A Single Dose of Intrathecal Morphine Without Local Anesthetic Provides Long-Lasting Postoperative Analgesia After Radical Prostatectomy and Nephrectomy.

PURPOSE: Pain after open urological procedures is often intense. The aim of the study was to compare the efficacy of intrathecal morphine with systemic analgesia approaches. DESIGN: Prospective, randomized, single-blind controlled study. METHODS: Patients undergoing open prostatectomy or nephrectomy were randomly divided into the intervention group or the control group. Patients in the intervention group received morphine 250 mcg in 2.5 mL saline intrathecally. Anesthesia was identical in both groups. All patients were admitted to the intensive care unit (ICU) postoperative and received paracetamol 1 g intravenously every 6 hours and diclofenac 75 mg intramuscularly every 12 hours. If postoperative pain exceeded four on the numeric rating scale, morphine 10 mg was administered subcutaneously. Pain intensity, time to first dose of morphine, morphine doses, and side effects were recorded. FINDINGS: In total, 41 patients were assigned to the intervention group and 57 to the control group. The time to administration of the first dose of morphine was significantly (P < .001) longer in the intervention group when compared to controls. This observation was also noted individually for patients undergoing nephrectomy (36.86 hours vs 4.06 hours) and prostatectomy (33.13 hours vs 4.5 hours). Many patients did not need opioids after surgery in the intervention group (nephrectomy 72% vs 3%, prostatectomy 75% vs 4.5%, P < .001). There was no significant difference in the incidence of side effects. CONCLUSIONS: The results of our study confirmed that preoperative intrathecal morphine provides long-lasting analgesia and reduces the need for postoperative systemic administration of opioids. Adverse effects are minor and comparable between groups.

Diverse pharmacovigilance jurisdiction-The right way for global drug safety?

PURPOSE: The purpose of this narrative review is to provide a comparison of several countries with different legislation and approaches to pharmacovigilance and to point out how these impact the number of adverse drug reactions (ADRs) that are reported to national competent authorities. METHODS: Legislative and statistical data regarding ADR reporting from various national competent authorities' websites, databases, and pharmacovigilance centers were used. In combination with the WHO pharmacovigilance quantitative indicator that was applied to evaluate the effectiveness of particular national pharmacovigilance systems in our scope. RESULTS: The study compared pharmacovigilance systems in six countries, focusing on ADR reporting from 2010 onwards. All countries required MAHs to report ADRs, while healthcare professionals' obligations varied. Per-capita ADR reports increased in all countries with available data, with the United States having a significantly higher reporting rate, possibly due to FDA campaigns. Despite starting later, China's per-capita reporting rate surpassed that of the Czech Republic and Japan. The study highlighted various measures taken by countries to enhance ADR reporting systems since the inception of their programs, contributing to the overall increase in reporting rates. CONCLUSIONS: ADR reporting is a global priority, with efforts made by different countries to strengthen their pharmacovigilance systems. Some success can be seen in gradually improving per-capita ADR reporting rates. The varying reporting rates and measures taken by each country may serve as a basis for further research and exchange of best practices to improve drug safety monitoring worldwide.

The Main Therapeutic Applications of Cannabidiol (CBD) and Its Potential Effects on Aging with Respect to Alzheimer's Disease.

The use of cannabinoids (substances contained specifically in hemp plants) for therapeutic purposes has received increased attention in recent years. Presently, attention is paid to two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). With respect to the psychotropic effects and dependence potential of THC (though it is very mild), its use is associated with certain restrictions, and thus the therapeutic properties of CBD are frequently emphasized because there are no limitations associated with the risk of dependence. Therefore, this review covers the main pharmacodynamic and pharmacokinetic features of CBD (including characteristics of endocannabinoidome) with respect to its possible beneficial effects on selected diseases in clinical practice. A substantial part of the text deals with the main effects of CBD on aging, including Alzheimer's disease and related underlying mechanisms.

The position and importance of pharmacovigilance in the Czech Republic and in the world.

Pharmacovigilance is an integral part of medicine. There is always a risk of side effects when using medication; these can be completely trivial, but there are side effects that can be life-threatening or fatal. Pharmacovigilance practices should prevent such side effects, or at least reduce their incidence, especially by developing preventive measures that are based on adverse drug reaction (ADR) data and the evaluations of these. This article discusses the general concept of pharmacovigilance and compares individual pharmacovigilance systems of several countries and regions.

Urapidil: an unknown / known antihypertensive.

