Pharmacological interventions for antipsychotic-related sialorrhea: a systematic review and network meta-analysis of randomized trials.

Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.

Time-to-onset of cold and flu symptom relief: A randomized, double-blind, placebo-controlled pilot study for a multi-symptom combination product.

OBJECTIVE: Evaluate effects of a multisymptom tablet on cold and flu symptoms within 4 hours post-administration. MATERIALS AND METHODS: This was a randomized, double-blind, placebo-controlled study in adults with cold and flu symptoms. Eligible participants with at least moderate common cold or flu symptoms and symptom onset ≤ 48 hours before screening were assigned to a single multiple-active-ingredient tablet (containing paracetamol, pseudoephedrine hydrochloride, dextromethorphan hydrobromide, and chlorpheniramine maleate) or placebo tablet. Participants rated severity of each symptom (sore throat, headache, extremity pain, nasal congestion, sneezing, runny nose, and cough) from 0 (absent) to 3 (severe) at 15 and 30 minutes and 1, 2, 3, and 4 hours post administration. The total symptom score (TSS) was calculated as the sum of the individual symptom scores (primary endpoint). Participants rated global response to treatment on a scale from 0 (ineffective) to 4 (excellent). Adverse events (AEs) were recorded throughout. RESULTS: Of 53 participants randomized, 52 received active tablet (n = 25) or placebo tablet (n = 27). Change from baseline in TSS throughout the 4-hour post-administration period was similar between groups. An efficacy criterion of 30% decrease in TSS at assessment points was not met (range, -1.91 to 8.94%). There were also no significant differences between groups in mean symptom scores for individual symptoms or global response to treatment. Four non-serious treatment-emergent adverse events occurred. CONCLUSION: In this exploratory pilot study, a multisymptom cold and flu tablet was well tolerated but did not differ from placebo tablet with regard to onset of action following a single dose.
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Safety profile of H1-antihistamines in pediatrics: an analysis based on data from VigiBase.

PURPOSE: H1-antihistamines are commonly used in infants and children for the relief of histamine-mediated symptoms in a variety of conditions. Little is known about their safety profile in these patients. We performed a comparative analysis of the safety profiles of H1-antihistamines using data from the WHO database (VigiBase). METHODS: We selected adverse drug reaction (ADR) reports on H1-antihistamines in children (0-16 years) up to June 2014 from VigiBase. ADRs were codified according to MedDRA terminology. The reporting odds ratios (RORs) with 95% confidence for drug-reaction pairs were calculated. RESULTS: The analysis was performed on 8918 reports related to antihistamines, corresponding to 19503 drug reaction pairs for 68 different drugs. Most of reports involved children aged 2 to 6 years (32%) and 6 to 12 years (34%). Most reported drugs were cetirizine (1608 reports, corresponding to 18%), loratadine (16%), and diphenhydramine (10%). ADRs were classified as serious in 23% of cases, and 400 cases had a fatal outcome. We found a significant associations for several drug-reaction pairs such as levocetirizine and epilepsy (ROR, 6.57; 95% confidence interval [CI], 1.51-28.53) and chlorphenamine and toxic epidermal necrolysis (ROR, 7.29; 95% CI, 2.39-22.2). CONCLUSIONS: H1-antihistamines are among the most used drugs in pediatrics, also in an off-label manner. Our data highlights associations with serious and unexpected ADRs. Educative intervention to clinicians and parents are needed to help doctors to make proper choices on the drug treatment and for the early detection of ADRs to maximize the benefits and reduce the risk of ADRs in these patients.

A phase I trial assessing the safety, tolerability, pharmacokinetic and pharmacodynamic characteristics of single-dose Auron Misheil therapy in healthy male subjects.

BACKGROUND AND OBJECTIVE: Auron Misheil therapy (AMT) is a combination of widely used pharmaceuticals and herbal components that has been used since the 1980s as a supportive therapy, mainly in end-stage cancer patients on a compassionate basis. This phase I study was conducted to assess the safety, tolerability, and pharmacokinetic (PK) and pharmacodynamic (PD) properties of AMT in a controlled trial environment. METHODS: The study was conducted in a single rising dose, double-blind, placebo-controlled design. Three groups of eight healthy male volunteers received one of three doses of AMT (0·011, 0·033 or 0·066 mL AMT/kg body weight intramuscularly; n = 6 per group) or placebo (n = 2 per group). RESULTS AND DISCUSSION: Auron Misheil therapy was shown to be well tolerated, revealing no severe or serious adverse events. There were no unexpected PK or PD results for any of the three components of AMT. CONCLUSIONS: These data provide important PK, PD and safety data for AMT, and support further controlled clinical investigation in patients with different types of cancer as an option for supportive care.

