Host-Guest Interaction Study of Olmesartan Medoxomil with ß-Cyclodextrin Derivatives.

Olmesartan medoxomil (OLM) is a selective angiotensin II receptor antagonist used in the treatment of hypertension. Its therapeutic potential is limited by its poor water solubility, leading to poor bioavailability. Encapsulation of the drug substance by two methylated cyclodextrins, namely randomly methylated ß-cyclodextrin (RM-ß-CD) and heptakis(2,3,6-tri-O-methyl)-ß-cyclodextrin (TM-ß-CD), was carried out to overcome the limitation related to OLM solubility, which, in turn, is expected to result in an improved biopharmaceutical profile. Supramolecular entities were evaluated by means of thermoanalytical techniques (TG-thermogravimetry; DTG-derivative thermogravimetry), spectroscopic methods including powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier-transform infrared (UATR-FTIR) and UV spectroscopy, saturation solubility studies, and by a theoretical approach using molecular modeling. The phase solubility method reveals an AL-type diagram for both inclusion complexes, indicating a stoichiometry ratio of 1:1. The values of the apparent stability constant indicate the higher stability of the host-guest system OLM/RM-ß-CD. The physicochemical properties of the binary systems are different from those of the parent compounds, emphasizing the formation of inclusion complexes between the drug and CDs when the kneading method was used. The molecular encapsulation of OLM in RM-ß-CD led to an increase in drug solubility, thus the supramolecular adduct can be the subject of further research to design a new pharmaceutical formulation containing OLM, with improved bioavailability.

The Benefits of a Comprehensive Cardiac Rehabilitation Program for Patients with Acute Coronary Syndrome: A Follow-Up Study.

BACKGROUND AND OBJECTIVES: Secondary prevention after acute coronary syndrome (ACS) is essential to reduce cardiovascular mortality and hospital readmission, ensuring patients return to normal with an improved quality of life. Thus, we investigate the benefits of a comprehensive cardiac rehabilitation (CR) program on lifestyle, risk factors and adherence to guideline-directed medical therapy (GDMT) in patients after ACS and myocardial revascularization through coronary artery by-pass grafting (CABG) or percutaneous coronary intervention (PCI). METHODS: This is a prospective, longitudinal study in consecutive post-CABG or PCI patients after ACS that participated or not in a comprehensive CR. Cardiovascular risk factors, quality of life and adherence to GDMT were analyzed in terms of assessing the benefit of 12 months of comprehensive CR on reaching guidelines secondary prevention targets. RESULTS: At the inclusion in comprehensive CR of all patients (n = 480), 85% had hypertension; 86% had elevated total cholesterol values; 69% were characterized by metabolic syndrome; 43% were obese; 31% were active smokers and 29% had type 2 diabetes mellitus. Only 26.66% (n = 128) followed the entire program for 12 months. No statistically significant differences in the prescription of GDMT at hospital discharge after myocardial revascularization between the CR (+) group (n = 128) versus CR (-) group (n = 352) (p > 0.05) were observed. After 12 moths, a significant adherence to GDMT in the CR (+) group vs. CR (-) group was recorded, as follows: antiplatelet agents (100% versus 96%, p = 0.001), beta-blockers (99% versus 92%, p = 0.02), ACE inhibitors/ARAB (89% versus 79%, p = 0.04), lipid-lowering drugs (100% versus 89%, p = 0.001). In total, 82% of the CR (+) patients had a significantly higher adherence at GDMT (82% versus 64%, p = 0.001). At 12 moths, the CR (+) group was characterized by significantly lower values than at the inclusion but some values still increased: systolic blood pressure (139.25 + 19.20 mmHg (p < 0.03)), total cholesterol (171.07 + 48.59 mg/dL (p = 0.0001)) and LDL-cholesterol (102.83 + 41.30 mg/dL (p = 0.009)). At the same time, the analysis of psychosocial factors using the HAD questionnaire revealed a statistically significant improvement in anxiety and depression scores: HAD-A score (9.1 ± 3.7 at T0 vs. 7.1 ± 4.2 at T1, p = 0.001) and HAD-D score (7.7 ± 3.19 at T0 vs. 6.4 ± 4.3 at T1, p = 0.003). A multivariable analysis, following GDMT, showed the actual value or information and training of patients regarding optimal cardiovascular risk factor control was independently associated with lower values of systolic blood pressure (R2 = 0.48), diastolic (R2 = 0.38), serum glucose (R2 = 0.48), glycated hemoglobin (R2 = 0.50), total cholesterol (R2 = 0.31), LDL-cholesterol (R2 = 0.30), HDL-cholesterol (R2 = 0.19) and serum triglycerides (R2 = 0.20). CONCLUSION: The twelve-month participation of post-ACS patients in comprehensive CR resulted in excellent post-revascularization management, as well as good adherence to guideline-directed medical therapy, provided further confirmation of the benefit of secondary prevention. Despite high adherence to drug treatments, targets for blood pressure, total cholesterol and LDL-cholesterol are inadequately achieved. Therefore, in the era of personalized medicine, patients with ACS should benefit from specific, comprehensive cardiovascular recovery programs that contain physiotherapists, psychologists, nutritionists and an experienced cardiologist in cardiovascular rehabilitation.

Sex-Related Differences in the Pharmacological Response in SARS-CoV-2 Infection, Dyslipidemia, and Diabetes Mellitus: A Narrative Review.

