Interactions of Analgesics with Cisplatin: Modulation of Anticancer Efficacy and Potential Organ Toxicity

Cisplatin (CDDP), one of the most eminent cancer chemotherapeutic agents, has been successfully used to treat more than half of all known cancers worldwide. Despite its effectiveness, CDDP might cause severe toxic adverse effects on multiple body organs during cancer chemotherapy, including the kidneys, heart, liver, gastrointestinal tract, and auditory system, as well as peripheral nerves causing severely painful neuropathy. The latter, among other pains patients feel during chemotherapy, is an indication for the use of analgesics during treatment with CDDP. Different types of analgesics, such as acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDS), and narcotic analgesics, could be used according to the severity of pain. Administered analgesics might modulate CDDP’s efficacy as an anticancer drug. NSAIDS, on one hand, might have cytotoxic effects on their own and few of them can potentiate CDDP’s anticancer effects via inhibiting the CDDP-induced cyclooxygenase (COX) enzyme, or through COX-independent mechanisms. On the other hand, some narcotic analgesics might ameliorate CDDP’s anti-neoplastic effects, causing chemotherapy to fail. Concerning safety, some analgesics share the same adverse effects on normal tissues as CDDP, augmenting its potentially hazardous effects on organ impairment. This article offers an overview of the reported literature on the interactions between analgesics and CDDP, paying special attention to possible mechanisms that modulate CDDP’s cytotoxic efficacy and potential adverse reactions.

Anesthetic management of emergency and planned endovideoscopic gynecological operations in the context of the COVID-19 novel coronavirus infection pandemic (review of the problem)

Purpose of the study. Extract original operational data containing information on the effect of non-steroidal anti-inflammatory drugs (NSAIDs) and the inclusion in the outcomes of the new coronavirus infection SARS-CoV‑19, descriptive analyzes and meta-analyzes, as in emergency and planned in gynecology, NSAIDs are used for the purpose of pain relief.Materials and methods. A systematic literature search was carried out to identify suitable studies in the electronic databases MEDLLINE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database (CBM), domestic publications of the Russian information and analytical portal eLibrary.ru. The time horizon of publications on the problems of pain relief in women during endovideoscopic operations was 20 years. The search for publications in all languages on the use of NSAIDs in the conditions of SARS-CoV‑19 in all patient populations, regardless of gender, age, severity of the condition, was carried out for 2019–2021. The last search query is of 12/20/2021.Results and conclusions. The solution to a number of problems of anesthesia can be the refusal to use narcotic analgesics for endovideoscopic operations for female infertility. There is no clear clinical indication of the effect of NSAIDs on the risk of infection or an increase in the severity of SARS-CoV‑19 disease.

Medications and Falls Experiences among Older People

Purpose: This study aimed to identify the status of drug use and analyze the effects of drug use on falls among older people.Methods: The data were collected from 285 community-dwelling older persons through interviewing with questionnaires and checking participants’ medication prescriptions and the drugs using the Korea Pharmaceutical Information Center’s (KPIC) website. The medications were classified into anatomical and therapeutic divisions based on the medications’ ingredients provided by the KPIC. x2 test, ANOVA, t-test, and logistic regressions were applied to analyze the data.Results: The finding showed that 81.4% of the older adults were taking medications. Older people taking antihyperlipidemic drugs were at 1.79 times higher risk for experiencing a fall (95% CI=1.01~3.16, p=.046), and hypnotic sedative and sleeping pills increased their fall risks 11.06 times (95% CI=1.27~96.07, p=.029) compared to those not taking the medications. Nonsteroidal antiinflammatory agents showed a 2.74 odds ratio (95% CI=1.23~5.73, p=.013) and narcotic analgesics increased the fall experience risk 8.56 times (95% CI=1.02~71.88, p=.048). Those with chronic diseases experienced falls 3.04 times more than those without chronic diseases.Conclusion: The study findings showed medications might be one of the important influencing factors on fall risks among older adults. Raising awareness of fall risks associated with medicines through health education and medication reviews by health professionals should be considered a strategy for preventing older adults' falls.

