Antitussive Agent Research Articles

Effectiveness of Peripheral Antitussives in Patients with Dry Postinfectious Cough

Abstract Background: Postinfectious dry cough can significantly worsen the quality of life of patients, which forces them to seek medical help. To relieve this symptom, peripheral antitussive agents are most often used, since they have a high profile of effectiveness and safety. Subjects and Methods: The study used levodropropizine, which was prescribed to a study group consisting of 100 patients with dry postinfectious cough, at a dosage of 10 ml (60 mg) 3 times a day for 7 days. The comparison group consisted of 34 patients with dry postinfectious cough who refused to take levodropropizine or had contraindications to taking it. On the 1st, 4th, and 8th days of the study, complaints were collected, an objective examination, and an assessment of cough intensity using 6-point scales for evaluating day and night cough, as well as a Visual Analog Scale were conducted. In addition, undesirable side effects were assessed at each visit. Results: It was found that during 7 days of treatment with levodropropizine, the intensity of cough on the above-mentioned scales significantly decreased, and no side effects were observed in any patient. Conclusions: The resolution of the cough syndrome occurred faster when taking a peripheral antitussive drug (levodropropizine). Moreover, no side effects were reported in any of the subjects. Therefore, peripheral antitussives have a high efficacy and safety profile against dry postinfectious cough.

In vitro plant regeneration and bioactive metabolite production of endangered medicinal plant Fritillaria cirrhosa

The bulb of Fritillaria cirrhosa D. Don is widely used for the anti-asthmatic, anti-tussive, and anti-cancer agents, etc., while the yield is limited by an endangered status, a long juvenile phase, and restricted growth habitat. Ancillary approaches to improve the bulb yield by micropropagation and bioactive metabolites production by bioreactor have not been established. Here is reported the plant regeneration, suspension cell culture, and bioactive metabolite production at different treatments. The embryogenic calli were successfully induced via the histomorphological identification. The highest proliferation times (4.11-fold) were observed with a select combination of hormones [NAA (0.2 mg/L) + 6-BA (1.0 mg/L) + GA3 (1.0 mg/L)] and culture conditions (red light and 20 °C), the highest content of imperialine (0.13 mg/g) was observed under blue light, total phenolic (0.52 mg/g) under red light, polysaccharides (36.57 mg/g) and total flavonoids (2.67 mg/g) as well as antioxidant capacity under white light. The plantlets were regenerated within 125 d from the induced embryogenic calli to acclimation and transplantation of seedlings. For the suspension cell culture, a 6.30-, 1.78-, 1.37-, and 1.51-fold increase of proliferation times, imperialine, polysaccharides, and total phenolic contents was observed at 40 d, respectively. Based on the above observations, an effective and complete in vitro approach has been proposed to regenerate plants and produce bioactive metabolites in F. cirrhosa.

Unlocking the food treasures: Trachyspermum ammi–A comprehensive exploration from field to pharmacology

AbstractRecent pharmacological research on Tracyspermum ammi has unveiled its diverse medicinal properties, bolstering its status as a notable herbaceous plant. Cultivated extensively in regions like Egypt, Iran, Afghanistan, Pakistan, and India, T. ammi has drawn attention due to its rich essential oil content, prominently thymol. Commonly used in food processing, such as in pickles, this plant exhibits a wide array of pharmacological effects, from diuretic and antibacterial properties to potential as an antitussive, antiplatelet, antihypertensive, bronchodilator, and antihyperlipidemic agent. While the medicinal potential of T. ammi is acknowledged, challenges persist in optimizing its efficacy. The preclinical and clinical trials of T. ammi have been performed and data are compiled to assess its efficacy in humans. Novel drug delivery systems, including nanoparticles, microemulsions, niosomes, and liposomes, among others, offer a means to overcome the constraints associated with conventional formulations. In conclusion, the comprehensive overview presented here highlights the morphological characteristics, food processing, chemical constituents, pharmacological significance, preclinical and clinical trials along with traditional use and novel dosage forms of T. ammi which underscores the need for modernization in drug delivery systems to maximize its therapeutic potential thereby advancing the addition of herbal medicines into contemporary healthcare practices.

Effect of Ambrosia arborescens Mill. ethanolic extract on breast cancer induced in rats.