Essential arterial hypertension is not a disease that would significantly adversely affect patients in their daily activities. At least mostly. Nonetheless, it has a significant negative impact on cardiovascular morbidity and mortality. The tight correlation with the degree of hypertension, the patients age and, of course, commorbidities and cardiovascular risk factors is obvious. Therefore, the goal of hypertensive therapy is not only to try to achieve optimal reduction of blood pressure, but in a broader sense to reduce the risk of the just mentioned consequences, i.e. to reduce morbidity and reduce mortality. The antihypertensive drug urapidil can also be used in pharmacotherapy, the brief description of which is the subject of this article.

SGLT-2 inhibition a useful tool in the treatment of heart failure with reduced and preserved ejection fraction.

Heart failure is highly prevalent in the population and, from a long-term point of view, a disease that is still difficult to treat. Although a number of medicinal solutions are offered in its treatment, there are still large reserves. The drug portfolio has recently been expanded to include the use of SGLT-2 inhibitors, initially for failure with reduced and now also with preserved ejection fraction. The question of the possibility of using these substances is discussed in the text, focusing on a possible explanation of their therapeutic benefit.

The role and current status of heme iron preparations in people with iron depletion.

Iron deficiency is a common but underestimated condition in the population. Its correlate is far from only sideropenic anemia, but is due to the variety of involvement of this element in a number of bio-chemical reactions; several other possible clinical manifestations can be expected. Appropriately selected oral supplementation is often necessary. Here, we should carefully consider the possible ratio of expected benefits and potential risks of side effects, or interaction with dietary components or concomitant medications. The available preparations are not equivalent; they differ not only in atomically different amounts of iron but also, above all, in the form that determines the way in which the iron will be absorbed. This ultimately defines the rate of adjustment for depletion and the tolerability of a particular product.

Inosine Pranobex Deserves Attention as a Potential Immunomodulator to Achieve Early Alteration of the COVID-19 Disease Course.

Since its licensing in 1971, the synthetic compound inosine pranobex has been effectively combating viral infections, including herpes zoster, varicella, measles, and infections caused by the herpes simplex virus, human papillomavirus, Epstein-Barr virus, cytomegalovirus, and respiratory viruses. With the emergence of SARS-CoV-2, new and existing drugs have been intensively evaluated for their potential as COVID-19 medication. Due to its potent immunomodulatory properties, inosine pranobex, an orally administered drug with pleiotropic effects, can, during early treatment, alter the course of the disease. We describe the action of inosine pranobex in the body and give an overview of existing evidence collected to support further efforts to study this drug in a rigorous clinical trial setup.

Correction: Beran et al. Inosine Pranobex Significantly Decreased the Case-Fatality Rate among PCR Positive Elderly with SARS-CoV-2 at Three Nursing Homes in the Czech Republic. Pathogens 2020, 9, 1055.

There was an error in the original article [...].

Inosine Pranobex Significantly Decreased the Case-Fatality Rate among PCR Positive Elderly with SARS-CoV-2 at Three Nursing Homes in the Czech Republic.

During the COVID-19 pandemic, the elderly population has been disproportionately affected, especially those in nursing homes (NH). Inosine pranobex (IP) has been previously demonstrated to be effective in treating acute viral respiratory infections. In three NH experiencing the SARS-CoV-2 virus epidemic, we started treatment with IP as soon as clients tested PCR+. In Litovel, CZ, the difference in case-fatality rate (CFR) for the PCR+ group using vs. not using IP was statistically significant, and the odds ratio (OR) was 7.2. When comparing all those taking IP in the three NH vs. the non-drug PCR+ group in Litovel, the odds ratio was lower for all three NH, but still significant at 2.9. The CFR in all three tested NHs, age range 75-84, compared to the CFR in all NHs in the Czech Republic, was significantly reduced (7.5% vs. 18%) (OR: 2.8); there was also a significant difference across all age groups (OR: 1.7). In our study with 301 residents, the CFR was significantly reduced (OR: 2.8) to 11.9% (17/142) in comparison to a study in Ireland with 27.6% (211/764). We think the effect of IP was significant in this reduction; nevertheless, these are preliminary results that need larger-scale trials on COVID-19 patients.

The benefits of ascorbate to protect healthy cells in the prevention and treatment of oncological diseases.

