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Efficacy and Safety of Oral Phenylephrine: Systematic Review and Meta-Analysis
Abstract
Oral phenylephrine is used as a decongestant, yet there has been no previously published systematic review supporting its efficacy and safety.
To assess the efficacy and safety of oral phenylephrine as a nonprescription decongestant.
MEDLINE, the Cochrane Central Registry of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, and the Federal Register were searched for English and non-English-language studies published through January 2007 that measured the effects of oral phenylephrine on nasal airway resistance (NAR) in patients with nasal congestion. The retrieved studies were supplemented with information from our personal files and by hand searches of the references in any of the studies. Additionally, a Web of Science Search was conducted using the Cited Reference function for all published clinical trials identified. Studies included in the analysis were randomized, placebo-controlled trials; studies of combination products were excluded. Two investigators independently extracted data on NAR, self-reported decongestant effects, and cardiovascular effects (ie, heart rate, blood pressure) from each of the included studies. Meta-analyses were performed for NAR and cardiovascular effects using a random effects model. Subjective decongestant effects were summarized.
Based on 8 unpublished studies that included 138 patients, phenylephrine 10 mg did not affect NAR more than placebo; the mean maximal difference in relative change from baseline between phenylephrine and placebo was 10.1% (95% CI -3.8% to 23.9%). Eight unpublished studies on phenylephrine 25 mg showed a significant reduction of maximal NAR compared with placebo of 27.6% (95% CI 17.5% to 37.7%). There was significant heterogeneity among the studies included in this analysis, which was partially attributable to different laboratories and methods used. Patient-reported decongestion was not consistently better for any phenylephrine dose compared with placebo, and NAR was a more sensitive measurement of efficacy. Phenylephrine showed no consistent effect on heart rate or blood pressure for doses of 25 mg or less.
There is insufficient evidence that oral phenylephrine is effective for nonprescription use as a decongestant. The Food and Drug Administration should require additional studies to show the safety and efficacy of phenylephrine.
... Decongestants are useful in alleviating the symptoms of nasal obstruction because they promote vasoconstriction inside the nasal mucosa by activating α-adrenergic receptors. However, these medications have little impact on symptoms like runny nose, itchy eyes, or sneezing; therefore, they may work best when combined with antihistamines or other medications [128], [129]. Prescribing nasal decongestants (alpha-sympathomimetic) should be limited to a few days at most, as prolonged use can lead to rebound effects on the nasal mucosa and habituation [130]. ...
... [128], [129] Pseudoephedrine This medication is not recommended for children under 4 years of age. ...
Allergic rhinitis is the most common chronic disease affecting children and is frequently undiagnosed and untreated due to their limited ability to express symptoms. This condition significantly impacts psychosocial well-being, learning capacity and quality of life and is associated with potential complications like asthma, sinusitis and otitis media. Recognizing signs such as allergic shiners, creases and salute is vital for identification. Allergic rhinitis arises from an immune overreaction to environmental allergens, triggering the release of inflammatory mediators. Symptoms include congestion, sneezing, itching and rhinorrhea. Treatment options emphasize environmental control, although complete allergen avoidance may not be feasible. Initial therapy comprises nonsedating second-generation oral antihistamines, while intranasal corticosteroids offer effective relief with fewer systemic side effects. Decongestants may be necessary and allergen immunotherapy injections can be considered for persistent cases. Clinicians must consider factors influencing compliance in pediatric patients. Rapid intervention and tailored management are crucial for improving outcomes and minimizing the allergic rhinitis impact in children.
... Moreover, due to similarity of chemical structure of pseudoephedrine and ephedrine to the addictive psychostimulant amphetamine which was initially used for the treatment of cold symptoms. Safety and tolerability concerns were issued about their illogical potential to be used as precursors for the manufacturing of methamphetamine (Kumarnsti et al., 1999;Eccles, 2006;Hatton et al., 2007;Laccourreye et al., 2015). ...
... Interestingly, the unheralded change that has been promoted by the FDA in formulation over the last 15 years of previously topically administered agents as decongestants, phenylephrine and pseudoephedrine, to ones now included in numerous oral OTC formations at least in the UK and USA. As identified by Eccles (2006) and Hatton et al., (2007), the re-introduction of oral phenylephrine as a decongestant by the FDA was based on: (i) the necessity to reduce the general availability of pseudoephedrine because of its potential to be used as a precursor for the production of methamphetamine and (ii) the finding of a meta-analysis of studies on oral phenylephrine generated more than twentyfive years earlier. It was not based on contemporary evidence of clinical efficacy using current research guidelines. ...
