Drugs Associated with Adverse Effects in Vulnerable Groups of Patients.

In recent years, a series of recommendations have been issued regarding the administration of drugs because of awareness of the serious side effects associated with certain classes of drugs, especially in vulnerable patients. Taking into account the obligation of the continuous improvement of professionals in the medical fields and the fact that we are in the midst of a "malpractice accusations pandemic", through this work, we propose to carry out a "radiography" of the scientific literature regarding adverse effects that may occur as a result of the interaction of drugs with the physiopathological particularities of patients. The literature reports various cases regarding different classes of drugs administration associated with adverse effects in the elderly people, such as fluoroquinolones, which can cause torsade de pointes or tendinopathy, or diuretics, which can cause hypokalemia followed by torsade de pointes and cardiorespiratory arrest. Also, children are more prone to the development of adverse reactions due to their physiological particularities, while for pregnant women, some drugs can interfere with the normal development of the fetus, and for psychiatric patients, the use of neuroleptics can cause agranulocytosis. Considering the physiopathological particularities of each patient, the drug doses must be adjusted or even completely removed from the treatment scheme, thus requiring the mandatory active participation both of clinician pharmacists and specialists in the activity of medical-pharmaceutical analysis laboratories within the structure of hospitals.

Particularities of Urinary Tract Infections in Diabetic Patients: A Concise Review.

Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients are more likely to develop infections, including many common infections, but also pathognomonic ones such as emphysematous pyelonephritis, malignant otitis externa, mucormycosis and Fournier's gangrene. Considering the fact that diabetic patients experience more frequently urinary tract infections (UTIs) with a worse prognosis than non-diabetic people, we conducted a review study based on data in the literature, following the particularities of UTIs in this group of patients, the risk factors, the mechanisms involved and the challenges in their management. The findings highlight that UTI in diabetic patients have some particularities, including a more frequent evolution to bacteremia, increased hospitalizations, and elevated rates of recurrence and mortality than non-diabetic patients. The possible risk factors identified seem to be female gender, pregnancy, older age, UTI in the previous six months, poor glycemic control and duration of diabetes. The mechanisms involved are related to glucosuria and bladder dysfunction, factors related to bacterial strains and host response. The bacterial strains involved in UTIs in diabetic patients and their antibiotic susceptibility profile are, with some exceptions, similar to those in non-diabetic people; however, the antimicrobial agents should be carefully chosen and the duration of the treatment should be as those required for a complicated UTI. The data related to the risk of developing UTIs in patients treated with SGLT-2 inhibitors, a new class of oral hypoglycaemic agents with cardiovascular and renal benefits, are controversial; overall, it was evidenced that UTIs occurred at the initiation of the treatment, recurrent infection was uncommon and the majority of UTIs responded to treatment with standard antibiotics. Moreover, interruption or discontinuation of SGLT-2 inhibitor as a result of UTI was rare and SGLT-2 inhibitors did not increase the risk of severe infections such as urosepsis and pyelonephritis.

Experimentally Induced Burns in Rats Treated with Innovative Polymeric Films Type Therapies.

Considering that microbial resistance to antibiotics is becoming an increasingly widespread problem, burn management, which usually includes the use of topical antimicrobial dressings, is still facing difficulties regarding their efficiency to ensure rapid healing. In this context, the main objective of this research is to include new oxytetracycline derivatives in polymeric-film-type dressings for the treatment of wounds caused by experimentally induced burns in rats. The structural and physico-chemical properties of synthesized oxytetracycline derivatives and the corresponding membranes were analyzed by FT-IR and MS spectroscopy, swelling ability and biodegradation capacity. In vitro antimicrobial activity using Gram-positive and Gram-negative bacterial strains and pathogenic yeasts, along with an in vivo study of a burn wound model induced in Wistar rats, was also analyzed. The newly obtained polymeric films, namely chitosan-oxytetracycline derivative membranes, showed good antimicrobial activity noticed in the tested strains, a membrane swelling ratio (MSR) of up to 1578% in acidic conditions and a biodegradation rate of up to 15.7% on day 7 of testing, which are important required characteristics for the tissue regeneration process, after the production of a burn. The in vivo study proved that chitosan-derived oxytetracycline membranes showed also improved healing effects which contributes to supporting the idea of using them for the treatment of wounds caused by burns.

Lethal toxicity induced by combined ingestion of dietary acetic acid and carbamazepine.

