Thiazide and thiazide-like diuretics: how to make the right choice?

Most patients with arterial hypertension (AH) require a combination treatment to achieve the goal blood pressure. According to Russian and international clinical guidelines on the treatment of AH patients, various antihypertensive drugs may be combined; however, not all combinations have similar profiles of safety and clinical efficacy. In this respect, special attention is given to combinations of renin-angiotensin-aldosterone system inhibitors and thiazide (hydrochlorothiazide) or thiazide-like (chlortalidone, indapamide) diuretics. Diuretics also differ in their mechanisms of action, presence of pleiotropic effects and organ-protective properties, effects on the prognosis, and in the evidence base. This review discusses the place of thiazide and thiazide-like diuretics in the treatment of patients with AH and provides an evaluation of major differences in pharmacological and clinical effects of drugs of the diuretic class.

[Modern issues of improving the prognosis in patients with atrial fibrillation after ischemic stroke].

The anticoagulant therapy with a priority of direct oral anticoagulants is an approach to the prevention of recurrent stroke in patients with atrial fibrillation (AF) that has presently proved its efficacy and is stated in international clinical guidelines. An extensive evidence-based database demonstrates advantages of rivaroxaban over other drugs of this class in secondary prevention of stroke in AF. Furthermore, these advantages are combined with the optimal safety profile. The rivaroxaban treatment may provide the most favorable prognosis due to the prevention of recurrent stroke in AF, reducing the rate of kidney disease progression, and slowing vascular atherosclerosis. An important beneficial feature of rivaroxaban is once-a-day intake, which is important in the context of a high incidence of cognitive disorders in this patient category, and may improve their compliance and, thus, help achieving the expected profile of treatment efficacy. Thus, rivaroxaban can be regarded as a drug of choice for secondary prevention of stroke in AF.

[What do we Mean by "Ideal" Blood Pressure Control?]

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.

[Drug-induced uveitis]. / Lekarstvenno-indutsirovannyi uveit.

In recent years, an increasing amount of attention has been paid to medicinal products as possible risk factors in the development of eye diseases. The frequency of diagnosed drug-induced uveitis is growing yearly, which can be attributed to the appearance of new drugs - biological agents (immune checkpoint inhibitors, BRAF and MEK inhibitors, vascular endothelial growth factor inhibitors, tumor necrosis factor-α inhibitors), as well as systemic bisphosphonates and some antiviral drugs. The time interval between the beginning of the drug use and the appearance of uveitis symptoms varies from several days to months. Common symptoms include eye pain, photophobia, the appearance of floating opacities, and reduced vision associated with active inflammatory changes in the retina and optic nerve and outcomes of those inflammations. Timely diagnosis, cancellation of the drug that caused uveitis and appointment of adequate anti-inflammatory therapy in most cases effectively stops the symptoms of the disease, which determines the relevance of attention to the prevalence, pathogenesis, diagnosis and treatment of drug-induced uveitis.

[Herpangina. Clinical case]. / Gerpeticheskaya angina ­ aktual'naya problema otorinolaringologicheskoi praktiki.

Enterovirus infections are a group of acute infectious diseases caused by enteroviruses (including Coxsackie A and B viruses, ECHO viruses), which clinically present symptoms of damage to the central nervous system, cardiovascular system, gastrointestinal tract, muscular system, mucous membranes and skin, fever. This article presents a clinical case of patient L., 12 years old, who admitted to an otorhinolaryngologist with clinical manifestations of herpangina. The diagnosis was confirmed by PCR. The patient was prescribed, adequate rehydration, diet with the exclusion of salty, spicy and fried foods, restriction of physical activity, exclusion of thermal procedures, Benzydamine Spray (Oralsept) 0.255 mg/dose, 6 doses 3 times/day, topically, on demand and inosine pranobex (Groprinosin) in a daily dose of 50 mg/kg of body weight: 1 tablet 500 mg 4 times a day for 7 days (at the rate of 1 tablet of 500 mg per 10 kg of body weight; for a patient weighing 41 kg - 4 tablets per day). On the 10th day from the onset of the disease, the docter noted a complete regression of clinical symptoms and the patient was discharged with recovery.