Background and purposes: Sympathomimetics have long been used as medications to relieve the symptoms associated with nasal congestion, but in the last 15 years, the worldwide market has moved from largely topical formulation to oral consumption. Many of the existing drugs are thought to cause vasoconstriction by activating α-adrenoceptors present on nasal mucosa and reduce local blood flow and swelling. This thesis aims to re-evaluate the activity of various sympathomimetic drugs on the nasal and extra-nasal blood vessels and better characterise the pharmacological characteristics of α-adrenoceptors on these vessels. In addition to that, I have explored the potential for lithium ions to modify the action of directly-acting sympathomimetics on both nasal and extra-nasal blood vessels and vasculature. Results: Isometric tension recordings of the porcine isolated splenic and nasal arteries showed that both noradrenaline and phenylephrine caused concentration-dependent contractions, but surprisingly were less potent (3-4-fold, respectively) in the latter vessel. Concentrations of phenylephrine known to occur in vivo following oral consumption (10-30nM) failed to either induce direct vasoconstriction or alter the magnitude and duration of electrically evoked contractions of the porcine vasculature. While pseudoephedrine failed to contract either nasal or extra-nasal vessels directly, it significantly enhanced electrically evoked noradrenergic contractions and increased the duration of responses. This effect was more marked in the nasal artery. Pharmacological characteristics of contractile responses to noradrenaline in porcine arteries, using a variety of selective and non-selective antagonists, revealed unsourmountable inhibition (Schild plot < 1) and evidence for the presence of two subtypes of α1-adrenoceptors. Attempts to reveal a constrictor role for α2-adrenoceptors in the splenic artery were only successfully provided by experimental conditions included both elevations of intracellular calcium ions and cyclic AMP. Comparison of the vasoconstrictor effect of phenethylamine derivatives, e.g. phenylephrine or metaraminol, in splenic and nasal arteries revealed that responses to high concentrations were not sustained. However, the presence of 1mM lithium increased the magnitude and duration of constrictor responses. This effect was not observed when α1-adrenoceptors were stimulated by imidazoline derivatives. Using the perfused porcine nasal snout revealed that various sympathomimetics were also able to increase perfusion pressure and the inclusion of 1mM lithium in the perfusate significantly increased the maximum response and duration of pressor responses to phenylephrine. Conclusion and implication: In summary, these data show that while the decongestant activity of topically applied phenylephrine could be accounted by a localised constrictor effect on nasal blood vessels, no mechanistic justification was uncovered for a naso-selective effect of orally consumed phenylephrine (10mg). In contrast, pseudoephedrine selectively enhanced noradrenergic contractions in the nasal vasculature. The major mediators of vasoconstriction in porcine blood vessels appear to involve two subtypes of α1-adrenoceptors (mainly α1A-adrenoceptors and probably α1B-adrenoceptors). For arterial vessels, α2-adrenoceptors could not be detected in vitro study without simultaneous elevation of cellular calcium ions and cyclic AMP. Finally, my findings raise the possibility that the nasal decongestant activity of topically applied phenylephrine may be enhanced by the presence of lithium ions, which may reduce the frequency of administration.
... In a recent meta-analysis, the administration of a 10 mg dose of phenylephrine did not significantly increase blood pressure, probably because of its low oral bioavailability. 442 This is supported by available case reports on hemorrhagic strokes, which occur mostly after parenteral or local administration, and only one case after oral administration is documented. 443 On the other hand, more pronounced effects of phenylephrine after higher oral doses are likely. ...
... 443 On the other hand, more pronounced effects of phenylephrine after higher oral doses are likely. 442 Phenylephrine is commonly combined with paracetamol, which doubles the bioavailability of phenylephrine, and thus likely increase the hypertensive effect of phenylephrine, but more data are needed. 444,445 Ischemic stroke is uncommon, but can occur even in young people after year-long misuse of nasally applied 1adrenoceptor agonists. ...
Cardiovascular diseases are a leading cause of morbidity and mortality in most developed countries of the world. Pharmaceuticals, illicit drugs, and toxins can significantly contribute to the overall cardiovascular burden and thus deserve attention. The present article is a systematic overview of drugs that may induce distinct cardiovascular toxicity. The compounds are classified into agents that have significant effects on the heart, blood vessels, or both. The mechanism(s) of toxic action are discussed and treatment modalities are briefly mentioned in relevant cases. Due to the large number of clinically relevant compounds discussed, this article could be of interest to a broad audience including pharmacologists and toxicologists, pharmacists, physicians, and medicinal chemists. Particular emphasis is given to clinically relevant topics including the cardiovascular toxicity of illicit sympathomimetic drugs (e.g., cocaine, amphetamines, cathinones), drugs that prolong the QT interval, antidysrhythmic drugs, digoxin and other cardioactive steroids, beta-blockers, calcium channel blockers, female hormones, nonsteroidal anti-inflammatory, and anticancer compounds encompassing anthracyclines and novel targeted therapy interfering with the HER2 or the vascular endothelial growth factor pathway.
... Its role as a key ingredient in the formulation of illicit substances led to its behind-the-counter regulation [17] and has subsequently been replaced by phenylephrine in OTC cold products over the last 15 years. Several studies found that phenylephrine is not different from placebo in treating cold symptoms [18][19][20][21][22]. In September 2023, as FDA panel issued the ruling that oral phenylephrine, grossing over $1.5 billion in the last year alone, is not effective for the treatment of cold and flu symptoms [23]. ...
