According to the ESC guidelines, cangrelor may be considered in P2Y12-inhibitor-naïve acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). The aim of this review is to summarize available evidence on the optimal maintenance therapy with P2Y12 receptor inhibitor after cangrelor. Transitioning from cangrelor to a thienopyridine, but not ticagrelor, can be associated with a drug-drug interaction (DDI); therefore, a ticagrelor loading dose (LD) can be given any time before, during, or at the end of a cangrelor infusion, while a LD of clopidogrel or prasugrel should be administered at the time the infusion of cangrelor ends or within 30 minutes before the end of infusion in the case of a LD of prasugrel. Administration of any oral antiplatelet agent at the end of a cangrelor infusion will also result in a transient period of increased platelet reactivity. The inter-individual variability of this period is difficult to predict because it depends on many factors related to the patient and the treatment. In addition, experimental studies indicate that cangrelor may exert a cardioprotective effect beyond the blockade of platelet aggregation. Considering the available data, the potential use of cangrelor in ACS patients goes well beyond the current indications. Furthermore, we believe that it might be prudent to avoid use of thienopyridines during and soon after a cangrelor infusion until conclusive data on the effect of the DDI on the clinical outcome are available. On the other hand, ticagrelor seems to be an optimal oral agent for continuation of P2Y12 inhibition in patients receiving cangrelor infusion.
- MeSH
- adenosinmonofosfát * analogy a deriváty terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- akutní koronární syndrom * terapie farmakoterapie diagnóza MeSH
- antagonisté purinergních receptorů P2Y * aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- inhibitory agregace trombocytů * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- koronární angioplastika * škodlivé účinky MeSH
- lékové interakce MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Cardiogenic shock (CS) is a devastating and fatal complication of acute myocardial infarction (AMI). CS can affect the pharmacokinetics and pharmacodynamics of medications. The unique properties of cangrelor make it the optimal P2Y12 inhibitor for CS-AMI, in terms of both efficacy and safety. The DAPT-SHOCK-AMI trial (ClinicalTrials.gov: NCT03551964; EudraCT: 2018-002161-19) will assess the benefits of cangrelor in patients with an initial CS-AMI undergoing primary angioplasty. This randomised, multicentre, placebo-controlled trial of approximately 550 patients (with an allowed 10% increase) in 5 countries using a double-blind design will compare initial P2Y12 inhibitor treatment strategies in patients with CS-AMI of (A) intravenous cangrelor and (B) ticagrelor administered as crushed tablets at a loading dose of 180 mg. The primary clinical endpoint is a composite of all-cause death, myocardial infarction (MI), or stroke within 30 days. The main secondary endpoints are (1) the net clinical endpoint, defined as death, MI, urgent revascularisation of the infarct-related artery, stroke, or major bleeding as defined by the Bleeding Academic Research Consortium criteria; (2) cardiovascular-related death, MI, urgent revascularisation, or heart failure; (3) heart failure; and (4) cardiovascular-related death, all (1-4) within 1 year after study enrolment. A platelet reactivity study that tests the laboratory antiplatelet benefits of cangrelor, when given in addition to standard antiplatelet therapy, will be conducted using vasodilator-stimulated phosphoprotein phosphorylation. The primary laboratory endpoints are the periprocedural rate of onset and the proportion of patients who achieve effective P2Y12 inhibition. The DAPT-SHOCK-AMI study is the first randomised trial to evaluate the benefits of cangrelor in patients with CS-AMI.