Comparison of methods of automatic bipolar sealing and monopolar coagulation in the surgical treatment of hemorrhoids in patients with diabetes

Comparison of LigaSure and traditional methods of surgical treatment of III and IV degree hemorrhoids in patients with diabetes mellitusHemorrhoids are submucosal nodules in the anal canal that contain venules, arterioles, and smooth muscle fibers. Hemorrhoidal disease is registered in approximately 5 % of the total population, especially after 40 years. Treatment is indicated only in symptomatic cases. These symptoms include pain, itching, bleeding, thrombosis and hemorrhoidal prolapse.Aim — to compare the clinical results of he­­mor­rhoidectomy using the electrocoagulation he­mostatic device LigaSure and the traditional Milligan—Morgan method in patients with diabetes mellitus. Materials and methods. The study included 65 patients of both genders aged 18—78 years with stage 3 and 4 hemorrhoids, who underwent hemor­rhoidec­tomy: from them, 33 subject were operated with LigaSure (the main group), and 32 patients with traditional Milligan—Morgan method (control group). The following patients’ data were analyzedretrospec­tively:gender, age, pre- and postoperative hemoglobin and hematocritlevels, surgery duration, the presence of thrombosis, the number of removed and residual hemorrhoids, hospitalization duration, early and late postoperative complications, the need for narcotic analgesics, the observationalperiod, and the time to return to normal daily activity. Results. The mean surgery duration was 16 (6—45) min in the study group and 21 (7—43) min in the control group. Narcotic analgesics in the postoperative period were used in 17 (53.1 %) patients in the control group and were not used in the study group. The timerequired for return to the normal daily activity was 6 (2—15) days in the study group and 8 (2—30) days in the control group. Conclusions. It has been shown that LigaSure gave betterresults of hemorrhoidectomy versus traditional methods in patients with diabetes mellitus in terms of surgery duration, hospitalizationperiod, postoperative pain relief needs, risk of postoperative bleeding, and time required to return to normal daily activity.

Analgesic properties of dealcoholized extract of Acorus Calamus Leaves

Opioid and non-narcotic analgesics, non-steroidal anti-inflammatory agents, anesthetics, antidepressants, myorelaxants, combined agents and phytopreparations are widely used for the treatment of pain syndrome. One of the promising phytogenic objects with potential analgesic properties is the Acorus calamus (Sweet Flag). The aim: the purpose of the study is to determine the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" test and in the test of tail heat immersion. Materials and methods. During the experimental study, the pharmacological methods have been used. The analgesic properties of DEAL were studied in mice on the "Hot plate" model using the Hot / Cold Plate (Bioseb, France) and in the test of the heat immersion in rats. The results. On the models of pain in the "Hot plate" and tail heat immersion tests, the analgesic effect of the dealcoholized extract of Acorus calamus leaves (DEAL) is determined. On the "Hot plate" model, the use of DEAL probably increased the duration of the latency period. According to the analgesic effect of DEAL and metamizol sodium were comparable to each other continues to 1 and 1.5 hours of experiment, but starting with 2 hours of experiment the analgesic action of metamizol sodium statistically exceeded the analgesic effect of DEAL. In the test of heat immersion tail in rats, DEAL increased the latency period of shocking of the rats’ tail compared to the starting background by 43.13 % as well as metamizol sodium by 66.6 %. The studies have shown the presence of moderate analgesic effects of DEAL in the investigated dose. Conclusions. The analgesic effect of a dealcoholized extract of Acorus calamus leaves (DEAL) on a model of pain in the "Hot plate" and heat tail immersion tests has been carried out. Under the "Hot plate" test in mice, DEAL produces a distinct analgesic effect, however, slightly inferior to the severity of metamizol sodium. Presence of moderate analgesic properties of DEAL has been verified in comparison with the metamizel sodium in thetail heat immersion test in rats. The obtained results indicate the influence of DEAL on the central mechanisms of pain formation

Plasma Calcifedol Concentration as a Marker of Vitamin D Deficiency in Newborns with Congenital Malformations

Diagnosis of vitamin D deficiency and its management is the most difficult problem of modern neonatology.The objective: to study the concentration of 25(OH)D3 in newborns of St. Petersburg depending on the presence of congenital malformations (CM).Subjects and methods. 60 newborns were examined, their gestational age made 39.4 (38-41) weeks. Children were divided into 2 groups: Group 1 – healthy children, Group 2 – children with CM.Results. Regardless of the presence of CM, the calcifedol plasma concentration was below 15 ng/ml. It was found that children with CM whose plasma calcifedol concentration was below 8.0 ng/ml needed long-term invasive mechanical ventilation (80.0 vs 40.0 hours; p < 0.005) and longer treatment in ICU (7.0 vs 4.0; p < 0,002). Negative correlations were revealed between calcifedol concentration, duration of narcotic analgesics administration (R = -0.44; p = 0.01), duration of mechanical ventilation (R = -0.49; p = 0.003) and stay in ICU (R = -0.54; p = 0.001).Conclusion. The most pronounced deficiency of calcifedol was in children with severe CM requiring long-term treatment in ICU.

