piperidines and Rhinitis

The present article summarizes anesthetic techniques used during functional endoscopic sinus surgery to decrease bleeding and aid in creating a clear surgical field. The applicable physiology behind these anesthetic techniques is reviewed with emphasis on the effect on bleeding and the surgical field. Deliberate hypotension, reverse Trendelenburg positioning, regional anesthesia, and cerebral monitoring are discussed.. There are mixed data as to whether traditional inhalation anesthesia or total intravenous anesthesia is superior with respect to better surgical fields and decreased blood loss. A review of the literature tends to favor total intravenous anesthesia. Cerebral oximetry and transcranial Doppler ultrasound are emerging techniques to monitor cerebral perfusion during deliberate hypotension.. Total intravenous anesthesia using propofol and remifentanil is the current favored technique for producing deliberate hypotension during endoscopic sinus surgery due to its hemodynamic stability and smooth rapid emergence.

Topics: Airway Management; Anesthesia; Anesthesia Recovery Period; Anesthetics, Inhalation; Anesthetics, Intravenous; Endoscopy; Female; Follow-Up Studies; Humans; Male; Paranasal Sinus Diseases; Patient Positioning; Piperidines; Propofol; Remifentanil; Rhinitis; Sinusitis; Treatment Outcome

We compared anesthesia with sevoflurane-remifentanil hydrochloride (SR) to total intravenous anesthesia with propofol-remifentanil hydrochloride (PR) in patients undergoing endoscopic sinus surgery for chronic rhinosinusitis in terms of sinonasal mucosal blood flow, the surgical field visualization score, and blood loss.. We performed a double-blinded prospective study at a tertiary care center in 23 adults scheduled to undergo endoscopic sinus surgery for chronic rhinosinusitis. The patients were randomized to receive SR or PR. The sinonasal mucosal blood flow was measured by optical rhinometry. The surgical field visualization score was based on the Boezaart scale.. The groups had similar clinical characteristics. During the 60- to 90-minute and 90- to 120-minute operative time windows, the blood flow was significantly greater in the PR group than in the SR group (p = 0.04 and p = 0.03, respectively). The amounts of blood loss in the PR and SR groups were 152.9 +/- 161.3 mL and 355.9 +/- 393.4 mL, respectively (p = 0.12). The median ratios of the surgical field visualization score to the number of sinuses operated on in the PR and SR groups were 2.1 and 1.8, respectively (p = 0.52).. The intraoperative blood flow, as determined by optical rhinometry, was significantly greater with anesthesia with PR than with anesthesia with SR, 1 hour into the procedure; however, this difference did not translate into differences in the amounts of operative blood loss or in the surgical field visualization scores.

Topics: Adult; Aged; Anesthesia, Inhalation; Anesthesia, Intravenous; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Loss, Surgical; Double-Blind Method; Endoscopy; Female; Humans; Male; Methyl Ethers; Middle Aged; Paranasal Sinuses; Pilot Projects; Piperidines; Propofol; Prospective Studies; Remifentanil; Rhinitis; Sevoflurane; Sinusitis

The single-dose effects of the cytochrome P-450 inhibitors erythromycin and ketoconazole on the steady-state pharmacokinetics and electrocardiographic repolarization pharmacodynamics of intranasal levocabastine, a potent and selective H1-receptor antagonist, were evaluated in healthy young male subjects. Two randomized, open-label, placebo-controlled, two-way crossover studies were performed. Levocabastine nasal spray was administered as two sprays per nostril (0.05 mg/spray) twice daily (for a total daily dose of 0.4 mg) for 6 days. On Day 7, a single dose of 0.2 mg was administered followed immediately by a single dose of either oral placebo, erythromycin 333 mg, or ketoconazole 200 mg. In all treatment groups, levocabastine was rapidly absorbed, with peak plasma concentrations reached at approximately 3 hours in the erythromycin study and 2.8 hours in the ketoconazole study. The mean terminal half-life was approximately 45 and 44 hours, respectively. In both studies, mean steady-state plasma concentrations and pharmacokinetics of levocabastine following the single doses of erythromycin or ketoconazole were not significantly different from corresponding values seen with the concomitant administration of the placebo. No clinically significant mean changes from baseline in QT or QTc (QT corrected for heart rate) intervals occurred in any of the treatment groups, and none of the subjects in either study experienced abnormally prolonged QTc intervals. Intranasal levocabastine was well tolerated, with no difference in the incidence of adverse events between treatment groups in either study; adverse events were generally mild in severity. Since levocabastine undergoes only minimal hepatic metabolism and is not a substrate for or an inhibitor of cytochrome P-450, the likelihood of systemic drug interactions with drugs affecting the cytochrome P-450 system is minimal.