- MeSH
- adenosinmonofosfát * analogy a deriváty terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- antagonisté purinergních receptorů P2Y aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- dvojitá slepá metoda MeSH
- fosfoprotein stimulovaný vazodilatátorem MeSH
- fosfoproteiny MeSH
- infarkt myokardu * komplikace MeSH
- inhibitory agregace trombocytů * škodlivé účinky terapeutické užití aplikace a dávkování MeSH
- kardiogenní šok * mortalita MeSH
- koronární angioplastika škodlivé účinky MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- randomizované kontrolované studie jako téma MeSH
- senioři MeSH
- ticagrelor * terapeutické užití aplikace a dávkování škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- protokol klinické studie MeSH
Remdesivir therapy has been declared as efficient in the early stages of Covid-19. Of the 339 patients (males 55.8%, age 71(59;77) years) with a detectable viral load, 140 were treated with remdesivir (of those 103 in the ICU and 57 immunosuppressed) and retrospectively compared with 199 patients (of those 82 in the ICU and 28 immunosuppressed) who were denied therapy due to advanced Covid-19. The viral load was estimated by detecting nucleocapsid antigen in serum (n = 155, median 217(28;1524)pg/ml), antigen in sputum (n = 18, COI 18(4.6;32)), nasopharyngeal antigen (n = 44, COI 17(8;35)) and the real-time PCR (n = 122, Ct 21(18;27)). After adjustment for confounders, patients on remdesivir had better 12-month survival (HR 0.66 (0.44;0.98), p = 0.039), particularly when admitted to the ICU (HR 0.49 (0.29;0.81), p = 0.006). For the immunocompromised patients, the difference did not reach statistical significance (HR 0.55 (0.18;1.69), p = 0.3). The other most significant confounders were age, ICU admission, mechanical ventilation, leukocyte/lymphocyte ratio, admission creatinine and immunosuppression. The impact of monoclonal antibodies or previous vaccinations was not significant. Despite frequent immune suppression including haemato-oncology diseases, lymphopenia, and higher inflammatory markers in the remdesivir group, the results support remdesivir administration with respect to widely available estimates of viral load in patients with high illness severity.
- MeSH
- adenosinmonofosfát * analogy a deriváty terapeutické užití MeSH
- alanin * analogy a deriváty terapeutické užití MeSH
- antivirové látky * terapeutické užití MeSH
- COVID-19 * virologie mortalita MeSH
- farmakoterapie COVID-19 * MeSH
- jednotky intenzivní péče MeSH
- lidé středního věku MeSH
- lidé MeSH
- péče o pacienty v kritickém stavu MeSH
- retrospektivní studie MeSH
- SARS-CoV-2 * účinky léků izolace a purifikace fyziologie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- virová nálož * účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Background: Remdesivir has recently been used more widely as an antiviral medication, possibly due to its potency against coronavirus.Aim: This study was aimed at detecting the toxicity of remdesivir on the liver and kidneys of albino rats at various doses, as well as the possibility of recovering to the normal structure of these tissues two weeks after drug discontinuation.Methods: Forty adult albino rats were divided into five groups (8 rats per group). The first group was the control group; the second group received 5 mg/kg remdesivir; the third group received 10 mg/kg for five days; and the fourth and fifth groups were withdrawal groups (treated as 2nd and 3rd groups then left for two weeks). After five days of treatment, the animals of the 1st, 2nd, and 3rd groups were sacrificed, while the animals of the withdrawal groups were killed after two weeks of drug discontinuation. Both the liver and kidneys were removed and prepared for histological examination.Results: Remdesivir-treated liver and kidneys showed histological alterations such as blood vessel congestion, mononuclear cell infiltration, and localized hepatocyte degeneration. Meanwhile, kidney sections revealed localized vacuolation of the tubular epithelium, focal glomerular tuft shrinkage with Bowman's space dilatation.Conclusion: Remdesivir is hepatotoxic and nephrotoxic mainly, at high doses. Even after drug withdrawal, structural alterations persist, particularly at high dosages, confirming that remdesivir toxicity is dose-dependent.
- Klíčová slova
- remdesivir,
- MeSH
- adenosinmonofosfát analogy a deriváty toxicita MeSH
- alanin analogy a deriváty toxicita MeSH
- antivirové látky * toxicita MeSH
- farmakoterapie COVID-19 škodlivé účinky MeSH
- histologické techniky MeSH
- játra účinky léků MeSH
- ledviny účinky léků MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
Kangrelor v dnešní době představuje jediný intravenózní inhibitor destičkového receptoru P2Y12 s klinicky prokázanou účinností pro snížení ischemických komplikací perkutánní koronární intervence (PCI). Dle souhrnu údajů o léčivém přípravku (SPC) je kangrelor doporučen u pacientů podstupující PCI, kteří nebyli léčení perorálním P2Y12 inhibitorem, nebo u nichž tato terapie není možná nebo vhodná. V následující kazuistice bude představen případ vysoce rizikového pacienta s komplexním intervenčním výkonem za použití tohoto přípravku (1).
