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1.
Pak J Pharm Sci ; 34(5): 1767-1776, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34803014

ABSTRACT

This study was aimed at synthesizing liposomes for the topical delivery of chlorpheneramine maleate using three-level factorial design. Each experiment consisted of a varying proportion of cholesterol, lecithin and a permeation enhancer mixture of Tween80 and polyethylene glycol (PEG1000), and resultant liposomes were extensively characterized. The drug release study was conducted at 6.0 pH, 37±1ºC temperature and 100 rpm rotation speed utilizing a cellophane membrane pouch in a USP type II dissolution apparatus. Among formulations, L5 was considered as the optimal formulation because of high drug loading (99.05%), 87.71% drug release within 4 hours, high drug loading and the optimized formulation was found to be stable during stability testing. This high drug loading and release was achieved at low level of cholesterol and lecithin (0.1: 0.3g) and high level of permeation enhancer mixture (0.2g) as revealed by the surface plots. The drug release from the optimized formulation followed Fickian diffusion as revealed by Korsmeyers-Peppas kinetic model. In summary, combination of PEG1000 and Tween80 with lecithin and cholesterol can be successfully used to develop liposomes that efficiently incorporated chlorpheneramine. This formulation therefore has the potential to be used as a topical anti-allergic product.


Subject(s)
Chlorpheniramine/chemistry , Drug Compounding/methods , Histamine Antagonists/chemistry , Liposomes/chemistry , Administration, Topical , Chlorpheniramine/administration & dosage , Drug Liberation , Histamine Antagonists/administration & dosage , Molecular Structure
2.
Am J Trop Med Hyg ; 105(1): 225-229, 2021 07 07.
Article in English | MEDLINE | ID: mdl-34232910

ABSTRACT

In French Guiana, a French overseas region partly located in the Amazon, "Africanized" bees, a hybrid species of Brazilian bees known as "killer bees," have been observed since 1975. Since then, several cases requiring long hospitalization times have been described, allowing for a better understanding of the physiopathological mechanisms of this particular envenomation. Here, we report on a series of 10 cases of patients simultaneously attacked by hundreds of killer bees and immediately treated by a prehospital medical team already on site. Between 75 and 650 stingers were removed per victim. The reference treatment for anaphylaxis using intramuscular injection of epinephrine, vascular filling, and oxygen therapy was administered to all patients without delay. A clinical description was provided, and biological tests were performed immediately after the envenomation. We therefore observe the existence of a two-phase, medically well-controlled systemic toxic reaction. Thus, all our patients left the hospital after 44 hours of monitoring with no complications or sequelae, despite levels of intoxication described as potentially fatal elsewhere in the literature.


Subject(s)
Bees/classification , Insect Bites and Stings/epidemiology , Acetaminophen/administration & dosage , Acetaminophen/therapeutic use , Adult , Analgesics, Non-Narcotic/administration & dosage , Analgesics, Non-Narcotic/therapeutic use , Animals , Anti-Infective Agents, Local/administration & dosage , Anti-Infective Agents, Local/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Chlorpheniramine/administration & dosage , Chlorpheniramine/therapeutic use , Epinephrine/therapeutic use , French Guiana/epidemiology , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/therapeutic use , Humans , Insect Bites and Stings/drug therapy , Male , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Middle Aged , Oxygen/therapeutic use , Prednisolone/administration & dosage , Prednisolone/therapeutic use , Saline Solution , Sympathomimetics/administration & dosage , Sympathomimetics/therapeutic use , Young Adult
3.
Am J Trop Med Hyg ; 105(1): 222-224, 2021 05 10.
Article in English | MEDLINE | ID: mdl-33970887

ABSTRACT

A hybrid species of Brazilian bee has proliferated on the South American continent since 1956. We describe a "killer bee" swarm attack on a 2-year-old girl in French Guiana. The patient weighed 10 kg, and approximately hundreds of bees' stingers were removed, that is, 10 stings/kg. Our patient survived without long-term sequelae. The management of her condition required admission into intensive care for renal failure due to acute tubular necrosis and severe rhabdomyolysis. We emphasize the importance of early medical intervention, clinical surveillance, and biological monitoring at the hospital to prevent a toxic chain reaction that could prove fatal within 72 hours.