Ambrosia arborescens Mill. (A. arborescens) is an aromatic plant used in traditional medicine as an anti-inflammatory, anti-tussive, anti-rheumatic, and anti-diarrheal agent. This study aimed to evaluate the effect of A. arborescens Mill. on a Rattus norvegicus var. albinus-induced breast cancer model. We collected A. arborescens from the province of Julcán, La Libertad Region, Per, and prepared an ethanolic extract using pulverized leaves macerated in 96° ethanol for 72 h with magnetic stirring. In the evaluation of anticancer activity, four experimental groups with 10 female rats each were formed: Group I (Control-7,12-dimethylbenz[a]anthracene [DMBA]), which received DMBA (single dose) and physiological saline solution for 4 months, and Groups II, III, and IV, which received DMBA (single dose) and 200, 400, and 600 mg/kg/day of the ethanolic extract of A. arborescens, respectively, for 4 months. The DMBA control group presented histological characteristics of ductal carcinoma in situ with necrotic and inflammatory areas, whereas the A. arborescens extract group showed a decrease in tumor volume and recovery of the ductal duct. Ethanol extract of A. arborescens leaves decreases tumor development in rats with induced breast cancer, and this effect is dose-dependent.

Modern Treatment of Dry Post-viral Cough. Focus on Efficiency and Safety

Cough is the most common symptom of bronchopulmonary diseases, about which patients consult the doctors of both primary and secondary care. Cough can be caused by diseases of the respiratory tract, digestive tract, and cardiovascular diseases. However, cough most often develops during acute respiratory viral infections (ARVI), which disrupts the patient’s normal activities and limits his work capacity. Since most respiratory infections are viral in nature, the use of antibacterial drugs will not only be of no benefit, but will also significantly worsen the patient’s condition. The objective: to analyze the effectiveness and tolerability of a combined antitussive agent, which includes codeine, thermopsis extract, licorice root and sodium bicarbonate, in the treatment of dry post-viral cough. Materials and methods. The study included 60 patients with a dry cough that caused by ARVI, namely: 49 (82%) men and 11 (18%) women. The average age of the patients was 46±4.7 years. Most of the subjects (90%) had smoking experience of more than 20 years. The research participants were divided into two groups of 30 people each. The groups were comparable by age, duration and severity of symptoms, as well as clinical manifestations of respiratory disease. The patients of the first group took a combined antitussive drug containing codeine, thermopsis extract, licorice root, and sodium bicarbonate for 5 days. Patients of the second group received alternative antitussive drugs. At the beginning and at the end of treatment, the severity of cough was determined on a visual analog scale and the physical, psychological and social conditions of patients in both groups were assessed using the Leicester Acute Cough Questionnaire. Results. As a result of the research, it was found that the patients of the first group, who received the combined antitussive drug, have achieved the desired treatment result much earlier and more effectively than the patients of the second group. The intensity of their cough decreased by 2.5 times during the treatment period. The patients of the first group also had better results of treatment, comparing indicators of physical, psychological and social conditions. In the control group, positive results of treatment were determined, although a less significant effect was found. Conclusions. The conducted study confirmed the high efficiency of the combined antitussive agent, which includes codeine, thermopsis extract, licorice root and sodium bicarbonate, in the treatment of dry debilitating cough caused by ARVI. Thanks to the use of this drug, the severity of cough significantly decreased, which led to a significant improvement in the general condition and quality of life of patients.

A novel electrochemical sensor based on a Cu-coordinated molecularly imprinted polymer and MoS2 modified chitin-derived carbon for selective detection of dextromethorphan.

Dextromethorphan (DXM) is a widely utilized central antitussive agent, which is frequently abused by individuals seeking its recreational effect. But DXM overdose can cause some adverse effects, including brain damage, loss of consciousness, and cardiac arrhythmias, and hence its detection is significant. Herein, an electrochemical sensor based on a Cu-coordinated molecularly imprinted polymer (Cu-MIP) was fabricated for its detection. For constructing the sensor, nitrogen-doped carbon nanosheets (CCNs) were prepared through calcining chitin under an argon atmosphere, and molybdenum disulfide (MoS2) was allowed to grow on their surface. Subsequently, the obtained MoS2/CCNs composite was employed to modify a glassy carbon electrode (GCE), and the Cu-MIP was electrodeposited on the electrode in a Cu-1,10-phenanthroline (Cu-Phen) solution containing DXM, where Cu2+ played a role in facilitating electron transfer and binding DXM. Due to the large specific surface area, good electrocatalytic properties and recognition of the resulting composite, the resulting Cu-MIP/MoS2/CCNs/GCE showed high selectivity and sensitivity. Under optimized experimental conditions, the peak current of DXM and its concentration exhibited a good linear relationship over the concentration range of 0.1-100 μM, and the limit of detection (S/N = 3) was 0.02 μM. Furthermore, the electrochemical sensor presented good stability, and it was successfully used for the determination of DXM in pharmaceutical, human serum and urine samples.