Kangrelor represents the only intravenous inhibitor of the platelet receptor P2Y12 with clinically proven effectiveness in reducing ischemic complications of percutaneous coronary intervention (PCI). According to the Summary of Product Characteristics (SPC), Kangrelor is recommended for patients undergoing PCI who have not been treated with an oral P2Y12 inhibitor or for whom this therapy is not possible or suitable. In the following case study, a high-risk patient undergoing a complex interventional procedure using this preparation will be presented (1).
- Klíčová slova
- Kangrelor,
- MeSH
- adenosinmonofosfát farmakologie terapeutické užití MeSH
- akutní koronární syndrom farmakoterapie MeSH
- antagonisté purinergních receptorů P2Y * farmakologie terapeutické užití MeSH
- infarkt myokardu * diagnóza terapie MeSH
- inhibitory agregace trombocytů farmakologie terapeutické užití MeSH
- lidé MeSH
- senioři MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- kazuistiky MeSH
Přehledový článek se věnuje nejnovějším strategiím a postupům v léčbě covidu-19 tři roky po jeho prvním výskytu. Důraz je kladen na využití těchto poznatků v medicínské praxi. V roce 2023 je cílená terapie infekce SARS-CoV-2 již založena na výsledcích robustních randomizovaných kontrolovaných studií. V rámci ambulantní péče je na prvním místě vždy nutné vyhodnotit, zda je možná u konkrétního pacienta léčba v domácím prostředí, či by měl být pacient odeslán k hospitalizaci. Pro ambulantně léčené pacienty s lehkým až středně těžkým průběhem covidu-19 dnes máme k dispozici perorální antivirotika nirmatrelvir/ritonavir a molnupiravir. Za hospitalizace zpravidla podáváme remdesivir v intravenózní podobě. U nejzávažnějších případů covidu-19 s hypoxemickým respiračním selháním je na místě podání kortikoidů. U všech pacientů nesmíme zapomínat na riziko tromboembolických komplikací. Klíčovým momentem v boji proti covidu-19 bylo zavedení aktivní imunizace, očkování stále vykazuje velmi dobrou ochranu proti závažnému průběhu covidu-19 a úmrtí.
The overview article mostly deals with the most recent strategies and procedures in covid-19 treatment three years after its first occurrence. Emphasis is put on using this knowledge in medical practice. In the year 2023 the targeted therapy for SARS-CoV-2 infection is based on the results of robust randomized controlled studies. In out-patient setting, the most important is to evaluate whether home treatment is an option for the specific patient or if the patient should be sent for hospitalization. For patients treated in out-patient care with mild or moderate infection of covid-19, today we have perioral antiviral drugs nirmatrelvir/ritonavir and a molnupiravir. During hospitalization we usually administer remdesivir in intravenous form. The most severe cases of covid-19 with hypoxemic respiratory failure benefit from administration of corticosteroids. We must not forget the risk of thromboembolic complications at all patients. Key moment in fight against covid-19 was introduction of active immunization, since vaccination still shows very good protection against severe covid-19 infection and death.
- Klíčová slova
- remdesivir, molnupiravir,
- MeSH
- adenosinmonofosfát analogy a deriváty aplikace a dávkování terapeutické užití MeSH
- antivirové látky MeSH
- COVID-19 komplikace patologie MeSH
- farmakoterapie COVID-19 * MeSH
- hormony kůry nadledvin terapeutické užití MeSH
- hydroxylaminy aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- tromboembolie prevence a kontrola MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Paratrimastix pyriformis is a free-living flagellate thriving in low-oxygen freshwater sediments. It belongs to the group Metamonada along with human parasites, such as Giardia and Trichomonas. Like other metamonads, P. pyriformis has a mitochondrion-related organelle (MRO) which in this protist is primarily involved in one-carbon folate metabolism. The MRO contains four members of the solute carrier family 25 (SLC25) responsible for the exchange of metabolites across the mitochondrial inner membrane. Here, we characterise the function of the adenine nucleotide carrier PpMC1 by thermostability shift and transport assays. We show that it transports ATP, ADP and, to a lesser extent, AMP, but not phosphate. The carrier is distinct in function and origin from both ADP/ATP carriers and ATP-Mg/phosphate carriers, and it most likely represents a distinct class of adenine nucleotide carriers.
