Tropical marine species - source of dangerous toxins

Saxitoxin (STX) and tetrodotoxin (TTX) are two of the most potent marine neurotoxins known. They are specific to some tropical marine species, but becauseof the global warming аand the temperature shift they have begun moving to different areas. Fugu fish has been seen in Croatia in the southern part of the Adriatic coast.Both can be used as a means for suicide and murder. STX is included in Schedule 1 of the Chemical Weapons Convention, which made it attractive for many government agencies and no longer interesting for toxinologists and seafood producers. TTX is known as the ` fugu` (puffer fish) poison and also as the mainagent in Haitian voodoo zombification rituals. However, intentional intoxications by STX and TTX are often not as toxic as badly prepared fugu meals or saxitoxin-infested shellfish.A precise diagnosis can determine whether a victim has been intentionally intoxicated. At the cellular level STX and TTX have an identical action - they block the passage of sodium ions upon the same site of the voltage-gated sodium channel. Their chief effect is to produce a muscular weakness that may progress tototal paralysis, but sensory disturbances are also common. Both poisons have a direct paralyzing effect on skeletal (striated) muscles as well as on nerve fibers.Death due to respiratory failure may not always be the outcome, but rather an incapacitation. The treatment of intoxication by STX and TTX is based on gastricevacuation, symptomatic relief and the body`s natural recovery mechanisms. Both toxins have some potential as pharmaceutical agents, but they are still associated with small animal experiments and need more examination and financing to advance

Incretin-mimetic drugs—nature, benefits, and risks

Incretins are gut-derived hormones that are secreted within minutes of a meal to regulate insulin secretion from the pancreas. Currently, the two best-studied incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Incretin-mimetic drugs are the GLP1-receptor agonists and the dual agonist of GIP and GLP-1 receptors. They represent the most modern and effective therapy for patients with type 2 diabetes mellitus. Their application is associated with an improvement in glycemic control, as well as many additional benefits for patients treated with them.The aim of this review is to analyze the available data on the benefits and risks of incretin mimetics.Among these benefits are a loss of body mass, a favorable influence on the lipid profile, a reduction in blood pressure, and beneficial effects on atherosclerotic cardiovascular disease, confirmed in a number of clinical studies.However, the use of this relatively new class of drugs may be associated with certain side effects. The most common are gastrointestinal symptoms, injection site reactions, headache, and nasopharyngitis, but these effects usually do not lead to discontinuation of therapy. Studies suggest an increased risk of pancreatitis and thyroid cancer in patients treated with these medications, but several meta-analyses have failed to confirm the relationship between their use and the development of these adverse effects. Ongoing and future studies should evaluate and further elucidate the cardiovascular and overall safety profile of GLP-1 receptor agonists and the dual agonist of GIP and GLP-1 receptors

The role of SGLT2 inhibitors in chronic heart failure treatment

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a new group of medications for heart failure (HF) patient treatment, regardless of diabetes being present as comorbidity. Nevertheless, the mechanisms for positive influence of SGLT2 inhibitors on HF patients are not perfectly clear.The potential mechanisms include glycosuria, diuresis, anti-hypertensive effect, weight reduction, increase in the mass of red blood cells and hematocrit, but neither of these mechanisms does fully explain the proven positive clinical results in HF patients treated with SGLT2 inhibitors.There are recent discussions of new mechanisms of SGLT2 inhibitors as improvements in myocardial energetics and ion homeostasis, improved autophagy, improved balance in adipokine secretion, and lowered cardiovascular oxidative stress and inflammation.Despite the mounting scientific data, more studies are still necessary in order to identify the mechanisms of SGLT2 inhibitors in HF patients. Nevertheless, the available evidence and clinical trials have led to the inclusion of these medications in the European Guidelines for the diagnosis and treatment of acute and chronic HF, for the treatment of HF patients with reduced ejection fraction (EF), and possibly in the future for HF patients with preserved EF.    