Subject(s)
Acute Kidney Injury/etiology , Bee Venoms/toxicity , Bees , Insect Bites and Stings , Acetaminophen/therapeutic use , Analgesics, Non-Narcotic/therapeutic use , Animals , Child, Preschool , Chlorpheniramine/administration & dosage , Chlorpheniramine/therapeutic use , Female , French Guiana , Furosemide/therapeutic use , Glucocorticoids/therapeutic use , Histamine H1 Antagonists/therapeutic use , Humans , Insect Bites and Stings/complications , Prednisolone/therapeutic use
4.
Int J Med Sci ; 18(4): 1075-1081, 2021.
Article in English | MEDLINE | ID: mdl-33456366

ABSTRACT

Catheter-related bladder discomfort (CRBD) associated with intraoperative urinary catheterization is a distressing symptom during recovery from anesthesia. Anticholinergics have been used to manage CRBD. Chlorpheniramine maleate (CPM) is a first-generation antihistamine, which also has anticholinergic effects. This study was undertaken to evaluate the efficacy of CPM in preventing CRBD. Seventy-six adults (19-65 years old) with American Society of Anesthesiologists physical status I, II, or III of either sex, undergoing elective ureteroscopic stone removal under general anesthesia were randomized into one of two groups (each n = 38). Group C (control) received a placebo, and group CPM received 8 mg of intravenous CPM before the induction of anesthesia. CRBD was assessed upon arrival in the post-anesthetic care unit at 0, 1, 2, and 6 h. The severity of CRBD was graded as none, mild, moderate, and severe. Tramadol was administered when the severity of CRBD was more than moderate. The incidence rate and overall severity of CRBD did not differ between the groups at any of the time points (р > 0.05). The incidence of moderate CRBD was higher in group C than in group CPM only at 0 h (26.3% vs. 5.3%, р = 0.025). However, fewer patients in the CPM group required rescue tramadol to relieve CRBD after surgery (31.6% vs. 60.5%, р = 0.011). CPM administration before the induction of anesthesia had little effect on the incidence and severity of CRBD after surgery, but it reduced the administration of tramadol required to control CRBD postoperatively.


Subject(s)
Chlorpheniramine/administration & dosage , Muscarinic Antagonists/administration & dosage , Pain, Postoperative/epidemiology , Ureteroscopy/adverse effects , Urinary Catheterization/adverse effects , Urolithiasis/surgery , Adult , Aged , Double-Blind Method , Female , Humans , Incidence , Male , Middle Aged , Pain Measurement , Pain, Postoperative/diagnosis , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Prospective Studies , Severity of Illness Index , Treatment Outcome , Ureteroscopy/instrumentation , Ureteroscopy/methods , Urinary Bladder/drug effects , Urinary Catheterization/instrumentation , Urinary Catheterization/methods , Urinary Catheters/adverse effects , Young Adult
5.
Am J Emerg Med ; 42: 192-197, 2021 04.
Article in English | MEDLINE | ID: mdl-32139204

ABSTRACT

BACKGROUND: Acute urticaria is a common dermatological condition in emergency departments (EDs). The main therapy involves controlling pruritus with antihistamines. Although guidelines have promoted the use of corticosteroids in addition to H1 antihistamines, well-designed clinical trials evaluating this approach are scarce. METHODS: Adult ED patients with acute urticaria and a pruritus score > 5 on a visual analog scale (VAS) were randomized into three groups: (i) IV chlorpheniramine (CPM) treatment, (ii) IV CPM and IV dexamethasone (CPM/Dex) and (iii) IV CPM and IV dexamethasone with oral prednisolone as discharge medication for 5 days (CPM/Dex/Pred). The primary outcomes were self-reported pruritus VAS scores at 60 min after treatment. We also evaluated 1-week and 1-month urticaria activity scores for 7 days and adverse events. RESULTS: Seventy-five patients (25 per group) were enrolled. The VAS scores of all groups decreased, but no significant difference was found in the VAS scores at 60 min after treatment between patients in the CPM group (n = 25) and those who received both CPM and dexamethasone (n = 50). At the 1-week and 1-month follow-ups, active urticaria (indicated by the urticaria activity score at 7 days) was more prevalent in the CPM/Dex/Pred group (n = 25) than in the control group. CONCLUSIONS: The present study did not find evidence that adding IV dexamethasone improves the treatment of severe pruritus from uncomplicated acute urticaria. Oral corticosteroid therapy may be associated with persistent urticaria activity. Due to the lack of clinical benefits and the potential for side effects, using corticosteroids as an adjunctive treatment is discouraged.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Histamine H1 Antagonists/administration & dosage , Urticaria/diagnosis , Urticaria/drug therapy , Acute Disease , Administration, Intravenous , Administration, Oral , Adolescent , Adult , Chlorpheniramine/administration & dosage , Dexamethasone/administration & dosage , Double-Blind Method , Female , Humans , Male , Middle Aged , Prednisone/administration & dosage , Thailand , Treatment Outcome , Visual Analog Scale , Young Adult
6.
Curr Drug Discov Technol ; 18(4): 492-502, 2021.
Article in English | MEDLINE | ID: mdl-32316895