Common cold viruses are leading triggers of asthma attacks, causing nearly two million hospitalizations per year and productivity losses approaching $40B. They also increase susceptibility to bacterial infections driving antibiotic use. Post-market clinical studies have questioned the efficacy of most over the counter (OTC) cough and cold ingredients against placebo in treating various symptoms. To our knowledge, only aspirin significantly improved overall illness severity compared to placebo and that was by about 25–30%. In this double-blind randomized placebo-controlled trial involving 157 participants, we sought to determine whether a throat spray containing a mucosal immune complex (MIC) (comprised of lysozyme, lactoferrin, and aloe) along with anti-inflammatory salicylates can increase the hereto reported efficacy of aspirin at reducing common cold symptoms. Previously published reports showed that the MIC can protect respiratory epithelia and lower inflammatory cytokines. Salicylates are naturally occurring plant compounds found in many common foods as well as wintergreen oil and are chemically similar precursors to aspirin (acetyl salicylate). Participants self-administered treatments (throat sprays every hour and tablets every four hours) and completed surveys at home over two days. Treatments included MIC spray mixed with 6 mg aspirin + placebo tablet (Treatment 1), MIC spray mixed with 6 mg wintergreen oil+ placebo tablet (Treatment 2), MIC spray mixed with 6mg wintergreen oil+ 325 mg aspirin tablet (Treatment 3). Participants included adult volunteers ages 21–66 (average 44), 54% female, 46% male, 46% African American, 8% Asian, 39% Caucasian, and 7% Hispanic, having common cold symptoms lasting less than two days. The main outcome measures included Sore Throat Pain Intensity (STPIS) 0–100 at 36 hours (primary endpoint) and Modified Jackson Score (MJS), a combination of eight cold symptoms (secondary endpoint). Both primary and secondary endpoints were met. Sore throat pain as measured by STPIS decreased 68–75% by 36 hours depending on treatment. Other symptoms such as nasal discharge, congestion, sneezing, cough, sore throat, and malaise as measured by MJS decreased 38–68% depending on treatment. In repeated measure within group analysis observing the same participants over multiple time points; the mean change of STPIS values and their percentage change from baseline to 36 hours were as follows: Placebo (-7.84 [95% CI -14.20 to -1.47];(-14%)), Treatment 1 (-42.41 [95% CI -48.30 to -36.52];(-75%)), Treatment 2 (-38.60 [95% CI -46.64 to -31.56];(-68%)), and Treatment 3 (-44.19 [95% CI -52.11 to -36.27];(-79%)). In repeated measure within group analysis all treatments significantly reduced cold symptom severity (MJS) from Days 1–2. Results were as follows: Treatment 1 (-2.26 [95% CI -3.04 to -1.47] (-38%)), Treatment 2 (-3.81 [95% CI -4.82 to -2.80];(-53%)), Treatment 3 (-4.49 [95% CI -5.62 to -3.57];(-69%)). As a result of this study, we conclude that supporting upper respiratory epithelia and reducing COX-mediated inflammation may be used to effectively treat common cold symptoms.
Trial registration: ClinicalTrials.gov Identifier: NCT06106880 Posted 30/10/2023.
... Its role as a key ingredient in the formulation of illicit substances led to its behind-the-counter regulation (17) and has subsequently been replaced by phenylephrine in OTC cold products over the last 15 years. Several studies found that phenylephrine is not different from placebo in treating cold symptoms (18)(19)(20)(21)(22). In September 2023, as FDA panel issued the ruling that oral phenylephrine, grossing over $1.5 billion in the last year alone, is not effective for the treatment of cold and flu symptoms (23). ...
Common cold viruses are leading triggers of asthma attacks, causing nearly two million hospitalizations per year and productivity losses approaching $40B. They also increase susceptibility to bacterial infections driving antibiotic use. Post-market clinical studies have questioned the efficacy of most over the counter (OTC) cough and cold ingredients against placebo in treating various symptoms. To our knowledge, only aspirin significantly improved overall illness severity compared to placebo and that was by about 25-30%. In this double-blind randomized placebo-controlled trial involving 157 participants, we sought to determine whether a throat spray containing a mucosal immune complex (MIC) (comprised of lysozyme, lactoferrin, and aloe) can increase the hereto reported efficacy of aspirin at reducing common cold symptoms. Previously published reports showed that the MIC can protect respiratory epithelia and lower inflammatory cytokines. Participants self-administered treatments (throat sprays every hour and tablets every four hours) and completed surveys at home over two days. Treatments included MIC spray mixed with 6mg aspirin + placebo tablet (Treatment 1), MIC spray + placebo tablet (Treatment 2), MIC spray + 325 mg aspirin tablet (Treatment 3). Participants included adult volunteers ages 21-66 (average 44), 54% female, 46% male, 46% African American, 8% Asian, 39% Caucasian, and 7% Hispanic, having common cold symptoms lasting less than two days. The main outcome measures included Sore Throat Pain Intensity (STPIS) 0-100 at 36 hours (primary endpoint) and Modified Jackson Score (MJS), a combination of eight cold symptoms (secondary endpoint).
Both primary and secondary endpoints were met. Sore throat pain as measured by STPIS decreased 68-75% by 36 hours depending on treatment. Other symptoms such as nasal discharge, congestion, sneezing, cough, sore throat, and malaise as measured by MJS decreased 38-68% depending on treatment. In repeated measure within group analysis observing the same participants over multiple time points; STPIS mean change from baseline to 36 hours was as follows: Placebo (-7.84 (-14%) [95% CI -14.20 to -1.47]; p<0.0001), Treatment 1 (-42.41 (-75%)[95% CI -48.30 to -36.52]; p<0.0001), Treatment 2 (-38.60 (-68%)[95% CI -46.64 to -31.56]; p<0.0001), and Treatment 3 (-44.19 (-79%) [95% CI -52.11to -36.27]; p<0.0001). In repeated measure within group analysis all treatments significantly reduced cold symptom severity (MJS) from Days 1-2. Results were as follows: Treatment 1 (-2.26 (-38%) [95% CI -3.04 - -1.47] p<0.0001), Treatment 2 (-3.81 (-53%) [95% CI -4.82 - -2.80] p<0.0001), Treatment 3 (-4.49 (-69%) [95% CI -5.62- -3.57]; p<0.0001).
