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Specialized Circulations in Susceptible Tissues
Published in Wilmer W Nichols, Michael F O'Rourke, Elazer R Edelman, Charalambos Vlachopoulos, McDonald's Blood Flow in Arteries, 2022
If, after cerebral damage, by stroke or trauma, high pulsatile pressure and flow velocity pulsations enter the brain and do not exit thereafter, they must be absorbed by the brain with loss of pulsatile energy therein. Simple modeling studies show that if the cerebral arteries are compressed and narrowed, flow pulsations and shear stress at the wall will be increased. Compression from outside the artery within the skull narrows the artery and increases pulsation in the longitudinal direction, i.e. flow velocity. Shear stresses under these conditions are likely to exceed the yield limit (around 400 dyne/cm2) and dislodge endothelial cells, favoring exudation of protein and fluid, then vascular disruption and thrombosis within the artery, as described by Fry (Fry, 1969a; Fry, 1969b; Fry, 1973). Such a mechanism can explain the arterial narrowing and obstruction often attributed to “spasm” in cerebral blood vessels at a distance, following subarachnoid hemorrhage. Favorable effects of the calcium-channel blocker nisoldipine, the drug usually employed under these circumstances (Brisman et al., 2006), may be a consequence of decreased wave reflection from the lower body and a decrease in carotid pressure augmentation rather than due to any local effect of the drug on cerebral arteries (Noda et al., 2006). Nitroglycerine may even be better.
Cardiovascular drug therapy in the elderly
Published in Wilbert S. Aronow, Jerome L. Fleg, Michael W. Rich, Tresch and Aronow’s Cardiovascular Disease in the Elderly, 2019
William H. Frishman, Wilbert S. Aronow, Angela Cheng-Lai
Calcium channel blockers are effective antihypertensive and antianginal drugs in older patients. Verapamil (80) and diltiazem (81) are especially valuable in treating hypertensive patients who also have supraventricular tachyarrhythmias. However, reports have suggested an increased mortality risk with calcium channel blockers, especially with the use of short-acting dihydropyridines in older subjects (111–113). With the use of longer-acting calcium blockers, such as the dihydropyridine nitrendipine, a strong mortality benefit was seen in patients with isolated systolic hypertension (114), although many were receiving concurrent beta-blocker therapy. In contrast, nisoldipine was shown to be less effective in protecting against cardiovascular mortality in diabetic patients with hypertension when compared to an enalapril-treated group (115).
Comparative study of nisoldipine-loaded nanostructured lipid carriers and solid lipid nanoparticles for oral delivery: preparation, characterization, permeation and pharmacokinetic evaluation
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Narendar Dudhipala, Karthik Yadav Janga, Thirupathi Gorre
Nisoldipine (ND) is (1,4-dihydropyridine derivative) a calcium channel blocker. It has a very poor oral bioavailability (< 5%) as it undergoes extensive first-pass metabolism in gut wall as it is a known CYP3A substrate [17,18] and lipophilic drug with logP of 3. Hence, the bioavailability of ND can be improved by deliver in the form NLCs, is an alternative approach. Previously, we developed and reported the SLNs of ND using central composite design. From the results, approximately 2.17-folds enhancement in the oral bioavailability and prolonged pharmacodynamic effect for 36 h was observed when compared with suspension [19]. Nekkanti et al. [20] reported the proliposomes and self-micro-emulsifying drug delivery systems of ND for the enhancement of oral bioavailability. But, the NLCs of ND was not developed so far. Therefore, an attempt was to develop NLCs of ND to improve oral bioavailability.
Effects of m-nisoldipine on the activity and mRNA expression of four CYP isozymes in rats
Published in Xenobiotica, 2018
Yupeng Sun, Yanyan Liu, Xia Zhang, Changchen Wan, Tao Lyu, Lantong Zhang
m-Nisoldipine[1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridinedicarboxylate methyl-2-methyl propylesters], as a new dihydropyridine calcium ion antagonist, was first synthesized in the School of Pharmacy at Hebei Medical University (Li et al., 2013). As the isomer of nisoldipine (the nitro is in the 2-position of the phenyl system), m-nisoldipine has a similar structure and shows homologous anti-hypertensive activity (Figure 1). Meanwhile, it displays more significant photostability and higher vascular selectivity than nisoldipine (Chen et al., 2012; Yang et al., 2013). Previous studies have revealed that CYPs play a critical role in the metabolism and disposition of m-nisoldipine (Yuan et al., 2014). However, the effects of m-nisoldipine on the CYPs remain unclear. Thus, it is necessary to assess the potential inhibition or induction effect of m-nisoldipine on CYPs (Antonissen et al., 2017).
Enhanced bioavailability and antihypertensive activity of nisoldipine loaded nanoemulsion: optimization, cytotoxicity and uptake across Caco-2 cell line, pharmacokinetic and pharmacodynamic studies
Published in Drug Development and Industrial Pharmacy, 2020
Veenu P. Mundada, Mitali H. Patel, Piyush K. Mundada, Krutika K. Sawant
Nisoldipine (NISO), a calcium channel blocker of the dihydropyridine class used in the treatment of hypertension, is a BCS class II drug. Its absolute bioavailability is only 5% due to pre-systemic metabolism in the gut wall [11]. It is also a CYP3A and P-gp substrate. Till now, authors have tried SLNs [12], NLCs [13] and proliposomes [14] to overcome these drawbacks.