Risk of hyperkalemia in heart failure patients and new treatment approaches

IntroductionHyperkalemia is a serious medical condition that can cause muscle weakness, paralysis and cardiac arrhythmias. In heart failure (HF), hyperkalemia is a frequent problem, because of several factors, such as chronic kidney disease (CKD), and because of medications, used to treat HF - angiotensin-converting enzyme inhibitors (ACEi)/Angiotensin II receptor blockers (ARBs) and mineralocorticoid receptor inhibitors (MRIs) that increase the serum potassium level, leading to a risk of hyperkalemia.Materials and Methods This is a retrospective study.  The risk factors, leading to hyperkalemia among 535 patients, hospitalized for HF at the St. Marina University Hospital in Varna in the period January 2010 - December 2014 were analyzed. ResultsSignificant part of the patients with HF have CKD as a comorbidity (56.3%), but they are treated with ACEi/ARBs (70.8%) and MRIs (34.2%), taking medications that increase the serum potassium level, leading to a risk of hyperkalemia. There are also a few patients per year (2.2%) who have hyperkalemia as a comorbidity, but they also must be treated with the same medications- ACEi/ARBs (91.7%) and MRIs (8.3%).ConclusionTwo new potassium binders - patiromer and sodium zirconium cyclosilicate, are included in the current guidelines (2016) as medications under consideration for regulatory approval. They are new therapeutic options for managing hyperkalemia in patients with HF and a risk of hyperkalemia. The current study reveals the importance of minimizing this adverse effect in order to provide optimal pharmacological treatment for patients with HF

Medicament therapy tendencies in hospitalized patients with chronic acute heart failure with preserved and reduced ejection fraction

Въведение / целиЦелта на нашето проучване беше да се установят тенденциите в прилаганото медикаментозно лечение при хоспитализирани по повод на сърдечна недостатъчност (СН) пациенти със запазена и потисната фракция на изтласкване. Това е постигнато чрез обобщаване и сравняване на информацията за предписваните медикаменти и потенциалните противопоказания и причини за неспазване препоръките за лечение на сърдечна недостатъчност.Материали и методиТова е ретроспективно проучване, обхващащо 535 пациенти, хоспитализирани в УМБАЛ „Света Марина` - Варна за периода от януари 2010 до декември 2014 година с диагноза хронична обострена сърдечна недостатъчност. Сравнени са процентите на предписваните кардиоактивни медикаменти - блокери на РААС, бета-блокери, антагонисти на минералкортикоидните рецептори и калциеви антагонисти при пациенти с хронична СН и редуцирана и запазена ФИ.РезултатиЗа последната 2014 година пациентите със СН са били предимно възрастни (средна възраст 72 години) жени (54.5%), по-често със СНзФИ (37.6%). При пациентите със запазена ФИ (сравнени с тези с редуцирана) приеманите бета-блокери, блокери на РААС и антагонисти на минералкортикоидните рецептори са били значимо по-малко (82.3%, 58.1% и 25.8% спрямо 84.6%, 64.1% и 64.1%), докато процентът на приеманите калциеви антагонисти - по-голям (40.3% спрямо 38.5%) в сравнение с групата със СНрФИ. Процентът на неспазване на препоръките за лечение на СНрФИ с оглед на противопоказанията е 25.6%, 12.8% и 17.9% съответно за блокери на РААС, бета-блокери и антагонисти на минералкортикоидните рецептори.ЗаключениеИма съществени разлики в лечението на СНрФИ и СНзФИ. Пациентите със СНзИФ приемат по-малко бета-блокери, блокери на РААС и антагонисти на минералкортикоидните рецептори, a повече калциеви антагонисти. Висок е процентът на неспазване на препоръките за лечение на СНрФИ спрямо останалата част от Европа, съобразен с противопоказанията. Тенденцията на хоспитализации по повод на СН е да са по-възрастни пациенти, с преобладаващ женски пол и СНзФИ.Introduction/AimThe aim of our research was to establish the trends in the applied medicament therapy in hospitalized patients with heart failure (HF) and preserved and reduced ejection fraction (EF). The results were achieved by summarizing and comparing the information about the prescribed medicaments and the potential contraindications and reasons for not adhering to the recommendations for heart failure treatment.Materials and MethodsThis is a retrospective study involving 535 patients hospitalized at the St. Marina University Hospital in Varna for the period from January, 2010 to December, 2014. All of them were diagnosed with chronic acute heart failure. The comparison included the percentages of the prescribed cardioactive medicaments - renin-angiotensin system (RAS) blockers, beta blockers, mineralcorticoid receptor antagonists and calcium antagonists in patients with chronic HF and reduced and preserved EF.ResultsFor the last year, 2014, the HF patients were predominantly older (average age of 72 years) women (54.5%), more frequently with HF with preserved EF (HFpEF) (37.6%). Among the patients with preserved EF (compared with those with reduced one), the intake of beta blockers, RAS blockers and mineralcorticoid receptor antagonists was significantly lower (82.3%, 58.1% and 25.8%, compared with 84.6%, 64.1% and 64.1%), whereas the percentage of the intake of calcium antagonists was higher (40.3% compared with 38.5%) than that of the group with HF with reduced EF (HFrEF). The percentage of non-adherence to the therapy recommendations for HFrEF, considering the contraindications, was 25.6%, 12.8% and 17.9%, respectively for RAS blockers, beta blockers and mineralcorticoid receptor antagonists.ConclusionThere are significant differences in the treatment of HFrEF and HFpEF. The HFpEF patients take less beta blockers, RAS blockers and mineralcorticoid receptor blockers, but more calcium antagonists. There is a high percentage of non-adherence to the therapy recommendations for HFrEF compared with the rest of Europe, considering the contraindications. The tendency in hospitalizations due to HF is for the patients to be older, predominantly female and with HFpEF

