Antihistaminic Agents Research Articles

Correlations in hydrochloride drugs with diverse pharmacological activities. Role of N-H…Cl bonds

In this work, the structural and vibrational properties of sixteen hydrochloride/hydrobromide drugs with different pharmacological activities have been compared and analysed in order to find some correlations among their properties and, mainly elucidate the role of N-H•••Cl bonds in them. Here, the properties of ten alkaloids: tropane, gramine, morphine, cocaine, methadone, naloxone, heroin and scopolamine as hydrochloride and hydrobromide including, the psychotropic 2-CB agent; three antihistaminic: diphenhydramine, cyclizine and promethazine and; three antihypertensive tolazoline, clonidine and guanfacine agents have been evaluated. All properties were predicted in gas phase and aqueous solution by using the hybrid B3LYP/6-31G* method and the same were evaluated in functions of their molecular weights. Here, stabilization and solvation energies, dipole moments and volumes in both media, atomic MK charges and bond N-H and N+Cl- lengths, N-H stretching modes of N-HCl bonds of hydrochloride and their cationic species and, frontier orbitals together with global electrophilicity and nucleophilicity descriptors were compared for those sixteen drugs. The results have shown that bonds N+Cl- lengths of all hydrochloride species are higher in solution, as compared with the values in gas phase. Hydrochloride species of alkaloids and antihistaminic agents in both media present higher positive MK values on the N atoms of N-HCl bonds while the species related to antihypertensive agents show higher negative MK values on the N atoms or low positive values. The species of guanfacine presents the higher number of donors and acceptors groups, higher dipole moment value in solution, low bond N-H lengths, higher negative charge on the N atom of N-HCl bond and, higher global electrophilicity index. Hydrochloride species of scopolamine and heroin present the more negative solvation energies while tolazoline the lower value. Hydrochloride species of 2-CB and diphendramine show the higher expansions volumes in solution while the species of naloxone, scopolamine and cocaine evidence volumes contractions in this medium. These studies show that the knowledge of hydration degrees, that is, the number of water molecules that hydrate the hydrochloride species are essential to understand the hydration process of these species in relation to the differences observed in solvation energies, volume variations and dipole moment values.

Metal allergy after the Nuss procedure for pectus excavatum: a review.

Minimally invasive repair of pectus excavatum (MIRPE) technique (the Nuss procedure) is a minimally-invasive method that is commonly used in the treatment of pectus excavatum. An allergic reaction to the metal alloy bar that is implanted in the thorax during the procedure is a reported complication. We briefly review current literature concerning epidemiology, mechanisms and research results of allergic reactions after Nuss bar implantation. This allergic reaction occurs in approximately 2.7% of patients and is caused by metals used in the medical implant. The most common symptoms include fever and skin lesions such as allergic dermatitis. Elevated levels of C-reactive protein is a frequent finding in laboratory tests. In order to minimize the risk of such complications, taking a detailed allergy-based medical history and conducting allergy tests, i.e. patch test are required. Allergic reactions can be managed with conservative treatment such as general or topical glucocorticosteroid therapy and antihistamine agents. Severe allergic reactions can be addressed by implant revision, replacement of the steel bar with a titanium substitute or removal of the stabilization at all. Although the risk of an allergic reaction to titanium is smaller it still exists, the titanium substitute is not routinely used due to its higher cost and lesser plasticity which has a negative impact on matching a stabilizing bar during the surgery. Surgeons treating pectus excavatum should remember about the possible allergic reactions after implantation of the metal bar and be familiar with methods of diagnosis and treatment of those complications.

A new stability indicating RP-HPLC method for determination of Bilastine in bulk and pharmaceutical formulation

Bilastine is an anti-histaminic agent used for the treatment of allergic disorders such as rhinoconjunctivitis and urticaria. A simple, new RP-HPLC method was developed and validated for the determination of purity of Bilastine in bulk and pharmaceutical dosage form. A Shimadzu ModelCBM-20A/20 Alite HPLC system equipped with PDA detector was used. The chromatographic separation was achieved using Phenomenex Gemini C18 column (150 mm × 4.60 mm i.d. 5μm particle size) with formic acid: methanol as mobile phase in the ratio of 50:50 v/v. The flow rate was maintained at 0.8mL/min. The detection was done at 282 nm. The retention time was found to be 2.167min. Bilastine showed linearity in the concentration range of 5–100 μg/mL with linear regression equation y = 15283x + 1079.7 (R2 = 0.9999). The % RSD for precession and accuracy studies were found to be < 2%.The LOD and LOQ were found to be 0.08931 and 0.27063, respectively. The proposed method was observed to be simple, economical and was validated according to the ICH guidelines for linearity, precision, accuracy and stability.