Health status is determined by the balance of oxidants and antioxidants which protects healthy cells against the threat of internal and external risk factors. Antioxidants such as ascorbate (vitamin C, ascorbic acid) are of fundamental importance in this respect. Ascorbate neutralizes potential damage caused by cellular oxidative stress which may be the greatest risk of damage to healthy tissue. Cellular oxidative stress is mediated by external factors (e.g. psychological stress, physical exertion, drugs, various diseases, environmental pollution, preservatives, smoking, and alcohol) and internal factors (products of cellular metabolism including reactive oxygen species). When the products of oxidative stress are not sufficiently neutralized, healthy cells are at risk for both mitochondrial and DNA damage. In the short term, cell function may deteriorate, while an increased production of proinflammatory cytokines over time may lead to the development of chronic inflammatory changes and diseases, including cancer. Although pharmaceutical research continues to bring effective chemotherapeutic agents to the market, a limiting factor is often the normal tissue and organ toxicity of these substances, which leads to oxidative stress on healthy tissue. There is increasing interest and imperative to protect healthy tissues from the negative effects of radio-chemotherapeutic treatment. The action of ascorbate against the development of oxidative stress may justify its use not only in the prevention of carcinogenesis, but as a part of supportive or complementary therapy during treatment. Ascorbate (particularly when administered parentally at high doses) may have antioxidant effects that work to protect healthy cells and improve patient tolerability to some toxic radio-chemotherapy regimens. Additionally, ascorbate has demonstrated an immunomodulatory effect by supporting mechanisms essential to anti-tumor immunity. Intravenous administration of gram doses of vitamin C produce high plasma levels immediately, but the levels drop rapidly. Following oral vitamin C administration, plasma levels increase slowly to relatively low values, and then gradually decay. With an oral liposomal formulation, significantly higher levels are attainable than with standard oral formulations. Therefore, oral administration of liposomal vitamin C appears to be an optimal adjunct to intravenous administration. In this review, the basic mechanisms and clinical benefits of ascorbate as an antioxidant that may be useful as complementary therapy to chemotherapeutic regimens will be discussed.

Diosmin - still an important modality in the treatment of venous insufficiency.

Chronic venous insufficiency is a highly prevalent disease in the western population. Unfortunately, there is no causal treatment yet. A key role in the recommended therapeutic approaches, especially in the early stages, is the compression therapy accompanied by pharmacotherapy. This includes, inter alia, micronized diosmin. The following text summarizes the basic knowledge of its properties that determine its clinical use.

Importance of vitamin D in gynecology.

Vitamin D is a lipophilic vitamin possessing a myriad of physiologic functions, including hormonal, in human body. It participates in calcium homeostasis and influences cells differentiation via genome. In the context of the broad research aimed at mapping its physiological effects in the human body it is obvious that it significantly interferes with the whole range of physiological and pathological conditions. This text briefly discusses its contribution to gynecology.

Inosine Pranobex: A Key Player in the Game Against a Wide Range of Viral Infections and Non-Infectious Diseases.

Inosine pranobex (IP), commonly known as inosine acedoben dimepranol, isoprinosine and methisoprinol, has been proven to positively impact the host's immune system, by enhancing T-cell lymphocyte proliferation and activity of natural killer cells, increasing levels of pro-inflammatory cytokines, and thereby restoring deficient responses in immunosuppressed patients. At the same time, it has been shown that it can affect viral RNA levels and hence inhibit growth of several viruses. Due to its immunomodulatory and antiviral properties, and its safety profile, it has been widely used since 1971 against viral infections and diseases, among which subacute sclerosis panencephalitis, herpes simplex virus, human papilloma virus, human immunodeficiency virus, influenza and acute respiratory infections, cytomegalovirus and Epstein-Barr virus infections. Following an analysis of almost five decades of scientific literature since its original approval, we here summarize in vivo and in vitro studies manifesting the means in which IP impacts the host's immune system. We also provide a synopsis of therapeutic trials in the majority of which IP was found to have a beneficial effect. Lastly, positive results from limited studies, suggesting the putative future use of IP in new therapeutic indications are briefly described. In order to support use of IP against viral infections apart from those already approved, and to establish its use in clinical practice, further well-designed and executed trials are warranted.Funding: Ewopharma International.

Medical cannabis in the treatment of cancer pain and spastic conditions and options of drug delivery in clinical practice.

The use of cannabis for medical purposes has been recently legalised in many countries including the Czech Republic. As a result, there is increased interest on the part of physicians and patients in many aspects of its application. This mini review briefly covers the main active substances of the cannabis plant and mechanisms of action. It focuses on two conditions, cancer pain and spasticity in multiple sclerosis, where its effects are well-documented. A comprehensive overview of a few cannabis-based products and the basic pharmacokinetics of marijuana's constituents follows. The review concludes with an outline for preparing cannabis (dried inflorescence) containing drug dosage forms that can be produced in a hospital pharmacy.