Type 2 diabetes mellitus is associated with increased arterial stiffness measured by the echo-tracking method

INTRODUCTION: Data for arterial stiffness (АS) in type 2 diabetes mellitus (Т2DM) patients is important for better management of cardiovascular complications and early therapeutic approach.AIM: The aim of this article is to obtain data for pulse wave velocity (PWVβ) and other AS parameters in patients with T2DM without cardiovascular atherosclerotic disease and compare them with controls.MATERIALS AND METHODS: This cross-sectional clinical investigation involves a sample of 100 patients with T2DM without cardiovascular complications and a control group of 30 healthy subjects.  In all patients one-point echo-tracking measurement of carotid artery (CA) stiffness with Aloka Prosound α7 machine were conducted and pulse wave velocity (PWVβ), β-stiffness index, arterial compliance (АС), augmentation index (AI), Peterson’s modulus (Ep) were measured.  RESULTS AND CONCLUSION: Our results showed the mean value of PWVβ on the left CA (L) in the group of patients with T2DM is 7.37 ± 1.32 m/sec and on the right CA (R) is 7.42 ± 1.33 m/sec. The performed t-test showed statistical significance of the differences of PWVβ (L) and PWVβ (R) in the studied group, compared to the control group (t = 3.764; p = 0.001 and t = 3.561; p = 0.001). The data showed significantly higher values of β-stiffness index (p = 0.001) and Ep (p = 0.001) in patients with T2DM compared to controls. AC was significantly lower in T2DM, when it is measured on the left CA (p = 0.001). AI was significantly higher in T2DM when it is measured on the right CA (p = 0.009).Patients with T2DM are associated with significantly increased AS parameters compared to controls

POTENTIAL DRUG-DRUG INTERACTIONS IN HEART FAILURE PATIENTS

Objective: The aim of the present study was to assess the prevalence, risk rating and the severity of hazardous pDDIs (potential drug-drug interactions) in the prescribed pharmacotherapy in the hospital discharged heart failure (HF) patients, primarily with co-administered drugs with narrow therapeutic index (statins, anticoagulants, antithrombotic drugs). Methods: The prescriptions of chronic heart failure patients for one year (January-December 2014) were analyzed for pDDIs through Lexi-interact® software. DDIs belonging to the categories D (Consider therapy modification) and X (Avoid combination) and/or severity of drug interaction-major, were selected for the study. Results: After reviewing the medical records of 985 patients, 239 patients were selected based on the criteria mentioned above. The average number of prescription drugs at hospital discharge was 7.27 medications (±1.84 SD) per patient. The total number of pDDIs was 1483 or approximately 6.2 (±3.89 SD) pDDIs per patient. With respect to the risk rating, in categories D and X were detected 76 (5.12 %) and 2 (0.13 %) pDDI, respectively. The major pDDIs were 108 (7.28 %). Conclusion: HF patients are at high risk of pDDIs. Screening of prescriptions for pDDIs and monitoring of pharmacotherapy in terms of response and associated adverse drug events will contribute to patient safety

