Pharmacological thrombolysis: what’s new?

Author(s):  
П.Г. Мадонов ◽  
С.В. Мишенина ◽  
Е.В. Ройтман ◽  
Н.А. Ищенко

Фармакологический тромболизис широко применяется для ликвидации жизнеугрожающих тромбозов. Эта медицинская технология постоянно усовершенствуется. Разрабатываются гибридные фармако-хирургические технологии. Наиболее широко применяется системный тромболизис на основе активаторов плазминогена. Также внедряются новые технологии систем- ного тромболизиса на основе новых препаратов — не активаторов плазминогена. Разработана концепция неплазминового фибринолиза. На её основе предложен метод фармакологического тромболизиса на основе ферментов субтилизинов. Pharmacological thrombolysis is widely used to eliminate life-threatening thrombosis. This medical technique is constantly improved. Hybrid pharmaco-surgical technologies are developed. The most widely used thrombolysis is the systemic thrombolysis based on plasminogen activators. New technologies of systemic thrombolysis based on new drugs being non-plasminogen activators are also introduced. The concept of non-plasmin fibrinolysis has been developed. On the basis of this concept a method of pharmacological thrombolysis based on subtilisins enzymes is proposed.

2019 ◽  
Vol 19 (28) ◽  
pp. 2554-2566 ◽  
Author(s):  
Aurelio Ortiz ◽  
Estibaliz Sansinenea

Background:: Candida species are in various parts of the human body as commensals. However, they can cause local mucosal infections and, sometimes, systemic infections in which Candida species can spread to all major organs and colonize them. Objective:: For the effective treatment of the mucosal infections and systemic life-threatening fungal diseases, a considerably large number of antifungal drugs have been developed and used for clinical purposes that comprise agents from four main drug classes: the polyenes, azoles, echinocandins, and antimetabolites. Method: : The synthesis of some of these drugs is available, allowing synthetic modification of the molecules to improve the biological activity against Candida species. The synthetic methodology for each compound is reviewed. Results: : The use of these compounds has caused a high-level resistance against these drugs, and therefore, new antifungal substances have been described in the last years. The organic synthesis of the known and new compounds is reported. Conclusion: : This article summarizes the chemistry of the existing agents, both the old drugs and new drugs, in the treatment of infections due to C. albicans, including the synthesis of the existing drugs.


Author(s):  
Fernando Scudiero ◽  
Antonino Pitì ◽  
Roberto Keim ◽  
Guido Parodi

Abstract Background Despite the fast-growing understanding of the coronavirus disease 2019 (COVID-19), patient management remains largely empirical or based on retrospective studies. In this complex scenario, an important clinical issue appears to be represented by the high prevalence of thromboembolic events, but the data regarding high-risk pulmonary embolism (PE) is still not available. Case summary A patient with COVID-19 developed sudden shortness of breath and hypoxia. Early echocardiographic diagnosis of high-risk PE related to right heart thrombus was performed. Systemic thrombolysis was administered with excellent clinical and haemodynamic response. Discussion Pulmonary thromboembolism is a common occurrence in severe COVID-19 infection. In our experience, systemic thrombolysis proved to be effective and for this reason may be considered for life-threatening PE in COVID-19 patients.


2021 ◽  
Vol 13 (1) ◽  
pp. 14-20
Author(s):  
Marisa Santos ◽  
◽  
Quenia Morais ◽  
Helena Cramer ◽  
Marcelo Assad ◽  
...  

Objective: Familial hypercholesterolaemia is a hereditary disease characterized by very high levels of low-density lipoprotein cholesterol and an elevated risk of early-onset cardiovascular disorders. New drugs provide alternatives for the treatment of patients with homozygous familial hypercholesterolaemia. The study aims to explore a practical application of multiple-criteria decision analysis on prioritization of new and emerging technologies for familial hypercholesterolaemia. Methods: The decision model was constructed using the MACBETH method. There were three stages: structuring the problem, measuring the performance of alternatives, and building the model. The weights for alternatives and levels were obtained by indirect comparisons, which evaluated the attractiveness of the performance levels of the criteria using the swing weights technique. Results: The drugs lomitapide, ezetimibe, evolocumab, and mipomersen were selected as alternatives for decision-making. “Cardiovascular Death”, “Stroke” and “Acute Myocardial Infarction” had the three most significant weights. The criteria with the lowest weights were “Comfort” and “LDL-C Reduction”. The top-ranked technology was evolocumab, with an overall score of 59.87, followed by ezetimibe, with a score of 37.21. Conclusion: How to apply the result of a higher score in the actual decisionmaking process still requires further studies. The case in question showed that evolocumab has more performance benefits than other drugs but with a cost approximately 50 times higher


