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Respiratory, endocrine, cardiac, and renal topics
Published in Evelyne Jacqz-Aigrain, Imti Choonara, Paediatric Clinical Pharmacology, 2021
Evelyne Jacqz-Aigrain, Imti Choonara
Heart failure is a state in which the heart, as a pump, is unable to sufficiently perfuse the organs at rest or during exercise, and to meet their metabolic demands. The approach to this condition has changed considerably over the last two decades, in both adult medicine and paediatrics. Traditionally, the approach was mainly “haemodynamic”, stimulating the failing heart muscle with inotropic drugs such as digitalis glycosides and vasoactive amines, or bipyridine derivatives such as amrinone and milrinone.
Interdependence Between Cardiac Function, Oxygen Demand, and Supply
Published in Samuel Sideman, Rafael Beyar, Analysis and Simulation of the Cardiac System — Ischemia, 2020
Joseph S. Janicki, Karl T. Weber, Ponnambalam Sundram
A similar response in efficiency was observed when a combination of positive inotropic agents, having different mechanisms of action, was administered to patients with documented idiopathic dilated cardiomyopathy.8 The combined effects of a beta adrenergic receptor agonist, dobutamine (15 |xg/kg/min), and a phosphodiesterase inhibitor, amrinone (1 mg/kg), on minute work were found to be additive without an adverse elevation in (MV̇O2) or the appearance of myocardial lactate production. Therefore, the clinical experience to date with positive inotropic agents indicates that, in the nonischemic, enlarged, and failing heart, cardiac performance is not restricted by a limitation in its O2 availability and myocardial efficiency is increased.
Anesthesia for Patients with Ventricular Assist Devices
Published in Wayne E. Richenbacher, Mechanical Circulatory Support, 2020
Patients supported with an LVAD may require inotropes prior to coming off CPB (Table 8.2). Systemic vasodilation may be a problem in this situation if the left atrial pressure is normal and systemic blood pressure low. Administration of moderate doses of norepinephrine bitartrate (0.05–0.1 μg/kg IV) may be necessary and on occasion more than one inotrope may be needed. If right ventricular dysfunction is present, but not severe enough to require an RVAD, administration of amrinone lactate or doubtamine hydrochloride may improve right ventricular function. Bleeding and coagulopathy is a concern after LVAD placement. Packed red blood cells (PRBC), fresh frozen plasma (FFP) and platelets are often necessary. Hemofiltration may be used after the patient has been weaned from CPB. Hemofiltration decreases third space fluid accumulation and reduces the potential for pulmonary and other complications related to interstitial edema. Reversal of heparin sodium is performed once hemodynamic stability is achieved after CPB has been discontinued. A test dose of protamine sulfate is administered and if no reaction occurs the full dose of protamine sulfate is slowly given.
Proteomics based drug repositioning applied to improve in vitro fertilization implantation: an artificial intelligence model
Published in Systems Biology in Reproductive Medicine, 2021
Roberto Matorras, Raquel Valls, Mikel Azkargorta, Jorge Burgos, Aintzane Rabanal, Felix Elortza, Jose Manuel Mas, Teresa Sardon
Amrinone is a phosphodiesterase inhibitor that prevents the degradation of cAMP. Since high intracellular cAMP levels are required for the initiation of decidualization, the drug may support this biological process. Amrinone also inhibits the production of TNFα, which plays a role in implantation, as discussed above. Amrinone is an excellent candidate that may promote decidualization while averting implantation failure induced by excessive TNF.
Treatment for beta-blocker poisoning: a systematic review
Published in Clinical Toxicology, 2020
Joe-Anthony Rotella, Shaun L. Greene, Zeff Koutsogiannis, Andis Graudins, Yit Hung Leang, Kelvin Kuan, Helen Baxter, Elyssia Bourke, Anselm Wong
Three animal studies have examined the effect of glucagon and a phosphodiesterase inhibitor (milrinone or amrinone) in treating propranolol toxicity induced in mongrel dogs [29,30,53]. Amrinone temporarily increased cardiac output, but had no effect on heart rate [30]. Milrinone increased cardiac output in mongrel dogs compared to controls but had no effect on heart rate [29,53]. Measures of survival between groups were not reported.
Effects of inhibition of phosphodiesterase 3B in pancreatic islets on insulin secretion: a potential link with some stimulatory pathways
Published in Archives of Physiology and Biochemistry, 2021
Agnieszka Kilanowska, Tomasz Szkudelski
Based on the literature data, it can be concluded that bipyridine derivatives, including amrinone, are one of the most effective inhibitors of PDE3B isoform in pancreas (Parker et al.1995). We have previously shown that inhibition of this enzyme by amrinone increases insulin secretion induced by 6.7 mM glucose in pancreatic islets of non-diabetic rats (Zywert et al.2014). In the current study, incubation of isolated pancreatic islets was performed for 15, 30 and 90 min to determine the time-dependent effects of amrinone on glucose-induced insulin secretion. It was demonstrated that in each of those intervals, there was a significant increase in insulin release in response to amrinone. These results provide a basis for a conclusion that the used inhibitor penetrates into β cells in a relatively short time, enhancing hormone secretion. This is in line with the outcomes of our preliminary study using pancreas perfusion in situ in non-diabetic rats (Zywert et al.2014). The obtained results also prove the effectiveness of amrinone in rat islets. The potentiation of insulin secretion, observed in the presence of amrinone, is associated with the increase of intracellular cAMP concentration, which is to a certain degree, a reflection of glucose metabolism in β cells. However, the intracellular pool of cAMP depends not only on the rate of its synthesis, but also the rate of degradation. Therefore, its concentration is also largely dependent on the activity of PDE, mostly PDE3B. It is estimated that out of all isoforms of phosphodiesterases, PDE3B is responsible for the hydrolysis of approximately 70% of cAMP in endocrine pancreas (Tengholm 2012). However, increased insulin secretion from isolated pancreatic islets depends on the concentration of glucose in the incubation buffer. In our studies, we did not observe changes in insulin secretion after exposure to glucose at 2.8 mM and with amrinone incubated with glucose at the same concentration (Figure 7).