Shivering Due to Repeat Dose of Tranexamic Acid: A Peculiar Case Series

Tranexamic acid (TXA) is a well-tolerated hemostatic agent that has been in clinical use for nearly 60 years. In this report, we describe for the first time 10 patients who experienced adverse reactions to repeat dose of TXA, which were not seen with the first dose. Shivering was found to be the most common adverse reaction. In half of the cases, shivering was associated with low-grade fever. On dechallenge and subsequent administration of steroids and antihistaminic agents, the reactions were controlled. On assessment with the World Health Organization–Uppsala Monitoring Centre scale, the causality was ascertained to be “Probable”.There is no clear postulated mechanism for shivering with TXA. We have postulated that hypersensitivity, fever, and shivering in these patients may be interlinked. In the light of this report, the physicians should take into account that repeated challenge with TXA may lead to adverse reactions in some patients and withdrawing the drug in such patients may be required.

Anaphylaxis-induced atrial fibrillation and anesthesia: Pathophysiologic and therapeutic considerations.

Atrial fibrillation is the most common cardiac arrhythmia in western society affecting more than 35 million individuals worldwide annually. It is a common postoperative complication and may also occur spontaneously during general and local anesthesia administration. Aging, diabetes mellitus, hypertension, and cardiovascular diseases including cardiomyopathies, congenital cardiac anomalies, heart failure, myocardial ischemia, pericarditis, previous cardiac surgery, vascular disease, and valvular heart disease are some correlated factors. Beyond age, increased incidence of atrial fibrillation has been correlated to autoimmune system activation as it is the underlying mechanism of persistent atrial fibrillation development. Current research supports an association between the complement system activation and lymphocyte-pro-inflammatory cytokines release with the cardiac conduction system and atrial fibrosis. The loss of CD28 antigen from CD4+ CD28+ T lymphocytes seems to play a major role in atrial fibrillation development and prognosis. Except atrial fibrillation, a variety of additional electrocardiographic changes, resembling those with digitalis intoxication may accompany anaphylaxis and particularly Kounis syndrome. Histamine is one well-known mediator in allergic and inflammatory conditions as physiologically regulates several cardiovascular and endothelial functions with arrhythmogenic potential. The increased oxidative stress, measured by the redox potentials of glutathione, has been correlated with atrial fibrillation incidence and prevalence. The use of antazoline, a first-generation antihistamine agent used for rapid conversion of recent-onset atrial fibrillation in patients with preserved left ventricular function and for rapid atrial fibrillation termination during accessory pathway ablation denotes that anaphylaxis-induced histamine production could be the cause of atrial fibrillation at least in some instances. The anaphylaxis diagnosis in anesthesia can be challenging owing to the absence of cutaneous manifestetions such as flushing, urticaria, or angioedema. Anticoagulation for stroke prevention, rate and rhythm control medications, invasive methods such as radiofrequency ablation or cryoablation of pulmonary veins as well surgical ablation constitute the treatment basis of atrial fibrillation. Understanding the underlying mechanisms of atrial fibrillation by cardiologists, anesthesiologists and surgeons, as well as potential treatments, to optimize care is of paramount importance.

SJÖGREN SYNDROME IN AN ALLERGIC PATIENT UNDER COMBINED THERAPY

A 70-year-old female patient was referred to the stomatology clinic for evaluation of an injury on her tongue. On medical history, it was found she was a patient with type 2 diabetes mellitus and hypertension, using antihypertensive, hypoglycemic, and antihistamine agents along with insulin, eye drops, and sedatives. She was also being seen by an endocrinologist. She is allergic to many medications (acetylsalicylic acid and its derivatives, dipyrone, and nonsteroidal anti-inflammatory drugs). On oral examination, the patient had a dry oral mucosa with little lubrication and mild candidosis of the tongue, treated by ketoconazole. The clinical diagnosis was Sjogren syndrome. Anti-SSA and anti-SSB were found to be positive. A rheumatoid factor (RF) test was within the normal limits, as was the hemogram. The patient has not yet consented to lip biopsy due to decompensated diabetes (glycated hemoglobin 7.6% and fasting glycemia 115 mg/dL). The patient was referred to the doctor for diabetes control and is under proper follow-up care.

