Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (V(D)) of [³H]paeonol in rat brain was about 6-fold higher than that of [¹⁴C]sucrose, the vascular space marker of BBB. The uptake of [³H]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [³H]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.
Animals ; Blood-Brain Barrier ; Brain ; Carotid Arteries ; Carotid Artery, Internal ; Central Nervous System ; Diphenhydramine ; Endothelial Cells ; Hydrogen-Ion Concentration ; In Vitro Techniques ; Membrane Potentials ; Perfusion ; Pyrilamine ; Rats ; RNA, Small Interfering ; Sodium ; Tramadol ; Transfection

The treatment of chronic spontaneous urticaria begins with antihistamines; however, the dose required typically exceeds that recommended for allergic rhinitis. Second-generation, relatively non-sedating H1-receptor blockers are typically employed up to 4 times a day. First-generation antihistamines, such as hydroxyzine or diphenhydramine (Atarax or Benadryl), were employed similarly in the past. Should high-dose antihistamines fail to control symptoms (at least 50%), omalizumab at 300 mg/month is the next step. This is effective in 70% of antihistamine-refractory patients. H₂-receptor blockers and leukotriene antagonists are no longer recommended; they add little and the literature does not support significant efficacy. For those patients who are unresponsive to both antihistamines and omalizumab, cyclosporine is recommended next. This is similarly effective in 65%–70% of patients; however, care is needed regarding possible side-effects on blood pressure and renal function. Corticosteroids should not be employed chronically due to cumulative toxicity that is dose and time dependent. Brief courses of steroid e.g., 3–10 days can be employed for severe exacerbations, but should be an infrequent occurrence. Finally, other agents, such as dapsone or sulfasalazine, can be tried for those patients unresponsive to antihistamines, omalizumab, and cyclosporine.
Adrenal Cortex Hormones ; Blood Pressure ; Cyclosporine ; Dapsone ; Diphenhydramine ; Histamine Antagonists ; Humans ; Hydroxyzine ; Leukotriene Antagonists ; Omalizumab ; Rhinitis, Allergic ; Sulfasalazine ; Urticaria*

BACKGROUND: Acute transfusion reaction occurs during or within a few hours of transfusion with 0.5~3% of blood transfusion. Febrile non-hemolytic transfusion reactions (FNHTRs) and allergic transfusion reactions (ATRs) are the most common transfusion reactions. Premedication with acetaminophen and diphenhydramine has been used to prevent these reactions in 50~80% of transfusions. The purpose of this study was to describe the frequency of premedication and FNHTRs and ATRs according to premedication in Korea. METHODS: Between January 1 and 31, 2013, analysis of the first transfusion was performed retrospectively with chart review. A total of 549 cases were analyzed with regard to product of blood, care area, premedication, and FNHTRs and ATRs. RESULTS: Premedication was administered in 88.2% (484/549) of transfusions; 4 mg chlorphenamine, a well-known antihistamine, was used as premedication in all cases. Occurrence of FNHTRs was 7.7% without premedication and 3.7% with premedication. Occurrence of ATRs was 0% without premedication and 0.8% with premedication. The frequency of premedication was related to care area but not blood products. CONCLUSION: Premedication use was more frequent than previously reported. However, the sample size in this study is small; therefore, conduct of further prospective multicenter studies is needed.
Acetaminophen ; Blood Group Incompatibility ; Blood Transfusion ; Chlorpheniramine ; Diphenhydramine ; Premedication ; Retrospective Studies ; Sample Size

This paper reports the establishment of a method for rapid identification 15 effective components of anti common cold medicine (paracetamol, aminophenazone, pseudoephedrine hydrochloride, methylephedrine hydrochloride, caffeine, amantadine hydrochloride, phenazone, guaifenesin, chlorphenamine maleate, dextromethorphen hydrobromide, diphenhydramine hydrochloride, promethazine hydrochloride, propyphenazone, benorilate and diclofenac sodium) with MRM by LC-MS/MS. The samples were extracted by methanol and were separated from a Altantis T3 column within 15 min with a gradient of acetonitrile-ammonium acetate (containing 0.25% glacial acetic acid), a tandem quadrupole mass spectrometer equipped with electrospray ionization source (ESI) was used in positive ion mode, and multiple reaction monitoring (MRM) was performed for qualitative analysis of these compounds. The minimum detectable quantity were 0.33-2.5 microg x kg(-1) of the 15 compounds. The method is simple, accurate and with good reproducibility for rapid identification many components in the same chromatographic condition, and provides a reference for qualitative analysis illegally added chemicals in anti common cold medicine.
Acetaminophen ; analysis ; Acetanilides ; analysis ; Amantadine ; analysis ; Aminopyrine ; analysis ; Anti-Inflammatory Agents, Non-Steroidal ; analysis ; Antipyretics ; analysis ; Antipyrine ; analogs & derivatives ; analysis ; Caffeine ; analysis ; Chlorpheniramine ; analysis ; Chromatography, Liquid ; Diclofenac ; analysis ; Diphenhydramine ; analysis ; Drug Contamination ; Drug Stability ; Ephedrine ; analogs & derivatives ; analysis ; Guaifenesin ; analysis ; Promethazine ; analysis ; Pseudoephedrine ; analysis ; Reproducibility of Results ; Salicylates ; analysis ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

