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Arterial Pressure Waveform Analysis
Published in Wilmer W Nichols, Michael F O'Rourke, Elazer R Edelman, Charalambos Vlachopoulos, McDonald's Blood Flow in Arteries, 2022
Use of sphygmocardiography may provide insight into adverse effects of antihypertensive therapy. Controversy on use of short-acting dihydropyridines in hypertension (Furberg et al., 1995) highlighted the potential of these drugs to accentuate myocardial ischemia. Short-acting nifedipine preparations often maintain or prolong left ventricular ejection duration, as well as causing tachycardia. Such an effect favors myocardial ischemia and can be measured as inappropriate reduction of diastolic duration and of subendocardial viability ratio. Importance of diastolic perfusion period in myocardial ischemia has been highlighted by Ferro et al. (1995) (Figure 14.12); sphygmocardiography permits measurement of the relevant indices of myocardial ischemia. Changes seen in this figure are unlikely to be relevant at rest but could be during tachycardia, when diastolic duration is further decreased (Prichard and Vallance, 2004).
Ion Channels and The Control of Uterine Contractility
Published in Robert E. Garfield, Thomas N. Tabb, Control of Uterine Contractility, 2019
A number of calcium entry blockers, including nifedipine, nicardipine, diltiazem, verapamil, and gallopamil have been shown to inhibit uterine contractions in various species including the rat, rabbit, sheep, monkey, and human.18 The dihydropyridines are the most potent and selective inhibitors of uterine tension and therefore are of considerable interest for both therapeutic and experimental purposes. In cardiac cells the concentrations of dihydropyridines, which give rise to half-maximal electrophysiological responses, are several orders of magnitude greater than the dissociation constant values determined from ligand experiments.19,20 Recent electrophysiological experiments in smooth muscle cells have demonstrated a voltage dependence of dihydropyridine antagonist action, and this has been postulated to account for the difference between the binding affinities and the dissociation constants determined from the pharmacological effects of these drugs.21,22
Pharmacokinetic-Pharmacodynamic Modeling of Reversible Drug Effects
Published in Hartmut Derendorf, Günther Hochhaus, Handbook of Pharmacokinetic/Pharmacodynamic Correlation, 2019
On the other hand, Francheteau et al.64 recently published a sophisticated, physiological PK/PD model to describe the effects of intravenous dihydropyridines on the cardiovascular system in healthy volunteers. These authors incorporated several hemodynamic parameters into a closed-loop feedback system that included the baroreceptor reflex; this physiological system was sensitive to both changes and rates of changes in arterial blood pressure. This physiological model was combined with a traditional PK/PD model that accounted for changes in systemic vascular resistance as primary effects of dihydropyridines. The model allowed adequate description of time profiles for cardiac output and mean arterial blood pressure following different intravenous infusion regimens with nicardipine. This model also allowed prediction of how PD effects depend on baseline cardiovascular parameters, e.g., hypertensive patients; it also mimics the physiological behavior of the cardiovascular system. However, due to the large number of variables and parameters, it requires simultaneous measurement of multivariate effect variables and prior knowledge of some of the system parameters.
Advances in small-molecule therapy for managing angina pectoris in the elderly
Published in Expert Opinion on Pharmacotherapy, 2019
Nida Waheed, Ahmad Mahmoud, Cecil A. Rambarat, Carl J. Pepine
Calcium channel blockers (CCBs) are effective antianginal treatments first introduced in the 1970s. They reduce myocardial ischemia by causing both dilatation of coronary vessels and peripheral vessels to reduce cardiac workload and also through negative inotropic effects. CCBs are divided into the dihydropyridines (nifedipine, nicardipine, nitrendipine, amlodipine) and non-dihydropyridines, which consist of the benzothiazepines (diltiazem) and phenylalkamines (verapamil). All CCBs relax vascular smooth muscle to dilate coronary and peripheral arteries and arterioles, reducing blood pressure. The dihydropyridines mainly affect vascular smooth muscle, whereas the benzothiazepines and phenylalkamines also significantly depress myocardial and sinoatrial node function. Each group is further divided into first-, second-, and third-generation CCBs. The first-generation drugs have rapid onset and short duration of action, while subsequent generations of CCBs are longer acting. This class of drugs is widely used for stable angina in the elderly with well-documented reductions in angina, increased activity tolerance, and improvement in quality of life [36] that does not appear to be diminished among the elderly.
Synthesis and in vivo anti-ulcer evaluation of some novel piperidine linked dihydropyrimidinone derivatives
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2018
Mashooq Ahmad Bhat, Mohamed A. Al-Omar, Ahmed M. Naglah
Pyrimidines have played an important role in the field of medicinal chemistry7. Pyrimidines are important scaffold in medicinal chemistry, because of their potential biological activities such as anti-tumour, anti-viral and anti-bacterial8–10. Some of them have been used as potential anti-hypertensive agents. 4-Aryl-1,4-dihydropyridines like nifedipine was first introduced as antihypertensive in 1975. Dihydropyridines are the most effective calcium channel blockers used for various cardiovascular diseases11. Anti-ulcer activities have been reported for several calcium channel blockers including nifedipine12. It is thus assumed that structural analogues of nifedipine may possess anti-ulcer potential. Dihydropyrimidines, popularly known as Biginelli’s compounds, are associated with broad spectrum of biological activities13,14. Derivatives of dihydropyrimidine have been reported to possess potent anti-ulcer and anti-secretory activity15,16.
Angiotensin axis antagonists increase the incidence of haemodynamic instability in dihydropyridine calcium channel blocker poisoning
Published in Clinical Toxicology, 2021
Jessica Huang, Nicholas A. Buckley, Katherine Z. Isoardi, Angela L. Chiew, Geoffrey K. Isbister, Rose Cairns, Jared A. Brown, Betty S. Chan
Dihydropyridines are often prescribed in combination with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin-II receptor blockers (ARBs). Combined therapy of dihydropyridines and ACEI/ARB may be superior to other first-line combinations such as beta-blockers with diuretics or ACEIs with diuretics in some patients [10,11]. In the renin-angiotensin-aldosterone system, ARBs block the Angiotensin (AT)-1 receptor of angiotensin-II and inhibit vasoconstriction [12] whilst ACEIs block angiotensin-converting enzyme (ACE) to inhibit the conversion of angiotensin I to angiotensin II, similarly leading to less vasoconstriction [13]. Overdoses of ARBs/ACEIs alone are relatively benign [14–17] and are rarely listed as the primary cause of poisoning deaths [4].