[The current position of hydrochlorothiazide among thiazide and thiazide-like diuretics]. / Postavení hydrochlorothiazidu mezi thiazidovými a thiazidum podobnými diuretiky.

Thiazide and thiazide-like diuretics are an important group of drugs used in the treatment of essential arterial hyper-tension. While their beneficial therapeutic effect in monotherapy is evident, they are increasingly used in fixed combinations, particularly with ACE inhibitors or sartans. The aim of this article was to summarize the current status of hydrochlorothiazide and compare its effects with other substances in this subgroup of diuretics.Key words: diuretics - HCTZ - hydrochlorothiazide - hypertension - chlorthalidone - indapamide - thiazide.

[A present view on ivabradine in the therapy of cardiovascular diseases]. / Soucasný pohled na ivabradin v lécbe kardiovaskulárních onemocnení.

Cardiovascular illnesses belong to diseases with the highest prevalence. They are also the most predominant reason of death in the vast majority of European countries. Hence, the offer of effective treatment of these dis-eases is absolutely crucial. This text focuses on the current therapeutical use of ivabradine in its approved indications - chronic stable angina pectoris and chronic heart failure - in the context of so far published relevant clinical trials.Key words: angina pectoris - bradines - heart failure - If current - ischemic heart disease - ivabradine.

[Current position of a fixed combination telmisartan with amlodipine in treatment of essential arterial hypertension]. / Soucasné postavení fixní kombinace telmisartanu s amlodipinem v lécbe esenciální arteriální hypertenze.

Nowadays, fixed drug combinations are very important part of pharmacotherapy in essential arterial hypertension. The ameliorated activity of RAAS system (ACE inhibitors or sartans) along with calcium-ion channel inhibitor results in additive decrease of blood pressure with concomitant beneficial safety profile. Both telmisartan and amlodipine possess very favorable pharmacological properties, what is reflected in results of performed clinical trials, in which they were used as combinations.Key words: amlodipine - calcium channel blockers - fixed combination - hypertension - sartans - telmisartan.

[What are biosimilars and what do they bring to us?]. / Co jsou a co nám prinásejí biosimilars?

Biosimilar medicines are a new category of medicinal products that substantially differ from generic preparations through the necessary submission of conclusive evidence of their therapeutic efficacy and therefore it is not sufficient to merely state their biological equivalence. Apart from the proven efficacy, also their safety is evaluated of course, with an emphasis on immunogenicity regarding biological nature of these substances. As a result, requirements for registration are much stricter. With regard to the current boom of the preparations labelled in a simplified way as biological or specifically targeted drugs, we can certainly expect a growing number of newly registered medicinal products in this category in the near future. Last year, a biosimilar insulin analogue of glargine was approved for administration at the level of the European Medicines Agency (EMA) in accordance with the aforementioned procedures; its efficacy and safety profile have been found within the registration studies practically identical, or non-inferior, to the original insulin analogue.

[Empagliflozin - the new representative of SGLT2 transporter inhibitors for the treatment of patients with diabetes 2 type]. / Empagliflozin - nový zástupce inhibitoru transportéru SGLT2 pro lécbu pacientu s diabetem 2. typu.

Empagliflozin is a new medicine used to reduce hyperglycemia in patients with type 2 diabetes. It belongs to the most advanced class of antidiabetic drugs, known as gliflozins, which prevent reabsorption of glucose through inhibiting SGLT2 sodium-glucose cotransporter. Thereby they cause therapeutic glycosuria, thanks to which a loss of approximately 70 g of glucose per day occurs. This not only effects the decrease in glycemia, but also the loss of body mass, since this excreted glucose cannot be used as an energetic substrate. The studies within phase 3 have proven the therapeutic efficacy of empagliflozin in monotherapy, in combination with the other oral antidiabec drugs and insulin. Another favourable effect of empagliflozin is a slight decrease in blood pressure. In May 2014, empagliflozin was approved for the treatment of patients with type 2 diabetes within the European Union 2014, since October 2014 it has been available in the Czech Republic and since 1 February 2015 empagliflozin (under the trade name Jardiance®) has been partially covered by the health insurance for the treatment of patients with type 2 diabetes either in combination with metformin or in combination with insulin (with or without metformin).