Topics: Administration, Intranasal; Adolescent; Adult; Anti-Bacterial Agents; Anti-Infective Agents; Area Under Curve; Biological Availability; Bradycardia; Cross-Over Studies; Drug Interactions; Electrocardiography; Erythromycin; Headache; Heart Block; Histamine H1 Antagonists; Humans; Ketoconazole; Male; Middle Aged; Piperidines; Rhinitis; Time Factors; Virus Diseases

In allergic rhinitis, a nasal H1-antihistamine spray seems to be well suited for usage on an as-needed basis, because it has a quick onset of action, and many patients prefer to take medicine only when they have symptoms. It is a prerequisite, however, that nasal hypersecretion during a rhinitis episode does not significantly reduce the efficacy of intranasal treatment by washing away the drug before it reaches the H1-histamine receptors. In order to investigate this problem, we have induced nasal hypersecretion with a methacholine challenge in one experiment and in four experiments we have washed the nasal cavities 0.5 min. before, 5 min. before, 0.5 min. after and 5 min. after intranasal use of the H1-antagonist, levocabastine. The symptom response to a subsequent histamine challenge was used as the effect parameter. Levocabastine reduced the number of histamine-induced sneezes with 81% (p < 0.0001) and the secretion weight with 62% (p < 0.001) compared with placebo. Neither methacholine-induced hypersecretion nor washing the nose with saline reduced the efficacy of the antihistamine spray. We conclude that experimentally induced nasal hypersecretion does not reduce the efficacy of the antihistamine spray, and probably the same applies to rhinorrhea during an acute episode of allergic rhinitis.

Topics: Administration, Intranasal; Adult; Analysis of Variance; Double-Blind Method; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Methacholine Chloride; Nasal Lavage Fluid; Nasal Mucosa; Nasal Provocation Tests; Piperidines; Rhinitis; Sneezing; Statistics, Nonparametric

The effect of levocabastine, a new specific H1 antagonist, has been investigated against a placebo in nasal provocation tests on 42 allergic patients divided into two parallel groups. The results obtained show that it significantly inhibited the nasal reaction to the allergen and seems to have a long-lasting effect in allergic patients.

Topics: Administration, Intranasal; Adolescent; Adult; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Provocation Tests; Piperidines; Rhinitis

Topics: Administration, Oral; Adolescent; Adult; Aged; Aminopyrine; Anti-Inflammatory Agents, Non-Steroidal; Antipyrine; Ascorbic Acid; Capsules; Child; Child, Preschool; Delayed-Action Preparations; Double-Blind Method; Drug Combinations; Drug Evaluation; Female; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Decongestants; Nylidrin; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Rutin

Topics: Adolescent; Adult; Aged; Chlorpheniramine; Clinical Trials as Topic; Drug Combinations; Ephedrine; Female; Humans; Male; Methods; Middle Aged; Nasal Decongestants; Phenylpropanolamine; Piperidines; Pulmonary Ventilation; Quaternary Ammonium Compounds; Rhinitis; Rhinitis, Allergic, Seasonal

Topics: Aged; Aminopyrine; Ascorbic Acid; Clinical Trials as Topic; Drug Synergism; Humans; Male; Middle Aged; Piperidines; Rhinitis; Rutin; Vasodilator Agents

Topics: Aged; Aminopyrine; Ascorbic Acid; Bufanolides; Clinical Trials as Topic; Delayed-Action Preparations; Hearing; Humans; Middle Aged; Piperidines; Rhinitis; Rutin; Taste

