds with respect to the predilection of the site of their action in vascular tissue. It is possible that such differences may be of clinical significance. As a class, the dihydropyridines exert reasonably distinct hemodynamic changes that may be of particular importance in the treatment of hypertension, cardiac failure, and regurgitant valvular lesions. Nicardipine hydrochloride is a newer agent that has undergone extensive evaluation in recent years. Pharmacologically and electrophysiologically, it resembles other dihydropyridines. Unlike nifedipine, however, it can be administered by both the intravenous and oral routes. There are additional differences between its properties and those of other calcium channel blockers. For example, nicardipine appears to produce a greater increase in coronary sinus blood flow than other calcium channel blockers. The clinical significance of this finding is unclear. In addition, nicardipine appears to increase myocardial contractility, even in patients with severe congestive cardiac failure. Nicardipine produces a dose-dependent decrease in blood pressure and systemic vascular resistance with increases in heart rate, left ventricular dP/dt, LV ejection fraction, cardiac output, and stroke work index, but no significant change in LV end-diastolic pressure. Clearly, the drug has negligible venodilator actions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Clinical pharmacology, pharmacokinetics, and hemodynamic effects of nicardipine. 196 96

The therapy of postoperative hypertension (POH) after head and neck surgery was evaluated in a prospective, randomized, double-blind trial. Nicardipine hydrochloride, a Ca channel-blocker for iv use, was compared with placebo. Patients were initially randomized to receive nicardipine infusion or placebo. Those not responding to placebo were given nicardipine infusion on an open basis. Hypertension was significantly better controlled in patients treated with nicardipine infusion compared with placebo (83% vs. 22%, p less than .002). Subsequently, six (86%) of seven of the placebo failures were successfully treated with nicardipine. There were no significant complications in either group. We conclude that the titratable infusion of nicardipine is an effective and safe method for the control of POH after surgery of the head and neck. Further studies are now warranted comparing nicardipine with other drugs currently used to treat this condition.
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PMID:Nicardipine infusion for postoperative hypertension after surgery of the head and neck. 220 2

Nicardipine hydrochloride, a new calcium channel blocker for intravenous use, has been compared with placebo in a prospective, randomized, double-blind trial on postoperative hypertension. Of 175 patients who signed preoperative consent, 24 (13.7%) met entry criteria. Hypertension was significantly better controlled in nicardipine-treated patients compared with those receiving placebo (93% versus 30%, p less than 0.05). All the placebo failures were subsequently successfully treated with nicardipine. There were no significant complications in either group. The authors conclude that nicardipine HC1 is an effective, safe therapy for postoperative hypertension. Further studies are now indicated comparing it with other drugs currently used to treat this condition.
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PMID:Postoperative hypertension: a prospective, placebo-controlled, randomized, double-blind trial, with intravenous nicardipine hydrochloride. 224 28

Nicardipine hydrochloride was administered intravenously to two groups of hypertensive patients: one group of 37 patients with mild to moderate hypertension and one group of 20 patients with severe hypertension. In the first group, doses of 0.5, 1, 2, and 4 mg/hr, as well as placebo, were infused for 48 hours in a double-blind fashion. Blood pressure and heart rate were monitored for this period and for the 24 hours after the infusion was discontinued. Significant decrements in blood pressure were noted with all doses; 4 mg/hr produced lowering that was greater than all other doses; 1 and 2 mg/hr produced lowering that was greater than 0.5 mg/hr but that were not different from each other. Excellent correlation of blood pressure reduction and plasma level was observed and linear kinetics existed. In the severe hypertensive patients, 1, 2, 4, 5, and 8 mg/hr were infused to established minimal and ineffective doses. One milligram per hour was an ineffective dose; 4, 5, and 8 mg/hr all produced significant reductions over the course of the study that were undistinguishable from each other. Two milligrams per hour produced modest reductions in blood pressure. Blood pressure reduction also correlated with plasma levels in the severe hypertensive group.
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PMID:Pharmacokinetics, pharmacodynamics, and minimum effective clinical dose of intravenous nicardipine. 235 65