Efficacy and safety of modified sequential three-step empirical therapy for chronic cough.

BACKGROUND AND OBJECTIVE: Sequential three-step empirical therapy is useful for the management of chronic cough. The purpose of this study was to evaluate the efficacy and safety of modified sequential three-step empirical therapy. METHODS: Consecutive patients (n = 240) with chronic cough were recruited and randomly assigned to receive modified (modified group) or primary (primary group) sequential three-step empirical therapy. The primary end-point was the overall rate of control of chronic cough. Secondary end-points were the rate of control of chronic cough at each step of therapy, the duration of treatment required, changes in cough symptom score, health-related quality of life and possible adverse effects. RESULTS: The study was completed by 106 patients in the modified group and 108 patients in the primary group. The overall rate of control of chronic cough was 88.7% in the modified group and 91.7% in the primary group (chi(2) = 0.54, P > 0.05). There were no obvious differences in the rate of control of cough at each step of therapy, the duration of treatment required, patterns of cough symptom scores or improvements in the health-related quality of life between the modified and primary groups. However, the incidence of drowsiness was significantly lower in the modified group than in the primary group (11.7% vs 21.7%, chi(2) = 4.32, P = 0.04). CONCLUSIONS: Modified three-step empirical therapy was as efficacious as primary three-step therapy for chronic cough, but was preferable because it had fewer side-effects.

Synthesis and pharmacological investigation of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4]triazolo[4,3-a] quinazolin-5-ones as a new class of H1-antihistaminic agents.

A series of novel 4-(3-ethylphenyl)-1-substituted-4H-[1,2,4] triazolo[4,3-a]quinazolin-5-ones (4a-j) were synthesized by the cyclization of 3-(3-ethylphenyl)-2-hydrazino-3H-quinazolin-4-one (3) with various one-carbon donors. The starting material, compound 3, was synthesized from 3-ethyl aniline by a new innovative route with improved yield. When tested for their in vivo H1-antihistaminic activity on conscious guinea pigs, all test compounds protected the animals from histamine induced bronchospasm significantly. Compound 4-(3-ethylphenyl)-1-methyl-4H - [1,2,4]triazolo[4,3-a]quinazolin-5-one (4b) emerged as the most active compound of the series and it is more potent (74.6 % protection) compared to the reference standard chlorpheniramine maleate (71 % protection). Compound 4b shows negligible sedation (10 %) compared to chlorpheniramine maleate (30 %). Therefore compound 4b can serve as the leading compound for further development of a new class of H1-antihistamines.

[Stevens-Johnson syndrome plus intrahepatic cholestasis caused by clindamycin or chlorpheniramine]. / Síndrome de Stevens Johnson más colestasis intrahepática inducido por clindamicina o clorfeniramina.

A 48-year-old woman was hospitalized with the diagnosis of hepatitis. She presented with symptoms of jaundice, headache, elevated bilirubin, and elevated hepatic enzymes. She related a recent episode of a bronchial infection that was treated during the previous eight days with paracetamol (500mg, 2 doses only), chlorpheniramine, betamethasone and clindamycin. After an initial clinical and laboratorial improvement, she began to complain of pruritus of the palms and soles. Thereafter, vesicles evolving to blisters developed and a deterioration of her general health ensued. Serologies for hepatitis A, B, and C viruses were negative. Intrahepatic cholestasis and Stevens Johnson Syndrome (SJS) were the final diagnosis. The association of the Stevens Johnson Syndrome and intrahepatic cholestasis simultaneously, related to adverse drug reactions, is very rare. The drugs reportedly involved are mainly antibiotics, such as ampicillin, vancomycin, amoxicillin/clavulinic acid and erythromycin. Other drugs involved are non-steroidal anti-inflamatory drugs, such as mefenamic acid, ibuprofen, and sulindac. The reactions can be minor or severe and can even cause death, an outcome that has been reported in patients of all races and ethnic groups, but appears to be more rare in patients of Latin origin. We present a discussion of this case and review the main characteristics of the Stevens Johnson Syndrome.