ABSTRACT

INTRODUCTION: Histamine, a biological amine, is considered as a principal mediator of many pathological processes regulating several essential events in allergies and autoimmune diseases. Numerous derivatives have been developed that strive with histamine at the H1 receptor and prevent binding of histamine at the H1 receptor, thereby preventing allergic reactions. Molecules containing a triazole ring fused with six-membered ring systems are found to possess broad applications in the field of medicine and industry. The present study is an attempt to characterize the impact of the nature of the substituent introduced at 5 positions of the-4H-1,2,4-triazole-3-thiol on their capacities to bind with the H1 receptor. METHODS: Molecular docking (PDB ID: 3RZE) revealed that synthesized derivatives and target proteins were actively involved in binding with Tyr-108, Thr-112, Ala-216, and Phe-432 subunits. A pharmacophore model, new 5-(4-substituted phenyl)-4-(phenylamino)-4-H-1,2,4-triazole-3- thiols (5a-5h) were designed and evaluated for H1-blocking activity using isolated segments from the guinea pig ileum. RESULTS: According to in silico analysis, all the compounds have a topological polar surface area (TPSA) less than 140 Å squared, so they tend to easily penetrate cell membranes. The results show that most of the compounds are non-inhibitors of CYP450 substrates that play a fundamental role in drug metabolism. Compounds 5d (50.53±12.03), 5h (50.62±12.33) and 7a (55.07±12.41) are more active than others. CONCLUSION: Finally, these derivatives were screened for H1 receptor antagonist activity using guinea pig ileum, taking chlorpheniramine maleate as a standard. Most of the compounds were found to possess better antihistamine activity.


Subject(s)
Histamine H1 Antagonists/pharmacokinetics , Receptors, Histamine H1/metabolism , Triazoles/pharmacokinetics , Animals , Chlorpheniramine/administration & dosage , Chlorpheniramine/pharmacokinetics , Drug Design , Drug Evaluation, Preclinical , Gastrointestinal Absorption , Guinea Pigs , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/chemical synthesis , Molecular Docking Simulation , Triazoles/administration & dosage , Triazoles/chemical synthesis
7.
BMJ Case Rep ; 13(7)2020 Jul 07.
Article in English | MEDLINE | ID: mdl-32641443

ABSTRACT

This is a case of a patient who presented with an urticarial rash 48 hours before developing symptoms of fever and a continuous cough. She subsequently developed angioedema of her lips and hands before testing positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Urticarial rashes occurring 48 hours before other symptoms of COVID-19 infection have been documented. This case demonstrates the importance of heightened awareness that not all urticarial rashes represent spontaneous urticaria and as a consequence, this may result in misdiagnosis and ultimately delayed diagnosis. This is the first reported case in the literature of urticaria with angioedema as a prodromal phenomenon of COVID-19.


Subject(s)
Angioedema , Chlorpheniramine/administration & dosage , Coronavirus Infections , Pandemics , Pneumonia, Viral , Prednisone/administration & dosage , Terfenadine/analogs & derivatives , Urticaria , Angioedema/diagnosis , Angioedema/etiology , Angioedema/physiopathology , Anti-Allergic Agents/administration & dosage , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/physiopathology , Diagnosis, Differential , Female , Humans , Middle Aged , Pneumonia, Viral/complications , Pneumonia, Viral/diagnosis , Pneumonia, Viral/physiopathology , Prodromal Symptoms , SARS-CoV-2 , Terfenadine/administration & dosage , Treatment Outcome , Urticaria/diagnosis , Urticaria/etiology , Urticaria/physiopathology
8.
Pharmacol Rep ; 72(4): 827-832, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32048250

ABSTRACT

BACKGROUND: This study sought to assess the cutaneous (peripheral) analgesic effects of antihistamine chlorpheniramine, compared with the long-lasting local anesthetic bupivacaine. METHODS: After chlorpheniramine and bupivacaine were subcutaneously injected under the dorsal skin of the rats, the cutaneous analgesia effect was quantitatively evaluated by scoring the number to which the animal failed to react (cutaneous trunci muscle reflex). The quality and duration of chlorpheniramine and bupivacaine on infiltrative cutaneous analgesia were compared. RESULTS: We revealed that subcutaneous chlorpheniramine, as well as the local anesthetic bupivacaine elicited cutaneous analgesia in a dosage-dependent manner. Based on their ED50s (50% effective doses), the relative potency was found to be chlorpheniramine [1.13 (1.05-1.22) µmol] < bupivacaine [0.52 (0.46-0.58) µmol] (p < 0.01). When comparing the ED25s, ED50s and ED75s, full recovery time induced by chlorpheniramine was longer (p < 0.01) than that induced by bupivacaine. CONCLUSIONS: Our preclinical data demonstrated that both chlorpheniramine and bupivacaine dose-dependently provoked the cutaneous analgesic effects. Chlorpheniramine with a more prolonged duration was less potent than bupivacaine in inducing cutaneous analgesia.