- MeSH
- adenosinmonofosfát metabolismus MeSH
- adenosintrifosfát metabolismus MeSH
- lidé MeSH
- mitochondriální membrány metabolismus MeSH
- mitochondrie metabolismus MeSH
- paraziti * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Nowadays, cangrelor is still the only intravenous antiplatelet drug that belongs to the P2Y12 inhibitors family. Its unique characteristics are possibilities of intravenous application and rapid onset and offset of action. In this case, we would like to present a patient with acute myocardial infarction in whom percutaneous coronary intervention could be very dangerous without the use of cangrelor. The reason was very high ischemic risk during complex coronary intervention. In addition to this indication, cangrelor could be very useful in other situations, when intravenous administration is the only way to inhibit platelets.
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- Klíčová slova
- Kangrelor,
- MeSH
- adenosinmonofosfát farmakologie terapeutické užití MeSH
- akutní koronární syndrom * farmakoterapie MeSH
- antagonisté purinergních receptorů P2Y aplikace a dávkování farmakologie terapeutické užití MeSH
- inhibitory agregace trombocytů aplikace a dávkování farmakologie terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- výsledek terapie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Klíčová slova
- remdesivir, nirmatrelvir, molnupiravir,
- MeSH
- adenosinmonofosfát analogy a deriváty MeSH
- alanin analogy a deriváty MeSH
- antivirové látky aplikace a dávkování farmakologie terapeutické užití MeSH
- COVID-19 terapie MeSH
- cytidin analogy a deriváty MeSH
- farmakoterapie COVID-19 * MeSH
- heparin nízkomolekulární aplikace a dávkování terapeutické užití MeSH
- hormony kůry nadledvin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- hydroxylaminy MeSH
- inhibitory virových proteáz aplikace a dávkování terapeutické užití MeSH
- lidé MeSH
- pasivní imunizace MeSH
- Check Tag
- lidé MeSH
By December 2019, humanity was challenged by a new infectious respiratory disease named coronavirus disease of 2019 or COVID-19. This is a viral infection based on the presence of the previously non-problematic coronavirus with assigned number 2. This virus causes severe acute respiratory distress and is known now as SARS-CoV2. Since SARS-CoV2 is an RNA virus, remdesivir and favipiravir, both broad-spectrum RNA polymerase inhibitors, were repurposed for treating COVID-19 patients. Remdesivir and favipiravir are antimetabolites, and they are structurally related to the naturally occurring structural elements of RNA. Both agents are prodrugs and must be activated intracellularly to exert their effects through numerous and different mechanisms of action. Efforts have been exerted to determine their efficacy and safety against COVID-19 through clinical trials. Clinical trials have shown an association of remdesivir with increased frequency of adverse effects (in comparison to favipiravir). Nevertheless, the data obtained with remdesivir resulted in its approval by the FDA on the 22nd of October 2020 for COVID-19 treatment. At present, remdesivir is being recommended by several treatment guidelines for the treatment of COVID-19 patients. The evidence in favor of favipiravir is compromised by the small number and low-quality of trials conducted. Favipiravir has shown various benefits when administered in mild and moderate cases of COVID-19, while remdesivir was more beneficial in more severe cases of the disease. Since the two agents are suitable for different groups of patients, both drugs can play a significant role in fighting this pandemic. The goal of this work is to summarize the information available on two antimetabolites - remdesivir and favipiravir - and to compare clinical experience obtained so far with these two agents in COVID-19 patients.
