Печеночный метаболизм клопидогреля

Departamentul Medicina Internă, Disciplina Sinteze clinice, USMF Nicolae Testemiţanu, Spitalul Clinic Municipal Sfânta TreimeThe purpose of the paper was to investigate the pathways of hepatic metabolism of clopidogrel by cytochrome P450 enzymes, depending on the genes encoding polymorphism. The bibliographic sources from 2001-2016 were explored in the databases: PubMed, Google Scholar, Cochrane. It was concluded that clopidogrel is biotransformed by the hepatic cytochrome P450 enzymes in its active metabolite. The pathway of biotransformation of clopidogrel into the active metabolite undergoes two oxidation steps, involving several enzymes of cytochrome P450, predominantly CYP3A4 and CYP2C19, which play a leading role in this process. Genes encoding cytochrome P450 enzymes may have different polymorphisms, producing enzymes with varying biotransformation activity of clopidogrel in the active metabolite.Целью данной работы было исследование печеночного метаболизма клопидогреля ферментами цитохрома P450 в зависимости от полиморфизма кодирующих их генов. Библиографические источники с 2001 по 2016 годы были изучены в базах данных: PubMed, Google Scholar, Cochrane. Был сделан вывод о том, что клопидогрель биотрансформируется ферментами печеночного цитохрома Р450 в его активном метаболите. Путь биотрансформации клопидогреля в активный метаболит претерпевает две стадии окисления с участием нескольких ферментов цитохрома Р450, преимущественно CYP3A4 и CYP2C19, которые играют ведущую роль в этом процессе. Гены, кодирующие ферменты цитохрома Р450, могут иметь разные полиморфизмы, производя ферменты с различной биотрансформационной активностью клопидогреля в активном метаболите

Therapy with clopidogrel based on CYP2C19 genotype

Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of MoldovaIntroduction. Combined therapy, clopidogrel plus aspirin, prevents secondary thrombotic in acute coronary syndromes (ACS), after percutaneous coronary interventions (PCI) with placement of a coronary artery stent. Clopidogrel is activated in the liver by cytochrome P450 enzymes. CYP2C19 is the principal enzyme. The most common loss-of-function variant is CYP2C19*2. This contributes to the decrease in the active metabolite of clopidogrel in the blood and reduce the effectiveness of clopidogrel therapy

Characteristics of arterial hypertension in elderly

State Medical and Pharmaceutical University “Nicolae Testemițanu”, Chișinău, Republic of MoldovaIntroduction: Cardiovascular diseases are responsible for about 17 million of deaths per year worldwide, representing almost a third of total mortality. Of these, 9.4 million of deaths a year are caused by complications of high blood pressure (hypertension). Hypertension causes at least 45% of deaths from cardiovascular disease and 51% of deaths from strokes celebration. In some populations, the number of hypertensive exceeds 50% between people over the age of 60 years. Purpose and objectives: Determination of the clinic-evolutionary features of hypertension in the elderly. Materials and methods: The study was conducted on a sample of 90 patients’ currents during October 2013-January 2014. Results: Based on the established goal we assigned patients into two groups: the first group is the active patients of working age to 65 years and the second group is represented by patients older than 65 years. Distribute these groups by sex was determined that both groups of woman sex prevail: in the group with patients up to 65 years - 63% and in the group of elderly patients - 53%. Following the distribution of patients with hypertension by age observed that patients aged up to 65 years represent - 33.4%, but patients over 65 years represent - 66.6%. Analyzing triggers hypertension in both groups was revealed that in patients up to 65 years predominate multiple factors (stress, coffee, alcohol) - 46.6%, the second factor is stress - 40% in elderly multiple factors predominate (stress, coffee, excessive consumption o f food) - 86.6%, stress as single - factor as 10%. HTA values is divided as follows: in patients up to 65 years dominate HTA of first degree 30% and second degree 40%, a controversy is observe in elderly patients where prevails hypertension of the third grade - 36.6% and hypertension isolated systolic - 41.6%. As concomitant diseases are prevalent in elderly patients - 58.3% compared to patients up to 65 years - 46.6%. Of these diseases in the elderly is frequently pathology: renal - 8.2%, articular - 20%, DZ - 15%, hypertensive encephalopathy - 10%. Analysis revealed dyslipidemia, in patients up to 65 years hypercholesterolemia - 60%, hypertriglyceridemia - 47%, hypercholesterolemia in elderly patients - 74%, hypertriglyceridemia - 52%. Conclusion: Analyzing all the particulars we determined hypertension in the elderly: major factors in the onset of hypertension are multiple factors (stress, coffee, excessive consumption of food). Blood pressure values indicate greater weight of third degree and HTA and isolated systolic hypertension and not least the presence of concomitant diseases and changes lipids is found in most elderly patients