Subject(s)
Analgesia/methods , Anesthetics, Local/administration & dosage , Bupivacaine/administration & dosage , Chlorpheniramine/administration & dosage , Histamine H1 Antagonists/administration & dosage , Pain Measurement/drug effects , Administration, Cutaneous , Animals , Dose-Response Relationship, Drug , Drug Therapy, Combination , Injections, Subcutaneous , Male , Pain Measurement/methods , Rats , Rats, Sprague-Dawley
10.
Drug Deliv Transl Res ; 9(6): 1017-1026, 2019 12.
Article in English | MEDLINE | ID: mdl-31049842

ABSTRACT

The aim of the present study was to fabricate a thermosensitive gel containing chlorpheniramine maleate (CPM)-loaded nanoparticles following intranasal administration for effective treatment of allergic rhinitis. Chitosan-based nanoparticles were prepared by a precipitation method followed by the addition of developed NPs within the poloxamer 407- and carbopol 934P-based mucoadhesive thermoreversible gel. Developed formulations were evaluated for particle size, PDI, % entrapment efficiency, and % cumulative drug permeation. NP3 formulation was found to be optimized on the basis of minimum particle size (143.9 nm), maximum entrapment efficiency (80.10 ± 0.414%), and highest drug permeation (90.92 ± 0.531%). The optimized formulation NP3 was then formulated into thermoreversible in situ gel. This intensifies the contact between the nasal mucosa and the drug and increases and facilitates the drug absorption which results in increased bioavailability. G4 formulation was selected as the optimized formulation on the basis of gelation ability and mucoadhesive strength. Histology was carried out to examine the damage caused by the optimized G4 formulation. Results revealed no visual signs of tissue damage thus indicated safe nasal delivery of nanoparticulate in situ gel formulation G4. Thus, intranasal CPM NP-loaded in situ gel was found to be a promising formulation for the management of allergic rhinitis.


Subject(s)
Anti-Allergic Agents/administration & dosage , Chitosan/administration & dosage , Chlorpheniramine/administration & dosage , Drug Carriers/administration & dosage , Nanoparticles/administration & dosage , Rhinitis, Allergic/drug therapy , Administration, Intranasal , Animals , Anti-Allergic Agents/chemistry , Chitosan/chemistry , Chlorpheniramine/chemistry , Female , Gels , Nanoparticles/chemistry , Nasal Mucosa/anatomy & histology , Nasal Mucosa/chemistry , Nasal Mucosa/drug effects , Nasal Mucosa/metabolism , Rabbits , Sheep
11.
Wilderness Environ Med ; 30(2): 203-207, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31006585

ABSTRACT

Centipede bites are a constant risk throughout tropical regions and have the rare potential for systemic side effects. We report a case of multiple centipede bites in South Sudan that was complicated by severe pain refractory to opioid analgesia and an unusual association with acute involuntary muscle contractions. Treatment with local anesthetic, antihistamines, and corticosteroids was effective. This report aims to add to the local literature; because of decades of internal conflict and poor infrastructure, reporting of health data from South Sudan is severely lacking. Further investigation into the pharmacological variation and activity of toxic peptides in centipede venom is recommended. As it stands, this case provides additional information on potential effects of centipede envenomation that should be useful to any healthcare providers preparing for the delivery of remote medical care throughout the Great Upper Nile region.