Th2 and Th17 immune response contribute to allergic rhinitis (AR) development. Targeting Th2 and Th17 response has been shown to ameliorate AR. Ibrutinib is an inhibitor for IL2-inducible T-cell kinase, which can promote Th2 and Th17 immune response. We sought to investigate the effect of ibrutinib on AR and the underlying mechanisms. We established house dust mite-induced AR mouse model and treated AR mice with ibrutinib. The symptoms of AR, serum level of immunoglobulin E, percentage of Th1, Th2, Th17, and Treg in nasal lymphoid tissues were monitored. We also established in vitro T cell differentiation cell culture model. The T cells were treated with ibrutinib and the expression of specific transcriptional factors and cytokines was measured. The activation of PLC-γ1/calcium/NFAT2 signaling pathway was detected. Ibrutinib treatment had no effects on the development of lymphocytes and myeloid cells, but alleviated AR symptoms and decreased Th2 cell population in nasal lymphoid tissue. Meanwhile, iburitnib suppressed Th2 and Th17 differentiation in vitro. Moreover, iburitnib prevented phosphorylation of PLC-γ1and nuclear translocation of NFAT2 in Th2 cells. Our results suggested that ibrutinib could ameliorate AR symptoms through suppression of Th2 differentiation in AR mouse model.

Topics: Adenine; Animals; Cell Differentiation; Cytokines; Disease Models, Animal; Mice; Mice, Inbred BALB C; Nasal Mucosa; Piperidines; Protein-Tyrosine Kinases; Rhinitis; Rhinitis, Allergic; Th2 Cells

The Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway play a key role in immune modulation, especially in the polarization of T helper cells. JAK inhibitors reduce inflammation by inhibiting the phosphorylation of STAT. We investigated whether a JAK inhibitor, tofacitinib, can reduce inflammation in a mouse model of chronic rhinosinusitis with nasal polyps (CRSwNP).. An eosinophilic CRSwNP model was induced using 4-week-old BALB/c mice. The therapeutic effects of topical tofacitinib were compared with the effects of triamcinolone acetonide (TAC). Polyp formation and eosinophilic infiltration were assessed by histology. Levels of phosphorylated STAT (pSTAT), eosinophil cationic protein, and eotaxin were measured by immunohistochemistry. Gene expression levels of GATA-3 was measured using quantitative PCR. The production of cytokines in sinonasal tissues, including interleukin IL-4, IL-5, IL-12, and interferon-γ, were measured using enzyme-linked immunosorbent assays (ELISA).. Topical tofacitinib administration significantly reduced the number of polyp-like lesions and the degree of eosinophilic infiltration, with an efficacy comparable with that of systemic TAC administration. Similarly, the levels of pSTAT6, eosinophil cationic protein, and eotaxin decreased with tofacitinib treatment. Tofacitinib decreased the gene expression level of GATA-3. Lastly, tofacitinib significantly decreased IL-4 and IL-5 production to a similar extent as that by systemic or topical TAC administration. Tofacitinib, but not TAC, significantly increased the production of interferon-γ.. Topical tofacitinib administration may be an effective treatment for eosinophilic CRSwNP by inhibiting phosphorylation of STATs.. N/A. Laryngoscope, 131:E1400-E1407, 2021.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Animals; Chronic Disease; Cytokines; Disease Models, Animal; Eosinophilia; Eosinophils; Humans; Janus Kinases; Male; Mice; Nasal Mucosa; Nasal Polyps; Piperidines; Pyrimidines; Rhinitis; Signal Transduction; Sinusitis; STAT Transcription Factors; Triamcinolone Acetonide