Hydroxyethyl starch (HES) solutions are synthetic non-protein colloid solutions used to treat hypovolemia. However, their use is not free from the risk of allergic reactions. A 42-year-old male was scheduled to undergo aortic-iliac-femoral bypass surgery for the treatment of arteriosclerosis obliterans. He had no history of allergy. Two hours after the start of surgery, and within minutes after HES administration, facial erythema, hypotension and bronchospasm developed. HES infusion was discontinued under the estimation of anaphylaxis. The patient received phenylephrine, ephedrine, diphenhydramine and hydrocortisone with hydration. After restoration of vital signs, surgery was performed without complications.
Adult ; Anaphylaxis ; Arteriosclerosis Obliterans ; Bronchial Spasm ; Colloids ; Diphenhydramine ; Ephedrine ; Erythema ; Hetastarch ; Humans ; Hydrocortisone ; Hypersensitivity ; Hypotension ; Hypovolemia ; Male ; Phenylephrine ; Vital Signs

Fibroblasts are responsible for the synthesis and degradation of various connective tissue components and soluble mediators of extracellular matrix metabolism. Few studies have been conducted concerning the expression of toll-like receptors (TLRs) in fibroblasts until now. This study aimed first to determine the quantitative expression of TLRs 1 to 10 in human skin fibroblasts and secondarily to explore any influence of expression by histamine, which is a well-known factor engaged in dermal inflammation. It was found that all 10 TLRs were expressed in fibroblasts. Interestingly, the expression of TLRs 4, 5, and 10 was increased after 2 and 6 hours of histamine treatment during culture. However, the expression of TLRs 2, 3, 6, 7, 8, and 9 was decreased after 6 hours of histamine treatment. Among the TLRs with a decreasing expression pattern, TLRs 7 and 8 showed a persistent tendency to decrease. All of these changes in TLR expression with histamine treatment were antagonized by treatment with diphenhydramine, a well-known antihistamine. Thus, these results suggest a role of histamine in the early phase of the dermal inflammatory reaction mediated by TLRs.
Connective Tissue ; Diphenhydramine ; Extracellular Matrix ; Fibroblasts ; Histamine ; Humans ; Inflammation ; Skin ; Toll-Like Receptors

PURPOSE: This study was designed to analyze the contributing factors, as well as the incidence and nature of the cardiac toxicity, in patients presenting with diphenhydramine overdose. METHODS: We retrospectively reviewed the medical records of the intoxicated patients who presented to the ED of Korea University Anam Hospital from January 2008 to December 2010. Those patients who visited due to a diphenhydramine overdose were selected and the following features were recorded for analysis: the general characteristics, vital signs, the amount of ingested diphenhydramine, the time interval from ingestion to presentation, the coingested drugs (if any), the toxicities and the ECG findings. Cardiac toxicity, while defined mainly in terms of the temporary ECG changes such as QTc prolongation, right axis deviation, QRS widening, high degree AV block and ischemic changes, also encompassed cardiogenic shock, which is a clinical finding. RESULTS: A total of eighteen patients were enrolled. Of the eighteen patients, eight had ingested diphenhydramine only, while ten had ingested other drugs in addition to diphenhydramine. The most commonly observed toxicity following diphenhydramine overdose included cardiac toxicity (78%). Cardiac toxicity was observed in all the patients who presented to the emergency department 2 hours after ingestion. The patients with QTc prolongation turned out to have ingested significantly larger amounts of diphenhydramine. CONCLUSION: QTc prolongation and right axis deviation were common findings for the patients with a diphenhydramine overdose. QTc prolongation was more likely to occur with ingesting larger amounts of diphenhydramine. Close monitoring is mandatory for patients who have ingested large amounts of diphenhydramine to prevent such potentially lethal cardiac toxicity.
Atrioventricular Block ; Axis, Cervical Vertebra ; Diphenhydramine ; Eating ; Electrocardiography ; Emergencies ; Humans ; Incidence ; Korea ; Medical Records ; Retrospective Studies ; Shock, Cardiogenic ; Vital Signs

OBJECTIVETo determine the effects of organic amine diphenhydramine on the 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide dye (MTT) reduction assay.