Subject(s)
Arthropod Venoms/poisoning , Arthropods , Bites and Stings/drug therapy , Adult , Analgesics, Opioid/administration & dosage , Anesthetics, Local/administration & dosage , Animals , Anti-Inflammatory Agents/administration & dosage , Chlorpheniramine/administration & dosage , Fentanyl/administration & dosage , Histamine H1 Antagonists/administration & dosage , Humans , Hydrocortisone/administration & dosage , Lidocaine/administration & dosage , Male , Military Personnel , Muscle Contraction/drug effects , Pain/drug therapy , Pruritus/drug therapy , South Sudan
12.
Mol Pharm ; 16(5): 2095-2105, 2019 05 06.
Article in English | MEDLINE | ID: mdl-30900905

ABSTRACT

The majority of active pharmaceutical ingredients (APIs) are bitter. Therefore, compliance can be a problem where adequate taste masking has not been achieved; this is most problematic in pediatrics. Taste masking is thus a key stage during pharmaceutical development with an array of strategies available to the formulation scientist. Solid oral dosage forms can be taste-masked quite simply by polymer coating, which prevents drug release in the mouth, without unwantedly impairing drug release further down the gastrointestinal tract. At the early stages of pharmaceutical development, an in vitro method for the assessment of taste masking is necessary given the lack of toxicological data preventing the use of human taste panels. Currently, there is no such tool allowing prediction of taste masking efficiency. In this study, drug dissolution in the context of aversive taste thresholds was proposed as a means to bridge this knowledge gap. Thus, a biorelevant buccal dissolution test was developed in which previously determined taste thresholds in vivo were used to evaluate taste masking efficiency: if drug release exceeded said thresholds, the formulation was deemed to be poorly taste-masked, and vice versa. This novel dissolution test was compared to the USP I (basket) dissolution test, and the biopharmaceutical implications of taste masking were also assessed by performing USP I (basket) dissolution testing in simulated gastric fluid (SGF). Chlorphenamine maleate, a model bitter BCS class 1 API, was layered onto sugar spheres and taste-masked using polymer coatings. An array of coating technologies were employed and assessed single blinded: two pH-independent water-insoluble coatings (Surelease:Opadry at 8, 12, and 16% weight gain and Opadry EC at 4, 6, and 8% weight gain) and a pH-dependent water-insoluble reverse-enteric coating (developmental fully formulated system based on Kollicoat Smartseal 100P at 10% weight gain). Both the biorelevant buccal and the USP I dissolution tests were capable of discriminating between both type and level of coating used. However, only the buccal dissolution test was able to provide absolute quantification of the level of taste masking achieved in the context of previously determined taste thresholds, while the USP I test merely provided a relative comparison between the different technologies assessed. When the release data from the buccal test were assessed in parallel to that in SGF, it was possible to predict in vitro optimized taste masking without compromising bioavailability. The fully formulated system based on Smartseal 100P was identified as the most effective coating and Surelease:Opadry the least effective. The developed methodology provides true insight for the formulator, enabling more informed patient-centric formulation decisions, better taste masking, and ultimately more effective medicines.


Subject(s)
Drug Compounding/methods , Drug Development/methods , Drug Liberation , Taste/physiology , Administration, Oral , Adolescent , Adult , Animals , Cellulose/analogs & derivatives , Cellulose/chemistry , Chlorpheniramine/administration & dosage , Chlorpheniramine/pharmacology , Female , Healthy Volunteers , Humans , Hydrogen-Ion Concentration , Inhibitory Concentration 50 , Male , Middle Aged , Rats , Single-Blind Method , Solubility , Sugars/chemistry , Young Adult
13.
Int J Clin Pharmacol Ther ; 56(12): 604-611, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30220290

ABSTRACT

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.
.


Subject(s)
Acetaminophen/administration & dosage , Analgesics, Non-Narcotic/administration & dosage , Antitussive Agents/administration & dosage , Chlorpheniramine/administration & dosage , Common Cold/drug therapy , Dextromethorphan/administration & dosage , Histamine H1 Antagonists/administration & dosage , Influenza, Human/drug therapy , Nasal Decongestants/administration & dosage , Pseudoephedrine/administration & dosage , Acetaminophen/adverse effects , Administration, Oral , Adult , Analgesics, Non-Narcotic/adverse effects , Antitussive Agents/adverse effects , China , Chlorpheniramine/adverse effects , Common Cold/diagnosis , Common Cold/virology , Dextromethorphan/adverse effects , Double-Blind Method , Drug Combinations , Female , Histamine H1 Antagonists/adverse effects , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Male , Middle Aged , Nasal Decongestants/adverse effects , Patient Satisfaction , Pilot Projects , Pseudoephedrine/adverse effects , Remission Induction , Tablets , Time Factors , Treatment Outcome
14.
J Pharm Sci ; 107(12): 3112-3122, 2018 12.
Article in English | MEDLINE | ID: mdl-30176251