2018 ◽  
Vol 2 ◽  
pp. 239821281881068 ◽  
Author(s):  
I. Mhairi Macrae ◽  
Stuart M. Allan

Since the inception of the British Neuroscience Association, there have been major advances in our knowledge of the mechanistic basis for stroke-induced brain damage. Identification of the ischaemic cascade led to the development of hundreds of new drugs, many showing efficacy in preclinical (animal-based) studies. None of these drugs has yet translated to a successful stroke treatment, current therapy being limited to thrombolysis/thrombectomy. However, this translational failure has led to significant improvements in the quality of animal-based stroke research, with the refinement of rodent models, introduction of new technologies (e.g. transgenics, in vivo brain imaging) and improvements in study design (e.g. STAIR, ARRIVE and IMPROVE guidelines). This has run in parallel with advances in clinical diagnostic imaging for detection of ischaemic versus haemorrhagic stroke, differentiating penumbra from ischaemic core, and improved clinical trial design. These preclinical and clinical advances represent the foundation for successful translation from the bench to the bedside in the near future.


2016 ◽  
Vol 42 (2-3) ◽  
pp. 429-450 ◽  
Author(s):  
Thomas J. Hwang ◽  
Aaron S. Kesselheim

Accelerating the development and approval of novel therapeutics has emerged as a key public health priority given the mortality, morbidity, and economic costs associated with infections caused by drug-resistant bacteria. However, there is limited empirical evidence to guide policymaking, such as the factors that may disadvantage antibiotics compared to other classes of drugs. In this Article, we empirically examine characteristics of the key clinical trials underpinning FDA's approval of antibiotics and other drugs over the past decade. Despite perceptions that antibiotic trials are larger and more difficult to conduct, we find that antibiotic trials are no larger than those conducted for drugs approved in other disease areas with high unmet medical needs, suggesting that policymakers may need to target other levers to meaningfully stimulate innovation. We discuss the risks and benefits of harnessing new and existing regulatory pathways to speed the approval of new drugs, particularly those intended to treat patients with serious and life-threatening infections, and we evaluate ways that proposals for new regulatory pathways could be improved to better prioritize and expedite the approval of therapies with the greatest potential for patient health benefits.


1989 ◽  
Vol 4 (1) ◽  
pp. 39-41 ◽  
Author(s):  
Kenneth Mattox

The oft-repeated historic development of the pneumatic lower body compression suit (MAST, PASG) for the presumed treatment of hypotension has been well-documented by McSwain(l). While the experimental and anecdotal clinical observations of Crile, Gardner, Wangenstein and Kaplan are interesting, they are not prospective, controlled, randomized clinical trials in humans(2,3,4,5). In the early 1970s, the EMS community was ripe for the bandwagon reflex to grasp at any and all gimmicks and gadgets which became available, regardless of a lack of evidence regarding their safety or danger to patients. Inventions such as the esophageal obturator airway, various darts, MAST, external cardiac bumpers, percutaneous trachea obturators, and many others simultaneously were thrust upon the unsuspecting and unprotected patient community. Some of these innovations may have been beneficial but others were dangerous. Contending that some intervention in a “life threatening, good Samaritan situation” was better than no interventional treatment or “stabilization” at all, the paramedics' blind faith in these modalities persisted. The Medical Device Amendment of 1976 (6), which requires safety and efficacy for devices, similar to that long in effect for new drugs, had not yet been enacted into law to require premarketing clearance of new medical devices. Building on blind faith and premature recommendations regarding in the unproven concept of MAST, the EMS community exercised poor judgment in recommending to state legislators that this unproven device be “required equipment” on board ambulances. Furthermore, this small cadre of “special interest groups” lobbied to have the MAST mandated as essential equipment in trauma centers(7,8). Although the minutes of the trauma planning meetings do not reflect the debate at the American College of Surgeons Committee on Trauma, numerous voices of advised constraint, said “go slow” on including the MAST as part of the ATLS course and the ACS optimal resources document.


