Enantioselective analysis of pheniramine in rat using large volume sample stacking or cation-selective exhaustive injection and sweeping coupled with cyclodextrin modified electrokinetic chromatography.

For the aim of simultaneously performing the enantioseparation and determination of the trace enantiomers in plasma samples, enantioseparation by HPLC using five kinds of chiral stationary phases were initially investigated. But unfortunately, enantioseparation could not be detected in reversed mobile phase mode with all the five columns. For this reason, two simple, economical and highly efficient online preconcentration methods, large volume sample stacking and sweeping (LVSS-sweeping) and cation-selective exhaustive injection and sweeping (CSEI-sweeping) both followed by the cyclodextrin modified electrokinetic chromatography (CDEKC) were examined in the present work. Parameters affecting the enantioseparation and enhancement efficiency of these two injection modes were monitored in detail, and migration order of the two enantiomers was identified by circular dichroism (CD) and HPLC. Upon optimization, two enantiomers were best separated with the improvement of sensitivity reaching 160-fold and 4000-fold respectively for LVSS-sweeping and CSEI-sweeping comparing with the normal CDEKC separation. Then the optimal condition of CSEI-sweeping-CDEKC was validated and showed high sensitivity (10 ng/mL for lower limit of quantification, LLOQ), satisfactory accuracy (96.8-111.6%) and precision (relative standard deviation, RSD within 9.4%). This demonstrated it to be a suitable strategy for the rapid enantioselective determination and quantitative analysis of pheniramine enantiomers in plasma samples. Therefore, the method was further applied in the enantiomeric analysis of pheniramine in rat pharmacokinetics and plasma protein binding investigations. Stereoselectivity in pharmacokinetics as well as plasma protein binding were observed, suggesting that the stereoselective protein binding might be responsible for the stereoselectivity in pharmacokinetics.

Hazards of antihistamine dependence in psychiatric patients: a case report.

Excessive use of over-the-counter (OTC) medications has been a growing public health problem. We present the case of a patient with avoidant personality disorder, social phobia, and dull normal intelligence, with dependence to pheniramine maleate. His anxiety symptoms, initially unresponsive to conventional treatment, reduced only after stopping pheniramine during inpatient care. This case emphasizes the need for awareness and regular monitoring of the use of OTC medications in vulnerable patient populations.

[Fixed pigmented erythema antihistamine H1: about 2 cases and review of the literature]. / Érythème pigmenté fixe aux antihistaminiques H1 : à propos de 2 cas et revue de la littérature.

We describe two cases of fixed drug eruptions induced by pheniramine (1(st) case) and loratadine (2(nd) case).

Effect of Dexamethasone and Pheniramine Maleate in Patients Undergoing Elective Laparoscopic Cholecystectomy.

INTRODUCTION: Laparoscopic cholecystectomy (LC) is elective surgical procedure for uncomplicated gallstone disease and gallbladder polyp. The objective of this study was to assess the efficacy of Dexamethasone and Pheniramine hydrogen maleate on reducing stress response and pain after surgery in patients undergoing laparoscopic cholecystectomy. METHODS: After obtaining approval from the institutional ethics committee and written informed consent, 120 patients undergoing elective laparoscopic cholecystectomy were enrolled in the study from Sep 2103 to Aug 2014 at Department of Surgery, Manipal College of Medical Sciences, Pokhara, Nepal. Patients were randomized to receive either 8mg/2ml of Dexamethasone + 45.5/2ml Pheniramine hydrogen maleate (treatment group, n= 60) or 5 ml of normal saline (control group, n=60) 90 minutes before skin incision. RESULTS: There was a reduction of total bilirubin, C-reactive protein (CRP) value and Visual Analogue Score (VAS) in treatment group as compared to control group (p <0.05). CONCLUSIONS: Use of Dexamethasone and Pheniramine hydrogen maleate prior to surgical skin incision helps to reduce both postoperative pain and acute physiological stress.

The ability of H1 or H2 receptor antagonists or their combination in counteracting the glucocorticoid-induced alveolar bone loss in rats.