Acetic acid is an organic acid that can be used in the food industry, which normally has an insignificant rate of adverse reactions when used rationally. However, irrational use can cause serious toxic effects and even death. In this context, the case of a death of a 52-year-old woman, involving the suspected voluntary use of food acetic acid, is presented, while toxicological and histopathological aspects were addressed for death mechanism elucidation. In this case, the pH value of 6.75 in blood, has shown severe metabolic acidosis after the ingestion of the large quantity of dietary acetic acid - about a liter. Also, the victim suffers from mental illness, carbamazepine being one of the treatment drugs. Liver damage, demonstrated by histopathological examination may be a consequence of both massive accumulation of carbamazepine in the liver and toxicity of food acetic acid. In conclusion, the hepatotoxicity induced by high level of carbamazepine was suspected of increasing the risk of multiple organ failure, in the context of acetic acid acute toxicity, highlighting the particularities of the case.

Pharyngeal-Esophageal Malignancies with Dermatologic Paraneoplastic Syndrome.

Systemic changes often send signals to the skin, and certain neoplastic diseases of the internal organs can also trigger skin manifestations. In this article, the authors make clinical photography presentations of the patients seen at our clinic with dermatologic paraneoplastic syndromes within pharyngeal-esophageal malignancies, describe several paraneoplastic dermatoses, and also review high-quality scientific literature in order to be able to highlight the dermatological signs of pharyngoesophageal malignant tumors. The majority of our patients with paraneoplastic dermatoses, filtering for pharyngoesophageal malignancies, had esophageal neoplasms, out of whom seven were female and two were male, making esophageal cancer more common within the paraneoplastic dermatoses within pharyngoesophageal malignancies. An early recognition of paraneoplastic dermatoses can diagnose neoplasms and sequentially contribute to a better prognosis for the patient. This matter is also useful for front-line medical personnel in order to improve early diagnosis of the underlying malignancy, curative interventions with prompt therapy administration and good prognosis.

Chitosan Microparticles Loaded with New Non-Cytotoxic Isoniazid Derivatives for the Treatment of Tuberculosis: In Vitro and In Vivo Studies.

Lately, in the world of medicine, the use of polymers for the development of innovative therapies seems to be a major concern among researchers. In our case, as a continuation of the research that has been developed so far regarding obtaining new isoniazid (INH) derivatives for tuberculosis treatment, this work aimed to test the ability of the encapsulation method to reduce the toxicity of the drug, isoniazid and its new derivatives. To achieve this goal, the following methods were applied: a structural confirmation of isoniazid derivatives using LC-HRMS/MS; the obtaining of microparticles based on polymeric support; the determination of their loading and biodegradation capacities; in vitro biocompatibility using MTT cell viability assays; and, last but not least, in vivo toxicological screening for the determination of chronic toxicity in laboratory mice, including the performance of a histopathological study and testing for liver enzymes. The results showed a significant reduction in tissue alterations, the disappearance of cell necrosis and microvesicular steatosis areas and lower values of the liver enzymes TGO, TGP and alkaline phosphatase when using encapsulated forms of drugs. In conclusion, the encapsulation of INH and INH derivatives with chitosan had beneficial effects, suggesting a reduction in hepatotoxicity and, therefore, the achievement of the aim of this paper.

Drugs frequently involved in inducing hypersensitivity reactions.

Adverse drug reactions represent a major public health problem, both from an economic point of view and, mainly, from the point of view of the induced pathology (iatrogenic diseases), being difficult to differentiate from other pathological conditions or even from the treated disease. Thus, these aspects prevent the use of the first-choice drugs needed for a particular treatment, in different therapeutic classes: beta-lactam antibiotics; sulfonamides; macrolide antibiotics; quinolones; non-steroidal anti-inflammatories; corticosteroids; Angiotensin converting enzyme (ACE) inhibitors; general anesthetics; biological drugs; antiepileptic drugs etc. On the other hand, adverse drug reactions represent a major problem for both clinical practice and preclinical research, in order to develop new drugs. Hypersensitivity reactions mainly refer to the adverse effects that can be harmful, disturbing, and sometimes fatal, that appear under the conditions of a normal immune system, including allergies and autoimmune reactions, both triggered by an immunological-allergic mechanism. The main purpose of this paper is to review the main classes of drugs involved in inducing hypersensitivity reactions.

Preparation and Antimicrobial Activity of Chitosan and Its Derivatives: A Concise Review.