Potential toxicity of chlorpheniramine plus chloroquine for the treatment of childhood malaria.

OBJECTIVES: To compare the adverse effects of two regimens of chlorpheniramine plus chloroquine (CP+CQ) in children who live in a country where chloroquine resistant malaria is endemic. METHODS: 99 children with acute uncomplicated malaria were randomised into two treatment groups. Group I received high dose chlorpheniramine (6 mg +12 mg/day for 7 days in children = 5 years; 8 mg + 18 mg/day for 7 days in those >5 years) plus chloroquine 10 mg/kg daily for 3 days. Group II received a 50% higher dose of chlorpheniramine plus chloroquine 10 mg/kg daily for 3 days. Outcome measures were vital signs, clinical response and parasite clearance on days 0-7 and day 14. RESULTS: Parasite clearance, fever clearance and cure rate were comparable for the two groups. Drowsiness occurred in 66.7% of high dose and 86.3% of higher dose CP+CQ subjects (p = 0.05). Compared to children treated with high dose, those treated with higher dose CP+CQ had significantly lower respiratory rates on day 2 (p = 0.001), day 6 (p = 0.015), and on day 14 (p = 0.003). CONCLUSION: The higher rates of drowsiness and lower respiratory rates in children treated with higher dose CP+CQ calls for caution in the clinical application of the higher dose combination. The higher dose has no additional benefit and may in fact be dangerous.

Chlorpheniramine-induced anaphylaxis: Two case reports and a retrospective review of pharmacovigilance database.

RATIONALE: Anaphylaxis is a serious allergic reaction which could be life-threatening. To date, it could be diagnosed by causality between clinical manifestations and triggers. But it is not always easy to find out the clue. Chlorpheniramine maleate (peniramin) is known to safe and it is an antihistamine commonly used to treat almost the whole allergic disease, including urticaria and allergic rhinitis. We recently experienced 2 cases of chlorpheniramine induced anaphylaxis. To document suspected cases of chlorpheniramine-induced adverse reactions, we analyzed a database spontaneously reported adverse drug reactions in the Ajou Regional Pharmacovigilance Center from 2011 to 2017. PATIENT CONCERNS: Two female patients presented urticaria and abdominal pain right after chlorpheniramine injection. DIAGNOSES: Both patients were diagnosed with symptoms. One patient confirmed by assistance with tryptase level and another one confirmed cross-reactivity by skin tests. INTERVENTIONS: One patient was instructed to avoid future administration of chlorpheniramine. The other patient was advised not to take chlorpheniramine, and piperazine derivatives including cetirizine/levocetirizine, but piperidine derivatives such as fexofenadine, loratadine, and ebastine can be available. OUTCOMES: The patients fully recovered after prompt treatment for anaphylaxis. After that, no recurrences were observed at the following. Among 54 patients with chlorpheniramine-induced adverse drug reactions from the Pharmacovigilance Center database, 17 (31.5%) were reported as anaphylaxis. LESSONS: Physicians should be aware chlorpheniramine could be a cause for allergic reaction. In addition, we suggest that serum tryptase level, skin prick test, and intradermal test could be considered as a supplementary test for diagnosing chlorpheniramine anaphylaxis and cross-reactivity should also be considered.

Long QT syndrome in chromosome 7q35q36.3 deletion involving KCNH2 gene: Warning for chlorpheniramine prescription.

BACKGROUND: The deletion of the distal 7q region is a rare chromosomal syndrome characterized by wide phenotypic manifestations including growth and psychomotor delay, facial dysmorphisms, and genitourinary malformations. METHODS: We describe a 6-year-old child with a 12-Mb deletion of the region 7q35q36.3. RESULTS: Among the deleted genes, two genes have cardiac implications: PRKAG2 (OMIM #602743), associated with hypertrophic cardiomyopathy, cardiac conduction disease, and sudden death, and KCNH2 (OMIM #152427), coding for a cardiac potassium channel involved in long QT syndrome, unmasked by the chlorpheniramine treatment. At same time, the SHH gene (OMIM #600725), encoding sonic hedgehog, a secreted protein that is involved in the embryonic development, is deleted. CONCLUSION: Our report underlines potential cardiac complications linked to the common pharmacological treatment in this rare multiorgan and proteiform disease.