As a result of this study, we conclude that supporting upper respiratory epithelia and reducing COX-mediated inflammation may be used to effectively treat common cold symptoms.
Trial registration ClinicalTrials.gov Identifier: NCT06106880 Posted 30/10/2023
... Current data shows that when taken orally in recommended doses, PHE does not have an impact on the cardiovascular system in people that don't have preexisting cardiovascular diseases [42,43]. However, certain studies have suggested that administering a 15 mg dose of PHE orally has led to a rise in blood pressure by 2.7 mmHg [44]. Additionally, administering high doses of phenylephrine (120-300 mg) determined an increase in blood pressure and bradycardia in healthy individuals [45]. ...
Nasal congestion leading to obstruction is one of the main symptoms in acute rhinosinusitis (common cold), other upper respiratory infections and allergic rhinitis. The EPOS 2020 guidelines place oral decongestants as an efficient therapy for the relief of nasal obstruction. In Romania, there are more than 50 available nasal decongestants, so it is very important for practitioners from all medical domains to be aware of recent data regarding their effectiveness and safety profile. Recent concerns raised by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) regarding the efficacy and safety of pseudoephedrine (PSE) and phenylephrine (PHE) emphasize the need for informed decision-making in prescribing. Notably, there were concerns raised about the association between PSE, reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES). EMA’s safety committee, Pharmacovigilance Risk Assessment Committee (PRAC), recently recommended measures to minimize risks of serious side effects when using medicines containing PSE. PRAC recommends that medicines containing PSE should not be used in patients with severe or uncontrolled hypertension and severe acute or chronic kidney disease or failure. Additionally, PRAC recommends healthcare professionals to counsel patients to discontinue the use of such medicines promptly and seek medical assistance if they experience symptoms suggesting PRES or RCVS, such as sudden onset of severe headache, confusion, vomiting, visual disturbances or seizures. While effectiveness of oral PSE is confirmed by clinical studies, expert consensus is unfavorable to PHE. Both in vitro and in vivo clinical pharmacology data indicate that neither the recommended doses nor higher doses of oral PHE demonstrate efficacy in alleviating symptoms of nasal congestion.
... [43] Phenylephrine has already been used in patients with nasal congestion and traumatic brain injury. [44,45] Thus, it is very valuable to test the effect of these inhibitors in vivo using the ALS-and FTD-related models. Cytoplasmic histones are frequently detected in response to stress. ...
Repeat dipeptides such as poly(proline‐arginine) (polyPR) are generated from the hexanucleotide GGGGCC repeat expansions in the C9orf72 gene. These dipeptides are often considered as the genetic cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). In the study, fluorescein isothiocyanate (FITC) labeled PR20 is used to investigate PR20‐induced cell death. The findings reveal that the cell death induced by PR20 is dependent on its nuclear distribution and can be blocked by a nuclear import inhibitor called importazole. Further investigation reveals that BRD4 inhibitors, such as JQ‐1 and I‐BET762, restrict cytoplasmic localization of PR20, thereby reducing its cytotoxic effect. Mechanistically, the inhibition of BRD4 leads to an increase in the expression of numerous histones, resulting in the accumulation of histones in the cytoplasm. These cytoplasmic histones associate with PR20 and limit its distribution within the nucleus. Notably, the ectopic expression of histones alone is enough to confer protection to cells treated with PR20. In addition, phenylephrine (PE) induces cellular hypertrophy and cytoplasmic distribution of histone, which also helps protect cells from PR20‐induced cell death. The research suggests that temporarily inducing the presence of cytoplasmic histones may alleviate the neurotoxic effects of dipeptide repeat proteins.
... In our systematic review of oral phenylephrine's efficacy in treating nasal congestion, we encountered contrasting findings compared to two prior systematic reviews and meta-analyses conducted in 2007 [17,18]. Those earlier studies suggested that oral phenylephrine was an effective treatment for nasal congestion associated with the common cold. ...
Nasal congestion is a common issue stemming from various factors such as allergies and anatomical variations. Allergic rhinitis frequently leads to nasal congestion. The pathophysiology involves inflammation, swelling, and mucus production in the nasal mucosa. Multiple treatments are available, including oral phenylephrine, an over-the-counter or prescription option. However, the effectiveness and safety of phenylephrine have been subjects of debate. This systematic review aims to provide an updated perspective on the efficacy of oral phenylephrine versus placebo in addressing nasal congestion in adults. We conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a systematic review involving searches on PubMed, Cochrane, and Scopus databases. Inclusion/exclusion criteria were defined to identify high-quality studies. The focus was on randomized controlled trials (RCTs) and case-control studies published in English between 1998 and 2023, involving adult populations. The interventions compared oral phenylephrine with placebo or standard care, with outcomes centering on changes in nasal congestion symptoms and nasal airway resistance. We identified four articles that met the criteria. These studies exhibited varied designs and populations. The findings consistently indicated that phenylephrine was not more effective than a placebo in relieving nasal congestion. This systematic review demonstrates that oral phenylephrine did not offer substantial relief from nasal congestion compared to a placebo in adults. The studies featured diverse designs, yet the prevailing conclusion was that phenylephrine's efficacy was limited. Safety assessments showed no life- threatening adverse events, with common side effects including headaches and mild discomfort. In summary, this systematic review indicates that oral phenylephrine is not significantly more effective than a placebo in alleviating nasal congestion in adults. Clinicians should explore alternative treatment options, considering the review's limitations. Additional research may be needed to clarify the role of oral phenylephrine in managing nasal congestion.