Synthesis of hydroxyethyl methyl morpholinium azide (HEM Morph)N3: A highly efficient new task specific azide-based ionic liquid and its dual application as an azide source and media for synthesis of some novel aromatic O-oxime ethers-1,2,3-triazole conjugates as a potential antihistaminic agents

The synthesis, characterization and application of hydroxyethyl methyl morpholinium azide (HEM Morph)N3 as a new azide-based ionic liquid (ABIL) has been described. (HEM Morph)N3 is used as a source of azide and reaction media for three components ‘Click’ Huisgen cycloaddition reaction between O-propargyl oxime ether and alkyl bromide to acquire novel aromatic O-oxime ethers-1,2,3-triazole conjugates as potential antihistaminic agents in good yields. The influence of parameters like temperature, amount of IL, type of azide-based ionic liquids and its reusability is investigated. The (HEM Morph)N3 is proved to be an efficient, thermally stable, inexpensive and recyclable azide-based ionic liquid which can be easily synthesized and used as both azide's source and reaction media for ‘Click’ Huisgen cycloaddition reaction.

Unexpected Ca2+-mobilization of oxaliplatin via H1 histamine receptors

Oxaliplatin is a widely used chemotherapeutic drug and represents the cornerstone of colorectal cancer therapy, in combination with 5-fluorouracil and folinic acid. As with many chemotherapeutic agents, its use is associated with a number of side effects, ranging from hypersensitivity reactions to haematological dyscrasias. Oxaliplatin also induces acute and chronic peripheral neuropathy.While it is likely that the haematological side effects are associated with its anti-proliferative effects and with the ability to form DNA adducts, the molecular mechanisms underlying peripheral neuropathy and hypersensitivity reactions are poorly understood, and therefore the choice of adequate supportive therapies is largely empirical.Here we show that an acute low dose oxaliplatin application on DRG neurons is able to induce an increase in intracellular calcium that is dependent on the Histamine 1 receptor (H1). Oxaliplatin-induced intracellular calcium rises are blocked by two selective H1 antagonist, as well as by U73122, a PLC inhibitor, and by 2-APB, a non-specific IP3 receptor blocker. Moreover, expression of the H1 receptor on HEK293 t cells unmasks an oxaliplatin-induced Ca2+-rise. Last, activation of H1 via either histamine or oxaliplatin activates TRPV1 receptors, a mechanism that has been associated with itch. These data, together with literature data that has shown that anti-histamine agents reduce the incidence of oxaliplatin-induced hypersensitivity, may provide a molecular mechanism of this side effect in oncological patients.

2238 An Unusual Case of Direct Acting Antiviral Potentiating Angioedema

INTRODUCTION: Hepatitis C Virus (HCV) is a leading cause of chronic liver disease and the most common reason for liver transplantation in the United States (US). The aim of direct acting antiviral (DAA) agents is to reduce progression to cirrhosis. There are newer well tolerated all-oral DAA agents, such as glecaprevir and pibrentasvir (GLE/PIB). We report an unreported adverse event in a treatment naive chronic hepatitis C genotype 1a patient: GLE/PIB induced angioedema. CASE DESCRIPTION/METHODS: A 63-year-old African American Male with a history of chronic hepatitis C infection (genotype 1a) without cirrhosis and hypertension on chronic lisinopril presented to the Emergency Room (ER) with acute onset facial and lip edema. Patient denied known environmental, food, or medication allergies. He denied unusual food intake. He recently started GLE/PIB. Vital signs were unremarkable. On physical examination, there was significant facial and lip swelling. Given the timing of symptoms, the side effect was suspected to be secondary to GLE/PIB. At this time, it was decided to stop the DAA and he was treated with steroids and antihistamine agents. At follow-up, the facial and lip edema had completely resolved. The HCV RNA level was obtained and surprisingly undetectable after only 4 days of therapy with a baseline of 5,080,000 IU/mL. However, at 12 week follow-up, he was again positive. DISCUSSION: Although GLE/PIB has a relatively good safety profile, angioedema is a potentially life threatening side effect that has not been reported as commonly. The underlying mechanism is not known, however it was hypothesized that co-administration with an Angiotensin Converting Enzyme (ACE) inhibitor may be related. We would recommend avoiding co-administration to prevent the rare but significant side effect, eliminating a potentially curative treatment regimen and the financial aspects of wasted expensive medication and expenses associated with hospitalization.