CC chemokines have been shown to play an important role in inducing selective recruitment of inflammatory cells into local allergic inflammatory sites. CC chemokines are also known as histamine releasing factors. We previously showed that histamine enhances transcription of CC chemokines from nasal mucosa which leads to further induction of histamine release. This cyclic cascade may cause prolonged allergic inflammation. The aim of this study is to clarify the relationship between histamine and CC chemokine production by using human nasal epithelial cells (HNECs) and to examine the potential of H1 receptor (H1R) antagonists in new therapeutic approaches for the treatment of nasal allergy.. HNECs were isolated from the nasal turbinates of patients diagnosed with nasal allergy. HNEC monolayers were cultured for 48 hours with or without histamine (10(-3) to 10(-5) mol/L). Furthermore, an H1R antagonist, either carebastine or olopatadine, was added to the supernatant (10(-3) to 10(-7) mol/L) 30 minutes before incubation with histamine. The expression of Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES) and monocyte chemotactic protein-1 (MCP-1) in the culture media were measured by ELISA.. The release of RANTES and MCP-1 was significantly upregulated by histamine compared with the control group. Both carebastine and olopatadine inhibited the release of CC chemokine production to the control level in both groups.. This study suggests that the interaction between histamine and CC chemokines may prolong allergic inflammation in human nasal mucosa. We also demonstrate the potential use of H1R antagonists in new therapeutic approaches to the treatment of nasal allergy through inhibiting this histamine-CC chemokine interaction.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Butyrophenones; Cells, Cultured; Chemokine CCL2; Chemokine CCL5; Chemokines, CC; Child; Dibenzoxepins; Dose-Response Relationship, Drug; Epithelial Cells; Female; Histamine; Histamine H1 Antagonists; Humans; Male; Middle Aged; Nasal Mucosa; Olopatadine Hydrochloride; Piperidines; Rhinitis; Rhinitis, Allergic, Perennial; Rhinitis, Allergic, Seasonal

H1-antihistamines are commonly used drugs, and probably the most frequently used for allergic diseases. They are pharmacologic inverse agonists of histamine at H1 receptor sites and try to shift the equilibrium of this receptor toward the inactive state, preventing H1 response. A wide variety of adverse effects have been attributed to antihistamines, and they can exceptionally induce skin reactions. We report the case of a patient with several episodes of urticaria induced by different families of antihistamines - piperazines and piperidines. We performed skin prick tests (SPT), patch tests and oral challenges to different antihistamines. We found positive SPT to some antihistamines, and positive oral challenge in others with negative SPT. The route of sensitization remained unclear, and our patient could not finally tolerate any antihistamine after the oral challenges we performed. We support the hypothesis that antihistamines may shift the H1 histamine receptor to the active conformation instead of the inactive conformation, prompting adverse reactions after dosing. This is the first report of urticaria induced by different antihistamines in the same patient with positive SPT to several others.

Topics: Adult; Conjunctivitis; Drug Hypersensitivity; Female; Histamine H1 Antagonists; Humans; Piperazines; Piperidines; Rhinitis; Urticaria

Topics: Arrhythmias, Cardiac; Butyrophenones; Histamine H1 Antagonists; Humans; Piperidines; Rhinitis; Treatment Outcome; Urticaria

Topical application of levocabastine hydrochloride (-)-[3S-[1(cis)-3 alpha,4 beta]]-1-[4-cyano-4-(4-fluorophenyl) cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylic acid monohydrochloride, inhibited the increase in dye leakage into the nasal cavity induced not only by antigen in actively sensitized rats but also by histamine in non-sensitized rats. The potency of levocabastine was stronger than that of ketotifen in inhibiting the increase of dye leakage in both cases. In addition, levocabastine as well as ketotifen exerted a more potent inhibition of the dye leakage induced by histamine than that induced by antigen. Levocabastine also exerted a significant inhibition on the dye leakage induced by substance P; again the effect of levocabastine was more potent than that of ketotifen. On the other hand, levocabastine elicited no remarkable influence on the dye leakage induced by either acetylcholine or platelet activating factor. However, ipratropium and (RS)-2-methoxy-3-(octadecylcarbamoyloxy)propyl 2-(3-thiazolio)ethyl phosphate were effective when the corresponding agonists were perfused, respectively.

Topics: Acetylcholine; Animals; Antigens, Helminth; Ascaris; Histamine; Histamine H1 Antagonists; Ketotifen; Male; Nasal Mucosa; Piperidines; Platelet Activating Factor; Rats; Rats, Wistar; Rhinitis; Substance P

Topics: Central Nervous System Stimulants; Humans; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Tripelennamine

Topics: Anti-Allergic Agents; Hyperthermia, Induced; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Tripelennamine; Urticaria

Topics: Humans; Piperidines; Rhinitis; Rhinitis, Allergic, Seasonal; Rhinitis, Vasomotor