... Previously, Stohs et al. performed a detailed systematic review of synephrine, but there was no meta-analysis on this topic with statistical evaluations; only a literature review was performed [70]. The only available meta-analysis examined oral phenylephrine on nasal airway resistance in patients with nasal congestion, which did not examine p-synephrine and did not analyze its weight loss effects [71]. ...
Synephrine has been used to promote weight loss; however, its safety and efficacy have not been fully established. The goals of our study were to give an overview of the safety and efficacy of p-synephrine, to systematically evaluate its efficacy regarding weight loss and to assess its safety, focusing on its cardiovascular side effects in a meta-analysis. PubMed, the Cochrane Library, Web of Science and Embase were searched for relevant studies. Only placebo-controlled, human clinical trials with synephrine intervention were included in the meta-analysis. The meta-analysis was reported according to the PRISMA guidelines using the PICOS format and taking into account the CONSORT recommendations. Altogether, 18 articles were included in the meta-analysis. Both systolic and diastolic blood pressure (DBP) increased significantly after prolonged use (6.37 mmHg, 95% CI: 1.02–11.72, p = 0.02 and 4.33 mmHg, 95% CI: 0.48–8.18, p = 0.03, respectively). The weight loss in the synephrine group was non-significant after prolonged treatment, and it did not influence body composition parameters. Based on the analyzed clinical studies, synephrine tends to raise blood pressure and heart rate, and there is no evidence that synephrine can facilitate weight loss. Further studies are needed to confirm evidence of its safety and efficacy.
... Guaifenesin (GFS), phenylephrine (PHE) and paracetamol (PAR) are active ingredients frequently combined in pharmaceutical formulations administered for short-term treatment of cold and flu symptoms (pain, nasal congestion, headache, fever and chesty cough) [1]. In such over-the-counter drugs, guaifenesin (3-(2-methoxyphenoxy)-1,2-propanediol) is an expectorant [2], phenylephrine (2-methylamino-1-3(-hydroxyphenyl)ethanol) is used as a decongestant [3] and paracetamol (N-(4-hydroxyphenyl) acetamide) acts as an analgesic and antipyretic agent [4]. ...
Guaifenesin (GFS), phenylephrine (PHE) and paracetamol (PAR), drugs used in combination for the relief of cold and flu symptoms, were determined at electrochemically pretreated pencil graphite electrode. Differential pulse voltammetry (DPV) was used for the first time for the concomitant determination of the target compounds based on the electro-oxidation of PAR at 0.43 V, PHE at 0.74 V and GFS at 1.14 V in Britton–Robinson buffer pH 6.0. Under optimized experimental conditions, two linear ranges were obtained for PAR (2.50 × 10−6 M–1.00 × 10−5 M and 1.00 × 10−5 M–1.00 × 10−4 M) and for PHE and GFS linearity was proved between 5.00 × 10−6 M–2.00 × 10−4 M and 2.50 × 10−6 M–2.00 × 10−4 M, respectively. The detection limits were 8.12 × 10−7 M for PAR, 1.80 × 10−6 M for PHE and 8.29 × 10−7 M for GFS. The selective and sensitive DPV method and the electrochemically treated electrode were employed for simultaneous analysis of the analytes in pharmaceutical samples with good recoveries.
... • Комбинированные препараты, включающие фенилэфрина гидрохлорид, не рекомендовано использовать при АГ, выраженном атеросклерозе коронарных артерий, ОИМ, тахиаритмиях [203,204]. (Уровень достоверности доказательств 4; уровень убедительности рекомендации С). ...
... The decongestants result in small improvements in nasal symptoms, according to the three meta-analyses [21][22][23] and a systematic review [23], but their clinical significance is uncertain. Oral decongestants were shown to decrease subjective nasal symptoms by 6% with a single dose and 4% with recurrent doses, but clinical relevance is uncertain [23]. ...
... Oral decongestants are not as effective as topic decongestants. The former may result in insomnia and irritability in 25% of patients, and their use should be avoided in young children [46]. ...
Purpose of review
Attention deficit hyperactivity disorder (ADHD) and allergic rhinitis (AR) constitute high-prevalence entities in the pediatric population, and both affect the quality of life of children and their families. Over the last decade, it has been stated that a high number of patients with ADHD show comorbidities with allergic diseases. The aim of this review is to assess the current information about the relationship between both entities.
Recent findings
According to some authors, a causal association between them has been proposed since they have genetic, environmental, and inflammatory physiopathological mechanisms in common. However, there is still some controversy on this issue. Sleeping disorders are present in both and should be assessed in patients who suffer these conditions. Therefore, proper treatment of AR and other atopic diseases may be beneficial for the clinical progress of ADHD. Reduction of AR unpleasant symptoms and improvements of sleep quality decrease the child’s irritability, and they may further improve their behavior pattern.