S(-) and R(+) species derived from antihistaminic promethazine agent: structural and vibrational studies

Structural and vibrational properties of free base, cationic and hydrochloride species derived from both S(-) and R(+) enantiomers of antihistaminic promethazine (PTZ) agent have been theoretically evaluated in gas phase and in aqueous solution by using the hybrid B3LYP/6-31G* calculations. The initial structures of S(-) and R(+) enantiomers of hydrochloride PTZ were those polymorphic forms 1 and 2 experimentally determined by X-ray diffraction. Here, all structures in aqueous solution were optimized at the same level of theory by using the polarized continuum (PCM) and the universal solvation model. As was experimentally reported, variations in the unit cell lead to slight energy, density, and melting point differences between the two forms but, this behavior is not carried through in isotropic condition, like in solution with non-chiral solvents. Hence, the N–C distances, Mulliken, atomic natural population (NPA) and Merz-Kollman (MK) charges, bond orders, stabilization and solvation energies, frontier orbitals, some descriptors and their topological properties were compared with the antihistaminic cyclizine agent. The frontier orbitals studies show that the free base species of both forms in solution are more reactive than cyclizine. Higher electrophilicity indexes are observed in the cationic and hydrochloride species of PTZ than cyclizine while the cationic species of cyclizine have higher nucleophilicity index than both species of PTZ. The presences of bands attributed to cationic species of both enantiomers are clearly supported by the infrared and Raman spectra in the solid phase. The expected 114, 117 and 120 vibration normal modes for the free base, cationic and hydrochloride species of both forms were completely assigned and the force constants reported. Reasonable concordances among the predicted infrared, Raman, UV-Vis and Electronic Circular Dichroism (ECD) with the corresponding experimental ones were found.

Comparing doxepin cream to oral antihistamines for the treatment of itch in burn patients: A multi-center triple-blind randomized controlled trial

BackgroundDoxepin cream, an antihistaminic agent, has shown promising results in the treatment of pruritus in burn patients. However, its effectiveness has not been studied comprehensively. ObjectiveTo evaluate whether doxepin cream is more effective than oral antihistamines in reducing pruritus. MethodsWe performed a multicenter triple-blind randomized controlled trial of twelve weeks randomizing burn patients ≥18 years with an itch intensity ≥3 on a Visual Analogue Scale (VAS) between doxepin hydrochloride 5% cream with placebo tablet or oral antihistamine (clemastine) with placebo cream. Primary endpoint was change in itch intensity. Secondary endpoints included impact of itch (Burn Itch Questionnaire), quality of life (SF-36), somnolence, and erythema (DermaSpectrometer). ResultsThirty-one (of the intended 108) subjects could be included: 13 were randomized to the doxepin and 18 to the clemastine group. The skewed distribution is attributable to the low inclusion rate. Both groups showed a significant reduction in itch intensity over a period of twelve weeks (doxepin p = 0.043, clemastine p = 0.019) with no difference between both groups in: mean itch intensity difference (p = 0.199), any of the domains (p = 0.940, p = 0.698, p = 0.859) of the Burn Itch Questionnaire, quality of life, somnolence (p = 0.143) and erythema (p = 0.796). ConclusionThe effectiveness of doxepin cream was similar to oral antihistamines in reducing itch. However, considering the study ’s limitations, a superior effect of doxepin cream cannot be completely ruled out. We recommend that future studies use a cross-over design so fewer inclusions are needed to obtain adequate power.

Allergic contact dermatitis of both eyes caused by alcaftadine 0.25%: a case report

BackgroundTo report the first case of allergic contact dermatitis (ACD) associated with alcaftadine 0.25% ophthalmic solution.Case presentationThe patient was a 51-year-old woman with no previous history of side effects to ophthalmic antihistamine agents. She had been prescribed alcaftadine 0.25% for allergic conjunctivitis. On first application of the medication, she did not experience any cutaneous reaction. One day later, after the second alcaftadine 0.25% application, both eyelids became swollen, and erythematous changes were evident. On slit-lamp examination, conjunctival injection was noted in the absence of conjunctival swelling or any other findings. Fundus examination was unremarkable. To evaluate the cause of ACD, a patch test was performed and 48 h later was noted to be positive for alcaftadine 0.25%. Based on the positive patch test, the patient was diagnosed with ACD caused by alcaftadine 0.25%. After 9 days of treatment, the swelling and erythema completely resolved.ConclusionsAlthough there have been no previous reports of alcaftadine 0.25%-associated ACD, it should be suspected in patients with swelling and erythematous change of both eyes after using alcaftadine 0.25%.