Despite the advantages presented by synthetic polymers such as strength and durability, the lack of biodegradability associated with the persistence in the environment for a long time turned the attention of researchers to natural polymers. Being biodegradable, biopolymers proved to be extremely beneficial to the environment. At present, they represent an important class of materials with applications in all economic sectors, but also in medicine. They find applications as absorbers, cosmetics, controlled drug delivery, tissue engineering, etc. Chitosan is one of the natural polymers which raised a strong interest for researchers due to some exceptional properties such as biodegradability, biocompatibility, nontoxicity, non-antigenicity, low-cost and numerous pharmacological properties as antimicrobial, antitumor, antioxidant, antidiabetic, immunoenhancing. In addition to this, the free amino and hydroxyl groups make it susceptible to a series of structural modulations, obtaining some derivatives with different biomedical applications. This review approaches the physico-chemical and pharmacological properties of chitosan and its derivatives, focusing on the antimicrobial potential including mechanism of action, factors that influence the antimicrobial activity and the activity against resistant strains, topics of great interest in the context of the concern raised by the available therapeutic options for infections, especially with resistant strains.

Designing of Chitosan Derivatives Nanoparticles with Antiangiogenic Effect for Cancer Therapy.

Angiogenesis is a physiological process involving the growth of new blood vessels, which provides oxygen and required nutrients for the development of various pathological conditions. In a tumor microenvironment, this process upregulates the growth and proliferation of tumor cells, thus any stage of angiogenesis can be a potential target for cancer therapies. In the present study, chitosan and his derivatives have been used to design novel polymer-based nanoparticles. The therapeutic potential of these newly designed nanoparticles has been evaluated. The antioxidant and MTT assays were performed to know the antioxidant properties and their biocompatibility. The in vivo antiangiogenic properties of the nanoparticles were evaluated by using a chick Chorioallantoic Membrane (CAM) model. The obtained results demonstrate that chitosan derivatives-based nanostructures strongly enhance the therapeutic effect compared to chitosan alone, which also correlates with antitumor activity, demonstrated by the in vitro MTT assay on human epithelial cervical Hep-2 tumor cells. This study opens up new direction for the use of the chitosan derivatives-based nanoparticles for designing of antiangiogenic nanostructured materials, for future cancer therapy.

New antimicrobial chitosan derivatives for wound dressing applications.

Chitosan is a non-toxic, biocompatible, biodegradable natural cationic polymer known for its low imunogenicity, antimicrobial, antioxidant effects and wound-healing activity. To improve its therapeutic potential, new chitosan-sulfonamide derivatives have been designed to develop new wound dressing biomaterials. The structural, morphological and physico-chemical properties of synthesized chitosan derivatives were analyzed by FT-IR, (1)H NMR spectroscopy, scanning electron microscopy, swelling ability and porosity. Antimicrobial, in vivo testing and biodegradation behavior have been also performed. The chitosan derivative membranes showed improved swelling and biodegradation rate, which are important characteristics required for the wound healing process. The antimicrobial assay evidenced that chitosan-based sulfadiazine, sulfadimethoxine and sulfamethoxazole derivatives were the most active. The MTT assay showed that some of chitosan derivatives are nontoxic. Furthermore, the in vivo study on burn wound model induced in Wistar rats demonstrated an improved healing effect and enhanced epithelialization of chitosan-sulfonamide derivatives compared to neat chitosan. The obtained results strongly recommend the use of some of the newly developed chitosan derivatives as antimicrobial wound dressing biomaterials.

Development and Characterization of Novel Films Based on Sulfonamide-Chitosan Derivatives for Potential Wound Dressing.

The objective of this study was to develop new films based on chitosan functionalized with sulfonamide drugs (sulfametoxydiazine, sulfadiazine, sulfadimetho-xine, sulfamethoxazol, sulfamerazine, sulfizoxazol) in order to enhance the biological effects of chitosan. The morphology and physical properties of functionalized chitosan films as well the antioxidant effects of sulfonamide-chitosan derivatives were investigated. The chitosan-derivative films showed a rough surface and hydrophilic properties, which are very important features for their use as a wound dressing. The film based on chitosan-sulfisoxazol (CS-S6) showed the highest swelling ratio (197%) and the highest biodegradation rate (63.04%) in comparison to chitosan film for which the swelling ratio was 190% and biodegradation rate was only 10%. Referring to the antioxidant effects the most active was chitosan-sulfamerazine (CS-S5) which was 8.3 times more active than chitosan related to DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging ability. This compound showed also a good ferric reducing power and improved total antioxidant capacity.

Sulfadiazine-Chitosan Conjugates and Their Polyelectrolyte Complexes with Hyaluronate Destined to the Management of Burn Wounds.