Summary
Even though this association has not been clearly proven, the allergic conditions and sleep features have to be taken into account in order to improve the patients’ quality of life.
... Phenylephrine is another overthe-counter decongestant, also used in combination products. A recent meta-analysis showed lack of efficacy of phenylephrine on both objective and subjective measures of nasal congestion compared to placebo [25]. In addition their most common side effects are insomnia and irritability which can be seen in as many as 25% of patients. ...
Nasal problems in children are very common and include a wide variety of diseases, the most common of which are allergic rhinitis and chronic rhinosinusitis. Two clinical scenarios are presented illustrating each of these common conditions and followed by a brief overview of presentation, diagnosis, and therapy based on most recent available data.
... 24 A small statistically significant effect on nasal airway resistance was calculated in one metaanalysis of a single dose of phenylephrine in patients with nasal congestion from a common cold 25 but not in a second study that used a more appropriate statistical analysis. 26 No clinical decongestant effect was seen during multiple daily doses in patients with nasal congestion from seasonal allergic rhinitis, even in doses up to 40 mg, four times the FDA-approved OTC dose. 27 Nasal corticosteroid sprays (also known as intranasal corticosteroids) are highly effective at decreasing inflammation in the nasal mucosa, thereby decreasing congestion and improving nasal air flow. ...
Background:
There are many nonprescription (over-the-counter [OTC]) medications available on pharmacy shelves marketed for relief of respiratory symptoms. The number of such medications has been increasing.
Objective:
This review provides an evidence-based examination of OTC products used for respiratory symptoms.
Methods:
Antihistamines, decongestants, mucolytics, antitussives, and intranasal steroids were selected as the most common OTC medications taken by adults and children for various respiratory symptoms. Controlled clinical trials of efficacy were identified by searching a medical literature data base. Those trials and key publications related to the pharmacokinetics and pharmacodynamics of the products were reviewed.
Results:
Comparisons of the various OTC antihistamines' ability to suppress the effects of histamine were related to their clinical benefit. Intranasal corticosteroids are the preferred agents for maintenance therapy of persistent nasal congestion and are highly effective for symptoms of inhalant allergy other than allergic conjunctivitis. The disconnect between marketing claims and evidence was demonstrated for antihistamines and oral alpha-1 adrenergic agonist decongestants. Data for OTC mucolytics and antitussives were insufficient to justify their use based on the evidence.
Conclusion:
There was little relationship between marketing claims and evidence regarding OTC medications used for respiratory symptoms. Analysis of data supported cetirizine, levocetirizine, and fexofenadine as the most effective of the OTC antihistamines. There were no data that supported the use of oral phenylephrine as a decongestant. Neither OTC mucolytics or antitussives provided sufficient evidence to justify their use.
... Decongestants may relieve nasal symptoms, but its clinical significance were still uncertain. [25][26][27] Nonsteroidal anti-inflammatory drugs were effective in relieving pain and fever in people with common cold, but ineffective in relieving other symptoms. 28 Antibiotics is not useful given the viral etiology of the disease. ...
Objective:
To assess the efficacy and safety of Reduqing granules in patients with common cold
with wind-heat syndrome (CCWHS).
Methods:
A randomized, double-blind, double-dummy, parallel, positive- controlled trial included
72 CCWHS patients was performed. The participants were randomly assigned to two groups,
Reduqing (RDQ) group and Lianhuaqingwen (LHQW) group, in a 1:1 ratio. Patients in RDQ group
received Reduqing granules and dummy Lianhuaqingwen capsules three times a day and patients in
LHQW group received Lianhuaqingwen capsules and dummy Reduqing granules three times daily.
The duration of treatment and follow-up were four days.
Results:
There were no statistically significant differences in total markedly effective rate and total
effective rate between RDQ group and LHQW group after treatment. Traditional Chinese Medicine
(TCM) symptom score was significantly reduced after treatment in RDQ group, as well as in
LHQW group. However, the difference of change in TCM symptom score between two groups was not
statistically significant (P > 0.05). There were no significant differences between two groups in the median
time to fever relief [RDQ group (4 ± 8) h vs LHQW group (4 ± 5) h] or the median time to fever
clearance (RDQ group 47 h vs LHQW 36 h). No serious adverse events were reported during the study.
Conclusion:
Compared with Lianhuaqingwen capsules, Reduqing granules achieved similar therapeutic
effect in the treatment of CCWHS and no drug-related adverse events were reported during
the study. Therefore, Reduqing granules might be effective and safe in the treatment of CCWHS.
... Several current systematic review articles provide an excellent overview of the different therapeutic options for acute rhinitis [35], [36]. The effectiveness of topical and oral decongestants has been investigated in several trials, with three meta-analyses [37], [38], [39] and one systematic review [40] found. The meta-analysis of Kollar and co-workers [37], in which seven crossover studies were re-analysed and the data pooled, confirmed the effectiveness of orally applied phenylephrine for the treatment of nasal obstruction in acute rhinitis. ...
Therapeutic decisions in otorhinolaryngology are based on clinical experience, surgical skills, and scientific evidence. Recently, evidence-based therapies have gained increased attention and importance due to their potential to improve the individual patient’s treatment and their potential at the same time to reduce treatment costs. In clinical practice, it is almost impossible to stay ahead of the increasing mass of literature and on the other hand critically assess the presented data. A solid scientific and statistical knowledge as well as a significant amount of spare time are required to detect systematic bias and other errors in study designs, also with respect to assessing whether or not a study should be part of an individual therapeutic decision. Meta-analyses, reviews, and clinical guidelines are, therefore, of increasing importance for evidence-based therapy in clinical practice.