Massive hemoptysis in mitral stenosis

State Medical and Pharmaceutical University “Nicolae Testemitanu”, Chisinau, Republic of MoldovaIntroduction: Massive hemoptysis is an uncommon but life-threatening emergency. The loss of at least 600 ml of blood within a 48-hour period has been associated with a high mortality rate. Although most commonly hemoptysis caused by valvulopathies is not massive enough to be life threatening, have been reported cases of asphyxia after pulmonary hemorrhage in patients with mitral stenosis. Hemoptysis and occurrence of pulmonary edema associated with end stage and severe mitral stenosis would be an indication for early surgery. Aim of the study: To assess the clinical, laboratory aspects and the presentation of a clinical case with massive hemoptysis and mitral stenosis occurred at mature age. Material and methods: The patient was hospitalized, examined, evaluated in Hospital "Saint Trinity", Chisinau. Results: Patient aged 45 years was hospitalized in Emergency Department due to pulmonary hemorrhage (>21/24 hours) and hemorrhagic shock. From anamnesis, the patient is known with rheumatic heart defect - mitral stenosis at the age of 25 years. It is of interest that massive hemoptysis in this patient occurred as a first manifestation of mitral stenosis. He administered anticoagulation therapy - Warfarin. Physical examination on admission revealed a normal weight patient in critical condition. Relative limits were deflected: left heart border - by 4 cm and right - by 2 cm, arrhythmic heart sounds, atrial fibrillation, diastolic murmur, distended jugular, peripheral edema at the calves, lower liver edge - 4 cm below the right costal border. Echocardiographic examination revealed the patient's hardened, calcified aorta walls, indurated annulus and aortic valves, calcified, with formation of the moderate regurgitation (II degree), mitral annulus calcification, mitral valves endured pronounced calcified stenosis formation, transmitral pressure gradient - 36 mmHg., mitral orifice area - 1,5 cm2, considerable dilatation of the left atrium, right atrium, moderate dilatation of the right ventricle, asymmetrical hypertrophy of the left ventricular myocardium, ejection fraction - 60%. Tricuspid valve insufficiency - IIIrd gr. Pulmonary artery valve insufficiency - IInd gr. Severe pulmonary hypertension, pulmonary artery pressure - 68 mmHg. Initial treatment consisted from antishock therapy (ice bag. airway maintenance, oxygen 2-4 1/min, permanent venous access, fluid resuscitation, hemostasis and hemodynamic correction), (3-blockers and digitalis administration. Patient's general condition improved by stopping hemoptysis and reducing dyspnea, but pulmonary bleeding complications required a special intervention-the reference to cardiac surgeon. Conclusion: Our patient's history and clinical course illustrate that severe hemoptysis may complicate moderate degrees of mitral stenosis. The patient had the high thromboembolic risk necessitated anticoagulation therapy. Mitral valve operation would appear to be beneficial in cessation of hemoptysis

Abordarea diagnostică și terapeutică a pacientului coronarian diabetic revascularizat