STEROID HORMONES AND THEIR METABOLITES IN WATER OF CENTRALIZED DRINKING WATER SUPPLY SYSTEMS AS ECOPOLUTANTS

Information about the presence of drugs and their metabolites in the water of centralized drinking water supply systems is presented; the main groups of drugs found in purified drinking water of large cities are given. The main groups of drugs found in a centralized drinking water supply system include antidepressants (amitriptyllin), antibacterial drugs of various groups (amoxicillin, ciprofloxacin, tetracycline, azithromycin), narcotic analgesics (cocaine, morphine, their derivatives), psychoactive stimulants, benzodiazepines, hormones (estrogen and its metabolites estrone and estriol). A high level of potential risk to public health is marked due to the presence of steroid hormones and their active metabolites in drinking water. The concept of endocrine dysregulating complexes is formulated. Such complexes can be of a different nature of origin, but all of them affect receptors for estrogen and progesterone. It leads to abnormalities of hormonal regulation, affects endogenous synthesis, transport and secretory function. From the standpoint of ecotoxicology, further ways of working out the problem of the presence of steroid hormones in drinking water are proposed: the development of theoretical approaches to substantiating hygienic standards concerning the monitoring of these compounds in the water of centralized drinking water supply systems.

Martorell’s ulcer: a literature review and own clinical observation

Introduction. Martorell’s ulcer is a rather rare pathology that occurs exclusively in patients with long-term and poorly controlled arterial hypertension and continues to be one of the poorly studied areas of modern surgery. There are few reports on the occurrence of this pathology in the medical literature and, as a rule, describe extremely rare clinical cases. The issues of etiology, pathogenesis and differential diagnosis of this disease continue to cause debate. The article provides a review of the literature on this rare surgical pathology, presents its own clinical observation, discusses the issues of diagnosis and treatment options for this disease.Clinical case. A 56-year-old patient was admitted with complaints of a non-healing trophic ulcer on the lateral surface in the lower third of the right leg since one year ago with severe pain syndrome not adequately controlled with non-narcotic analgesics. he received treatment in an outpatient department and in the hospital, underwent courses of rheological therapy to the ulcer region as a local therapy, used a wide range of dressings of domestic and foreign origin. No positive effect was reported on the top of already administered combination therapy, the ulcer continued to increase in size. A Martorell’s ulcer was diagnosed, and a decision was made to provide a course of presurgical conservative rheological therapy with PGE1 (VAP 20 mg), antibiotic therapy, and local therapy aimed at maximal ulcer necrotic tissue clearance before the forthcoming planned surgical treatment. The patient underwent the surgery – autodermatoplasty of the trophic ulcer of the right leg with a mesh graft, continued local treatment of the ulcer using dressings with peruvian balsam and other medications on an outpatient basis without chemical and biological components from the antiseptics and healing stimulants group. Two months after the surgery, the patient had no complaints, the pain syndrome in the ulcer region completely regressed, no edema occurred in the lower operated leg, the right let ulcer completely healed with the formation of a permanent scar.Conclusion. Surgical management is the final and definitive treatment for Martorell’s chronic hypertensive ulcer and should be carried out promptly to minimize the spread of the ulcer and minimize a pain syndrome.

Modern Approaches to the Elimination of Visceral Pain

In modern medicine, one of the most common situations requiring emergency care is biliary or renal colic as a manifestation of abdominal pain syndrome. In both cases, smooth muscle spasm plays an important role in the pathogenesis of visceral pain syndrome. Taking into account the fact that, regardless of the chosen treatment tactics, at the first stage it is necessary to stop pain, the question arises about the choice of a drug strategy for the relief of these conditions. It used to be thought that the more intense the pain, the more indications for the prescription of narcotic drugs, which were considered reference analgesics. In recent years, the world has become embroiled in an «opioid crisis». This prompted clinicians to consider the use of drugs from other groups, namely, non-steroidal anti-inflammatory drugs and antispasmodics alone or in combination, which turned out to be no less effective and, often, safer in comparison with narcotic analgesics. New opportunities for effective treatment of visceral pain are opened by the drug Neospastil® (PJSC «Pharmaceutical Company «Darnitsa»), which combines the benefits of nonsteroidal anti-inflammatory drugs (ketorolac tromethamine) with antispasmodic effect of cholinolytics, ganglioblockers and phenytoin phenytoin. The drug increases the effectiveness of analgesia, as well as the control of muscle spasm.