ABSTRACT

The landscape of thin films is continuously evolving as an attractive self-administration mean to drive patient compliance. This work reports incorporation of drugs into various polymeric compositions using spin coating technology to screen amorphous solid dispersion film formation for buccal applications. Polarized light microscopy and differential scanning calorimetry were used for characterization. Physical stability was assessed after films storage at 0% RH/25°C for 6 months. Chlorpheniramine maleate, theophylline, and famotidine were used as model drugs and mixed with Opadry amb II® or Kollicoat IR®. Acryl-EZE II® or Zein was also used as surface (design I) or surface and base polymers (design II). Of all the drug-Opadry combinations, only chlorpheniramine was amorphously dispersed up to 25% (w/w). In contrast, Kollicoat IR® resulted in amorphous dispersions of all the tested drugs, suggesting that it has a better solubilization capacity. Drugs prepared in design II achieved higher in vitro release compared to respective design I, indicating that lower content of Acryl-EZE II® or Zein can decrease drug release over 3 h. It has been also revealed that Zein could improve physical stability of the aged theophylline solid-dispersed films. Release kinetics of model drugs were satisfactory when described by first-order kinetics, facilitated through anomalous transport of both diffusion and polymer swelling.


Subject(s)
Drug Delivery Systems/methods , Polymers/chemistry , Administration, Buccal , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/chemistry , Chlorpheniramine/administration & dosage , Chlorpheniramine/chemistry , Drug Liberation , Famotidine/administration & dosage , Famotidine/chemistry , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/chemistry , Histamine H2 Antagonists/administration & dosage , Histamine H2 Antagonists/chemistry , Humans , Polyvinyls/chemistry , Solubility , Theophylline/administration & dosage , Theophylline/chemistry , Zein/chemistry
15.
A A Pract ; 11(7): 181-183, 2018 Oct 01.
Article in English | MEDLINE | ID: mdl-29672323

ABSTRACT

We describe 2 patients who developed anaphylactic shock after sugammadex administration during anesthesia. Both had no history of prior sugammadex administration. The serum tryptase concentrations were elevated after the allergic reaction. Basophil activation testing 1 month after the events was positive for sugammadex in 1 patient, and negative in the other. However, it was positive for light-exposed sugammadex solution in both patients, suggesting a possible allergic reaction to a denatured compound of sugammadex generated by light exposure of the sugammadex solution.


Subject(s)
Anaphylaxis/immunology , Light/adverse effects , Sugammadex/adverse effects , Aged , Anaphylaxis/chemically induced , Anaphylaxis/drug therapy , Anesthesia/adverse effects , Basophils/cytology , Chlorpheniramine/administration & dosage , Chlorpheniramine/therapeutic use , Female , Humans , Male , Methylprednisolone/administration & dosage , Methylprednisolone/therapeutic use , Young Adult
16.
Am J Chin Med ; 46(1): 55-68, 2018.
Article in English | MEDLINE | ID: mdl-29298517

ABSTRACT

This study investigated the influence of the histamine H1 receptor antagonists, chlorpheniramine (CHL) and pyrilamine, on the analgesic effects of acupuncture in mice. Nociceptive response was evaluated by the acetic acid-induced abdominal writhe test. Electroacupuncture (EA) at bilateral ST36 reduced the manifestations of acetic acid-induced abdominal writhing, whereas needle insertion without electrostimulation had no such effect. Notably, EA treatment was not associated with any analgesic effects in mice pretreated with naloxone. Low doses of CHL (0.6[Formula: see text]mg/kg; p.o.) or pyrilamine (2.5[Formula: see text]mg/kg; i.p.) as monotherapy did not affect acetic acid-induced abdominal writhing. However, when each agent was combined with EA, acetic acid-induced abdominal writhing was reduced by a greater extent when compared with EA alone. Interestingly, the effects of CHL on acupuncture analgesia were not completely reversed by naloxone treatment. Acetic acid induced increases of phospho-p38 expression in spinal cord, as determined by immunofluorescence staining and Western blot analysis. These effects were attenuated by EA at ST36 and by low doses of histamine H1 receptor antagonists, alone or in combination. Our findings show that relatively low doses of histamine H1 receptor antagonists facilitate EA analgesia via non-opioid receptors. These results suggest a useful strategy for increasing the efficacy of EA analgesia in a clinical situation.