Cocaine-like neurochemical effects of antihistaminic medications.

The pattern of activation of dopamine (DA) neurotransmission in the nucleus accumbens (NAc) of rats produced by H(1) histamine antagonists which have behavioral effects like those of psychostimulant drugs was examined. Diphenhydramine and (+)-chlorpheniramine were compared with triprolidine, a potent and selective H(1) antagonist and (-)-chlorpheniramine which is less active than its enantiomer at H(1) receptors. Affinities of the drugs to DA, serotonin, and norepinephrine transporters at H(1) receptors and potencies for DA uptake inhibition in striatal synaptosomes were determined to assess mechanisms by which the compounds increased DA levels. Intravenous diphenhydramine (1.0-3.0 mg/kg) (+)- and (-)-chlorpheniramine (1.0-5.6 mg/kg) but not triprolidine (1.0-3.0 mg/kg) elicited a cocaine-like pattern of stimulation of DA transmission with larger effects in the NAc shell than core. The absence of stereospecific effects with chlorpheniramine enantiomers along with the lack of an effect with triprolidine suggest that the effects on DA transmission were not related to H(1) receptor antagonism. Although in vivo potencies were not directly related to DA transporter affinities, it is hypothesized that actions at that site modulated by other actions, possibly those at the serotonin transporter, are primarily responsible for the neurochemical actions of the drugs on DA neurotransmission and might underlie the occasional misuse of these medications.

Analysis of disease-dependent sedative profiles of H(1)-antihistamines by large-scale surveillance using the visual analog scale.

Sedation is the most frequent side effect of H(1)-antihistamines, and, sometimes, it may be life-threatening for patients. Evaluation of the sedative properties of H(1)-antihistamines is important to improve the patients' quality of life (QOL). Therefore, we carried out a large-scale surveillance quantified through a questionnaire using visual analog scale (VAS) from 1,742 patients. The results showed that the degree of sleepiness caused by some nonsedative second-generation antihistamines, including fexofenadine, olopatadine and cetirizine, was disease dependent. In atopic dermatitis, an unexpectedly low VAS score of sleepiness was obtained for the first-generation antihistamine d-chlorpheniramine, which is similar to those obtained for bepotastine and epinastine. d-Chlorpheniramine also showed a high VAS score in efficacy. Meanwhile, fexofenadine showed a higher VAS score of sleepiness in atopic dermatitis than those obtained in the other allergic diseases including allergic rhinitis, urticaria and asthma. In asthma, a higher VAS score of sleepiness was found for olopatadine, ebastine and cetirizine, when compared with d-chlorpheniramine. On the other hand, bepotastine showed the lowest VAS score for sleepiness. Our findings suggest the existence of unknown factors influencing the sedative properties of H(1)-antihistamines. Therefore, appropriate H(1)-antihistamines may need to be selected, depending on allergic diseases, to improve patients' QOL.

Enhanced efficacy of amodiaquine and chlorpheniramine combination over amodiaquine alone in the treatment of acute uncomplicated Plasmodium falciparum malaria in children.

OBJECTIVE: To evaluate the comparative efficacy of amodiaquine (AMQ) alone and the combination of AMQ and chlorpheniramine (CP) in the treatment of acute uncomplicated malaria in children. SUBJECTS: Of the 110 children enrolled in the study, 103 with acute uncomplicated malaria, aged 6 months to 12 years, were evaluated using the 14-day modification of the WHO field test. The patients were randomized to 2 groups. Group 1 received supervised treatment with AMQ alone (10 mg AMQ base/kg daily for 3 days), while group 2 received supervised treatment with AMQ (same dose as group 1) plus CP (AMQCP) for 7 days. RESULTS: Both treatment regimens were well tolerated and no patient was withdrawn as a result of recurrent vomiting or drug-related adverse events. There was no significant difference in mean fever and parasite clearance times. The cure rates at day 7 were 90.2 versus 100% (rho = 0.027) for AMQ versus AMQCP, while the day 14 cure rates were 85.9 versus 98.1% for AMQ versus AMQCP, respectively (rho = 0.016). CONCLUSION: The combination of AMQ plus CP proved significantly more effective than AMQ alone in the treatment of acute uncomplicated falciparum malaria, most probably due to the enhancement of the antimalarial effect of AMQ by CP. The combination of AMQCP could be a better alternative to AMQ alone as a companion drug in artemisinin-based combination therapies.