Comparative analysis of essential oil containing raw materials of honeyherb (Lippia dulcis Trevir.) under different growing conditions

The use of plant raw materials is one of the areas of modern pharmaceutical science in the production of herbal drugs. In this regard, one of the oldest medicinal plants, Lippia dulcis Trevir (Phyla scaberrima (Juss. ex Pers.) Moldenke) from Verbenaceae family, is of great interest. According to traditional Mexican medicine, Lippia dulcis is used in the treatment of colds, coughs, bronchitis, and digestive disorders as an anti-inflammatory, antitussive, antipyretic, expectorant, emollient and diuretic agent.
 The aim. The aim of our study was to identify and determine the quantitative content of essential oils by GC/MS method in Lippia dulcis herb shoots.
 Materials and methods. The determination of the essential oil composition of Lippia dulcis was conducted using Agilent Technologies' 6890 chromatograph with mass spectrometric detector 5973 (Agilent Technologies, USA).
 Results. The GC/MS method 19 components of essential oil were identified in L. dulcis shoots grown in open soil conditions, the total content of which was 1274.82 μg/g, in L. dulcis shoots grown in closed soil conditions - 23, the total content of which was 2361.11 μg/g. Thus, the total content of essential oil in shoots of L. dulcis grown in closed soil conditions was 1.8 times higher than in shoots of L. dulcis grown in open soil conditions.
 Conclusions. The component composition of the essential oil of L. dulcis shoots harvested from plants grown in open soil conditions (LD-1) and closed soil conditions (LD-2) was investigated using the chromato-mass spectrometric method. The following pharmacologically important components - camphor, germacrene D, caryophyllene, α-bisabolene - were found in both samples of the essential oil of L. dulcis shoots in significant quantities, which indicates the prospects for further technological and pharmacological studies of honey herb raw materials

Search for the Natural Remedies for the Treatment of Dry Cough

Search for the Natural Remedies for the Treatment of Dry Cough

Population pharmacokinetic modeling of levodropropizine: extended application to comparative analysis between commercial formulations and exploration of pharmacokinetic effects of diet.

Levodropropizine, a nonopioid antitussive agent, is being increasingly used in clinical practice with the development of several formulations for symptomatic relief of acute and chronic bronchitis. However, scientific and quantitative population pharmacokinetic analyses of levodropropizine are lacking. Moreover, no integrated quantitative comparison has been performed between formulations. This study quantitatively evaluated and predicted pharmacokinetic properties of formulations through population pharmacokinetic model-based comparisons of commercially available formulations. Plasma concentration profile results from bioequivalence studies of 60-mg immediate release (IR) levodropropizine tablets in 40 healthy Korean males were used as population pharmacokinetic modeling data. For interindividual variability in levodropropizine pharmacokinetics, body surface area was identified as an effective covariate that was positively correlated with peripheral compartment distribution volume. Population pharmacokinetic model for IR tablets well-described the levodropropizine syrup and capsule datasets, suggesting no significant differences in pharmacokinetics among IR tablets, syrups, and capsules of levodropropizine. In contrast, pharmacokinetic profiles differed between 90-mg controlled release (CR) and IR levodropropizine tablets; however, separate parameter estimation was possible by applying the same model structure. In terms of pharmacokinetics, twice-daily regimen of 90-mg CR tablets was equivalent to thrice-daily regimen of 60-mg IR tablets. However, at steady-state, interindividual plasma concentration variability within population was reduced by approximately 36.71-83.18%. For levodropropizine CR tablets, a high-fat diet significantly delayed gastrointestinal absorption but maintained overall plasma exposure equivalent. This study provides useful quantitative judgment data for precision medicine of levodropropizine and can be helpful in predicting the pharmacokinetics of levodropropizine based on commercialized formulation switching.

Gender Differences in Antitussive Prescriptions for Chronic Cough in Korea.

