This study was undertaken to observe the effects of centrally administred antihistamines on the blood pressure. Diphenhydramine(DPH), a H1-receptor antagonist, and ranitidine(RAN), a H2-receptor antagonist were administered intracerebroventricularly(icv) on urethane-anesthetized rabbits. 1) Both DPH and RAN administered intraccebroventricularly increased blood pressure, however the intravenous(iv) adminstration of them did not affect blood pressure. The pressor response to icv DPH was dose-dependent, but that to icv RAN was not. 2) The pressor response to icv DPH(1mg) was either markedly attenuated or reversed to depressor response by the pretreatment with icv phentolamine(250,500ug), and iv chlorisondamine(0.1, 1mg/Kg) and iv phenoxybenzamine(1mg/Kg). In cord-sectioned rabbtis, icv RAN) 1mg) did not produce pressor response. 3) The pressor responsr to icv RAN(1mg) was not affected by the pretreatment with icv phentolamine(500ug), iv chlorisondamin(1mg/Kg) and iv phenoxybenzamine(1mg/Kg), and iv phenoxybenzamine(1mg/Kg). RAN also producted pressor response in cordsectioned rabbits. These results suggest that the pressor response to icv DPH is elecited by increasing peripheral sympathetic tone via the stimulation of central alpha-adrenoreceptors and the pressor response to icv RAN is produced by releasing some humoral facotr which can increase blood pressure.
Blood Pressure ; Diphenhydramine* ; Histamine Antagonists ; Rabbits* ; Ranitidine*

Insufficient nocturnal sleep often triggers off various forms of psychosomatic diseases in the aged. The result is that we turn to medication. However, nurses and caregivers should try to seek other ways to cope with the situation without depending on drugs so that the old people could lead a safe and comfortable life. Not a few users of our facility suffer from circadian rhythm sleep disorders in addition to cerebrovascular disease, senile dementia and other impairments. They are asleep during the daytime and awake by night. Homa 1) says one of the principal causes of sleep-wake rhythm disorders is inadequate environmental light. We were also interested in the study by Mito et al. that sleep disorders were ameliorated by sunbathing because sunlight helps restore the damaged adjustment function of the biological clock. Hama et al. have observed that two-hour exposure to light stimulation (over 25,000 Lux) in the morning is effective in adjusting sleep-wake rhythm. Based on these observations, we tried experiments in our facility. This paper is a report of our findings thus far obtained about the benefit of the morning sunlight.
Sleep ; Rhythm ; Sleep brand of diphenhydramine hydrochloride ; Old episode ; Morning

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

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

In order to elucidate the mast cell changes challenged by various antihistaminic preparations and its role to the mast cells challenged by inflammation, male albino rats weighing 120-130gm were used for this investigations. Benadryl hydrochloride, Phenergan hydrochloride and Chlor-Trimeton maleate were choosed for antihistaminic challengers and ultraviolet ray was irradiated for an inflammatory challenger. 1. When rats were challenged by various antihistaminics the numbers of mast cell reached to the least after 2 days and later followed by an increasing mast cell numbers. 2. The mast cell changes were severer in order of Phenergan hydrochloride, Benadryl hydrochloride and Chlor-Trimeton maleate. 3. Degranulated mast cell was proportionally increased as the numbers of mast cell decrease after being challnged by antihistaminics and also it was decreasing when the numbers of mast cell were re-increasing
Animals ; Chlorpheniramine ; Diphenhydramine ; Humans ; Inflammation* ; Male ; Mast Cells* ; Promethazine ; Rats ; Ultraviolet Rays*

A 21-year-old woman ingested 1,250 mg of diphenhydramine in a single overdose. Diphenhydramine, a rare ingredient in over-the-counter medication, is used to treat insomnia in Korea. Toxicity is usually limited to anticholinergic symptoms. The standard approach to therapy for the treatment of diphenhydramine overdose is supportive care, including physostigmines and sodium bicarbonates. Here, we review the literature and for the first time report a case of acute diphenhydramine overdosage in Korea, complicated with seizures.
Bicarbonates ; Diphenhydramine ; Female ; Humans ; Korea ; Physostigmine ; Seizures ; Sleep Initiation and Maintenance Disorders ; Sodium ; Young Adult

Mg2+ is an important regulator of many cardiac functions. However, regulation of intracellular Mg2+ activity in the heart is not well characterized. To assess the effect of histamine H2-receptor stimulation on intracellular Mg2+ regulation, changes in extracellular Mg2+ concentration were examined under a variety of conditions in perfused guinea pig hearts. Mg2+ in the cardiac perfusate was measured by atomic absorbance spectrophotometry. The histamine (10(-6) M induced a marked Mg2+ efflux from the heart. The H2-receptor antagonists, cimetidine (10(-5) M), ranitidine (10(-5) ND, but not a H1-receptor antagonist, diphenhydramine (3 X 10(-6) M), completely blocked the histamine-induced Mg2+ efflux. The Mg2+ efflux could also be induced by forskolin (3 X 10(-6) M), 8-Cl-cAMP (2 X 10(-4) M), permeable cAMP analogue, or dimaprit, (10(-5) M). However, the carbachol (10(-5) M) considerably decreased the efflux of Mg2+. In the presence of papaverine (10(-5) M), a phosphodiesterase inhibitor, dimaprit-induced Mg2+ efflux was potentiated. These results suggest that a significant Mg2+ efflux from perfused guinea pig heart by histamine can be induced by the histamine H2-receptor stimulation and it is suggested that cytosolic cAMP may be linked.
Animals ; Carbachol ; Cimetidine ; Colforsin ; Cytosol ; Dimaprit ; Diphenhydramine ; Guinea Pigs* ; Guinea* ; Heart* ; Histamine* ; Magnesium ; Papaverine ; Ranitidine ; Spectrophotometry

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

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*