Discipline of Clinical Syntheses, 2Cardiology Discipline, Nicolae Testemitanu SUMPh, Municipal Clinic Hospital ”St Trinity”Background. Diabetes mellitus (DM) is associated with an increased risk of coronary heart disease morbidity and mortality. Coronary atherosclerosis is generally more aggressive and widespread in people with diabetes and is frequently asymptomatic. Objective of the study. To describe the particularities of the diagnostic and therapeutic approach of a revascularized diabetic coronary patient Material and Methods. 60-year-old man, disabled gr. II, hospitalized in the Endocrinology department, with type 2 diabetes decompensation, suspicion of cardiogenic shock and non-intensive anginal pain, but which required the use of vasodilators (nitrates: 20mg / 24 hours) at home. The patient was investigated clinically and paraclinically by electrocardiography, echocardiography, angiocoronarography. Results. Known patient with hypertension, chronic atrial fibrillation (AF), DM, old myocardial infarction (MI) and coronary angioplasty on the circumflex artery (Cx) segment III and anterior descending artery (LAD), with implantation of 2 pharmacological stents active (DES). Recently performed angiocoronarography showed bicoronary atherosclerotic lesions: subocclusive critical stenosis on the intermediate artery (IR), stenoses moderate-severe on LAD, and previously implanted stents were patent. At this stage, myocardial revascularization included the placement of 2 DES on IR. He was discharged with the recommendations: insulin therapy, dual antiplatelet therapy, vasodilators, statins. Conclusion. The peculiarities of the presented case are the characteristic of the angina syndrome with weakly expressed pain on the background of uncontrolled type 2 diabetes, the progression of atherosclerosis with the involvement of the coronary artery IR and stents implanted 7 years previously on LAD.Introducere. Diabetul zaharat (DZ) este asociat unui risc crescut de morbiditate și mortalitate a bolilor coronariene. Ateroscleroza coronariană este, în general, mai agresivă și mai răspândită la persoanele diabetice și frecvent este asimptomatică. Scopul lucrării. Descrierea particularităților abordării diagnostice și terapeutice a unui pacient coronarian diabetic revascularizat. Material și Metode. Bărbat de 60 ani, invalid gr. II, internat în secția Endocrinologie, cu decompensarea DZ de tip 2, suspecție de șoc cardiogen și durerii anginoase neintensive, dar care au necesitat utilizarea de vasodilatatoare (nitrați: 20mg/24 ore) la domiciliu. Pacientul a fost investigat clinic și paraclinic prin electrocardiografie, ecocardiografie, angiocoronarografie. Rezultate. Pacientul cunoscut cu HTA , fibrilație atrială (FA) cronică, DZ, infarct miocardic (IM) vechi și angioplastie coronariană pe artera circumflexă (Cx) segmentul III și artera descendentă anterioară (LAD), cu implantarea a 2 stenturi farmacologic active (DES). Angiocoronarografia efectuată recent a atestat leziuni aterosclerotice bicoronariene: stenoză critică subocluzivă pe artera intermediară (IR), stenoze moderat-severe pe LAD, iar stenturile implantate anterior erau patente. La această etapă, revascularizarea miocardică a inclus plasarea de 2 DES pe IR. A fost externat cu recomandările: insulinoterapie, tratament dublu antiplachetar, vasodilatatoare, statine. Concluzii. Particularitățile cazului prezentat sunt caracteristica sindromului anginos cu durere slab exprimată pe fon de DZ de tip 2 necontrolat, progresia aterosclerozei cu implicarea de artere coronare noi și stenturi implantate 7 ani anterior patente

Вызовы антиагрегационной терапии у коронарных пациентов после cтентирования коронарных артерий

Challenges in antiplatelet therapy in coronary patients after percutaneous coronary interventionO valoare importantă în prevenirea și progresia proceselor trombotice la pacienții coronarieni ocupă utilizarea agenților antiplachetari. Terapia antiplachetară dublă include acidul acetilsalicilic și blocantul receptorilor P2Y12 – adenozin 5’-difosfat pentru pacienții cu intervenție coronariană percutană, utilizată în scopul scăderii ratei evenimentelor cardiace majore sau prevenirii reapariției a complicațiilor trombotice. În acest articol a fost studiată rata evenimentelor ischemice și hemoragice la pacienții care administrează terapia antiplachetară dublă după 6 luni de la intervenția coronariană percutană cu implantare de stent farmacologicВызовы антиагрегационной терапии у коронарных пациентов после cтентирования коронарных артери

Кровотечения у пациентов, получающих двойную антитромбоцитарную терапию (аспирин + ингибитор P2Y12 - клопидогрел)Ё

