Mini Reviews in Medicinal Chemistry - Volume 18, Issue 6, 2018

Historically, quinidine was the first medicine used in the therapy of heart arrhythmias. Studies in the early 20th century identified quinidine, a diastereomer of the antimalarial quinine, as the most potent of the antiarrhythmic substances extracted from the cinchona plant. Quinidine is used by the 1920s, as an antiarrhythmic agent to maintain sinus rhythm after the conversion from atrial flutter or atrial fibrillation and to prevent recurrence of ventricular tachycardia or ventricular fibrillation. Its value in chronic prophylaxis of relapse of ventricular arrhythmia was brought under suspicion after publishing of meta analysis that showed that the application of quinidine increases mortality. Due to numerous proofs of increased risk for the appearance of ventricular arrhythmia and sudden death, as well as a number of other adverse effects and drug interactions, quinidine was withdrawn from use and in the recent years has become unavailable in many countries. On the other hand, recent studies have demonstrated that quinidine is the only oral medication that has consistently shown efficacy in preventing arrhythmias and terminating storms due to recurrent ventricular fibrillation, in patients with Brugada syndrome, idiopathic ventricular fibrillation and early repolarization syndrome. Quinidine is also the only antiarrhythmic drug that normalized the QT interval in patients with the congenital short QT syndrome. The aim of this review is to provide good insight into pro and contra arguments for quinidine use in ventricular arrhythmias evidence based on recently published literature.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a channelopathy characterized by adrenergic mediated ventricular arrhythmia. Untreated CPVT is a malignant syndrome with more than 50% of arrhythmic events and up to 25% of fatal or near-fatal cardiac events at 8 years follow-up. Prevention of sudden cardiac death starts with exclusion of competitive sports. Beta blockers (BB) are the cornerstone pharmacological therapy for the prevention of cardiac event in CPVT patients. Dose of BB should be highly tolerable, preferably nadolol. Efficiency of BB is undeniable but uncompleted. Therefore, on top of BB, one can propose the use of Calcium channel blockers or Class 1c antiarrythmic drugs. Indeed Flecainide allows reducing exercise- induced premature ventricular contraction and ventricular arrhythmia. Pharmacological management should be a stepwise approach with BB as the first line of choice. At each step of therapeutic changes, heart rhythm during exercise should be monitored by Holter monitoring and exercise testing. If the pharmacological management fails, left cardiac sympathetic denervation or implantation of cardioverter defibrillator should be considered.

Vasovagal reaction, resulting in bradycardia and/or hypotension in response to a number of stimuli, is usually self-limiting, but potentially life-threatening exceptions have been described. Pharmacological treatment of proven efficacy is still lacking and the administered compounds are often chosen on the basis of either case reports or outdated small studies with a short-term follow up. In refractory cases, pacemaker implantation may be considered, although no responder patients represent a severe challenge for clinicians. The aim of this review is to examine the state of the art about this controversial issue.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, with a familial recurrence risk of 3%. Despite performing an optimal surgical repair, TOF patients may feature a poor medium and long-term survival rate: atrial re-entrant tachycardia will develop in more than 30% of patients and high-grade ventricular arrhythmias will be seen in about 10% of patients. These life-threatening arrhythmias and consequent sudden death continue to represent serious complications following TOF repair. Radiofrequency ablation and implantable cardioverter defibrillator are today the most effective therapeutic tools in these subjects, while the administration of antiarrhythmic drugs (Ib agents, beta blockers, and amiodarone), widely prescribed in the past, is now limited to few conditions. However pharmacological therapy still plays a role in the management of those patients who are resistant to the above stated invasive electrophysiological treatments.

Long QT syndrome (LQTS) is an arrhythmogenic disorder characterized by repolarization abnormalities with a tendency to cause life threatening cardiac events. The first manifestation of the syndrome may be sudden death, therefore, early diagnosis and therapy is of great importance. LQTS can be congenital or acquired. The latter is most commonly seen in hospitalized patients and such individuals have an easily recognizable and reversible precipitating factor (electrolyte disturbances, certain drugs etc.). Congenital LQTS, a less prevalent condition, is considered to be part of the greater family of disorders called channelopathies. Extensive research over the past decade allowed better understanding of the underlying molecular mechanisms and unmasking of the genetic substrate of these patients. Both pharmacological and interventional therapies (left cardiac sympathetic denervation, ICDs) have been used in the treatment of congenital long-QT syndrome. This review will focus solely on the pharmacologic therapy of this potentially lethal inherited disorder summarizing current knowledge regarding b-blocker use, taking into account novel and more targeted approaches such as gene-specific therapy.

Four distinguished although overlying stages make up the methodical procedure of wound healing, which are hemostasis, inflammation, proliferation and remodelling. Multiple sclerosis (MS) is described as an incessant inflammatory central nervous system disease, and is linked with neurodegeneration, demyelination, as well as susceptibility to oxidative pressure. Obesity signifies a swiftly developing danger to the wellbeing of populations in a rising number of nations. Usually called diabetes mellitus (DM) by medical practitioners, diabetes details a collection of metabolic diseases within which the individual has raised blood glucose, either due to an insufficiency of insulin generation, or the lack of suitable response by the body to insulin, or both. Conventionally, the pomegranate, as well as its flowers, leaves, fruit juice and tree bark, has been applied in the treatment of conditions including acidosis, haemorrhage, diarrhoea and microbial contagions. Extracts of pomegranate have been established to contain intense anti-inflammatory, antioxidant as well as antitumor features in vivo as well as ex vivo. Of late, beneficial consequences of decrease of fat have been illustrated employing the pomegranate as well as its extracts. Several of the favourable consequences are associated with the availability of anthocyanins, tannins, and considerably elevated amounts of antioxidants, as well as flavonoids and polyphenols. A summary of the endeavours applied to deal with the possible advantages of the pomegranate towards healing wounds, Alzheimer's disease (AD), diabetes mellitus (DM) and obesity, as well as an appraisal of the efficiency of intervention through the pomegranate and its extracts is provided in this article.

Numerous studies have indicated that marine natural products are one of the most important sources of the lead compounds in drug discovery for their unique structures, various bioactivities and less side effects. In this review, the marine natural products with cardiovascular pharmacological effects reported after 2000 will be presented. Their structural types, relevant biological activities, origin of isolation and information of strain species will be discussed in detail. Finally, by describing our studies as an example, we also discuss the chances and challenges for translating marine-derived compounds into preclinical or clinical trials.