In the present study polyelectrolyte complexes (PECs) based on new sulfadiazine-chitosan conjugates with sodium hyaluronate have been developed with potential use in treatment of burn wounds. The PECs were chemically characterized using Fourier Transform-Infrared Spectroscopy, Scanning Electon Microscopy and Near Infrared Chemical Imaging Technique. The swelling behavior and in vitro sulfadiazine release were also investigated. The antimicrobial activity was evaluated towards three bacterial strains: Escherichia coli, Listeria monocytogenes and Salmonella thyphymurium. The developed PECs demonstrated their antimicrobial efficiency against tested bacterial strains, the PECs containing sulfadiazine-modified chitosan being more active than PECs containing unmodified chitosan.

The synthesis and the biological evaluation of new thiazolidin-4-one derivatives containing a xanthine moiety.

Starting from theophylline (1,3-dimethylxanthine) new thiazolidin-4-one derivatives 7a1₋7, 7b1₋7 have been synthesized as potential antidiabetic drugs. The structure of the new derivatives was confirmed using spectral methods (FT-IR, ¹H-NMR, ¹³C-NMR). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing power, the total antioxidant activity and the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be implicated in a variety of pathological events, such as diabetes mellitus and its micro- and macrovascular complications. The results of chemical modulation of the thiazolidin-4-one intermediaries 6a, 6b through condensation with several aromatic aldehydes is the improvement of the antioxidant effect. All benzylidenethiazolidin-4-one derivatives 7a1₋7, 7b1₋7 are more active than their parent thiazolidin-4-ones. The most active compounds are the ones obtained by reaction of condensation with 4-hydroxybenzaldehyde (compounds 7a5, 7a6), 4-dimethylaminobenzaldehyde (compounds 7a6, 7b6) and 2-nitrobenzaldehyde (compounds 7a7, 7b7).

Synthesis and biological evaluation of new 2-azetidinones with sulfonamide structures.

New series of N-(arylidene)hydrazinoacetyl sulfonamides 4a1-6, 4b1-6 and N-(4-aryl-3-chloro-2-oxoazetidin-1-yl)aminoacetyl sulfonamides 5a1-6, 5b1-6 were synthesized. The structures of the new derivatives was confirmed using spectral methods (FT-IR, 1H-NMR, 13C-NMR). The antibacterial activities of these compounds against Gram positive (Staphylococcus aureus ATCC 6583, Staphylococcus epidermidis ATCC 12228, Enterococcus faecalis ATCC 25912) and Gram negative (Klebsiella pneumoniae CIP 53153, Proteus vulgaris CIP 104989, Citrobacter freundii CIP 5732, Enterobacter cloacae CIP 103475, Escherichia coli ATCC 25922, Pseudomonas aeruginosa CIP 82118) bacterial strains were evaluated using the broth micro-dilution method. Compound 4a2 displayed the highest antibacterial activity, especially against Staphylococcus epidermidis, Enterococcus faecalis and Pseudomonas aeruginosa. The antioxidant potential of the synthesized compounds was also investigated according to ferric reducing power, total antioxidant activity and DPPH radical scavenging assays. All tested compounds showed excellent antioxidant activity in comparison with sulfadiazine and sulfisoxazole which were used as parent sulfonamides. Moreover, some of them showed an antioxidant activity comparable with that of ascorbic acid. In general, the compounds designed based on a sulfadiazine skeleton (compounds 4a1-6, 5a1-6) are more active than those obtained from sulfisoxazole (compounds 4b1-6, 5b1-6), and the N-(arylidene)hydrazinoacetyl sulfonamide derivatives 4a1-6, 4b1-6 are more active than their azetidionone analogues 5a1-6, 5b1-6.

Synthesis and evaluation of antioxidant activity of some new benzylidene-thiazolidine-xanthine derivatives.

UNLABELLED: The International Diabetes Federation reported that 246 million adults worldwide had diabetes mellitus and the prevalence of this syndrome was expected to increase continuously. AIM: To design new compound with potential antidiabetic and antioxidant activity. MATERIAL AND METHODS: New benzylidene-thiazolidine derivatives (BT2a-2e) were obtained by condensation of xanthine-thiazolidine-4-one (TZ-4-one) with aromatic aldehydes. The synthesized compounds were characterized by spectral method (IR, 1H-NMR, 13C-NMR) and their antioxidant potential has been also evaluated. RESULTS: The synthesized compounds have important antioxidant effects as compared to xanthine-thiazolidine derivatives. The most active compounds were those obtained by condensation with 4-dimethylaminobenzaldehyde (BT2c) and 4-nitro-benzaldehyde (BT2e). CONCLUSIONS: The chemical modulations performed on the structure of TZD-4-one have a good influence on their antioxidant potential.