In patients with coronary artery disease, percutaneous coronary interventions (PCI) are the mainstay of treatment for those presenting with acute coronary syndrome (ACS); PCI has also been widely adopted in patients with chronic coronary syndromes. Adjuvant pharmacotherapy, especially antithrombotic therapy, is the key to reducing local thrombotic complications and systemic ischemic events among patients undergoing percutaneous coronary interventions, but is inevitably associated with the occurrence of bleeding events. Prasugrel and ticagrelor are preferred over clopidogrel in patients with ACS in the absence of contraindications. Despite this, clopidogrel remains the most widely used. In this article, the bleeding events that occurred during 6-12 months of dual antiplatelet therapy (aspirin + P2Y12 inhibitor clopidogrel) in patients who underwent myocardial revascularization by PCI, the factors that favored their occurrence and the use of the prediction score were studied.La pacienții cu boală coronariană, intervențiile coronariene percutanate (PCI) reprezintă piatra de temelie a tratamentului pentru cei care prezintă un sindrom coronarian acut (SCA); PCI a fost, de asemenea, adoptată în mare măsură la pacienții cu sindroame coronariene cronice. Farmacoterapia adjuvantă, în special terapia antitrombotică, este cheia pentru reducerea complicațiilor trombotice locale și a evenimentelor ischemice sistemice, la pacienții supuși intervențiilor coronariene percutanate, dar este inevitabil asociată cu apariția evenimentelor de sângerare. Prasugrel și ticagrelor sunt preferate față de clopidogrel la pacienții cu SCA în absența contraindicațiilor. În pofida acestui fapt, clopidogrelul rămâne a fi cel mai utilizat. În acest articol au fost studiate evenimentele de sângerare apărute pe parcursul a 6-12 luni de terapie dublă antiplachetară (aspirină + inhibitorul P2Y12 clopidogrel) la pacinții care au fost supuși revascularizării miocardice prin PCI, factorii care au favorizat apariția acestora și utilizarea scorului de predicție.У пациентов с ишемической болезнью сердца чрескожные коронарные вмешательства (ЧКВ) являются краеугольным камнем лечения пациентов с острым коронарным синдромом (ОКС) и пациентов с хроническим коронарным синдромом. Адъювантная фармакотерапия, особенно антитромботическая терапия, является ключом к снижению местных тромботических осложнений и системных ишемических событий у пациентов, перенесших чрескожные коронарные вмешательства, но неизбежно связана с возникновением кровотечений. Прасугрел и тикагрелор предпочтительнее клопидогрела у пациентов с ОКС при отсутствии противопоказаний. Несмотря на это, клопидогрел остается наиболее широко используемым. В данной статье мы изучили кровотечения, возникающие в течение 6-12 мес двойной антитромбоцитарной терапии (аспирин + ингибитор P2Y12 клопидогрел) у пациентов, перенесших реваскуляризацию миокарда методом ЧКВ, и прогностические факторы, благоприятствующие их возникновению

Hipertensiunea arterială preexistentă și impactul asupra severității la pacienții cu COVID-19