The Sea – A Source Of Bioactive Substances

Seventy-five percent of the Earth's surface is covered in water. The marine environment provides a huge ecological resource, including a variety of marine plants and animals, and is an exclusive reservoir for bioactive substances many of which have structural and chemical characteristics that are absent in natural terrestrial products. These marine organisms are researched as antibacterial, immunomodulating, antifungal, anti-inflammatory, anti-carcinogenic, antimicrobial, neuroprotective, analgesic and antimalarial agents with some of them having proven themselves as homeopathic monoremedies.At present, there are ten drugs of marine origin approved in different parts of the world, and thirteen compounds are at different stages of clinical trials. There are many marine compounds/molecules that are in the pre-clinical stage of testing. Substances of marine origin are also used in homeopathy, 6 monoremedies extracted from marine organisms are registered in Bulgaria.  Marine pharmacology presents a huge field for research of medicines of marine origin, but nevertheless the available registered drugs derived from marine organisms are relatively limited. Interest in marine species is on the rise. The explanation for this is more than four billion years of evolution invested in the combined chemistry of marine organisms’ bioactive substances, aimed at appropriate and effective biological activity.

Medical supplies on ships

It is mandatory for every ship sailing under Bulgarian flag to be equipped with the necessary medical and sanitary materials to ensure the safety of the crew. All requirements about medical care on ships are described in the Merchant Shipping Code and more specifically in Ordinance № 9.The document outlines requirements for different types of mandatory drugs and sanitary materials, people responsible for the implementation of the Ordinance and the control authorities.The ships are classified in three categories (A, B, C), the drugs are classified in four appendices. Тhe first appendix contains the international nonproprietary names of all mandatory drugs with their dosage forms. They are classified according to the ATC classification. The quantities are in accordance with ships category. The second appendix contains all types of sanitary materials, which are mandatory. In the next appendix are listed different types of dangerous materials (explosives, poisonous gases, radioactive substances, flammable substances, etc.). In appendix 4 are listed drugs required in the event of accidents on ships carrying dangerous materials.Using literature data, we can identify that there are numerous fundamental differences in the drug supply process on land compare to open sea, specifically in a European country such as Bulgaria. Although the main purpose of this process is the well-being of the crew, the law does not require the supervision of a Master in Pharmacy. Whether this impairs the physical and/or financial access to medicines, medical and sanitary products of potential patients should be the subject of further research

Sea climate therapy—a current overview and possibilities for application in Bulgaria

The therapeutic use of seawater and sea resources dates back to ancient times. However, there is a need for in-depth study and summarization of the available clinical possibilities of modern thalassotherapy.Contact with sea water, sand and/or healing mud, methodical exposure to the sunlight, as well as environmental factors (atmosphere, temperature, humidity, wind, air pressure), are the basis of today‘s treatment procedures suitable for both children and geriatric patients. Due to the unique chemical composition of seawater, anti-inflammatory and immunomodulatory effects on the human body have been reported. Even short-term treatment by the sea can be used to relieve dermatological conditions such as psoriasis, atopic dermatitis, vitiligo, etc.In combination with physical exercises, thalassotherapy improves the symptoms of rheumatoid arthritis, rheumatic fibromyalgia, ankylosing spondylitis, psoriatic arthritis, and non-inflammatory joint processes. Separately, sea treatment is used to improve ventilatory performance in patients with bronchial asthma. The possibility of additional treatment for chronic inflammatory gynecological diseases, ovarian failure, neurovegetative disorders, menopausal symptoms and others has also been reported.The growing interest in natural treatments in recent years is an argument for conducting additional and even larger studies to explore the possibilities of modern thalassotherapy. Moreover, clinical data from recent years reinforce the potential for the development of maritime health tourism in Bulgaria