[Treatment of chronic heart failure: is deprescribing possible?]

Deprescribing is a scheduled withdrawal, dose reduction, or replacement of a medicine with a safer one. Several groups of medicinal products (MPs) are used simultaneously in the treatment of chronic heart failure. This increases the risk of adverse drug reactions, particularly in elderly and senile patients. A systematic search for literature allowed evaluating possibilities of deprescribing for the following pharmaceutic groups: 1) MPs influencing the renin-angiotensin-aldosterone system; 2) beta-blockers; 3) digoxin; and 4) diuretics. Three systematic reviews and several studies were analyzed to determine the most feasible and potentially optimal regimens of deprescribing in CHF. It was established that in CHF, deprescribing has a very limited potential for use due to the documented, obvious effect of some MP groups on prediction and severity of clinical symptoms in CHF patients.

[Hypertension and insomnia].

Insomnia is frequently detected in patients with arterial hypertension (AH): from 19% to 47.9% of all cases according to epidemiological studies. On the other hand, the frequency of hypertension in patients with insomnia ranges from 21.4% to 50.2%, whereas in patients without insomnia, from 11.0% to 41.8%. In single studies in which patients with insomnia underwent ambulatory blood pressure monitoring (ABPM), these patients showed higher nocturnal blood pressure levels. Recent data suggests that insomnia is also a risk factor for hypertension. Among the pathogenetic mechanisms explaining the relationship between hypertension and insomnia, an increase in the activity of the main neuroendocrine stress systems, sympatho - adrenal and hypothalamic - pituitary - adrenal, and the frequent presence of concomitant anxiety disorders are discussed. To determine the sleep quality in patients with insomnia, the Pittsburgh Sleep Quality Index (PSQI) is most often used, patients with hypertension in a number of studies had higher total PSQI score compared to individuals with normal blood pressure. PSQI score correlates with systolic and diastolic blood pressure level, as well as with the presence of non - dipper blood pressure profile. Both hypertension and insomnia are associated with impaired cognitive functions. However, the relationship between cognitive impairment and insomnia is rather contradictory, which is most associated with the methodology for assessing cognitive functions and differences in the initial clinical and demographic characteristics of the examined patient population.

[Drug-induced glaucoma]. / Lekarstvenno-indutsirovannaya glaukoma.

Glaucoma is seen as a heterogeneous group of diseases characterized by optical neuropathy with associated visual field loss; one of the main risk factors for its development is increased intraocular pressure (IOP). In the case of drug-induced glaucoma (DIG), patients develop elevated IOP, optic neuropathy and visual field defects associated with the use of certain drugs. Corticosteroids are one of the most well-known classes of drugs that can cause an increase in IOP through the open-angle mechanism. Drug-induced glaucoma, which develops similarly to open-angle glaucoma, can also be caused by some non-steroidal anti-inflammatory agents, antibodies to the endothelial growth factor, etc. Classes of drugs that can cause angle-closure glaucoma include topical anticholinergic or sympathomimetic drops, tricyclic antidepressants, monoamine oxidase inhibitors, antihistamines, antiparkinsonian drugs, antipsychotic drugs, antispasmodics. Products containing sulfa group drugs can cause DIG due to a different closing angle mechanism involving a forward rotation of the ciliary body. It is important for medical practitioners to be aware of this unwanted drug reaction in order to prevent, detect and treat DIG. In the case of drug-induced increase in IOP, if the underlying disease allows discontinuation of drugs, this measure usually leads to normalization of IOP. In cases when the patient's IOP does not normalize after discontinuation of steroids or when they must continue to take corticosteroids, the administration of topical drugs for the treatment of glaucoma should be considered.

[Drug-induced toxic optic neuropathy]. / Lekarstvenno-indutsirovannaya toksicheskaya opticheskaya nevropatiya.

