Pathogenetic features of acute naphazoline poisoning in children

Introduction: Acute poisoning by nasal decongestants is an important issue in pediatrics due to physiological and anatomical characteristics of the child’s body and pharmacokinetics of drugs in early childhood. Epidemiology: The number of poisonings by this group of drugs ranged from 4% to 39% during the period from 2000 to 2018. All the studies reported that the most severe degree of intoxication was observed in children aged 1–3 years. Mechanism of action of nasal decongestants: The peculiarity of selective alpha2-adrenergic agonists is that when taken orally, misused or overdosed, they lose their selectivity for the target receptor. As a result, the drug causes acute poisoning and most often this effect occurs in children and adolescents. Clinical features and diagnostic criteria: Clinical signs of acute poisoning can appear both as a result of an overdose of the nasal decongestants and due to a therapeutic use of the drug according to the instruction. The symptoms are manifested by hypothermia, skin pallor, bradycardia, arterial hypotension, profuse sweating, and acrocyanosis. Imidazoline receptors and new opportunities: It is assumed that toxic effect of topical decongestants occurs not only by activation of alpha2-adrenergic receptors, but also through their influence on the selective imidazoline receptors. Based on the structure of these drugs, it is assumed that imidazoline receptors are the primary binding site for these drugs. Conclusion: Understanding the described mechanisms of alpha2-adrenergic agonist action and peculiarities of the child’s symptoms in acute poisoning is necessary for the timely diagnosis and selection of the correct treatment strategy.

Adrenoceptors in GtoPdb v.2021.3

The nomenclature of the Adrenoceptors has been agreed by the NC-IUPHAR Subcommittee on Adrenoceptors [60, 186]. Adrenoceptors, α1 The three α1-adrenoceptor subtypes α1A, α1B and α1D are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. -(-)phenylephrine, methoxamine and cirazoline are agonists and prazosin and doxazosin antagonists considered selective for α1- relative to α2-adrenoceptors. [3H]prazosin and [125I]HEAT (BE2254) are relatively selective radioligands. S(+)-niguldipine also has high affinity for L-type Ca2+ channels. Fluorescent derivatives of prazosin (Bodipy FLprazosin- QAPB) are used to examine cellular localisation of α1-adrenoceptors. α1-Adrenoceptor agonists are used as nasal decongestants; antagonists to treat symptoms of benign prostatic hyperplasia (alfuzosin, doxazosin, terazosin, tamsulosin and silodosin, with the last two compounds being α1A-adrenoceptor selective and claiming to relax bladder neck tone with less hypotension); and to a lesser extent hypertension (doxazosin, terazosin). The α1- and β2-adrenoceptor antagonist carvedilol is used to treat congestive heart failure, although the contribution of α1-adrenoceptor blockade to the therapeutic effect is unclear. Several anti-depressants and anti-psychotic drugs are α1-adrenoceptor antagonists contributing to side effects such as orthostatic hypotension. Adrenoceptors, α2 The three α2-adrenoceptor subtypes α2A, α2B and α2C are activated by (-)-adrenaline and with lower potency by (-)-noradrenaline. brimonidine and talipexole are agonists and rauwolscine and yohimbine antagonists selective for α2- relative to α1-adrenoceptors. [3H]rauwolscine, [3H]brimonidine and [3H]RX821002 are relatively selective radioligands. There are species variations in the pharmacology of the α2A-adrenoceptor. Multiple mutations of α2-adrenoceptors have been described, some associated with alterations in function. Presynaptic α2-adrenoceptors regulate many functions in the nervous system. The α2-adrenoceptor agonists clonidine, guanabenz and brimonidine affect central baroreflex control (hypotension and bradycardia), induce hypnotic effects and analgesia, and modulate seizure activity and platelet aggregation. clonidine is an anti-hypertensive (relatively little used) and counteracts opioid withdrawal. dexmedetomidine (also xylazine) is increasingly used as a sedative and analgesic in human [31] and veterinary medicine and has sympatholytic and anxiolytic properties. The α2-adrenoceptor antagonist mirtazapine is used as an anti-depressant. The α2B subtype appears to be involved in neurotransmission in the spinal cord and α2C in regulating catecholamine release from adrenal chromaffin cells. Although subtype-selective antagonists have been developed, none are used clinically and they remain experimental tools. Adrenoceptors, β The three β-adrenoceptor subtypes β1, β2 and β3 are activated by the endogenous agonists (-)-adrenaline and (-)-noradrenaline. Isoprenaline is selective for β-adrenoceptors relative to α1- and α2-adrenoceptors, while propranolol (pKi 8.2-9.2) and cyanopindolol (pKi 10.0-11.0) are relatively selective antagonists for β1- and β2- relative to β3-adrenoceptors. (-)-noradrenaline, xamoterol and (-)-Ro 363 show selectivity for β1- relative to β2-adrenoceptors. Pharmacological differences exist between human and mouse β3-adrenoceptors, and the 'rodent selective' agonists BRL 37344 and CL316243 have low efficacy at the human β3-adrenoceptor whereas CGP 12177 (low potency) and L 755507 activate human β3-adrenoceptors [88]. β3-Adrenoceptors are resistant to blockade by propranolol, but can be blocked by high concentrations of bupranolol. SR59230A has reasonably high affinity at β3-adrenoceptors, but does not discriminate between the three β- subtypes [320] whereas L-748337 is more selective. [125I]-cyanopindolol, [125I]-hydroxy benzylpindolol and [3H]-alprenolol are high affinity radioligands that label β1- and β2- adrenoceptors and β3-adrenoceptors can be labelled with higher concentrations (nM) of [125I]-cyanopindolol together with β1- and β2-adrenoceptor antagonists. Fluorescent ligands such as BODIPY-TMR-CGP12177 can be used to track β-adrenoceptors at the cellular level [8]. Somewhat selective β1-adrenoceptor agonists (denopamine, dobutamine) are used short term to treat cardiogenic shock but, chronically, reduce survival. β1-Adrenoceptor-preferring antagonists are used to treat cardiac arrhythmias (atenolol, bisoprolol, esmolol) and cardiac failure (metoprolol, nebivolol) but also in combination with other treatments to treat hypertension (atenolol, betaxolol, bisoprolol, metoprolol and nebivolol) [507]. Cardiac failure is also treated with carvedilol that blocks β1- and β2-adrenoceptors, as well as α1-adrenoceptors. Short (salbutamol, terbutaline) and long (formoterol, salmeterol) acting β2-adrenoceptor-selective agonists are powerful bronchodilators used to treat respiratory disorders. Many first generation β-adrenoceptor antagonists (propranolol) block both β1- and β2-adrenoceptors and there are no β2-adrenoceptor-selective antagonists used therapeutically. The β3-adrenoceptor agonist mirabegron is used to control overactive bladder syndrome. There is evidence to suggest that β-adrenoceptor antagonists can reduce metastasis in certain types of cancer [189].