PS1390 PRELIMINARY DATA: PHASE 1B STUDY OF FEASIBILITY/SAFETY OF ISATUXIMAB SHORT DURATION FIXED VOLUME INFUSION IN COMBINATION WITH POMALIDOMIDE AND DEXAMETHASONE FOR RELAPSED/REFRACTORY MULTIPLE MYELOMA

Background:Isatuximab is an anti‐CD38 monoclonal antibody with multiple mechanisms of action. This Ph1b open‐label, multicenter study (NCT02283775) of isatuximab in combination with pomalidomide (pom) and dexamethasone (dex) for relapsed and refractory multiple myeloma (RRMM) had two parts; part A identified the recommended dose of 10 mg/kg of isatuximab using weight‐based infusion volume in mg/hour (h) (J Clin Oncol 2018; 36 Suppl;3038).Aims:To evaluate the feasibility and safety of a fixed volume infusion (rate in mL/h) of isatuximab (10 mg/kg) in combination with pom/dex in RRMM.Methods:Patients (pts) with RRMM had received ≥2 prior lines including lenalidomide and a proteasome inhibitor (PI). Isatuximab 10 mg/kg was administered from a 250 mL fixed infusion volume. First infusion: initiated at 25 mL/h and increased gradually to 150 mL/h if no infusion reaction (IR). Second infusion: initiated at 50 mL/h, increased gradually up to 300 mL/h if no IR. Third and subsequent infusions: initiated at a fixed infusion rate of 200 mL/h until the total volume was infused. Standard prophylactic medication with antihistaminic and antipyretic agents without post‐infusion corticosteroid prophylaxis was given. Primary endpoint: incidence of grade (GR) ≥3 IRs during the first 6 isatuximab infusions. Secondary endpoints included duration of infusion and safety. Statistical analyses are based on the all treated pts who had completed ≥6 isatuximab infusions or discontinued early by the preliminary analysis cut‐off date of 02Jan2019.Results:Of 34 pts (all treated), 24 (70.6%) were still on treatment. Median age 64 years (range 46–85; majority [19/34, 55.9%] aged &lt;65). All pts were previously treated with a PI and immunomodulatory drug. Median number of cycles was 3.5 with 32 (94.1%) pts having started at least 2 cycles (minimum 5 infusions) and 17 (50.0%) pts having started at least 4 cycles (minimum 9 infusions). Overall median duration of exposure was 13.4 weeks (range 1–37). Median relative dose intensities for isatuximab, pom, and dex were 94.8%, 85.9% and 91.1%, respectively. Median duration of infusion decreased from 3.94 h in first infusion to 1.25 h from third infusion onwards (table).IRs (any GR) were reported in 16/34 (47.1%) pts and in 16/317 (5.0%) infusions. All IRs were GR2, only occurred during the first isatuximab infusion, and were handled through infusion interruption with pts recovering the same day. No delayed onset IRs occurred. Three (8.8%) pts discontinued due to treatment‐emergent adverse events (2 severe infections; 1 sudden death) and GR≥3 infections were reported in 14.7%. GR4 neutropenia and GR4 thrombocytopenia were observed in 39.4% and 12.1% pts, respectively.imageSummary/Conclusion:Isatuximab 10 mg/kg administered in a 250 mL fixed infusion volume with infusion rate in mL/h had a considerably shorter infusion time (median 75 minutes) compared with reported infusion schedule in mg/h (median 174 minutes) for third and subsequent infusions. IRs after the first infusion or IRs with delayed onset were not reported. The general safety profile of the simplified infusion was manageable and consistent with previous observations for this combination of isatuximab with pom and dex.

A Review Exploring Therapeutic Worth of 1,3,4-Oxadiazole Tailored Compounds.

