• YAKHAK HOEJI
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• v.37 no.2
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• pp.119-123
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• 1993

A spectrophotomertic method is proposed for the determination of antihistamines. The method is based on solvent extraction of the ion pair formed between antihistamines and colored picric acid into chloroform. The binding state of antihistamines-picric acid complexes were presumed by IR and $^{1}$H-NMR spectra as intermolecular hydrogen bonding. This method was applicable to the determination of antihistamines in the pharamaceutical preparations.

• Clinical and Experimental Pediatrics
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• v.62 no.2
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• pp.75-78
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• 2019

Although rare, antihistamines can cause adverse effects, including drug-induced eruptions or anaphylaxis. A 4-year-old child visited the pediatric department of a hospital for skin eruptions after administration of antihistamines, (e.g., ucerax [hydroxyzine] or leptizine [levocetirizine]), for cholinergic rashes; he did not have pruritus. Skin prick, intradermal, and drug provocation tests were performed to determine the relationship between the antihistamines and eruptions. Levocetirizine induced wheals in the skin prick test and a rash in the oral drug provocation test. In contrast, ketotifen induced no reaction in the skin prick test but showed a positive reaction in the oral provocation test. Our case report highlights that children can experience the same types of adverse reactions as seen in adults, and cross-reactivity between various antihistamines can occur.

• YAKHAK HOEJI
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• v.50 no.2
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• pp.129-135
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• 2006

Two Antihistamines, terfenadine and astemizole have been withdrawn from major markets for the reason that these durgs have been reported to induce QT interval prolongation associated with the onset of Torsades do Pointes (TdP), resulting in a life-threatening ventricular arrhythmia. In this study, we investigated effects of diphenhydramine on electrocardiograms and hemodynamic parameters in conscious telemetered dogs. We validated and defined the sensitivity of the test system by monitoring basal parameters and using positive control substance, terfenadine. Single administration effects were tested during 24 hours for each test drug at dose 1 mg/kg, 10 mg/kg, 30 mg/kg, 100 mg/kg. We monitored QT, QTc, heart rate, blood pressure and body temperature after administering test drugs. In conscious telemetered dogs, diphenhydramine significantly prolonged $QT\;(6.8\%\;of\;basal)\;and\;QTc\;(7.8\%\;of\;basal)$ at 100 mg/kg. Other parameters were not affected significantly. These findings suggest that antihistamines could induce important clinical relevance for patients taking excessive dosages of conventional antihistamines and those at risk of developing cardiac arrhythmias. Future studies that include other antihistamines and other classes will be necessary to predict the torsadogenic risk of drugs in humans.

• YAKHAK HOEJI
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• v.43 no.5
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• pp.642-651
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• 1999

Nonsedating antihistamines do net cause sedation in therapeutic doses because these drugs hardly cross the blood-brain barrier. Since most of the peripheral side dffects of conventional antihistamines are related to their muscarinic receptor blocking action, the present study was performed to investigate whether nonsedating antihistamines interact with the muscarinic receptors and discriminate the muscarinic receptor subtypes in the rat cerebral microsomal fraction which containes both $M_1,{\;}M_2,{\;}M_3{\;}and{\;}M_4$ receptors. Five nonsedating antihistamines at high concentrations inhibited [$^3H$]QNB binding to the muscarinic receptor in a dose-dependent manner. The inhibition curves of these drugs except loratadine which showed positive cooperativity (nH=1.55) were steep (nH=1), indicating interaction with a single homogenous population of the binding sites. Astemizole, clemizole and mequitazine increased the $K_D$ value for [$^3H$]QNB without affecting the binding site concentrations, and this increase in the $K_D$ value resulted from the ability of these drugs to slow [$^3H$]QNB-receptor association. The Ki values of astemizole, clemizole and mequitazine for the inhibition for the inhibition of [$^3H$]QNB binding to muscarinic receptor were 0.58, 5.99 and $0.007{\;}{\mu}M$, respectively. However, loratadine and terfenadine inhibited noncompetitively [$^3H$]QNB binding with the normalized $IC_50$ value of about $2{\;}{\mu}M$. These results demonstrate that; 1) astemizole, clemizole and mequitazine interact directly with the muscarinic receptor at high concentrations; 2) muscarinic receptor blocking potency of these drugs varies widely among drugs; 3) these drugs do not discriminate between muscarinic receptor subtypes.

• YAKHAK HOEJI
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• v.18 no.2
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• pp.133-144
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• 1974

The metal indicator, acidic azo dyes NN, EBT and Calcon are utilized to analyse quantitatively chlorpheniramine, tripelenamine and diphenhydramine forming insoluble ion pair in aqueous solution at proper pH values between the acidic azo dyes and the sample molecules, these compexes are extracted by organic polar solvents, and organic layer is determined spectrophotometrically. Generally, the absorption maxima of the complexes are shifted to longer wavelengths compare to the absorption maxima of the dyes themselves. The binding ratio of the ion pair forming complex molecules in chloroform soln, are as follows ; NN-antihistamines (chlorpheniramine, tripelennamine, diphenhydramine) are NN-1 to antihisamine-1, EBT-antihistamines are EBT-2 to antithistamines a and Calcon-antihistamines are Calcon-3 to antithistamines-1. These coomplexes in chloroform soln. are very stable, and show higher absorbance than the other organic polar solvents. The binding state of complexes were presumed intermolecular hydrogen bond by their infrared spectra. In the mixture solution of three samples, the aqueous phase is buffered at pH 1.0, and benzene is used to extract ion pair of diphenhydramine EBT complex selectively. At pH 1.0 of aqueous layer, Calon-diphenhydramine complex is also extracted selectively by benzene. However, in this case very small amount of chlorpheniramine-calcon calcon simultaneously. The binding state of diphenhydramine-EBT and diphenhydramine-calcon in benzene are smae as the complexes in chloroform. But the absorption maxima of the complexes in benzene are shifted to shorter wavelenlgths than the complexes in chloroform.