Сare pathways of children with acute rhinological symptoms

Acute respiratory diseases are one of the most common reasons for visiting a doctor in pediatric practice. Most episodes of this pathology have a viral etiology, signs of inflammation from the upper respiratory tract and proceed with symptoms of acute rhinitis (acute nasopharyngitis). The most of episodes of acute rhinitis last no more than 10 days and end with the patient’s recovery. The most common complications of acute rhinitis in children are acute rhinosinusitis and acute otitis media. These diseases are often mild and rarely have complications. However, a large number of patients with acute respiratory diseases increases the likelihood of a situation in which the doctor will encounter a problem patient. The article proposes care pathways for practitioners to manage patients with acute rhinological symptoms lasting up to 10 days and from 10 days to 3 months. The care pathways are based on several key points. No1: each patient must be analyzed for the presence of alarming symptoms, upon detection of which the patient should be urgently hospitalized. No2: all patients should be dynamically observed by a doctor until complete recovery, the patient should not receive treatment without the supervision of a doctor. No3: the basis of treatment is drugs for symptomatic therapy, which are selected depending on the dominant symptom that has the greatest impact on the patient’s well-being. To eliminate nasal mucosal edema, it is rational to use nasal decongestants (original oxymetazoline) for children of all ages; the course and dosages are determined according to the age of the child. Antibacterial drugs should be prescribed strictly according to indications in the presence of convincing data for the bacterial etiology of the disease.

