Standard Nifedipine Research Articles

Antioxidant and antihypertensive potential of Ledebouria hyderabadensis

Ledebouria hyderabadensis is a new species found in the city limits of Hyderabad, Telangana, India, in 2012. Ethanolic extract of L. hyderabadensis bulbs was measured for its antioxidant and antihypertensive. Phytochemical investigation revealed that the plant contains glycosides, saponins, flavonoids, tannins, carbohydrates, amino acids. Acute toxicity studies performed according to OECD 423 guidelines, where a single dose of 5, 50, 300 and 1000 mg/kg of ethanolic extract of L. hyderabadensis bulbs administered to rats did not displayed any toxic symptoms. Therefore 1000 mg/kg is chosen as the therapeutic dose. The ethanolic extract of L. hyderabadensis bulbs exhibited the DPPH and NO free radical scavenging activity in dose dependent manner than ascorbic acid with IC50 value 54.08 µg/ml and 64.67 µg/ml. The L. hyderabadensis extract exhibited statistically significant (p < 0.05) ACE enzyme inhibition IC50 values (59.64µg/ml) when compared to the standard Captopril (IC50=24.67µg/ml). DOCA salt treatment at the 100 mg/kg, and 200 mg/kg doses, significantly reduced the Mean Systolic Blood Pressure (MSBP) (198.8&169.4) compared with the standard Nifedipine (132.6) and the negative control (122.6).

Identification and Investigation of Chalcone Derivatives as Calcium Channel Blockers: Pharmacophore Modeling, Docking Studies, In vitro Screening, and 3D-QSAR Analysis.

The chalcones were reported to have many biological activities by showing affinity towards many enzymatic targets. The effect of nitric oxide (NO) on calcium channel was extensively studied in different animals; the study was also carried out for NO donor drug and its effect on calcium channel. Till date, the inhibition of calcium channel is of prime importance in the medicinal chemistry to discover newer vascular smooth muscle relaxant drugs. The main objective of this work is to carry out in silico and in vitro evaluation of NO donor chalcones for calcium channel blocking potency. The present work includes in silico evaluation of chalcone derivatives for calcium channel blocking potency. The promising scaffolds were identified after pharmacophore modeling and docking study. The in vitro screening of 21 lead molecules for calcium channel blocking potency was carried out on pulmonary veins of adult goat, IC50 values were determined and 3D QSAR was performed. The pharmacophore modeling revealed that hydrogen bond donor, hydrogen bond acceptor, and hydrophobic groups are important features for calcium channel blocking activity. The docking study revealed the existence of hydrophobic, hydrogen bond and Vander wall's interactions between amino acid residues and ligands. The in vitro screening showed that the compounds AI6, Ca2, and D8 were potent, produced 4.756, 3.608 and 5.211 μM of IC50 respectively, whereas the standard Nifedipine showed the potency of 1.304 μM of IC50. The 3D QSAR study explained the importance of different steric and electrostatic parameters and their correlation for L type calcium channel blocking activity. This study showed that the chalcone scaffold with NO donor capacity is promising for designing novel calcium channel blockers to treat vascular disorders.

Nifedipine in Ischemic Heart Disease

Until the 1980s, Prinzmetal’s variant angina was difficult to treat—nitrates and β-blockers usually did not control symptoms or signs of ischemia. In 1980, Antman et al1 reported the first clinical experience in the United States of the use of nifedipine in patients with Prinzmetal’s angina. They used nifedipine capsules to treat 127 patients with Prinzmetal’s angina, which reduced the weekly occurrences of angina from 16 to 2, reduced nitroglycerin requirements, completely controlled angina in 63% of patients, and reduced the frequency of angina by at least 50% in 87% of cases. Since that time, a number of trials with different calcium channel blockers, including nifedipine, diltiazem, verapamil, amlodipine, and others, have consistently shown that these agents are efficacious in reducing the morbidity of Prinzmetal’s variant angina.2 Additional studies showed that calcium channel blockers, including nifedipine, were effective in patients with chronic stable angina pectoris3 ; they not only reduced symptoms but also reduced objective evidence of ischemia on exercise treadmill tests,4 5 reduced ST-segment changes on ambulatory ECG monitoring,6 increased coronary artery blood flow,7 8 9 and improved ventricular dysfunction associated with ischemia.10 Numerous studies showed that the calcium channel blockers were effective as antihypertensive agents and lacked many of the side effects of diuretics and β-blockers.11 Of course, all drugs have limits, and not all cardiovascular drugs are appropriate for all cardiovascular situations. Calcium channel blockers are no exception. In 1984, Muller et al11 showed for the first time that nifedipine capsules did not reduce the size of myocardial infarction (MI) and did not prevent patients with threatened MIs from infarcting. Patients who received nifedipine capsules in the setting of myocardial infarction had a higher 2-week mortality (7.5%) versus placebo (2.3%) but 6-month mortality was similar between nifedipine-treated (10.8%) and …

Once-daily therapy for angina pectoris with nifedipine gastrointestinal therapeutic system: Dosing and clinical efficacy