Subject(s)
Abdominal Pain/physiopathology , Abdominal Pain/therapy , Chlorpheniramine/administration & dosage , Chlorpheniramine/pharmacology , Electroacupuncture , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/pharmacology , Nociception/drug effects , Nociception/physiology , Pyrilamine/administration & dosage , Pyrilamine/pharmacology , Transcutaneous Electric Nerve Stimulation/methods , Abdominal Pain/chemically induced , Acetic Acid/adverse effects , Animals , Drug Combinations , Male , Mice, Inbred ICR , Pain Measurement
17.
Hum Exp Toxicol ; 37(4): 343-349, 2018 Apr.
Article in English | MEDLINE | ID: mdl-28425352

ABSTRACT

BACKGROUND: Accidental drug overdose is a common problem in young children. We examined the influence of formulation and dose in enquiries for different gastro-oesophageal reflux disease treatments in children under 5 years to the UK's National Poisons Information Service. METHODS: Overdose characteristics with ranitidine, omeprazole or domperidone were compared with those of metoclopramide and the H-1 antagonist chlorphenamine, for the period 1 July 2007 to 30 June 2015. RESULTS: There were a total of 1092 ranitidine, 618 domperidone and 1193 omeprazole cases; 669, 281 and 424, respectively, were single agent enquiries; of these 77% (517) of ranitidine, 52% (145) domperidone and 32% (135) omeprazole cases occurred in children <5 years. In comparison, 17% (34/424) of metoclopramide and 53% (533/1013) of chlorphenamine were <5 years; 79% (410/517) of ranitidine overdose enquiries in children <5 years were under 6 months of age, higher than domperidone (68/145, 47%; p < 0.05), omeprazole (8/135, 6%), chlorphenamine (13/553, 2%) or metoclopramide (1/34, 3%) (all p < 0.01). In children aged <6 months, 101 were 10-fold overdoses, 86 with ranitidine. CONCLUSIONS: Tenfold overdoses in children (<5 years) were a feature of ranitidine enquiries, likely due to the high concentration of the syrup. This has relevance to other liquid formulations used for non-licenced indications in young children. Such therapeutic errors cause significant carer anxiety and healthcare utilization. Assistance is needed from manufacturers and legislators in modifying formulation so that drugs can be safely used in young children. Education of prescribers and carers is also needed to reduce the incidence of such errors that cause significant carer anxiety and healthcare utilization.


Subject(s)
Drug Overdose/epidemiology , Gastrointestinal Agents/poisoning , Poison Control Centers , Ranitidine/poisoning , Age Factors , Child, Preschool , Chlorpheniramine/administration & dosage , Chlorpheniramine/poisoning , Databases, Factual , Domperidone/administration & dosage , Domperidone/poisoning , Drug Compounding , Drug Overdose/diagnosis , Female , Gastrointestinal Agents/administration & dosage , Humans , Incidence , Infant , Male , Metoclopramide/administration & dosage , Metoclopramide/poisoning , Omeprazole/administration & dosage , Omeprazole/poisoning , Ranitidine/administration & dosage , Risk Factors , United Kingdom/epidemiology
18.
J Clin Pharmacol ; 58(4): 494-503, 2018 04.
Article in English | MEDLINE | ID: mdl-29136286

ABSTRACT

Two pediatric studies characterized brompheniramine and chlorpheniramine pharmacokinetics in a total of 72 subjects, aged 2 to 17 years. A single age-/weight-based oral dose, ranging from 1 to 4 mg, was administered with 2 to 6 oz of water at least 2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed using high-pressure liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were estimated using noncompartmental methods; relationships with age were assessed using linear regression. Results indicated that for brompheniramine and chlorpheniramine, Cmax was similar across age groups, although it tended to occur earlier in the youngest group. AUC was ∼15% to 30% higher in the oldest age group. As expected, CLo and Vz /F increased with age; however, following allometric scaling, no age-related differences existed. Because the increase with age for both parameters was similar, no age-related differences in t1/2,z existed (∼15 hours). Overall, the single doses were well tolerated. Sedation was the most common reported AE and appeared to be more prevalent in the 2- to 5-year-old group. Overall, these results indicate that an age/weight dosing nomogram using a 4-fold range of doses achieves similar Cmax and AUC.


Subject(s)
Anti-Allergic Agents/pharmacokinetics , Brompheniramine/pharmacokinetics , Chlorpheniramine/pharmacokinetics , Histamine H1 Antagonists/pharmacokinetics , Administration, Oral , Adolescent , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/adverse effects , Brompheniramine/administration & dosage , Brompheniramine/blood , Child , Child, Preschool , Chlorpheniramine/administration & dosage , Chlorpheniramine/blood , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/blood , Humans
19.
J Int Med Res ; 45(4): 1378-1385, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28606015