BACKGROUND: The aim of the present study was to compare between three possible osteoporotic treatments in prevention of glucocorticoid-induced alveolar bone loss. METHODS: Fifty adult female Wistar rats with an average weight 150-200 g were randomized into five groups: group I (control) was intraperitoneally injected with saline. The other experimental groups (II & III, IV & V) were intraperitoneally injected with 200 µg/100 g body weight dexamethasone. The experimental groups III, IV and V received intraperitoneal injection of 10 mg/kg/day pheniramine maleate (H1 receptor antagonist), ranitidine hydrochloride (H2 receptor antagonist) and concomitant doses of both H1 & H2 receptor antagonists respectively. After 30 days, the rats have been sacrificed. The mandibles were examined histologically, histochemically and histomorphometrically. The bone mineral density was measured using dual-energy X-ray absorptiometry (DEXA). RESULTS: Histopathologically the glucocorticoid group showed wide medullary cavities with wide osteocytic lacunae. These marrow cavities were reduced in the prophylactic groups (III, IV) but increased in group V. Bone histomorphometric analysis revealed improvement in static bone parameters in groups III and IV and deterioration in group V in comparison to group II. The DEXA revealed significant reduction in the bone mineral density in all experimental groups compared to the control group. CONCLUSIONS: In a rat model, the administration of H1 or H2 receptor antagonists separately could minimize the alveolar bone loss caused by the administration of glucocorticoids while concomitant administration of both H1 and H2 receptor antagonists deteriorated the bone condition.

Effects of dexamethasone and pheniramine hydrogen maleate on stress response in patients undergoing elective laparoscopic cholecystectomy.

BACKGROUND: Laparoscopic cholecystectomy (LC) still leads to significant postoperative nausea and vomiting (PONV) and pain. Our aim was to evaluate the efficacy of dexamethasone or pheniramine hydrogen maleate, either alone or combined, in reducing the stress response and symptoms after LC. METHODS: Patients were randomly assigned to 1 of 4 groups, each consisting of 20 patients: control, dexamethasone (8 mg/2 mL), pheniramine hydrogen maleate (45.5 mg/2 mL), and the combined group. The drugs were given before anesthesia induction. RESULTS: C-reactive protein levels (CRP) and visual analog scale (VAS) scores were significantly less in the dexamethasone (P = .003) and combined groups (P < .001). Both dexamethasone (P < .001) and pheniramine hydrogen maleate (P = .005) significantly reduced PONV. CONCLUSIONS: Dexamethasone significantly reduced postoperative pain and the systemic acute-phase response, whereas these effects were only partially attained with pheniramine hydrogen maleate. Both dexamethasone and pheniramine hydrogen maleate significantly reduced PONV. An additive effect seemed to occur if these drugs were used in combination.

Assessment of protective effects of methylprednisolone and pheniramine maleate on reperfusion injury in kidney after distant organ ischemia: a rat model.

BACKGROUND: Ischemia/reperfusion (I/R) injury of tissues is a common problem that cardiovascular surgeons are faced with. Suppression of inflammation, which plays an important role in the pathogenesis of I/R injury, may reduce this damage. The aim of this study is to investigate the protective effects of methylprednisolone (MP)--a potent anti-inflammatory agent--and pheniramine maleate (FM)--an antihistamine that also has some anti-inflammatory effects--on reperfusion injury of kidneys developing after ischemia of the left lower extremity of rats. METHODS: Twenty-eight randomly selected male Sprague-Dawley rats weighing 320 to 370 g were divided into four groups, each consisting of seven rats. Group 1 was the control group. Group 2 was the sham group. Rats in group 3 were subjected to I/R and given FM, and rats in group 4 were subjected to I/R and given MP. A tourniquet was applied at the level of the left groin to subjects in group 2 after induction of anesthesia. One hour of ischemia was performed, and no drug was administered. In group 3, half of a total dose of 10 mg/kg FM was administered before ischemia, and the remaining half was given intraperitoneally before reperfusion. In group 4, subjects received a single dose of 50 mg/kg MP intraperitoneally in the 30th minute of ischemia. Kidneys of all subjects were removed after 24 hours. Extracted tissues were investigated regarding histological and biochemical parameters. RESULTS: Malondialdehyde--the end product of lipid peroxidation as an important indicator of I/R injury--levels were significantly lower in group 3 than in group 2 (P < 0.05). Malondialdehyde levels were also lower in group 4 than in group 2, but this difference was insignificant (P > 0.05). Superoxide dismutase and glutathione peroxidase enzyme activities were found to be significantly higher in group 3 than in group 2 (P < 0.05). However, there was no difference between group 4 and group 2 in terms of these activities. Histological examination demonstrated that both MP and FM had protective effects against I/R injury, but this effect was more potent for FM than for MP. CONCLUSIONS: FM has a protective effect against reperfusion injury in rat kidney after distant organ ischemia.