2021 ◽  
Vol 23 (11) ◽  
Author(s):  
Laura D’Erasmo ◽  
Simone Bini ◽  
Marcello Arca

Abstract Purpose of Review This review aims to summarize the most recent published literature concerning lomitapide and volanesorsen that are approved for the use in HoFH and FCS patients, respectively. Moreover, it will briefly revise the published evidence on novel, non-approved treatments that are under evaluation for the management of these rare forms of dyslipidemias Recent Findings The definition of rare dyslipidemias identifies a large number of severe disorders of lipid metabolism of genetic origin. Among them were homozygous familial hypercholesterolemia (HoFH) (OMIM #143890) and familial chylomicronemia syndrome (FCS) (OMIM #238600), which are characterized by a markedly impaired cholesterol- and triglyceride-containing lipoproteins metabolism. They are being particularly associated with poor health outcomes and quality of life. Considering the severity of these diseases, common lipid-lowering drugs are often ineffective or do not allow to achieve the recommended lipid targets to prevent the development of complications. Nowadays, several new drugs have been found to effectively treat HoFH and FCS with an acceptable safety profile. Summary Treating patients with HoFH and FCS remains very challenging. However, novel treatment options are emerging and might be considered in addition to conventional therapy for managing these diseases. These novel drugs will possibly change the natural history of these two rare and life-threatening diseases.


2019 ◽  
Vol 178 (2) ◽  
pp. 69-72
Author(s):  
A. N. Ryazanov ◽  
V. V. Soroka ◽  
S. P. Nokhrin ◽  
E. P. Mikhelson ◽  
I. D. Magamedov ◽  
...  

The article describes the clinical experience of treatment of life-threatening pathology by minimally invasive methods. There is a long-term stable positive result after the operation. The introduction of new technologies in medicine minimizes the risk of postoperative complications, contributing to a favorable outcome of the disease.


Author(s):  
Anatoly Peskov

Doping became, as many experts note, not only more diverse, highly specialized, and efficient, but also dangerous for the health of athletes. One of the main factors that allows athletes to escape responsibility is corruption. The author pays particular attention to research and new technologies in the field of sports medicine, including generating new kinds of doping. The chapter also examines the practice of international standard on granting exceptions on therapeutic use of drugs. The author suggests reconstructing the existing system of criminal and administrative law to develop new enforcement mechanisms in the fight against doping to impose a ban on the testing of new drugs on professional athletes.


Author(s):  
Jimmie L. Joseph ◽  
David P. Cook

New technologies can lead to social upheaval and ethical dilemmas which are unrecognized at the time of their introduction. Medical care technology has advanced rapidly over the course of the past two decades and has frequently been accompanied by unforeseen consequences for individuals, the medical profession and government budgets, with concomitant implications for society and public policy (Magner, 1992; Marti-Ibanez, 1962). Advances in information technology (IT) during the last decade and a half are now impacting the medical profession, and the delivery of medical advances, in ways that will impact public policy debates for the foreseeable future. The World Wide Web (Web) makes information that was once the eminent domain of medical professionals available to average citizens who are increasingly demanding medical treatments from the leading edge of medical technology. For example, CenterWatch (www.centerwatch. com) provides a wealth of information concerning clinical trials and offers a conduit by which patients can become involved in such studies. The availability of such information has also led to patients suffering from life-threatening diseases not part of such clinical trials to request special access to potentially life-saving therapies. As a result, the Web is increasing the complexity of answering public policy questions surrounding what medical technologies to make available to the public, who will be eligible to receive new medical treatments, and at what cost.


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