1,3,4-Oxadiazole, a five-membered aromatic ring can be seen in a number of synthetic molecules. The peculiar structural feature of 1,3,4-oxadiazole ring with pyridine type of nitrogen atom is beneficial for 1,3,4-oxadiazole derivatives to have effective binding with different enzymes and receptors in biological systems through numerous weak interactions, thereby eliciting an array of bioactivities. Research in the area of development of 1,3,4-oxadiazole-based derivatives has become an interesting topic for the scientists. A number of 1,3,4-oxadiazole based compounds with high therapeutic potency are being extensively used for the treatment of different ailments, contributing to enormous development value. This work provides a systematic and comprehensive review highlighting current developments of 1,3,4-oxadiazole based compounds in the entire range of medicinal chemistry such as anticancer, antifungal, antibacterial, antitubercular, anti-inflammatory, antineuropathic, antihypertensive, antihistaminic, antiparasitic, antiobesity, antiviral, and other medicinal agents. It is believed that this review will be of great help for new thoughts in the pursuit for rational designs for the development of more active and less toxic 1,3,4-oxadiazole based medicinal agents.

Long-term follow-up of intradermal injection of methylene blue for intractable, idiopathic pruritus ani

BackgroundWhile various medical treatments such as topical steroid ointment, antihistamine agent, and sedatives have been used for treating idiopathic intractable pruritus ani, they are not long-term solutions, due to the high recurrence rate. The aim of this study was to determine the effect of methylene-blue intradermal-injection therapy for treating patients with idiopathic intractable pruritus ani. Symptom improvement and recurrence rates were determined with a long-term follow-up.MethodsA retrospective study was conducted from January 2011 to October 2013 on consecutive patients with intractable pruritus ani treated with methylene-blue intradermal injection. The therapy included 5 ml of 1% methylene blue and 15 ml of 1% lidocaine. Follow-up included a physical exam and satisfaction-score survey (1 = much worse, 2 = worse, 3 = no improvement, 4 = much better, 5 = gone completely) before treatment, 6 weeks after treatment, and 3 years after treatment to check patient status and recurrence rate.ResultsOf 103 treated patients, 96 were able to attend the 6-week follow-up visit. There were 58 (60.4%) males and 38 (39.6%) females with a mean age of 48.34 ± 10.21 years. Their mean satisfaction score at 6 weeks was 4.23 ± 0.86. Of the total of 96 patients, 9 (9.4%) patients scored 3 or less in their satisfactions score at 6 weeks. 62 (64.6%) patients were evaluated 3-year post-treatment. The satisfaction score at 3 years after treatment was 4.74 ± 0.57. Besides the 9 patients who initially failed treatment, 4 of the remaining 53 patients scored 3 or less in their satisfaction score surveys. Thus, the recurrence rate at 3 years was 7.5% (4/53).ConclusionsMethylene-blue intradermal injection can result in a high symptom improvement rate with low recurrence rate for patients with idiopathic pruritus ani.

Developmental history of sublingual immunotherapy

Allergen immunotherapy is the only curative treatment for IgE-mediated allergic diseases in contrast to symptomatic treatment such as anti-histamine agents. Subcutaneous immunotherapy (SCIT) has been introduced in Japan for treatment of allergic rhinitis and/or asthma caused by pollens and/or house dust mites (HDM) in early 1960s, and the clinical efficacy has been well-known. However, the major drawbacks of SCIT are necessity of repeated painful injections as well as the risk of severe systemic adverse reactions. Sublingual immunotherapy (SLIT) was developed to resolve these issues. In Japan, Japanese cedar (JC) pollen SLIT-drop was developed initially for treatment of JC pollinosis, and approved for patients of 12 years of age and older in 2014. For adolescent and adult patients with HDM-allergic rhinitis, HDM SLIT-tablet was launched in 2015 and subsequently approved to be also available for pediatric patients (<12 years of age) in 2018. Moreover, JC pollen SLIT-tablet for JC pollinosis was approved in 2018 for all patients with no age limit. Here, we also describe that the formulation technologies of SLIT tablets and distribution of allergens after sublingual administration as well as the development of SLIT drop/tablets.