Chronic rhinosinusitis in cystic fibrosis: a review of therapeutic options

Purpose Chronic rhinosinusitis (CRS) is observed in almost 100% of patients with cystic fibrosis (CF). CF-related CRS treatment is extremely challenging because of the underlying genetic defect leading to its development. CRS in CF is often refractory to standard therapy, while recurrences after surgical treatment are inevitable in the majority of patients. This study provides a precise review of the current knowledge regarding possible therapeutic options for CF-related CRS. Methods The Medline and Web of Science databases were searched without a time limit using the terms “cystic fibrosis” in conjunction with “otorhinolaryngological manifestation”, “rhinology” and “sinusitis”. Results Precise guidelines for CF-induced CRS therapy are lacking due to the lack of large cohort randomized controlled trials. None of the existing therapeutic agents has already been recommended for CRS in CF. Therapy targeting the underlying genetic defect, intranasal dornase alfa administration, and topical delivery of colistin and tobramycin showed promising results in CF-related CRS therapy. Besides the potential effectiveness of nasal steroids, strong recommendations for their usage in CF have not been provided yet. Systemic corticosteroid usage is controversial due to its potential negative influence on pulmonary disease. Ibuprofen revealed some positive effects on CF-related CRS in molecular and small cohort studies. Intranasal irrigation with saline solutions could relieve sinonasal symptoms. Nasal decongestants are not recommended. Endoscopic sinus surgery is the first-line surgical option for refractory CRS. Extensive surgical approaches should be considered as they could improve long-term outcomes in CRS. Conclusion Further studies are warranted to establish consensus for CF-related CRS therapy.

Observational study investigating Ectoin® Rhinitis Nasal Spray as natural treatment option of acute rhinosinusitis compared to treatment with Xylometazoline

Introduction Symptomatic relief of acute rhinosinusitis is commonly achieved with nasal decongestants. The current observational study investigated the efficacy and safety of treatment of acute rhinosinusitis with Ectoin® Rhinitis Spray compared to or in combination with Xylometazoline-containing decongesting nasal spray. Methods Patients with acute rhinosinusitis applied either Ectoin® Rhinitis Spray, Xylometazoline nasal spray or a combination of both products. Rhinosinusitis symptoms were assessed, and nasal oedema and endonasal redness were determined by rhinoscopy. Patient diaries based on the validated SNOT (Sino Nasal Outcome Test) questionnaire evaluated rhinosinusitis parameters over time and influences of the disease on quality of life. Following treatment, investigators and patients judged the efficacy and tolerability. Results Ectoin® Rhinitis Spray diminished common rhinosinusitis symptoms such as nasal obstruction, nasal secretion, facial pain/headache, and smell/taste impairment. Upon treatment over 7 days, rhinosinusitis sum scores decreased statistically significantly (p < 0.001) by − 64.25%, which was comparable to that achieved with Xylometazoline-containing decongesting nasal spray (− 67.60%). No side effects were observed during treatment with Ectoin® Rhinitis Spray, whereas treatment with Xylometazoline-containing nasal spray resulted in nasal mucosa dryness. Concomitant treatment with both products diminished the development of nasal dryness and required fewer applications of Xylometazoline-containing nasal spray. Conclusion Ectoin® Rhinitis Spray is an effective, natural treatment option for acute rhinosinusitis, which may be used as monotherapy or as add-on treatment with a Xylometazoline-containing nasal spray. The concomitant use of Ectoin® Rhinitis Spray might reduce the needed dose of decongestant nasal spray and counteract bothersome side effects such as dry nasal mucosa. Trial registration The current study was registered in the ClinicalTrials.gov database under the identifier: NCT03693976 (date of registration: Oct 3, 2018).

Nasal decongestants in the treatment of nasal obstruction

Nasal congestion is one of the most common symptoms of common colds and rhinitis, due to an inflammatory reaction, vasodilation, increased nasal blood flow and vascular permeability. Nasal obstruction is often a multifactorial problem, in addition to infectious causes, it can be caused by a combination of anatomical aberrations, swelling of the nasal mucosa and enlargement of the turbinates. Anatomical and structural problems, such as nasal septum deviation and nasal valve collapse, are usually treated surgically. Drug therapy of nasal obstruction is aimed at reducing edema and inflammation of the nasal mucosa. Pharmacotherapy of nasal obstruction is aimed at reducing inflammation and/or swelling of the mucous membrane. Decongestants are widely prescribed to relieve symptoms. The drugs used have different mechanisms of action and include systemic and topical drugs. This article discusses decongestants as a treatment for nasal obstruction. When applied topically, the drugs of this group act directly on the α2 and α1-adrenergic receptors of the nasal cavity, causing vasoconstriction, a decrease in the volume of the nasal conch, an increase in nasal patency, and relieving the symptoms of obstruction. The existing risk of developing side effects, both systemic and local, is reduced with atopic exposure and proper dosing of the drug used. Preferably, the use of drugs with low bioavailability. The suppression of the ciliated epithelium can be caused not only by the pathological process, but also by the composition of drugs. The value is given to the acidity of the buffer system. The optimal pH value of intranasal agents is about 6 (neutral range). The combination with anticholinesterase substances reduces the production of pathological discharge. The use of multi-component medicines allows you to restore nasal breathing and suppress excessive nasal secretion. One of the effective and safe drugs of topical action is Xylometazoline, as a monocomponent agent or in combination with ipratropium bromide.