• Clinical and Experimental Pediatrics
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• v.49 no.6
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• pp.593-601
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• 2006

Allergic rhinitis is a common disease of childhood characterized by nasal, throat, and ocular itching, rhinorrhea, sneezing, nasal congestion. Those affected with allergic rhinitis often suffer from associated inflammatory conditions of the mucosa, such as allergic conjunctivitis, rhinosinusitis, asthma, otitis media with effusion, and other atopic conditions, such as eczema and food allergies. Allergic rhinitis must be diagnosed and treated properly to prevent complications and impaired quality of life. Despite a high prevalence, allergic rhinitis isoften undiagnosed and inadequately treated, especially in the pediatric population. The first step in treatment is environmental control when appropriate. It may be difficult to eliminate all offending allergens effectively to reduce symptoms, so medications are often required. Many different classes of medications are now available, and they have been shown to be effective and safe in a large number of well-designed, clinical trials. Antihistamines are effective in treating immediate symptoms of sneezing, pruritus, watery eyes, and rhinorrhea. Second generation antihistamines are the preferred antihistamines because of their superior side effect profile. Thus, decongestants are commonly used with oral antihistamines. Intranasal corticosteroids are the most effective therapy for allergic rhinitis. Leukotriene modifier may be as effective as antihistamines in treating allergic rhinitis symptoms. Cromolyn sodium is an option for mild disease when used prophylactically, and ipratropium bromide is effective when rhinorrhea is the predominant symptom. When avoidance measures and medications are not effective, specific immunotherapy is an effective alternative. Only immunotherapy results in sustained changes in the immune system. Because of improved understanding of the pathogenesis, new and better therapies may be forthcoming. The effective treatment of allergic rhinitis in children will reduce symptoms and will improve overall health and quality of life, making a happier, healthier child.

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.261-269
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• 2006

• YAKHAK HOEJI
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• v.37 no.4
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• pp.397-407
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• 1993

The muscarinic antagonist l-[benzilic-4,4'-$^3H$]quinuclidinyl benzilate([$^3H$]QNB) bound to a single class of muscarinic receptor with high affinity in guinea pig ileal membranes. The $K_{D}$ and B$_{max}$ values for [$^3H$]QNB calculated from analysis of saturation isotherms were 54 pM and 156fmol/mg, respectively. H$_{1}$-blockers inhibited [$^3H$]QNB binding to ileal membranes with $K_{i}$ values ranged from 0.008 $\mu{M}$ to 1.6 $\mu{M}$. The pseudo-Hill coefficients of H$_{1}$-blockers for inhibition of [$^3H$]QNB binding to the ileal membranes were close to unit. The $K_{i}$ values for H$_{1}$-blockers were similar to the $K_{M}$ values calculated by Schild plot of functional data obtained from inhibition of the carbachol-induced contraction in guinea-pig ileum, suggesting that binding of H$_{1}$-blockers vs [$^3H$]QNB in ileal membranes represents an interaction with a receptor of physiological relevance. The $K_{H}$ values of H$_{1}$-blockers for H$_{1}$-receptor estimated from inhibition of the histamine-induced contraction were the range of 0.15 nM to 56.5 nM. The $K_{M}$/K$_{H}$ ratio of H$_{1}$-blockers varied over a wide range of 3 to 2300. Thus, the antihistaminic potencies of H$_{1}$-blockers do not correlate with their antimuscarinic potencies, which suggest that antihistamines have different antimuscarinic potencies in therapeutic blood levels causing similar antiallergic effect. Among 13 traditional antihistaminics examined in this study, drug having the highest and the lowest $K_{M}$/K$_{H}$ ratio is triprolidine and diphenidol, respectively. The present results demonstrate that the antimuscarinic property of antihistamines is not necessary for their antiallergic effect, and data on the affinity of antihistamines for muscarinic and H$_{1}$-receptors can be an important parameter in the selection and evaluation of these drugs.

• Analytical Science and Technology
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• v.28 no.2
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• pp.86-97
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• 2015

Recently, the consumption of dietary supplements has increased because of people’s greater interest in health. Unfortunately, the sales of dietary supplements containing unauthorized substances such as drugs have also increased. We developed a rapid, accurate method for the simultaneous determination of antihistamines using liquid chromatography tandem mass spectrometry with a multiple reaction monitoring mode. The limit of detection (LOD) and limit of quantification (LOQ) of the instrument used in this method were in the ranges 0.0003-0.3 and 0.0009-0.6 µg mL⁻¹, respectively. The linearity of the method was > 0.99. The precision levels of the method were 0.1-9.8% (intra-day) and 0.3-9.6% (inter-day), and the levels of accuracy of the method were 82.7-115.0% (intra-day) and 84.3-113.0% (inter-day). The mean of recovery of the method was in the range of 83.9-117.9% and the RSD of the stability was less than 5.9%.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.113-125
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• 1994

Many types of drugs affect functions of tile gastrointestinal tract. Investigators may be interested in discovery or pharmacological characterization of drugs as therapeutic agents intended for treatment of gastrointestinal disorders or in identification of gastrointestinal side effects of drugs intended for non-gastrointestinal indications. Examples of drug categories often associated with significant gastrointestinal side effects include cardiovascular drugs, antibiotics (erythromycin in particular), anti-inflammatory drugs, antiemetics, analgesics (especially opiates), antihistamines, antidepressants, and antipsychotics. Whether tile objective is development of gastrointestinal therapeutic agents or evaluation of gastrointestinal side effects, appropriate laboratory models for experimentation are essential.