The nifedipine gastrointestinal therapeutic system (GITS) is a promising new formulation that provides continuous release of nifedipine over the course of 24 hours with once-daily dosing. Results from a 14-week, open-label, crossover multicenter trial completed by 91 patients with chronic stable angina pectoris demonstrate that patients treated with standard nifedipine capsules may be switched to equivalent total 24-hour doses of nifedipine GITS and achieve comparable or improved efficacy (due to improved compliance) with a more favorable side-effects profile. Furthermore, in a subset of 10 patients who underwent sequential exercise testing, exercise responses obtained throughout 12 weeks of treatment with nifedipine GITS were comparable to measurements obtained during treatment with nifedipine capsules and demonstrated that tolerance did not occur. These patients also experienced significantly fewer vasodilatory side effects during treatment with nifedipine GITS compared with nifedipine capsules. Thus, nifedipine GITS represents a sound pharmacologic approach to the management of ischemic disease; and with once-daily dosing and a favorable side-effect profile this agent affords the potential for better patient compliance and efficacy without concern about the development of tolerance.

Comparative dosing and efficacy of continuous-release nifedipine versus standard nifedipine for angina pectoris: Clinical response, exercise performance, and plasma nifedipine levels

To assess the dosing equivalency and the early and late antianginal efficacy of a gastrointestinal therapeutic system for once-daily, continuous-release nifedipine (N-GITS), 10 patients with stable angina pectoris, who were previously receiving chronic treatment with nifedipine, completed a 12-week trial comparing N-GITS with standard nifedipine. All patients (nine men and one woman; mean age 54 ± 2 [SEM] years) who were receiving standard nifedipine (mean dose 40 ± 5 mg/24 hr) for more than 2 weeks (mean 8 ± 2 months, range 2 to 36 months) were switched to an equivalent once-daily dose (39 ± 5 mg/24 hr) of N-GITS. Standard nifedipine and N-GITS were compared by symptom-limited exercise treadmill tests with a baseline test (A) performed 3 hours after a standard dose of nifedipine. Exercise tests were also performed after 2 weeks of treatment with N-GITS 3 hours (B) and 24 hours (C) after the drug was given, and after 12 weeks of treatment with N-GITS, 24 hours after dosing (D). Results of exercise tests showed no significant difference in mean exercise time—(A) 422 ± 25 vs (B) 426 ± 36 vs (C) 438 ± 35 vs (D) 487 ± 37 seconds. Likewise, there was no significant mean difference in peak double product, resting heart rate, peak exercise heart rate, or resting or maximal systolic blood pressure for any of the exercise test points. Furthermore, five patients (50%) reported side effects with standard nifedipine (all vasodilator-flushing, dizziness, or both), which resolved after treatment with N-GITS ( p ± 0.05). Only one patient (10%) reported side effects with N-GITS (ankle edema). In summary, in patients with angina pectoris, N-GITS at equivalent doses maintains similar exercise performance compared to standard nifedipine without evidence of tolerance and with less nifedipine vasodilator side effects at lower drug levels.

Slow Release vs Standard Nifedipine - Interindividual Variation is Seen

Slow Release vs Standard Nifedipine - Interindividual Variation is Seen

Nifedipine gastrointestinal therapeutic system in stable angina pectoris: Results of a multicenter open-label crossover comparison with standard nifedipine

To compare the clinical efficacy and dose equivalency of standard nifedipine versus a new gastrointestinal therapeutic system (GITS) formulation of nifedipine, 98 patients with chronic stable angina pectoris participated in a 14-week, multicenter, open-label, cross-over trial. All patients were administered nifedipine capsules for one month prior to study entry and continued receiving other antianginal, non-calcium blocker medications. Ninety-one patients (93 percent), 80 men and 11 women, mean age 62 ± 1 years, completed the trial, which included two weeks receiving standard nifedipine followed by 12 weeks receiving nifedipine GITS starting at a dosage equal to the 24-hour total dose of nifedipine capsules and titrated upward as necessary. However, throughout the trial, mean nifedipine dosage was similar on nifedipine GITS compared with standard nifedipine. Angina frequency was significantly less with nifedipine GITS at Weeks 6, 10, and 14 (0.8 episodes/week) compared with baseline with standard nifedipine (1.3 episodes/week, p <0.05). Likewise, nitroglycerin consumption was also less at Weeks 6, 10, and 14, but only significantly less at Week 6 (nifedipine 1.2/week versus nifedipine GITS at six weeks, 0.7/week; p <0.05). Resting hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, were not significantly different with standard nifedipine versus nifedipine GITS during the 12-week study. Total incidences of side effects were similar for both treatments (standard nifedipine, 16; nifedipine GITS, 17). However, incidence of vasodilator side effects (flushing, dizziness, and light-headedness) was significantly less frequent with nifedipine GITS (standard nifedipine, 12; nifedipine GITS, six; p <0.05). Thus, results from this open-label, crossover trial suggest that nifedipine GITS dosing is similar to multidose standard nifedipine with equivalent 24-hour efficacy for nifedipine GITS.