Background: We investigated the differences in the characteristics and prognoses between the sexes of patients with chronic cough who were prescribed antitussive agents, using a Korean population-based database. Methods: Claims data from South Korea's Health Insurance Review and Assessment (HIRA) service were analyzed. This retrospective observational cohort study considered chronic cough patients aged 18 years and older who were consistently prescribed antitussive agents for more than 2 months between 1 January 2017 and 30 June 2019. Results: Among the 207,989 patients treated for chronic cough, the prevalence of unexplained cough was higher in women (men: 6.2% vs. women: 9.7%) and the prevalence of persistent cough was higher in men (men: 16.8% vs. women: 14.3%). The gap in the proportion of COPD, lung cancer, ILD, GERD, and TB between women and men were largest around the age range of 60-70 years. With the exception of those in their 60s and 70s, women were more likely to have chronic cough and persistent cough than men. Women were more likely to discontinue medication after treatment completion than men. Only 53.9% of patients discontinued cough medication for more than 6 months after treatment completion. Within 12 and 18 months, respectively, 8.9% and 11.9% of them revisited the hospital for chronic cough. Via Cox regression analysis, an age in the 60s or 70s and explained cough were independently associated with a higher risk of revisit for treatment. Conclusions: Among patients treated for chronic cough, there were distinct differences in cough characteristics and prescription status between men and women. Our data highlight the need for a new personalized treatment approach to chronic cough, taking into account the gender, age, and underlying diseases of patients. Further research is needed to determine whether appropriate underlying disease control and gender-specific treatment are effective for managing chronic cough.

B-330 Homogeneous Enzyme Immunoassay for Hydrocodone

Abstract Background Hydrocodone is a semi-synthetic derivative of codeine and produces opioid-like effects similar to morphine. Hydrocodone (Trade names: Vicodin, Lortab, Hycodan, Vicoprofen) is one of the most frequently prescribed opioids in the U.S. as an antitussive (cough suppressant) and narcotic analgesic agent for the treatment of moderate to severe pain. Its ease of prescription and opioid-like effects has led to widespread drug diversion and abuse. The two commercially available homogeneous immunoassays for the detection of hydrocodone in urine at a cutoff of 300 ng/mL suffer undesirable cross-reactivity to oxycodone and morphine at concentrations below 25 000 ng/mL. ARK Diagnostics has developed the ARK Hydrocodone Assay to detect hydrocodone at a cutoff of 300 ng/mL with no cross-reactivity to oxycodone, morphine, and codeine at concentrations below 100 000 ng/mL. Methods The ARK™ Hydrocodone Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, with a cutoff of 300 ng/mL and semi-quantitative range up to 800 ng/mL. The performance of this assay was evaluated on the Beckman Coulter AU680 Automated Clinical Chemistry Analyzer. Precision, spiked recovery, specificity, Histogram Overlap Analysis of ±25% controls and the cutoff, and method comparison with LC-MS/MS were evaluated. Results In semi-quantitative mode, total precision ranged from 3.9% to 9.9%CV. Spiked recovery of hydrocodone ranged from 86.2% (720 ng/mL) to 102.9% (240 ng/mL). The active metabolite, hydromorphone, showed an approximate equivalence to the 300 ng/mL hydrocodone cutoff at 299 ng/mL (100.3% cross-reactivity). Histogram overlap analysis showed no overlap between cutoff and control levels. Method correlation with LC-MS/MS using authentic urine samples showed an excellent agreement with a specificity of 100% and sensitivity of 96.9% (98 positives and 128 negatives). Conclusion The ARKTM Hydrocodone Assay measures hydrocodone and its metabolite hydromorphone in human urine with acceptable performance. The assay is sensitive, rapid, and applicable to a wide range of clinical chemistry analyzers.

Levodropropizine: A promising peripherally acting antitussive agent

Cough is one of the most frequent symptom for patients to seek medical attention. Cough can be associated with many disease processes and the ultimate treatment depends on determining the etiology and diagnosis. Antitussive agents with different mechanisms of action have been developed in the past, but there are still very few medications that seem to be effective without any side effects especially related to central nervous system (CNS). Levodropropizine is an antitussive agent which acts peripherally and is a non-opioid cough medication that is in use since many years as a symptomatic therapy for cough. Levodropropizine has potent antitussive activity mainly due to peripheral effects by inhibiting the activation of vagal C-fibers. In fact, levodropropizine has been proven effective in controlling cough and is devoid of the central depressant effect. Levodropropizine oral suspension (30mg/5ml) is approved by drug approval body of India, Drug Controller General of India (DCGI) for the management non-productive cough in adults. Levodropropizine is approved in some of the European countries and in Asian countries. It is widely used in Republic of Korea for the symptomatic treatment of cough in both adults and children above 2 years of age. Levodropropizine has the utmost level of benefit in comparison with central antitussive agents namely codeine and dextromethorphan for the patients with cough due to acute and chronic bronchitis.