Uticaj alergijskog konjuktivitisa na debljinu horoidee

Background: To examine the effects of allergic conjunctivitis and its treatment upon choroidal thickness (ChT) using topical antihistaminic agents. Methods: 60 eyes of 30 children and adolescents with allergic conjunctivitis and 60 eyes of 30 healthy controls participated in the study. Inclusion criteria for patient groups were best-corrected visual acuity 20/20 or better, normal intraocular pressure (IOP) and no systemic or ocular diseases other than allergic conjunctivitis. Healthy controls recruited from children and adolescents who had no ocular or chronic systemic disorders and had best-corrected visual acuity 20/20 or better and normal IOP. ChT was measuredby using Enhanced Depth Imaging Optical Coherence Tomography (EDI-OCT) before and after treatment by antihistamine agents. Results: Subfoveal choroidal thicknes mean value was 364.1 ± 63.8 m in the allergic conjunctivitis group and the first-month values after the treatment were 333.5 ± 52.1 m. Subfoveal choroidal thickness means value in the control group was 320.6 ± 80.9 m. There was a statistically significant decrease in ChT after treatment of allergic conjunctivitis patients and there was a significant difference in terms of baseline ChT values between the allergic conjunctivitis group and the control group. There was no significant difference between one month after treatment values and the mean values of the control group. Conclusions: Our results demonstrate that ChT can increase in allergic conjunctivitis patients and can become normal again with topical antihistamine treatment. In order to support choroidal thickness to be a marker for the diagnosis and follow-up of allergic conjunctivitis, further studies with larger samples and longitudinal studies are needed.

Developmental History of Sublingual Immunotherapy

Allergen immunotherapy is the only curative treatment for IgE-mediated allergic diseases in contrast to symptomatic treatment such as anti-histamine agents. Subcutaneous immunotherapy (SCIT) has been introduced in Japan for treatment of allergic rhinitis and/or asthma caused by pollens and/or house dust mites (HDM) in early 1960s, and the clinical efficacy has been well-known. However, the major drawbacks of SCIT are necessity of repeated painful injections as well as the risk of severe systemic adverse reactions. Sublingual immunotherapy (SLIT) was developed to resolve these issues. In Japan, Japanese cedar (JC) pollen SLIT-drop was developed initially for treatment of JC pollinosis, and approved for patients of 12 years of age and older in 2014. For adolescent and adult patients with HDM-allergic rhinitis, HDM SLIT-tablet was launched in 2015 and subsequently approved to be also available for pediatric patients (<12 years of age) in 2018. Moreover, JC pollen SLIT-tablet for JC pollinosis was approved in 2018 for all patients with no age limit. Here, we also describe that the formulation technologies of SLIT tablets and distribution of allergens after sublingual administration as well as the development of SLIT drop/tablets.

Design, Synthesis, Biological Evaluation, and In Silico ADMET Studies of 1,8-Naphthyridine Derivatives as an H1-receptor Inhibitor

In the present study, 1,8-naphthyridine-3-carboxylic acid derivatives (5a1, 5a2, 5b1, and 5b2) were designed, synthesized, and screened for their in vitro H1-antihistaminic activity. H1R inhibitory activity of the synthesized derivatives was calculated by the modified Van Arman technique, histamine-induced bronchoconstriction in guinea pigs. A good bronchorelaxant effect of compounds was observed in histamine-contracted guinea pig tracheal chain through H1-receptor antagonism. In addition, the hypothetically resulted compounds are checked for their reliability on other in silico drug designing online web services like SwissADME predictor. In silico ADMET analysis results show that all the derivatives had negligible toxicity, good absorption, and solubility profile. These compounds may serve as possible lead for establishing safe and effective antihistaminic agent(s).

Adverse reactions associated with long-term drug administration in Mycobacterium avium complex lung disease.

The number of patients with non-tuberculous mycobacterial lung disease (NTM-LD) worldwide has been increasing. Mycobacterium avium complex lung disease (MAC-LD) accounts for 90% of NTM-LD. MAC-LD necessitates long-term treatment, but adverse reactions with long-term administration of drugs are poorly understood. To evaluate adverse reactions with long-term administration of drugs for MAC-LD. We conducted a retrospective single-centre medical chart review of 364 patients administered two or more drugs between July 2010 and June 2015. The prevalence and median time to onset of adverse reactions were as follows: hepatotoxicity 19.5%, 55 days; leucocytopaenia 20.0%, 41 days; thrombocytopaenia 28.6%, 61.5 days; cutaneous reactions 9.3%, 30 days; ocular toxicity 7.7%, 278 days; and increase in serum creatinine 12.4%, 430.5 days. Multivariate analysis showed that rifampicin use was independently associated with thrombocytopaenia, and ethambutol use was independently associated with increases in serum creatinine. The main adverse reactions appeared within 3 months after start of treatment. Most patients were able to continue treatment with liver-supporting therapy, antihistamine agents or desensitisation therapy; however, ocular toxicity must be monitored for up to 1 year after start of treatment.