Drug-induced optic neuropathy is a group of disorders in which medications cause degeneration of the optic nerve. The true prevalence of drug-induced neuropathy has not been studied, although the percentage of patients who develop optic nerve damage is known for individual medications. The common pathophysiological mechanisms are believed to be mitochondrial damage and imbalance of intracellular and extracellular free radical homeostasis. Typical symptoms of drug-induced neuropathy are reduced visual acuity in the central area, which is often bilateral, visual field disturbances, dyschromatopsia, and edema of the optic nerve head. Early detection of drug-induced optic neuropathy can potentially prevent or minimize serious complications. For patients who develop drug-induced optic neuropathy, treatment is based on timely diagnosis and cancellation of the provoking drug. In most patients, vision usually recovers a few weeks or months after discontinuation of previous therapy, but there have been cases of irreversible vision loss. In addition to withdrawal of the drug that caused optic nerve lesion, treatment of drug-induced neuropathy may include use of drugs and treatment methods prescribed by neurologists for peripheral neuropathy, however, such treatment is seldom based on evidence.

[Rhinitis medicamentosa]. / Lekarstvenno-indutsirovannyi rinit.

One type of non-allergic non-infectious rhinitis is represented by a heterogeneous group of rhinitis medicamentosa, which can be divided into several pathogenetic types. The most common rebound nasal congestion associated with the use of topical decongestants. Excessive use of intranasal decongestants leads to a decrease in the number of alpha-adrenoreceptors on the surface of cell membranes and uncoupling their connection with the G-protein and the development of tachyphylaxis. To prevent the development of rebound nasal congestion caused by topical decongestants, it is important to limit the frequency of their use. In most cases, the duration of the use of vasoconstrictor drugs should be limited to 5-7 days, according to Patient information leaflets for the drugs. However, in patients who have had a history of episodes of rebound nasal congestion, which develops including the previously indicated periods, the duration of decongestant therapy should be limited to 3 days. Rhinitis associated with local inflammation is caused by the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs. Currently, the so-called "aspirin triad" is well known - a combination of bronchial asthma, rhinosinusitis (often polyposis) and intolerance to ASA. Neurogenic rhinitis develops due to the use of drugs that violate vascular tone, for example, antihypertensive drugs or type 5 phosphodiesterase inhibitors. Drug-induced rhinitis has a significant impact on the patient's quality of life: nasal congestion, rhinorrhea, secondary night apnea, insomnia as a result of nasal breathing disturbances, headaches, irritability, weakness after sleepless nights disturb patients to a large extent. Timely diagnosis and withdrawal of a provocative drug, the use of topical corticosteroids in case of severe rhinitis are the basis of the treatment of rhinitis medicamentosa. In severe cases, there is a need, including surgical treatment, such as, for example, submucosal laser destruction of the lower nasal concha.

[Drug-induced dysphonia]. / Lekarstvenno-indutsirovannaya disfoniya.

Drug-induced dysphonia is a non-life-threatening adverse drug reaction, however, this complication can significantly worsen the quality of life of patients, especially those in voice-speaking professions. The aim of the work was to search for information about the prevalence, etiology, pathogenesis, and features of treatment and prevention of drug-induced dysphonia. In the case of some drugs, the true prevalence may be higher than described in the literature, due to the fact that dysphonia is in most cases mild, reversible and, in comparison with other undesirable drug reactions, rarely attracts the attention of both the patient and practitioners.

[Single Pill Indapamide and Perindopril Arginine Combination: Optimal Coupling of Vascular Protection and Hemodynamic Risk Factors Reduction in Patients with Essential Arterial Hypertension].