Ambroxol: A potential therapeutics against neurodegeneration

Ambroxol hydrochloride is a pharmacological chaperone approved by FDA as an expectorant. Currently, it is used as an antitussive and anti-asthmatic agent. Besides mucolytic properties, ambroxol has antioxidant, anti-inflammatory, and anesthetic properties. Its effects on the central nervous system (CNS) are currently being explored. Ambroxol has been reported to inhibit microglial activation and decreases proinflammatory cytokines in the brain. It crosses the blood-brain barrier and may be neuroprotective in Parkinson's, Amyotrophic lateral sclerosis, Gaucher disease, neuroinflammation, and spinal cord injury. Here we review the CNS effects of ambroxol and its therapeutic potential against neurodegenerative disorders.

INDIan Consensus on the mAnagemenT of cOugh at pRimary care setting (INDICATOR).

Cough has a prevalence of 9.6% globally and 5-10% in India. Though it is a reflex action, it affects an individual's quality of life (QoL) when uncontrolled. There was a need to create an integrated guidance document on managing cough focused on primary care physicians in the Indian setting. This consensus intends to bridge this gap by providing clinical recommendations to diagnose and manage cough in primary healthcare in India. The modified Delphi method was used to arrive at a consensus on clinical statements. The panel comprised 10 experts, including pulmonologists, otolaryngologists, a pediatrician, and a general physician. The statements were discussed under the following domains: definition, etiology, diagnosis, and treatment. A total of 109 clinical statements were framed, with 75 reaching consensus, 13 reaching near consensus, and 21 reaching no consensus. The experts recommended empiric use of nonopioid antitussive agents for symptomatic relief of acute dry cough. The use of oral antihistamines, oral decongestants, or mucoactive agents as a part of fixed-dose combinations (FDCs) in cough associated with rhinitis or upper airway cough syndrome (UACS) can be considered for symptomatic relief. Maintaining good hydration is important to manage a productive cough. Codeine-based preparations are to be considered as a last resort in patients with an unexplained chronic cough when other treatments have failed. Additionally, insights were captured on red flag signs, nonpharmacologic therapy, special populations, and referral to higher centers. Experts have also proposed a management algorithm with an integrated care pathway approach for acute, subacute, and chronic coughs. The present consensus fills the existing need and may guide the physician to successfully diagnose and manage cough in the primary healthcare setting in India.

A Newer Approach in the Management of Cough: A Review on Levodropropizine

Safe and effective antitussive therapy remains a significant area of unmet need for cough management. Antitussive drugs are commonly used cough suppressants and include centrally acting (opioids and non-opioids) cough suppressants and peripherally acting antitussives. Authors searched PubMed, Google Scholar and additional studies from reference lists via cross-referencing to identify studies assessing levodropropizine for the treatment of cough. Of the 748 studies identified, 13 were included. Recent clinical evidence, guideline recommendations and findings from this review suggest that levodropropizine is a peripheral antitussive which reduces cough intensity, frequency, and nocturnal awakenings in children and adults and provides better efficacy outcomes with a more favourable risk/benefit ratio compared to centrally acting antitussive agents which pose greater safety concerns and present an unacceptable risk–benefit profile. This review is aimed at Indian primary care physicians for making effective cough management decisions where the clinical evidence needs to be translated to clinical practice. Key messages The usage of currently available centrally acting antitussive agent is greatly limited by their central depressing action and frequent side effect. The findings of this review indicate that levodropropizine is an effective antitussive agent and well tolerated in the management of cough in patients of all ages.

Screening and Partial Characterization of Secondary Metabolite of Salacia korthalsiana Miq. (Polipog) Root Decocted Extract

A cough is a sudden and often repetitive reflex that helps clear the air passages from secretions, irritants, and foreign particles, including microbes. Coughing can be due to a respiratory tract infection or choking, smoking, air pollution, asthma, chronic bronchitis, medications, and a variety of many other factors which becomes an emerging health problem in the globe. This study investigated the role of Salacia korthalsiana Miq. (Polipog) root decoction as anti-coughing agent through screening and partial characterization of secondary metabolite. The physical properties determined in the root sample were: boiling point 99.3 , brownish red in color with a pleasant odor; pH 5.86 and soluble in water and ethanol which makes the Polipog root extract polar. Phytochemical screening was used for the determination of active chemical properties for anti-cough. Further, Fourier Transform Infrared spectroscopy were used to determine the active functional group for anti-cough. Among the chemical properties determined for anti-cough only steroids and saponins are present, which is an antitussive and expectorant agent. Fourier Transform Infrared analysis showed that the main functional groups present are: the amine and ethers, which are medically active for medicinal purposes. Therefore, Polipog roots are positively active for anti-cough.