Postoperative Complications of Conventional Polypectomy Versus Endoscopic Sinus Surgery

Objective: To compare the postoperative complications of conventional polypectomy versus Endoscopic sinus surgery. Study Design: This is cross sectional study. Setting: Study carried out at E.N.T department, Tertiary care hospital from April 2019 - March 2020. Materials & Methods: 52 out of which 32 were male and 20 were female. Benign nasal polyps within 14 yrs to 80 years from emergency and out- patient department both were included in our study. Only recurrent and neoplastic lesions were not inclusive of this study. Postoperatively the patient was prescribed with oral antibiotics, nasal decongestants and nasal douche with normal saline, followed by local steroids after 1.5 months. The post operative evaluation (both endoscopic and clinical) was done at 2 weeks, 6 weeks and 3 months post operatively and data was recorded. Statistical package for social sciences (SPSS) software version 20.0. Results: A total of 52 patients were recruited for the study with age ranging from 18 to 40 years. The mean age was 24.65± SD 4.12. There were 32 (61.53%) males and 20 (38.46%) female patients. Two weeks were observed postoperative complications. The intranasal complications after simple intranasal polypectomy i.e. bleeding (SIP 8(30.76%) Versus ESS 5(19.23%)), crusting (SIP 10(38.46%) Versus ESS 6(23.07%)), Synechiae formation (SIP 3(11.53%) Versus ESS 1(3.84%)), recurrence 0% were observed. At upto 6th weeks observed the intranasal complications after simple intranasal polypectomy i.e. bleeding (SIP 5(19.23%) Versus ESS 2(7.69%)), crusting (SIP 6(23.07%) Versus ESS 2(7.69%)), Synechiae formation (SIP 2(7.69%) Versus ESS 1(3.84%)), recurrence 0% were observed. Three months were observed the intranasal complications after simple intranasal polypectomy i.e. bleeding (SIP 1(3.84%) Versus ESS 0%), crusting (SIP 0% Versus ESS 0%), Synechiae formation (SIP 4(15.38%) Versus ESS 3(11.53%)), recurrence 3(11.53%) were observed only in simple intranasal polypectomy group. While the intraorbital and intracranial complications were not observed. Conclusion: We would like to conclude our study in favor of ESS to be superior to other intranasal polypectomy procedures in terms of post operative complications.

Complete atrioventricular block due to ingestion of Visine eye drops

Visine eye drops are a commonly used topical drug for irritation of the eye. The active component in Visine eye drops is tetrahydrozoline. Tetrahydrozoline is an imidazoline derivative found in several ophthalmic and nasal decongestants. Exposure is common in young children, who unintentionally ingest it, but cases have been rising in the adult population. The main systemic effects are bradycardia and hypotension due to activation of the central alpha-adrenergic receptors. In this case report, a 76-year-old man presents with bradycardia after 24 hours following ingestion of 120 mL of 0.05% tetrahydrozoline (eight bottles of Visine eye drops) in a suicide attempt. His initial ECG demonstrated complete heart block and QT prolongation. Subsequent ECGs showed unremitting first-degree atrioventricular block and QT prolongation. Here, we are presenting the first case of complete heart block following tetrahydrozoline consumption.

The basic principle of pathogenetic therapy of purulent-inflammatory pathology of ENT organs

The nature of the clinical manifestations of purulent-inflammatory diseases of the ENT organs is determined, first of all, by the localization of the process, and in addition, by the severity of the reactions of general and local inflammation. In this regard, the authors of the article propose to consider the main factors of pathogenesis that determine the sequence and relationship of the stages of the inflammatory response: edema, redness, fever, pain and dysfunction. A special role in the implementation of the regulatory mechanisms of inflammation belongs to active molecules, the so-called inflammatory mediators. The authors of the article consider the main cellular and plasma mediators, concluding that most of the effects they carry out are accompanied by a violation of the integrity of the vascular wall, exudation, edema and tissue swelling. A similar reaction is, in general, nonspecific and is observed in a number of inflammatory diseases of the ENT organs, such as acute rhinitis, allergic rhinitis, acute sinusitis, eustachitis, acute otitis media. This circumstance allows the authors to conclude that a local therapeutic effect is necessary on this particular link of pathogenesis. To this end, the authors of the article propose the use of nasal decongestants, drugs with an alpha-adrenomimetic effect, which effectively relieve swelling of the nasal mucosa and facilitate nasal breathing. In clinical practice, preparations based on xylometazoline have proven themselves well.