Pharmacological responses vary by sex in several illnesses. This narrative review summarizes sex variations in pharmaceutical response in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Infection with SARS-CoV-2 is more severe and deadly in men than women. This may be attributed to immunological responses, genetics, and hormones. Some research shows that men may respond better to genomic vaccinations and females to antiviral medications such as remdesivir (Moderna and Pfizer-BioNTech). In dyslipidemia, women tend to have greater HDL-C and lower LDL-C than men. Some studies show that females may need lower statin dosages than men to obtain equal LDL-C reductions. Ezetimibe co-administered with a statin significantly improved lipid profile indicators in men compared to women. Statins reduce dementia risk. Atorvastatin decreased dementia risk in males (adjusted HR 0.92, 95% CI 0.88-0.97), whereas lovastatin lowered dementia risk in women (HR 0.74, 95% CI 0.58-0.95). In diabetes mellitus, evidence suggests that females may have a higher risk of developing certain complications such as diabetic retinopathy and neuropathy, despite having lower rates of cardiovascular disease than males. This could be the result of differences in hormonal influences and genetic factors. Some research shows females may respond better to oral hypoglycemic medications such as metformin. In conclusion, sex-related differences in pharmacological response have been observed in SARS-CoV-2 infection, dyslipidemia, and diabetes mellitus. Further research is needed to better understand these differences and to develop personalized treatment strategies for males and females with these conditions.

An Up-to-Date Article Regarding Particularities of Drug Treatment in Patients with Chronic Heart Failure.

Since the prevalence of heart failure (HF) increases with age, HF is now one of the most common reasons for the hospitalization of elderly people. Although the treatment strategies and overall outcomes of HF patients have improved over time, hospitalization and mortality rates remain elevated, especially in developed countries where populations are aging. Therefore, this paper is intended to be a valuable multidisciplinary source of information for both doctors (cardiologists and general physicians) and pharmacists in order to decrease the morbidity and mortality of heart failure patients. We address several aspects regarding pharmacological treatment (including new approaches in HF treatment strategies [sacubitril/valsartan combination and sodium glucose co-transporter-2 inhibitors]), as well as the particularities of patients (age-induced changes and sex differences) and treatment (pharmacokinetic and pharmacodynamic changes in drugs; cardiorenal syndrome). The article also highlights several drugs and food supplements that may worsen the prognosis of HF patients and discusses some potential drug-drug interactions, their consequences and recommendations for health care providers, as well as the risks of adverse drug reactions and treatment discontinuation, as an interdisciplinary approach to treatment is essential for HF patients.

COVID-19 Related Myocarditis and Myositis in a Patient with Undiagnosed Antisynthetase Syndrome.

BACKGROUND: The clinical presentation of SARS-CoV-2 varies from patient to patient. The most common findings noted were respiratory tract infections, of different severity grades. In some cases, multi-organ damage was noted. Due to its high potential for causing severe systemic inflammation such as myositis and myocarditis, patients should be properly investigated, which carries high chances of SARS-CoV-2 being easily missed if not investigated on time and which can result in more fatal outcomes. CASE REPORT: We present a case of COVID-19 infection in a non-vaccinated male patient, who presented to our clinic with no symptoms of respiratory involvement but with severe muscle aches. Cardiac markers and procalcitonin levels were high, and concentric hypertrophy of the left ventricle, severe hypokinesia of the interventricular septum and of the antero-lateral wall, hypokinesia of the inferior and posterior wall and an ejection fraction of the left ventricle being around 34% was noted. Coronary angiography showed no lesions. Corticosteroids and antibiotics were instituted which showed improvement. A possible link to an autoimmune process was suspected, due to the presence of anti-PL-7 antibody, suggesting an antisynthetase syndrome. CONCLUSION: Each and every patient should be thoroughly investigated, and presently little is known in regards to this virus. Studies focusing on possible relationships between the COVID-19 and autoimmune disease can help to potentially generate better outcomes.

Solid State Stability and Kinetics of Degradation for Candesartan-Pure Compound and Pharmaceutical Formulation.

The aim of this work was to assess the impact of an excipient in a pharmaceutical formulation containing candesartan cilexetil over the decomposition of the active pharmaceutical ingredient and to comparatively investigate the kinetics of degradation during thermolysis in an oxidative atmosphere under controlled thermal stress. To achieve this, the samples were chosen as follows: pure candesartan cilexetil and a commercial tablet of 32 mg strength. As a first investigational tool, Universal attenuated total reflection Fourier transform infrared (UATR-FTIR) spectroscopy was chosen in order to confirm the purity and identity of the samples, as well as to check if any interactions took place in the tablet between candesartan cilexetil and excipients under ambient conditions. Later on, samples were investigated by thermal analysis, and the elucidation of the decomposition mechanism was achieved solely after performing an in-depth kinetic study, namely the use of the modified non-parametric kinetics (NPK) method, since other kinetic methods (American Society for Testing and Materials-ASTM E698, Friedman and Flynn-Wall-Ozawa) led to inadvertencies. The NPK method suggested that candesartan cilexetil and the tablet were degraded by the contribution of two steps, the main being represented by chemical degradation and the secondary being a physical transformation. The excipients chosen in the formulation seemed to have a stabilizing effect on the decomposition of the candesartan cilexetil that was incorporated into the tablet, relative to pure active pharmaceutical ingredient (API), since the apparent activation energy for the decomposition of the tablet was 192.5 kJ/mol, in comparison to 154.5 kJ/mol for the pure API.