[Experimental study on nasal mucosa injury and repair induced by nasal decongestants in guinea pigs].

Objective: To observe the process of nasal mucosa injury and repair induced by nasal decongestants in guinea pigs Methods: Sixty-five male guinea pigs were randomly divided into 4groups by digital random method.The guinea pigs in Group A (20 guinea pigs)were treated with 2 sprays of 0.1% Naphazoline 6 times a day for 2 weeks; Group B (20 guinea pigs)with 2 drops of 1% Ephedrine 6 times a day for 2 weeks; Group C(20 guinea pigs) with 2 sprays of Naphazolin hydrochloride and Chlorphenamine Maleate Nasal Spray 8 times a day for 2 weeks.Group D (5guinea pigs)did not do any intervention as a control group.At the end of first and second weekend, 6 guinea pigs randomly selected from each group were observed the morphological changes of the nasal cavity with nasal endoscope and pathological microscope.Two weeks after stopping use of decongestant, 24 animals were grouped.Three guinea pigs were selected randomly from each group to form Group E (n=9) and Group F (n=9)respectively. The 6 remaining guinea pigs falled into Group G. Group E received 2 sprays of Mometasone Furoate Nasal Spray once a day for 2 weeks; Group F received 1 ml 2.3% saline to wash the nasal cavities once a day for 2 weeks.Group F was used to show the natural progess without any treatment.At the end of the third and fourth weekend, nasal endoscopic and pathological microscopes were used to observe the nasal cavity structure and the pathological changes of nasal mucosa. Results: Nasal mocusa congestion and edema were observed with nasal endoscopy after 2 weeks of using nasal decongestant. Cell edema, blood vessel expansion, acute and chronic inflammatory cell infiltration, cilium lodging or loss were observed under the pathological microscope in GroupA, B, C. After using MometasoneFuroate Nasal Spray and 2.3% saline for 2 weeks, the above changes were all recovered in Group E and F. No recovery was found in Group G. Conclusions: Short-term and over dose of nasal decongestant can result in the injury of nasal mucosa in guinea pigs, and the injury is much severe as using decongestant last longer.MometasoneFuroate nasal spray and 2.3% saline can repair the injury.

Gabapentin versus dexchlorpheniramine as treatment for uremic pruritus: a randomised controlled trial.

BACKGROUND: Uremic pruritus is a common symptom in chronic renal failure patients with undefined pathophysiology. Initial treatment involves topical therapy mainly in the form of moisturizers, however, in many cases, this is not sufficient to relieve itching. Systemic adjuvant therapy is therefore necessary, which commonly includes oral antihistamines, with limited success. Positive effects have been reported for gabapentin. OBJECTIVES: To evaluate the efficacy and safety of gabapentin vs. dexchlorpheniramine in reducing uremic pruritus. MATERIALS & METHODS: A randomized, controlled, double-blinded clinical trial for haemodialysis patients with persistent pruritus was performed. Pre-randomisation, cold cream was used for 15 days by 71 participants. Those with pruritus who remained in the study (60 patients) were randomised to receive gabapentin (30 patients; GABA group) or dexchlorpheniramine (30 patients; DEX group) for 21 days. The primary outcome was the decrease in pruritus score and improvement in quality of life. RESULTS: After cold cream use, the participants demonstrated a 37.5% median reduction in Visual Analogue Scale (p<0.01) and a 50% reduction in Quality of Life in Dermatology (DLQI) score (p<0.01). There was an additional reduction of pruritus in both groups (p<0.01), with no difference between the two (p>0.7). The median DLQI was reduced from 2 to 1 in the GABA group and from 2 to 0 in the DEX group. Nineteen patients (32%) reported mild/moderate side effects without differences between the groups. CONCLUSIONS: Uremic pruritus was reduced upon treatment with gabapentin or dexchlorpheniramine with good safety profiles; no difference was observed between the two treatments.

Chlorpheniramine and ephedrine in combination for motion sickness.