Nicardipine hydrochloride, a dihydropyridine calcium entry-blocking drug, was administered to 66 patients with severe hypertension during three protocols designed to examine the efficacy and safety of this investigation drug. It was shown that nicardipine was uniformly effective in lowering blood pressure to a therapeutic goal of 95 mm Hg. Time to achieve therapeutic effect was dose dependent, and steady-state blood levels were achieved after 8 to 12 hours. Reductions in both systolic and diastolic blood pressure but not changes in heart rate were correlated with plasma concentrations of nicardipine. In dose-ranging studies, the minimal effective dose of nicardipine appeared to be 2 mg/hr; 1 mg/hr was an ineffective dose, and little additional effect was seen above 4 mg/hr. Side effects were modest and consisted of those associated with vasodilation--headache, flushing, and feelings of warmth. In the initial group of patients studied, local thrombophlebitis occurred in a substantial number of patients. This was seen only after 14 hours of infusion. In subsequent studies, the infusion site was changed after 12 hours, and no further cases of thrombophlebitis were seen. Nicardipine appears to be therapeutic agent for parenteral use that shows promise in the treatment of severe hypertension.
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PMID:Intravenous nicardipine hydrochloride: treatment of patients with severe hypertension. 240 13

Nicardipine hydrochloride is the first intravenous dihydropyridine calcium antagonist to become available in the United States. Its chemical structure makes it unique among its drug class and confers clinically useful properties for the treatment of acute cardiovascular conditions, such as ischemia, hypertension, congestive heart failure, cerebrovascular disease, and related disorders. For patients with coronary artery disease, IV nicardipine reduces myocardial oxygen demand by reducing afterload and increases myocardial oxygen supply through coronary vasodilatation. Preliminary data suggest that nicardipine also has cardioprotective and vascular antispastic effects. Nicardipine has been shown to be effective in the treatment of mild to moderate hypertension both as monotherapy and in combination with other antihypertensive agents. In congestive heart failure, nicardipine enhances left ventricular pumping activity and augments coronary blood flow beyond that required by increased myocardial oxygen consumption. Its lack of major effects on sinoatrial and atrioventricular conduction makes it safe for use in patients with certain types of conduction disturbances. Nicardipine's rapid onset and short duration of action are additional advantages for use in the management of acute cardiovascular disorders.
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PMID:Intravenous nicardipine: cardiovascular effects and clinical relevance. 307 10

We performed a multicentre, phase IV, open-label clinical trial to examine the clinical usefulness of a continuous infusion of nicardipine hydrochloride to control hypertension in 31 patients with acute aortic dissection. Target blood pressure levels were reached within 15 min in 16 patients; in 15-30 min in 10 patients; in 30-45 min in three patients; and in 45-60 min in two patients. Baseline average systolic, diastolic and mean arterial blood pressures were 147 +/- 23 mmHg, 82 +/- 18 mmHg and 104 +/- 18 mmHg, respectively, with third-day pressures significantly reduced at 119 +/- 12 mmHg, 69 +/- 9 mmHg and 86 +/- 8 mmHg. Blood pressures after discontinuation of the infusion were not significantly different from those measured on the third day of infusion and no definite adverse effects attributable to the treatment were observed. Nicardipine hydrochloride was both effective and safe at controlling blood pressure in patients with acute aortic dissection.
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PMID:Nicardipine hydrochloride injectable phase IV open-label clinical trial: study on the anti-hypertensive effect and safety of nicardipine for acute aortic dissection. 1216 54

Nicardipine hydrochloride (NC-HCl), a calcium channel blocker for the treatment of chronic stable angina and hypertension, seems to be a potential therapeutic transdermal system candidate, mainly due to its low dose, short half-life, and high first-pass metabolism. The objective of the present study was to evaluate its flux and elucidate mechanistic effects of formulation components on transdermal permeation of the drug through the skin. Solubility of NC-HCl in different solvent systems was determined using a validated HPLC method. The solubility of drug in various solvent systems was found to be in decreasing order as propylene glycol (PG)/oleic acid (OA)/dimethyl isosorbide (DMI) (80:10:10 v/v) > PG > PG/OA (90:10 v/v) > polyethylene glycol 300 > ethanol/PG (70:30 w/w) > transcutol > dimethyl isosorbide (DMI) > ethanol > water and buffer 4.7 > 2-propanol. Propylene glycol was then selected as the main vehicle in the development of a transdermal product. As a preliminary step to develop a transdermal delivery system, vehicle effect on the percutaneous absorption of NC-HCl was determined using the excised skin of a hairless guinea pig. Vehicles investigated included pure solvents alone and their selected blends, chosen based on the solubility results. In vitro permeation data were collected at 37 degrees C, using Franz diffusion cells. The skin permeation was then evaluated by measuring the steady state permeation rate (flux) of NC-HCl, lag time, and the permeability constant. The results showed that no individual solvent was capable of promoting NC-HCl penetration. Permeation profiles of the drug through hairless guinea pig skin using saturated solutions of drug were constructed. Among the systems studied, the ternary mixture of PG/OA/DMI and binary mixture of PG/OA showed excellent flux. The flux value of the ternary system was nearly three times higher than the corresponding values obtained for the binary solvent. A similar trend also was observed for the permeation constant, while the values of lag time were reversed. The ternary mixture was then selected as a potential absorption enhancement vehicle for the transdermal delivery of drug. In general, higher fluxes were observed through hairless guinea pig skin as compared with the human stratum corneum. Based on the results obtained from the release study of NC-HCl from saturated solutions of the drug, a novel lecithin organogel (microemulsion-based gel) composed of soybean lecithin, propylene glycol, oleic acid, dimethyl isosorbide, and isopropyl myristate was developed as a possible matrix for transdermal delivery of NC-HCl. In vitro percutaneous penetration studies from this newly developed gel system through giunea pig skin and human stratum corneum revealed that the organogel system has skin-enhancing potential and could be a promising matrix for the transdermal delivery of nicardipine. Furthermore, higher permeation rates were observed when nicardipine free base was incorporated into the gel matrix instead of hydrochloride salt.
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PMID:Transdermal delivery of nicardipine: an approach to in vitro permeation enhancement. 1251 Dec 2