METHODSThe primarily cultured cortical astrocytes were incubated with various concentrations of diphenhydramine for 24 h. To analyze the effects of diphenhydramine and other organic amines on the MTT assay, the data obtained from the MTT assay were compared with the results obtained from morphological observation and hoechst 33342 and propidium iodide (PI) nucleus double staining.

RESULTThe MTT assay showed that diphenhydramine (10(-4)mol/L), pyrilamine (10 (-4)mol/L) and zolantidine (10 (-5)mol/L) caused a significant increase in MTT reduction in astrocytes. However there was no proliferation, apoptosis or necrosis detected by hoechst and PI nucleus double staining. Light microscopy revealed that exocytosis of formazan granules was inhibited by diphenhydramine.

CONCLUSIONDiphenhydramine and other organic amines may enhance MTT reduction by suppression of MTT formazan exocytosis in astrocytes, which may affect the results of cell viability studies.

Animals ; Astrocytes ; drug effects ; metabolism ; physiology ; Cell Survival ; Cells, Cultured ; Diphenhydramine ; pharmacology ; Drug Interactions ; Formazans ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Tetrazolium Salts ; pharmacokinetics

The antihistaminic drug diphenhydramine is mainly used as a sedative, hypnotic and antiemetic. In many countries it is available over-the-counter, very common, and generally regarded as a harmless drug. However, diphenhydramine overdose can result in cardiotoxicity due to its ability to block fast sodium channels in a manner analogous to classic Vaughan-Williams type IA antidysrhythmic agents. As such, cardiotoxicity from diphenhydramine resembles that of the tricyclic antidepressant agents. Here we report a case of a 52 year old man who ingested 2,000 mg of diphenhydramine and presented with an altered mental state and an electrocardiographic change. His electrocardiogram showed sinus tachycardia with a rate 145 beat/min, a QRS interval of 88 ms, and a QTc of 556 ms. He had a wide anion gap metabolic acidosis. He was treated with intravenous sodium bicarbonate and supportive therapy. His clinical manifestations waned and he was transferred to another hospital nearby his hometown.
Acid-Base Equilibrium ; Acidosis ; Diphenhydramine ; Electrocardiography ; Humans ; Sodium Bicarbonate ; Sodium Channels ; Tachycardia, Sinus

PURPOSE: The previous studies on H1 antihistamine overdose have generally been limited to cases of acute doxylamine succinate (DS) poisoning, yet there have been some studies on diphenhydramine (DPH) overdosing. But many clinicians consider the two drugs to be very similar and to have similar ingredients. The purpose of this study was to clarify the toxicologic characteristics and clinical outcomes between DS and DPH poisoning/overdose. METHODS: We reviewed the medical and intensive care records of the patients with acute DS or DPH poisoning and who admitted to our emergency department from January 2008 and April 2010. We collected patient information regarding the features of the poisoning and the clinical and demographic characteristics. The patients were assessed for the clinical outcomes, the GCS, the PSS (Poisoning Severity Score) and the SOFA (Sequential Organ Failure Assessment). RESULTS: Fifty seven patients (45 cases of DS poisoning and 12 cases of DPH poisoning) were enrolled. Compared with the DS group, the DPH group had higher incidences of intubation, serious mental change, QTc prolongation and ECG conduction abnormality (p=0.041, <0.001, 0.014 and 0.044, respectively). The DPH group had a higher PSS and a longer ICU stay. The peak CPK time and the CPK normalization time were longer for the patients with rhabdomyolysis due to DS poisoning. CONCLUSION: Two common H1 antihistamines, doxylamine and diphenhydramine, are in the same ethanolaminestructural class, but the toxico-clinical outcomes are different according to many aspects. Therefore, clinicians could take a careful approach for the differential diagnosis and management between DS and DPH poisoning.
Diagnosis, Differential ; Diphenhydramine ; Doxylamine ; Electrocardiography ; Emergencies ; Histamine Antagonists ; Humans ; Incidence ; Critical Care ; Intubation ; Rhabdomyolysis ; Succinic Acid