Combined drugs in the treatment of acute respiratory viral infections: a review of research results

Acute respiratory infections are of the greatest economic significance among all infectious diseases in the Russian Federation. There are no drugs with a direct antiviral effect for most acute respiratory viral infections, which efficacy would have been proven in the numerous clinical trials and confirmed by the results of meta-analyses today. The use of various combinations of antipyretic, anti-inflammatory and antioxidant drugs is the most common method of symptomatic and pathogenetic therapy of acute respiratory viral infections (ARVI). The purpose of this review is to analyse and systematize the results of preclinical and clinical trials aimed at studying the safety and efficacy of fixed-doses combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy. The search of scientific publications was carried out in the PubMed, ClinicalKey ELSEVIER and Google Scholar databases. The search depth was 10 years. The results of numerous comparative and placebo-controlled trials showed that the use of fixed-dose combinations of paracetamol, pheniramine maleate, phenylephrine hydrochloride and ascorbic acid in the ARVI therapy was pathogenetically justified, safe, and effective in relieving symptoms such as fever, rhinitis, cough, muscle and joint pain, sore throat, and headache. The combination drugs can ease the patient’s condition and help shorten the duration of the illness provided that they are administered in due time. Meanwhile, the pathogenetic effects of combination drugs aimed at localizing the focus of inflammation and minimizing the risk of complications warrant further research.

Possible antivirulent activity of some agents against clinical isolates of Pseudomonas aeruginosa

Background: Pseudomonas aeruginosa has developed different mechanisms of resistance against antibiotics and became one of the most life-threatening pathogens. Fighting against its virulence Factors are an alternative therapeutic target. Objective: This study was directed towards the investigation of anti-quorum sensing activity and inhibitory action on virulence factors of different agents including antibacterial agents to which Pseudomonas aeruginosa isolates are resistant and non-antibacterial agents. Methodology: Anti-quorum sensing activity of ceftriaxone, ceftazidime (CAZ), cefepime (FEP), vancomycin (VA), paracetamol (PA), and pheniramine maleate (PHE) investigated as well as their ability to reduce other virulence factors including protease, hemolysin, and pyocyanin production. Results: This study showed that 3rd and 4th generations cephalosporins could be used as anti-quorum sensing agents effectively in the treatment of Pseudomonas aeruginosa infections, however, vancomycin, paracetamol, and pheniramine maleate had no effect on inhibiting the studied virulence factors. Conclusion: From our study we conclude that although cephalosporins at the used concentrations did not show anti-pseudomonal activity they were effective as anti virulent agents that could be utilized in therapeutically in controlling Pseudomonas aeruginosa infections.

Intra-arterial injection of bradykinin produces reflex cardiorespiratory changes involving histamine receptors in anesthetized rats

Objectives: It is well known that intra-arterial injection of nociceptive agent produces vasosensory reflex responses altering cardiorespiratory parameters. The role of various inflammatory mediators is also implicated in the regulation of these reflex responses. However, the role of histamine in this regard is not clear. This study was performed to understand the role of H1 and H2 receptors in modulating the cardiorespiratory responses evoked after i.a. injection of bradykinin (BK). Materials and Methods: Male albino rats were anesthetized with an intra-peritoneal injection of urethane (1.5 g/kg). Tracheostomy was performed to keep the respiratory tract patent. The femoral artery was cannulated proximally by pediatric i.v. cannula (24 G, double ported). This cannulation was used for the blood pressure (BP) recording as well as for the drugs instillation as it contains double port with injection valve. The effect of BK (1 µM) on BP, electrocardiographic, and respiration was recorded for 30 min. The respiratory frequency, respiratory minute volume, mean arterial pressure, and heart rate were computed from the original tracings and the data were presented as mean ± SEM. Results: Intra-arterial injection of BK produced immediate hyperventilatory (50% from initial), hypotensive (40% from initial), and bradycardiac responses (17% from initial) of shorter latency (5–8 s) indicating the neural mechanisms in producing the responses. Pre-treatment with pheniramine maleate significantly attenuated the BK-induced hyperventilatory (11% from initial), hypotensive (8% from initial), and bradycardiac responses (2% from initial). Conclusion: Our data provide evidences for the involvement of H1 and H2 receptors in producing the BK-induced vasosensory reflex responses modulating the cardiovascular parameters in anesthetized rats.