OBJECTIVE: to investigate the impact of indapamide / perindopril single-pill combination (I / P SPC) on arterial stiffness parameters, blood pressure (BP) level and BP variability (BPV) in middle-aged patients with stage II grade 1-2 essential arterial hypertension (EAH). Materials and methods. We retrospectively formed a group of patients with stage II grade 1-2 EAH who had not previously received regular antihypertensive therapy (AHT) (n=52, mean age 52.9±6.0 years). All patients were treated with I / P SPC and all of them achieved target office BP level (less than 140 / 90 mm Hg). After 12 weeks of follow-up (from the time of reaching the target BP) assessment of AHT effectiveness (general clinical data, ambulatory blood pressure monitoring [ABPM], volume sphygmography, echocardiography), and vascular stiffness evaluation were performed. RESULTS: At the end of follow-up office systolic BP (SBP), diastolic BP (DBP), pulse BP, day-time, night-time and 24­hour SBP and DBP significantly (p<0.001 for all) decreased. According to the ABPM data day-time, nighttime, and 24­hour systolic BPV significantly decreased (p=0.029, p=0.006 and p<0.001, respectively); day-time and 24­hour diastolic BPV also significantly decreased (p=0.001 and p<0.001, respectively). Day-night standard deviation (SDdn) significantly decreased too (p=0.002 and p<0.001, respectively). Volumetric sphygmography showed significant decrease of right cardio-ankle vascular index (CAVI) (from 8.20±1.29 to 7.58±1.44, p=0.001) and of left CAVI (from 8.13±1.40 to 7.46±1.43, p<0.001), as well as reduction of the number o f patients with a right- and / or left-CAVI >9.0 (from 32.7 to 11.5 %, p=0.018). According to assessment of arterial stiffness using the Vasotens24 software package, the arterial stiffness index (ASI) significantly (p<0.001) decreased from 153.5±29.9 to 138.3±20.0 (by -9.2±13.1 %). Transthoracic echocardiography data demonstrated significant decrease (p<0.001) in effective arterial elastance (from 1.82±0.43 to 1.58±0.36 mm Hg; by -11.85±16.29 %) and significant (p<0.001) increase in the arterial compliance - from 1.27±0.34 to 1.54±0.38 mm Hg / ml (+26.95±38.06 %). CONCLUSION: In AHT naive patients 40-65 years old with stage II grade 1-2 EAH therapy with I / P SPC provided effective 24­hour BP control, reduced BPV and improved arterial stiffness parameters.

[Mechanisms for the Development of Blood Pressure Variability and the Potential of Antihypertensive Drugs in Their Correction].

Blood pressure variability (BPV) is the fluctuations of blood pressure over a certain period of time under the influence of various factors. The issue of increased BPV is of particular clinical importance due to high predictive value of this parameter as a risk factor for fatal and non-fatal cardiovascular, cerebrovascular and renal events. It is proved that in the BPV increasing, the key role is played by impairments in arterial baroreflexes, which, in turn, are mediated by increased vascular stiffness, impact of angiotensin II and the sympathetic nervous system, endothelial dysfunction, nitric oxide deficiency and aging, including the vascular aging. Antihypertensive drugs that targeting largest amount of pathophysiological mechanisms in BPV increasing have a most advantages in correcting excessive pressure fluctuations. In this regard such drugs are perindopril and amlodipine, which can eliminate almost the entire spectrum of increased BPV causes and, therefore, optimally reduce the cardiovascular risk.

[The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications].

In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed. The authors conducted a search, systematization and analysis of studies regarding the association between cardiovascular risk and combined use of individual medications from PPI class with clopidogrel, and these results are presented in the review. Currently available data do not allow to answer the question about the differences between individual PPIs in their impact on the risk of adverse cardiovascular events due to the small number of such studies, design heterogeneity, differences in the inclusion criteria and end points as well as in the rate of administration of individual PPIs.

[Drug-induced hearing loss as a manifestation of drug-induced ototoxicity]. / Lekarstvenno-indutsirovannaia tugoukhost' kak proiavlenie lekarstvenno-indutsirovannoi ototoksichnosti.