ABSTRACT

Objectives We evaluated infusion-related reactions associated with cetuximab combination chemotherapy comprising an H1-receptor antagonist plus dexamethasone as anti-allergy premedications for patients with head and neck cancer. Methods We retrospectively evaluated 248 patients who received a cetuximab combination regimen between December 2012 and August 2015. All patients received 5 mg intravenous dichlorpheniramine (H1-receptor antagonist), and dexamethasone (DEX) was adjusted from 6.6 mg to 13.2 mg according to the emetogenic risk. Results We identified 248 subjects, including 13 (5.2%) with infusion-related reactions (grade 1 in five [2.0%], grade 2 in seven [2.8%], and grade 4 in one [0.4%]). The incidence of these reactions in cetuximab combination regimens, each employing an H1-receptor antagonist, using a higher dose of dexamethasone (13.2 mg) was not significantly lower compared with those using 6.6 mg DEX (2.4% vs 8.3%, respectively; p = 0.43). Twelve patients experienced infusion-related reactions associated with the first cetuximab administration, and one reaction occurred after the third administration. Conclusions The incidence of infusion-related reactions was lower compared with those of previous studies. Dexamethasone combined with an H1-receptor antagonist was useful for preventing allergic responses. The incidence of infusion-related reactions was not lower with 13.2 mg dexamethasone, and 6.6 mg DEX prevented infusion-related reactions.


Subject(s)
Antineoplastic Agents, Immunological/adverse effects , Cetuximab/adverse effects , Chlorpheniramine/administration & dosage , Dexamethasone/administration & dosage , Head and Neck Neoplasms/drug therapy , Histamine H1 Antagonists/administration & dosage , Adult , Aged , Antineoplastic Agents, Immunological/administration & dosage , Cetuximab/administration & dosage , Female , Humans , Hypersensitivity/prevention & control , Incidence , Infusions, Intravenous , Male , Middle Aged , Premedication , Retrospective Studies , Young Adult
20.
Am J Med ; 130(9): 1114-1116, 2017 09.
Article in English | MEDLINE | ID: mdl-28601540

ABSTRACT

BACKGROUND: The relationship between anaphylaxis and cardiovascular events has been reported in the past. While skin and respiratory symptoms are usually the most common and the first to appear, cardiovascular complications play a key role and represent the leading cause of death in anaphylaxis. METHODS: We report 3 episodes of atrial fibrillation triggered by anaphylaxis. Allergy and cardiology studies were performed. In both patients, the etiological agent was identified: Anisakis simplex hypersensitivity and food allergy. RESULTS: The heart is the source and target of chemical mediators released during an allergic reaction. In the heart, there are plenty of mast cells, and they are predominantly located around the coronary adventitia and in close contact with small vessels in the muscle wall. The release of mediators can influence ventricular function, heart rate, and coronary artery tone. Anaphylaxis can trigger any kind of arrhythmia. In these cases, the very interesting point of discussion was: which should be first, treating anaphylaxis or cardiac events? The other controversial point was the use of epinephrine, the first line of treatment for anaphylaxis. Recommendations about epinephrine in cardiac patients during an anaphylactic event are still a major dilemma. CONCLUSIONS: We emphasize the importance of the priority of establishing protocols between cardiologist and allergist in treatment of cardiac complications during anaphylaxis, and we warn about the correct diagnosis of arrhythmias in anaphylaxis in order to treat them as soon as possible, to prevent other consequences and complications.


Subject(s)
Anaphylaxis/complications , Atenolol/administration & dosage , Atrial Fibrillation/etiology , Chlorpheniramine/administration & dosage , Epinephrine/therapeutic use , Food Hypersensitivity/complications , Methylprednisolone/therapeutic use , Urticaria/complications , Actinidia/adverse effects , Actinidia/immunology , Administration, Intravenous , Adult , Aged, 80 and over , Anaphylaxis/drug therapy , Anaphylaxis/etiology , Animals , Anisakis/immunology , Anisakis/parasitology , Anti-Arrhythmia Agents/administration & dosage , Anti-Arrhythmia Agents/immunology , Anti-Arrhythmia Agents/therapeutic use , Anti-Inflammatory Agents/administration & dosage , Anti-Inflammatory Agents/therapeutic use , Arachis/adverse effects , Arachis/immunology , Atenolol/immunology , Atenolol/therapeutic use , Atrial Fibrillation/drug therapy , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/therapeutic use , Chlorpheniramine/therapeutic use , Drug Therapy, Combination , Epinephrine/administration & dosage , Food Hypersensitivity/diagnosis , Food Hypersensitivity/drug therapy , Food Hypersensitivity/etiology , Gadiformes/immunology , Gadiformes/parasitology , Histamine H1 Antagonists/administration & dosage , Histamine H1 Antagonists/therapeutic use , Humans , Hypodermoclysis , Male , Methylprednisolone/administration & dosage , Urticaria/etiology , Urticaria/immunology
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