This review is an update of the availability of external evidence for the treatment of nasal obstruction and rhinosinusitis. It becomes evident that both groups of diseases differ significantly in the availability of external evidence. Furthermore, it becomes obvious that surgical treatment options are normally based on evidence of significantly lower quality than medical treatment options.
... Pseudo is a stimulant that releases adrenaline, whereas phenyl does not have this effect. Whereas the efficacy of pseudo as a nasal decongestant is supported by numerous controlled trials, there is little evidence that oral phenyl performs better than placebo [13]. See Eccles [14] for a detailed comparison between pseudo-and phenyl-based nasal decongestants. ...
Objectives:
Restrictions on retail purchases of pseudoephedrine are one regulatory approach to reduce the social costs of methamphetamine production and use, but may impose costs on legitimate users of nasal decongestants. This is the first study to evaluate the costs of restricting access to medications on consumer welfare. Our objective was to measure the inconvenience cost consumers place on restrictions for cold medication purchases including identification requirements, purchase limits, over-the-counter availability, prescription requirements, and the active ingredient.
Methods:
We conducted a contingent choice experiment with Amazon Mechanical Turk workers that presented participants with randomized, hypothetical product prices and combinations of restrictions that reflect the range of public policies. We used a conditional logit model to calculate willingness-to-accept each restriction.
Results:
Respondents' willingness-to-accept prescription requirements was 9.76-9.68 (12.33) per box of pseudoephedrine product. Participants were willing to pay 1.66-$6.52) per box to purchase pseudoephedrine-based products over phenylephrine-based products.
Conclusions:
Restricting access to medicines as a means of reducing the social costs of non-medical use can imply large inconvenience costs for legitimate consumers. These results are relevant to discussions of retail access restrictions on other medications.
... Similarly, Hatton et al have reported in a meta-analysis, that phenylephrine causes a rise in HR and BP, which is insignificant in a normotensive individual. 14 The reason for the significant rise in HR in our study could be because of the fact that eight patients received two NDs simultaneously by same or different routes. Use of more than one ND may not provide additional benefit, as they act through the same receptor ( 1 ), although their adverse effects are added up. ...
Background
Nasal decongestants (NDs) are frequently prescribed over the counter (OTC) drugs for cough and cold. These are sympathomimetic drugs, which act through α1 and β1 adrenoceptors to cause vasoconstriction and positive inotropic, chronotropic and dromotropic effect on the heart. This study was conducted to assess the pattern of utilization of the NDs and their effect on heart rate (HR) and blood pressure (BP). Patients were observed for any other adverse drug reactions (ADRs).
Materials and methods
Randomly 100 prescriptions containing NDs were collected from the otorhinolaryngology OPD and were analyzed. All these patients were examined for HR and BP on day 0, 3 and 7 of administration of NDs. Any ADRs were also recorded.
Results
Mean ND used per patient was 1.08/patient. Commonly prescribed NDs were phenylephrine (72.2%), pseudoephedrine (12.9%), phenylpropanolamine (6.5%), xylometazoline (6.5%) and oxymetazoline (1.8%). Eight patients received two NDs orally and/or topically. There was a significant rise in heart rate on day 7 (p < 0.05). However, the rise in BP was insignificant both on days 3 and 7. Frequently observed ADR's included headache, palpitations and dizziness.
Discussion
Some NDs are known to raise the HR and BP. Baseline BP monitoring should be done to avoid any further rise in BP and HR. being an OTC drug there are more chances of adverse effects of these NDs. It is suggested that NDs should be prescription only drugs, till adequate evidence is available regarding their safety.
How to cite this article
Rehan HS, Chopra A, Kumar S. To Study the Utilization Pattern of Nasal Decongestants and their Effects on Heart Rate and Blood Pressure. Clin Rhinol An Int J 2012;5(3):91-94.
In this study, (24) male animals were used, which were divided randomly into four groups. Each groupincluded (6) animals, which are: the control group that was given drinking water and food daily, and thegroup of rats treated with pseudoephedrine at a dose of (40) mg / Kg of body weight for a period of (30)days, the group of rats treated with pseudoephedrine at a dose of (40) mg / kg of body weight for a periodof (40) days, the group of rats treated with pseudoephedrine at a dose of (40) mg / kg of body weight for aperiod of (50) days, the animals dosed the drug by the oropharyngeal tube at a dose of (1) ml, and after theend of the experiment, the animals were scarified , brain samples were taken and preserved with formalinat a concentration of 10% until the tissue sections were made, when the meningeal membrane appeared theupper layers of the cerebral cortex in the group treated with pseudoephedrine for a period of 30 days wereclose to normal, while the group treated with pseudoephedrine for a period of (40) days showed shrinkagein the deep layers of the cerebral cortex and hemolysis in many blood vessels, and the meningeal membraneappeared.