Spinal anesthesia with diphenhydramine and pheniramine in rats.

The aim of this study was to evaluate the local anesthetic effects of pheniramine and diphenhydramine, two histamine H1 receptor antagonists, on spinal anesthesia and their comparison with lidocaine, a commonly used local anesthetic. After rats were injected intrathecally with diphenhydramine and pheniramine, the dose-response curves were obtained. The potency and duration of diphenhydramine and pheniramine on spinal anesthesia were compared with lidocaine. We showed that diphenhydramine and pheniramine produced dose-dependent spinal blockades in motor function, proprioception, and nociception. On a 50% effective dose (ED50) basis, the rank of potency of drugs was diphenhydramine=pheniramine>lidocaine (p<0.05 for the differences). In equianesthetic doses (ED25, ED50, and ED75), the block duration caused by diphenhydramine was longer than that caused by pheniramine or lidocaine (p<0.01 for the differences). Diphenhydramine, but not pheniramine or lidocaine, elicited longer duration of sensory block than that of motor block at the same dose of 1.75 µmol. These preclinical data reported that diphenhydramine with a more sensory-selective action over motor blockade demonstrated more potent and longer-lasting spinal blockades, compared with pheniramine or lidocaine.

Modulation of in vivo immunoglobulin production by endogenous histamine and H1R and H2R agonists and antagonists.

The present study was designed to delineate the immunomodulatory role of histamine receptors (H1R and H2R) and their antibody generation in a rabbit model. Six groups containing 18 rabbits each received either vehicle (sterile distilled water, 1 ml/kg x b.i.d), histamine (100 µg/kg x b.i.d.), H1R agonist (HTMT, 10 µg/kg x b.i.d.), H2R agonist (amthamine, 10 µg/kg x b.i.d.), H1R antagonist (pheniramine, 10 mg/kg x b.i.d.) or H2R antagonist (ranitidine, 10 mg/kg x b.i.d.). All animals were subsequently immunized with an intravenous injection of sheep red blood cells (SRBC). Estimations of total serum immunoglobulins (Igs), immunoglobulin M (IgM) and immunoglobulin G (IgG) were performed by ELISA and hemagglutination assay (HA) at days 0 (pre-immunization), 7, 14, 21, 28 and 58 (post-immunization). Both the ELISA and the HA showed similar production of Igs, IgM and IgG but the results were found comparatively more significant by ELISA as opposed to HA. Results showed that histamine could influence a detectable antibody response to SRBC early (i.e., at day 7), which lasted until day 58. Immunomodulatory processes showed suppression of an Ig generation in the H1R-antagonist group with enhancement in the H2R-antagonist group. The H1R-agonist group showed an increased Ig production in comparison to the H2R-agonist group. The IgM production was inhibited in the H1R-antagonist group as compared to the H2R-antagonist group, and it was also suppressed in H1R-agonist group as compared to H2R-agonist group. IgG production was inhibited in the H1R-antagonist group as opposed to the H2R-antagonist group. In contrast, the H1R-agonist group increased IgG production as compared to the H2R-agonist group. All the results were found to be statistically significant (p < 0.05 or p < 0.01). In conclusion, histamine and its receptor (H1R and H2R) agonists enhance antibody production by triggering the histamine receptors (H1R and H2R), and both the H1R antagonist and the H2R antagonist positively or negatively regulate the antibody production. The findings of this study may have clinical significance.

The lollipop with strawberry aroma may be promising in reduction of infusion-related nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells.