Nicardipine is a water soluble calcium channel antagonist, with predominantly vasodilatory actions. Intravenous (IV) nicardipine (Cardene IV), which demonstrates a relatively rapid onset/offset of action, is used in situations requiring the rapid control of blood pressure (BP). IV nicardipine was as effective as IV nitroprusside in the short-term reduction of BP in patients with severe or postoperative hypertension. A potential role for IV nicardipine in the intraoperative acute control of BP in patients undergoing various surgical procedures (including cardiovascular, neurovascular and abdominal surgery), and in the deliberate induction of reduced BP in surgical procedures in which haemostasis may be difficult (e.g. surgery involving the hip or spine) was demonstrated in preliminary studies. Preliminary studies also indicated the ability of a bolus dose of IV nicardipine to attenuate the hypertensive response, but not the increase in tachycardia, after laryngoscopy and tracheal intubation in anaesthetised patients. In large, well designed studies, IV nicardipine prevented cerebral vasospasm in patients with recent aneurysmal subarachnoid haemorrhage; however, overall clinical outcomes at 3 months were similar to those in patients who received standard management. Small preliminary studies have investigated the use of IV nicardipine in a variety of other settings, including acute intracerebral haemorrhage, acute ischaemic stroke, pre-eclampsia, acute aortic dissection, premature labour and electroconvulsive therapy.In conclusion, the efficacy of IV nicardipine in the short-term treatment of hypertension in settings for which oral therapy is not feasible or not desirable is well established. The ability to titrate IV nicardipine to the tolerance levels of individual patients makes this agent an attractive option, especially in critically ill patients or those undergoing surgery. Potential exists for further investigation of the use of this agent in clinical settings where a vasodilatory agent with minimal inotropic effects is appropriate.
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PMID:Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indications. 1697 41

Nicardipine hydrochloride (Nic), a calcium channel antagonist, is used for the treatment of hypertension. In the present study, we estimated its effects on the levels and activities of hepatic cytochrome P450 isoforms in spontaneously hypertensive rats given p.o. with Nic at a dose of 0.5, 2.5, 5, or 12.5 mg/kg at 24-hr intervals for 14 days. Therapeutic effects on the development of hypertension were observed at doses of 5 and 12.5 mg/kg/day. Significant increases in the levels of mRNAs and enzyme activities of hepatic P450 isoforms, CYP1A1 and/or CYP1A2, by 14-day repetitive treatment with Nic were observed at lower therapeutic doses, whereas the increase in protein levels for CYP1A2 was observed at a higher therapeutic dose of 12.5 mg/kg/day. Likewise, the activities of hepatic CYP2B and CYP3A subfamily enzymes were increased by the 14-day-treatment of Nic only at a therapeutic dose (12.5 mg/kg/day), whereas their mRNA and protein levels were increased at lower therapeutic doses. To date, the dihydropyridine family, including Nic, has been believed to have inhibitory effects on the activity of various cytochrome P450 enzymes, especially human CYP3A4. However, the present findings demonstrate for the first time that Nic-repetitive treatments at a therapeutic dose result in significant increases in the expressions and activities of hepatic CYP1A, CYP2B, and CYP3A subfamily enzymes. Therefore, the effects of dihydropyridine family on cytochrome P450 enzymes have to be further validated to provide information on its safe and beneficial therapeutic application.
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PMID:Induction of hepatic cytochrome P450 isoforms by nicardipine at therapeutic doses in spontaneously hypertensive rats. 1732 96


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