Background. The prevalence of pre-existing hypertension seems to be higher in COVID-19 patients who develop severe disease versus those who do not. Studies have reported hypertension as one of the most common comorbidities (30%) in patients with COVID19, frequently associated with acute respiratory disorders. Objective of the study. The aim of the study was to assess the presence of hypertension and the impact on severity of patients with COVID-19 Material and Methods. We included 92 inpatients (≥18 years old) in a prospective multicentre cohort hospitalized at Municipal Clinical Hospitals No. 1 and No. 3 (Chisinau, Moldova), the diagnosis being confirmed in laboratories specialized in SARS CoV2 RT-PCR detection. Patients were investigated clinically and paraclinically according to WHO Provisional Forms for reporting COVID-19 infection. Results. Of the 92 cases with COVID-19, (mean age 61.51±3.42 years), without gender predominance (men 51.2% determine the vs 48.8% women), 54 (58.69%) reported at least one cardiovascular comorbidities. The rate of hypertension was (34.7%) and predominated compared to the presence of diabetes (13.04%, p <0.001), cerebrovascular disease (8.6% p <0.001) and chronic obstructive pulmonary disease (17.3%, p <0.001). Stratification of patients by severity revealed the coexistence of pre-existing hypertension in severe vs. non-severe COVID-19 patients (75.92% vs. 59.78%, respectively, p <0.001), with advanced age (81.23 vs 57.33 years, respectively, p <0.001) and death accounting for 7.61%. Conclusion. The presence of hypertension and advanced age in patients with COVID-19 severity of patients and increased mortality. Introducere. Prevalența hipertensiunii preexistente pare a fi mai mare la pacienții cu COVID-19 care dezvoltă boala severă. Studiile efectuate au raportat hipertensiunea ca una din cele mai frecvente comorbidități (cu o rată de până la 30%) la pacienții cu COVID19, frecvent asociată cu tulburări respiratorii acute. Scopul lucrării. Scopul studiului constă în evaluarea prezenței hipertensiunii arteriale preexistente și a impactului asupra severității pacienților cu COVID-19. Material și Metode. S-au inclus în studiul prospectiv de cohortă multicentrică 92 de pacienți (≥18 ani) cu COVID-19 spitalizați la Spitalele clinice municipale nr.1 și nr.3 din Chișinău, diagnosticul fiind confirmat în laboratoarele specializate, în detecția PCR SARS CoV2. Pacienţii au fost investigaţi clinic şi paraclinic conform formularelor provizorii ale OMS pentru raportarea cazurilor de infecție cu COVID-19. Rezultate. Din cele 92 de cazuri cu COVID-19, (vârsta medie 61, 51 ±3, 42 ani), fără predominare de gen (bărbați 51,2% vs 48,8% femei), 54 (58,69%) au raportat cel puțin o cormobiditate cardiovasculară. Rata hipertensiunii arteriale a fost de (34, 7%) și predomina comparativ cu prezența diabetului zaharat (13, 04%, p< 0,001), bolilor cerebrovasculare (8, 6% p< 0,001) și bolilor pulmonare obstructive cronice (17,3% p< 0,001). Stratificarea pacienților în funcție de severitate a relevat coexistența hipertensiunii arteriale preexistente la pacienții COVID-19 sever vs non-sever (75, 92% vs 59,78%, respectiv, p<0,001) și vârstă înaintată (81,23 vs 57,33 ani, respectiv, p<0,001), decesul constituind 7,61%. Concluzii. Prezența hipertensiunii arteriale preexistente și vârsta înaintată la pacienții cu COVID-19 determină gradul de severitate a pacienților și mortalitatea crescută

Holter monitoring of paroxytic atrial fibrilation. Clinical case

Departamentul Medicină Internă: Disciplina de sinteze clinice, IP USMF „Nicolae Testemițanu”, CSF Galaxia, IMSP SCM “Sf. Treime”, Conferința Științifică „Centrul Medical «Galaxia» la 20 de ani”Fibrilația atrială paroxistică se estimează că cuprinde între 25% și 62% din cazurile de fibrilație atrială observate de către practicieni atât în cadrul spitalizării, cât și în cel de îngrijire primară. Prevalența raportată variază foarte mult, datorită diferențelor dintre definiții și diferitele populații studiate. În plus, prevalența fibrilației atriale paroxistice ar putea fi subestimată, deoarece majoritatea studiilor epidemiologice depind de episoadele simptomatice, dar fibrilația atrială paroxistică asimptomatică este frecvent depistată la monitorizarea Holter. Scopul studiului a fost de a monitoriza prin metoda Holter fibrilația atrială paroxistică la un pacient cu astm bronșic exacerbat. Monitorizarea Holter a înregistrat paroxismele de FA fără manifestări simptomatice, ceea ce a permis elucidarea diagnosticului și tratamentul oportun individual al pacientului.It is estimated that paroxysmal atrial fibrillation includes between 25% and 62% of cases of atrial fibrillation observed by the practitioners in hospitalization as well as in primary care. The reported prevalence can vary a lot because of the differences between definitions and different studied populations. Moreover, the prevalence of paroxysmal atrial fibrillation could be underestimated because the majority epidemiological studies depend on episodic symptoms, but asymptomatic paroxysmal atrial fibrillation is frequently detected by Holter monitoring. The objective of this study is to monitor the paroxysmal atrial fibrillation of a patient with asthma exacerbation by the Holter method. Holter monitoring recorded the paroxysms of atrial fibrillations without symptoms, which helped us to determine the diagnose and the individual treatment for the patient