Benzonatate as a local anesthetic.

Benzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade. Benzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis. Benzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations. This study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations.

Role of antitussive agents in the treatment of acute respiratory viral infections and influenza

Viral upper respiratory infection (VURI)-associated acute cough is the most common symptom worldwide among children and adults. It causes serious economic and social problems both for individual patients, patients’ families, and the health care system as a whole. There is still no effective pharmacological agent capable of interfering with all the main pathophysiological mechanisms involved in VURI-associated acute cough. This circumstance partly explains the increased prevalence of the prolonged course of acute respiratory infections, when the cough takes on the features of subacute or post-infectious course. The pathophysiology of this symptom is being actively investigated to optimize the treatment of cough. A viral infection provokes an acute cough induced by various irritative stimuli, the main one being secretions from the respiratory tract, which directly acts on reflexogenic areas of the mucosa. Inflammatory mediators also play an important role, acting on the peripheral sensory terminations of airways. Inflammatory mediators also induce post-infectious bronchial hyperreactivity, which is an important component of the pathogenesis of post-infectious cough. Recently, researchers are becoming increasingly interested in the role of the voluntary or conscious cough component, which is implemented due to the cortical response to afferent information from the receptors of the upper respiratory tract.This hypothesis explains the ineffectiveness of central antitussive agents in patients with viral infection-associated dry cough and expands the possibilities of peripheral antitussive agents represented by levodropropizine. In addition to the action on nerve endings, the agent also affects inflammatory mediators, which enhances its ability to break the “vicious circle” of this symptom, prevents the development of post-infectious cough and promotes rehabilitation of the bronchial tree. The efficacy and safety of levodropropizine has been demonstrated in clinical trials in both children and adults.

Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study.

Cough is a wearisome and exasperating symptom affecting the daily life of the infected patient. Cough due to coronavirus disease 2019 (COVID-19) causes excessive morbidity in human populations globally. Apart from the morbidity associated with cough, it also enhances the transmission of this viral infection through droplets. Therefore, curbing cough is crucial to limit its spread. Patients often administer over-the-counter products and antitussive agents, which have no proven benefit. The present study was undertaken to find out if cough associated with COVID-19 and other indicative clinical outcomes is alleviated with a budesonide/formoterol fixed-dose combination (FDC) metered-dose inhaler (MDI). A prospective observational study was conducted in mild COVID-19 patients who presented with a cough score ≥8 at presentation. Patients who were initiated on ICS-LABA MDI were observed as group A and those who were not initiated on MDI were observed as Group B. Cough symptom score (at baseline and on day 3 and day 7), the incidence of hospital admission and/or death, and need for mechanical ventilation were documented. Prescribing patterns of anti-cough medications were also noted and analysed. Compared to group B, a higher mean cough score reduction was noted for group A patients at day 3 and day 7 when compared to the baseline, and this was significant at P < 0.001. A significant negative correlation was also observed between mean latency of MDI initiation from the symptom onset and mean cough score reduction. Analysis of the proportion of patients prescribed medications to treat cough showed that overall, 10.78% did not require these, with a greater proportion in group A compared to group B. Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 who were treated with ICS-LABA MDI along with usual care benefitted significantly in terms of symptom reduction compared to usual care.

Papaver somniferum in seventeenth century (Italy): archaeotoxicological study on brain and bone samples in patients from a hospital in Milan

In this paper, we present the results of toxicological analyses of preserved brain tissue and bone samples from the remains of the seventeenth century patients of the Ospedale Maggiore, the main hospital in Milan and one of the most innovative hospitals in Europe from the Renaissance period. Beneath it, the crypt functioned as the burial place for the deceased of the hospital. In this multidisciplinary study of the remains, toxicological analyses in particular were performed with HPLC–MS/MS on different biological samples from nine individuals. Anthropological, paleopathological, histological, radiological examinations and radiocarbon dating were also carried out. As a result, archeotoxicological analyses revealed the presence of codeine, morphine, noscapine and papaverine, derived from Papaver somniferum, a plant present in the hospital pharmacopeia used as a narcotic, analgesic, astringent, coagulant, and antitussive agent. Such analyses have shed light on the pharmacological therapies administered to the patients near the time of death and have implemented our knowledge of medical treatment and drug administration in the 1600’s.