The ability of drugs to have an ototoxic effect has been studied for a long time, however, the true prevalence of this undesirable phenomenon is unknown, which is due to the use of various audiological protocols, a wide range of reactions to drugs in different ethnic groups, and most importantly, the lack of caution with regard to otological symptoms due to their reversibility or lack of immediate threat to life. Drug-induced ototoxicity is a functional disorder of the inner ear (cochlea and/or vestibular apparatus) or eighth pair of cranial nerves. Pharmacotherapy, associated with the development of ototoxic drug reactions, may remain undervalued for a long time, often until irreversible hearing impairment is formed. The most frequently prescribed drugs that cause ototoxic phenomena include anticancer drugs, antibacterial drugs of the aminoglycoside group, loop diuretics, calcium channel blockers, non-steroidal anti-inflammatory drugs, antimalarial drugs, salicylates, etc. Monitoring the degree of hearing impairment before and during therapy is important in preventing the development of drug-induced ototoxicity and makes it possible to consider alternative treatment regimens in a timely manner. It is in this connection that the role of participation in the appointment of rational pharmacotherapy to patients with a potential risk of developing otological phenomena of a clinical pharmacologist and audiologist undoubtedly increases.

Myocardial Strain and Stiffness Parameters as a Novel Target of Antihypertensive Treatment.

In the review, the clinical significance of increased myocardial stiffness and strain impairment in the settings of arterial hypertension is considered. The mechanisms of increasing myocardial stiffness as a part of hypertensive heart disease are presented. Particular attention is paid to the role of the sympathetic nervous system activation as one of the triggers that induce the connective tissue alteration of cardiac interstitium. The possibilities of echocardiography in the early noninvasive detection of myocardial strain abnormalities are discussed. New ultrasound parameters for describing stiffness properties of the heart are presented. From the evidence-based medicine point of view, the prognostic significance of increasing myocardial stiffness as a risk factor of the adverse cardiovascular events, as well as the possibility of its management with different antihypertensive drugs, is considered. Finally, there are presented clinical trials data, indicating high potential of the highly selective ^1-adrenoblocker bisoprolol for of correction myocardial stiffness and strain impairment.

[Atrial fibrillation as Risk Factor for Development of Cognitive Function Impairment and Dementia. Potential of Anticoagulant Therapy in Their Prevention].

This article presents an overview of data of Russian and foreign literature on possible associations between cognitive impairment and atrial fibrillation (AF). It includes modern classification of cognitive impairment, mechanisms of the effect of AF on cognitive functions and development of dementia, recommendations for the prevention of cognitive impairment in patients with AF. Special attention is paid to the assessment of cognitive status, and safe anticoagulant therapy, which is a priority in the prevention of cognitive impairment in patients with AF. Analysis of literature showed greater efficacy and safety of drugs from the group of Non-vitamin K Antagonist Oral Anticoagulants (NOAC), rivaroxaban in particular, in comparison with warfarin. Drugs from the NOAC group can be recommended for prevention stroke, cognitive impairment and dementia in elderly patients with AF.

[Day-by Day Blood Pressure Variability: Methodological Aspects, Prognostic Value, Effects of Antihypertensive Therapy].

In this article we present problems of prognostic value of day-by-day blood pressure (BP) variability, its role in development and progression of damage of target organs in arterial hypertension, and impact on risk of cardiovascular, cerebral-vascular complications, and mortality. We also discuss methodological aspects of assessment of day-by-day BP variability. The article contains literature data on effects of antihypertensive therapy on variability of home BP, and consideration of evidence base of possibilities of the fixed amlodipine/perindopril combination for lowering day-by-day BP variability.

[Sympathetic Nervous System Activation in Pathogenesis of Development of Essential Hypertension and Its Role in Target-Organs Damage in Young and Middle Aged Adults: the Cardioprotective Capabilities of Bisoprolol].

The article discusses various mechanisms of developmentt and progression of arterial hypertension in young and middle aged adults. It emphasizes the predominant role of hypersympathicotonia in the development of the disease in this category of patients. Various mechanisms are considered, by means of which the increase of activity of the sympathetic nervous system leads to elevation of arterial pressure and potentiates early damage of target organs, first of all, damage of the heart. The data of numerous studies demonstrating pronounced cardioprotective effects of a highly selective representative of the class of ß-blockers bisoprolol in young and middle aged hypertensive patients are presented.

[Cognitive Disorders and Dementia in Old Patients With Arterial Hypertension].

The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.