Nausea and vomiting during the infusion of cryopreserved peripheral blood stem cells (PBSC) are common. The aim of this study was to explore the effect of lollipop with strawberry aroma on the infusion-related nausea and vomiting of cryopreserved autologous PBSCs. We compared 2 groups of adult patients receiving lollipop with strawberry aroma during cryopreserved PBSC infusions or not to assess the incidences of nausea and vomiting occurring during infusions. All patients received granisetron 3 mg i.v. twice a day, and lorazepam 1 mg every 4 hours orally for prophylaxis of the nausea and vomiting during conditioning phase and infusion day. Before infusion, all patients were premedicated with pheniramine maleate 45.5 mg i.v. and paracetamol 500 mg orally. The patients had no evidence of nausea or vomiting prior to cryopreserved PBSC infusions. The patients with ongoing nausea or vomiting owing to conditioning regimens and/or receiving additional antiemetics were excluded from the study. One hundred fifty-eight patients who consecutively underwent autologous stem cell transplantation for malignancy were included in the study. The first 110 patients (median age: 42.5, range: 17-75) were observed for the infusion related adverse effects only. The consecutive 48 patients (median age: 48, range: 18-80) were given a lollipop with strawberry aroma during cryopreserved PBSC infusions and observed for the infusion-related adverse effects. The 2 groups were comparable with respect to age, sex, diagnosis, stem cell collection methods, conditioning regimens administered, total mononuclear cell dose infused, number of total nucleated cells (TNCs) infused, number of CD34+ cells infused, number of bags infused, total volume infused, amount of dimethylsulfoxide (DMSO), and infusion rate. Patients who received a lollipop with a strawberry aroma during infusions had significantly less nausea (6.3%, n = 3 versus 21.8%, n = 24, P = .02) and vomiting (2%, n = 1 versus 13.6%, n = 15, P = .04) than the ones who did not (observation only group). Other infusion-related adverse events were as follows; hypoxia, cough, dyspnea, abdominal cramping, tachycardia, hiccup, fever, chills, chest pain, hypotension, hypertension, agitation, sore throat, and arrhythmia. Incidences of each of these adverse events were <5% in both groups and were comparable. The use of a lollipop with a strawberry aroma during infusion of cryopreserved autologous PBSCs may be promising in reduction of infusion-related nausea and vomiting, with an easy administration at a very cheap cost.

A comparison of the clinical efficacy of pheniramine maleate/naphazoline hydrochloride ophthalmic solution and olopatadine hydrochloride ophthalmic solution in the conjunctival allergen challenge model.

BACKGROUND: The signs and symptoms of allergic conjunctivitis include ocular redness and itching. Two treatment options currently indicated for acute ocular allergic reaction are pheniramine maleate 0.3%/naphazoline hydrochloride 0.025% ophthalmic solution, an over-the-counter antihistamine/vasoconstrictor combination; and olopatadine hydrochloride 0.1% ophthalmic solution, a prescription antihistamine/mast cell stabilizer. OBJECTIVE: This study was designed to compare, at onset of action, the relative effectiveness of pheniramine/naphazoline and olopatadine, when administered before conjunctival allergen challenge (CAC), using the ocular allergy index (OAI) as the primary end point. METHODS: This was a prospective, randomized, double-masked, contralateral, active- and placebo-controlled, single-center study of the CAC model. The first 2 study visits established and confirmed the subjects' ocular allergic reaction (no medication administered). At visit 3, the subjects were randomly assigned to 1 of 3 contralateral (right eye vs left eye) treatment combinations: pheniramine/naphazoline + olopatadine, pheniramine/naphazoline + placebo, or olopatadine + placebo. Medication was given 10 minutes before CAC. The subjects' erythema in the ciliary, conjunctival, and episcleral vessel beds; eyelid swelling; chemosis; and itching were evaluated at 7, 12, and 20 minutes after CAC. The OAI was calculated as a composite score of 6 signs and symptoms of allergic conjunctivitis to assess global severity. Between-treatment differences in OAI scores were used to evaluate efficacy. Subjects were asked their eye drop preference at the conclusion of visit 3. RESULTS: Subjects (n = 83) ranged in age from 20 to 70 years (mean, 42.5 years), 61.4% (n = 51) were female, and 94.0% (n = 78) were white. Both pheniramine/naphazoline and olopatadine were associated with significantly lower OAI scores than placebo at all 3 time points (all, P < 0.001). OAI scores were significantly lower with pheniramine/naphazoline than with olopatadine at 12 and 20 minutes (P = 0.005 and P = 0.001, respectively). CONCLUSION: In this patient sample, studied in a CAC model of onset of action, prophylactic pheniramine/naphazoline was more effective than olopatadine and placebo in alleviating the signs and symptoms of the acute ocular allergic reaction, as measured by the OAI.

A case of pheniramine dependence.

Abuse and addiction of histaminergic agonists and antagonists were investigated. The withdrawal signs may become after using drugs such as L-histidine, histamine-N-methyl, promethazine, pheniramine, astemizole, etc. Some medicines which include these active metabolites could lead to dependence cause different side effects. This case suggests that pheniramine abuse also could to dependence. We should pay attention to trend of pheniramine and other histaminergic drugs dependence and need to regulate the market by law more severely.