BACKGROUND: Chlorpheniramine is effective against motion sickness, but produces sedation. To reduce chlorpheniramine's sedating effect and increase its effectiveness, ephedrine was combined with chlorpheniramine to prevent motion sickness. METHODS: Chlorpheniramine (C) and chlorpheniramine plus ephedrine (Chlorphedra) were studied in a randomized, double blind, crossover trial. Eighteen normal subjects were randomized to six different orderings of placebo, C (12 mg) or Chlorphedra (12 mg C + 50 mg ephedrine). They ingested the medication 3.25 hours before off vertical axis rotation in a rotating chair. Cognitive testing with both objective and subjective tests was performed before drug ingestion, at peak drug effect and following rotation. RESULTS: Both C and Chlorphedra significantly increased chair time compared to placebo [6.6 to 10.3 minutes (C), 10.2 minutes (Chlorphedra), p<0.01]. Subjects reported significantly more sleepiness on the Karolinska sleepiness scale after taking C (3.3 placebo, 4.9 C (p<0.005)) but not with Chlorphedra (3.3 placebo, 3.1 Chlorphedra). Chlorphedra resulted in significantly higher reported alertness, clearheadedness and attentiveness compared to C. Deficits seen on objective tests with C were corrected with Chlorphedra. Subjects noted more side effects with Chlorphedra. CONCLUSION: Ephedrine does not increase the effectiveness of chlorpheniramine against motion sickness, but counteracts sedative and performance effects successfully.

Serotonin syndrome in dextromethorphan ingestion responsive to propofol therapy.

An 18-year-old male developed a severe serotonin syndrome after recreational ingestion of Coricidin HBP (chlorpheniramine 4 mg and dextromethorphan hydrobromide 30 mg). Propofol infusion rapidly normalized his agitation, neuromuscular hyperactivity, and autonomic instability. Confirmatory analysis demonstrated a dextromethorphan serum concentration of 930 ng/mL. Dextromethorphan can produce serotonin syndrome in the absence of another serotonergic drug.

Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: Anti-inflammatory, antihistaminic, and skin barrier protection properties.

BACKGROUND: Unwanted side effects such as dryness, hypersensitivity, and cutaneous photosensitivity are challenge for adherence and therapeutical success for patients using treatments for inflammatory and allergic skin response. AIMS: In this study, we compared the effects of two dermatological formulations, which are used in inflammatory and/or allergic skin conditions: dexchlorpheniramine maleate (DCP; 10 mg/g) and promethazine (PTZ; 20 mg/g). METHODS: We evaluated both formulations for phototoxicity potential, skin irritation, anti-inflammatory and antihistaminic abilities, and skin barrier repair in vitro and ex vivo using the standard OECD test guideline n° 432, the ECVAM protocol n° 78, and cultured skin explants from a healthy patient. Ultraviolet A was chosen as exogenous agent to induce allergic and inflammatory response. RESULTS: Both PTZ and DCP promoted increases in interleukin-1 (IL-1) synthesis in response to ultraviolet A (UVA) radiation compared to control. However, the increase observed with PTZ was significantly greater than the DCP, indicating that the latter has a lower irritant potential. DCP also demonstrated a protective effect on UVA-induced leukotriene B4 and nuclear factor kappa B (NF-κB) synthesis. Conversely, PTZ demonstrates more robust UVA antihistaminic activity. Likewise, PTZ promoted a significantly greater increase in the production of involucrin and keratin 14, both associated with protective skin barrier property. CONCLUSION: In conclusion, these data suggest possible diverging UVA response mechanisms of DCP and PTZ, which gives greater insight into the contrasting photosensitizing potential between DCP and PTZ observed in the patients.

Torsades de pointes induced by concomitant use of chlorpheniramine and propranolol: An unusual presentation with no QT prolongation.

Drug-induced torsades de pointes (TdP) is a rare but potentially fatal adverse effect of commonly prescribed medications including cardiac and noncardiac drugs. Importantly, many drugs have been reported to cause the characteristic Brugada syndrome-linked electrocardiography (ECG) abnormalities and/or (fatal) ventricular tachyarrhythmias. Chlorpheniramine and propranolol have the arrhythmogenic effects reported previously. A review of literature revealed a large number of case reports of chlorpheniramine or propranolol use resulting in QTc prolongation, TdP, or both. However, we wish to report the case of a patient who was treated with a combination of chlorpheniramine and propranolol, whose ECG showed no QT prolongation but who suffered from cardiac arrest due to TdP.