Cardiac Pharmacology Innovations

 The advent of drugs able to modulate the renin–angiotensin system , and more recently the neprilysin inhibitor sacubitril together with a RAS blocker, has improved the result of the many cardiovascular and renal conditions. In particular, coronary failure , post-myocardial infarction, and hypertension are the cardiovascular clinical syndromes during which RAS inhibition (and in coronary failure , together with neprilysin inhibition) has greatly improved morbidity and mortality. This chapter aims to provide an appraisal of RAS and neprilysin inhibitors regarding their pharmacological properties with respect to mechanism(s) of action, pharmacokinetics, monitoring, adverse effects, and drug interactions. NTG enhances myocardial oxygen delivery and reduces myocardial oxygen demand.NTG is a smooth muscle relaxant that causes vasculature dilation.2 Nitrate-­mediated vasodilation occurs with or without intact vascular endothelium. Nitrites, organic nitrites, nitroso compounds, and other nitrogen oxide–containing substances(e.g., nitroprusside) enter the smooth muscle cell and are converted to reactive nitric oxide (NO) or S-nitrosothiols, which stimulate guanylate cyclase metabolism to produce cyclic guanosine monophosphate (cGMP) . A cGMP-dependent protein kinase is stimulated with resultant protein phosphorylation in the smooth muscle. This leads to a dephosphorylation of the myosin light chain and smooth muscle relaxation. Vasodilation is also associated with a reduction of intracellular calcium. Sulfhydryl (SH) groups are required for formation of NO and the stimulation of guanylate cyclase. When excessive amounts of SH groups are metabolized by prolonged exposure to NTG, vascular tolerance occurs. The addition of N-acetylcysteine, an SH donor, reverses NTG tolerance. The mechanism by which NTG compounds are uniquely better venodilators, especially at lower serum concentrations, is unknown but could also be associated with increased uptake of NTG by veins compared with arteries.  

High Impact List of Articles

Relevant Topics in Clinical