Determination of naphazoline HCl, pheniramine maleate and their official impurities in eye drops and biological fluid rabbit aqueous humor by a validated LC-DAD method

Analysis of naphazoline HCl, pheniramine maleate and three selected impurities in their quinary mixture, eye drops and spiked rabbit aqueous humor.

Effect of methonolic extract of Vitex negundo on haloperidol induced catalepsy in albino mice

Background: Plants are being used in traditional medicine since history of mankind. The knowledge of these medicinal plants has accrued in the course of many centuries leading to medicinal systems in India such as Ayurveda, Unani and Siddha. Objective: In the present study, we evaluated the anticataleptic efficacy of Vitex negundo, a polyherbal formulation in haloperidol induced catalepsy in mice.Methods: Five groups (n=6) of male albino mice were used in the study. Catalepsy was induced by i.p. administration of haloperidol (1 mg/kg). The degree of catalepsy (cataleptic score) was measured as the time the animal maintained an imposed posture. We compared the anticataleptic efficacy of Vitex negundo (50, 100, 200 mg/kg) with standard received Pheniramine maleate 10 mg/kg, i.p.Results: In vehicle treated animals, haloperidol (1 mg/kg. i.p.) produced the maximum catalepsy at 180 min (46.78±3.78 min). Standard treated as Pheniramine maleate 10 mg/kg, i.p. shows maximum at 120 min. 19.24±1.32. Test herb, i.p. Methanolic extract of Vitex negundo (50, 100, 200 mg/kg, i.p.) significantly potentiated haloperidol induced catalepsy at each time interval, in a dose dependent manner. At dose 50, 100 and 200mg/kg, extract of Vitex negundo (Linn.) roots showed maximum cataleptic score 12.34±0.78, 14.43±0.43 and 15.43±0.67 min, respectively at 120 minutes in haloperidol treated animals.Conclusions: The present study indicates that the methanolic extract of Vitex negundo reduces haloperidol-induced catalepsy in mice.

Methods of the matrix analysis and graphic ranking of the array of the experimental IR spectroscopy data in studying the inter-component processes in the mixture of pheniramine maleate and naproxen

A widespread use of complex pharmacotherapy entails the necessity of studying the processes occurred in pharmaceutical mixtures. IR spectroscopy is one of the methods used to assess the stability of substances. To increase the efficiency of interpretation of the IR spectra of mixtures, a method combining matrix methods and graphic ranking of the array of experimental data has been developed. This approach has been tested for the analysis of model mixtures of pharmaceutical substances naproxen and pheniramine maleate. Absorption spectra were obtained on an Avatar 360 FT-IR ESP Fourier transform spectrometer (Nicolet, USA) using an ATR (primary attenuation total reflection) attachment Smart Perfbmer (optical crystal ZnSe; spectral range 1.35 - 26.6 pm, 7400 - 375 cm4). The obtained IR spectra were processed using Thermo Scientific Specta embedded software. Graphs for graphical ranking were plotted in the coordinates of the mixture heating temperature —relative frequency intensity. The points on the graph represent the relative intensity of the bands for a mixture kept at a certain temperature, whereas the curves with which they are connected reflect the processes occurring in the structure of the substance. Common trends in the relative intensity for different frequencies (at the same temperature) and/or for a number of frequencies of a certain characteristic region, indicates the unidirectionality of the process. Graphic ranking is applied to the characteristic bands of pyridine and aliphatic nitrogen of pheniramine maleate and characteristic frequencies of the intermolecular hydrogen bond and carbonyl group of naproxen. We also used the method of mathematical ranking of the matrices of transmittance values. For the characteristic bands of the studied compounds, a combined use of graphical and mathematical ranking allowed us to infer a change in the structure of naproxen and pheniramine maleate under the impact of elevated temperatures: the salt of pheniramine and maleic acid in aliphatic nitrogen has one structural conformation, whereas the binding force depends on the temperature.