The most common forms of rhinitis characterized by a runny nose, sneezing, nasal congestion, and nasal itching are allergic, infectious, occupational, hormonal, drug-induced, and idiopathic rhinitis. Allergic rhinitis (AR) is the most common form of rhinitis. In the evaluation made in five different centers in Turkey, the frequency of doctor-diagnosed AR was reported as 11.8–36.4% in the last year [1]. When we look at the world in general, it is a disease that affects 10–30% of Americans, 20–25% of Canadians, and 40% of the general population [2, 3].
In most instances, childhood hypertension does not have an identifiable cause aside from a clear association with obesity. In a small percentage of cases, a source of the hypertension can be identified. Common secondary causes of hypertension include kidney disease, renovascular disease, varied endocrine disorders, and drug-induced hypertension. Prescribed and over-the-counter medications, herbal supplements, and illicit substances have all been linked to hypertension. Hypertension induced by medications, herbal supplements, and illicit drugs should be considered in any child with new-onset hypertension or worsening control of existing hypertension, especially when the rise in blood pressure is abrupt and extreme. Fortunately, blood pressure typically returns to normal values soon after stopping the offending agent, and pharmacologic intervention is usually not required.
Norepinephrine (NE) is a monoamine neurotransmitter and is mainly released from the locus coeruleus in the brain. Locus coeruleus has about 20,000 neurons that produce NE and project to many different regions of the brain. The α1 and α2 receptors have been found to influence attention, fear, working memory, and spatial learning. β1 and β2 have been found to work on fear memory, auditory fear, memory retrieval, and spatial reference. Tyrosine hydroxylase is the rate-limiting enzyme in both NE and dopamine synthesis. Based on the specific receptor affinity, noradrenergic drugs are classified into selective or direct-acting drugs and nonselective or indirectly acting drugs.
Chronic rhinoconjunctivitis is an increasingly common condition that is now recognized to have a major impact on human health. Persistent nasal dysfunction may have significant effects on physical and emotional functioning, which result in absences from school and work, reduced worker productivity, and impaired school performance. In addition, chronic nasal inflammation may aggravate or lead to the development of other significant disorders, including asthma, rhinosinusitis, and middle ear disease. Recent improvements in our understanding of the pathophysiology of rhinitis are providing key insights into the development of new treatments, including novel immunologic therapies. This chapter presents an overview of the epidemiology, diagnosis, pathophysiology, and treatment of allergic and non-allergic rhinitis.
Common cold and flu are the most common diseases of mankind and there are numerous over the counter (OTC) medicines that provide relief of symptoms of these disease syndromes. The chapter first discusses the mechanism of symptoms of colds and flu, and then discusses the most common symptomatic treatments; analgesics, nasal decongestants, antitussives, antihistamines and anticholinergics, expectorants, mucolytics, menthol products, nasal sprays, and mouth washes and lozenges for treatment of sore throat. The mechanism of action, efficacy, safety and therapeutic value of each category of medicines is discussed.
Oral and oropharyngeal cancers (OPC) are a major global health concern traditionally caused by tobacco and alcohol abuse. The last decade has revealed the emerging role of Human Papilloma Virus (HPV) as a major etiological factor for oropharyngeal cancer predominantly in the developed world. Cancers affecting both these subsites are distinct entities. Changes have been incorporated in the recent staging system with recognition of the prognostic importance of depth of invasion (DOI) and extranodal extension (ENE) for oral cancers as well as the favourable biology of HPV-related cancers necessitating a separate staging system and attempts at deintensification of treatment. Oral cancers are predominantly treated by primary surgery and oropharyngeal cancers with non-surgical approaches. The advent of transoral robotic surgery (TORS) has resulted in its exploration of its role for select oropharyngeal cancers. There has been an emergence of recent new data which has resulted in changes in traditional management protocols of these cancers.
Medical therapy is a corner stone in treating various ENT-related conditions. Medical therapy can be delivered locally, which is effective in many ENT conditions and reduces unnecessary systematic side effects, or systematically which is on the other hand, still needed way of therapy for many conditions and infections, but it is crucial to use systematic treatment judiciously when it is really indicated. Local medical therapy in ENT is where various medications might be delivered locally by different devices (inhalers, nasal sprayers, and drops). This chapter is going to make a tour about most used medications in ENT, focusing in some details about antibiotics and steroids and mentioning about the usage of decongestant, antihistamines, medications for motion sickness, and vertigo. Drug names are hard to memorize, but you’re going to be familiar with them with time, never panic if you don’t recall them from the first time.
Esta publicación se enmarca en el ámbito de la Aerobiología, cuyo objeto de estudio es el transporte de organismos a través del aire, en ambientes exteriores e in-teriores. La importancia del problema que aquí se aborda está directamente relacionada con la calidad ambiental y la salud de la población. Esperamos que la misma despier-te el interés de profesionales e investigadores de la salud, como de Entes Gubernamentales. Asimismo, aspiramos a contribuir al conocimiento del público en general, y parti-cularmente de los pacientes que padecen alergias estacio-nales, sobre las especies vegetales consideradas alergógenas y sus ciclos de floración y permanencia en el aire para un mejor manejo de las afecciones. Este volumen contiene consideraciones generales acerca de las diversas etapas del proceso aerobiológico que carac-teriza a la dinámica de los microorganismos suspendidos en el aire en ambientes exteriores e interiores. Se presen-ta la información sobre los tipos polínicos arbóreos y her-báceos en forma de fichas que contienen información so-bre: familia, nombre científico de la planta, nombres vul-gares, hábito, descripción de la planta, floración, tipo de polinización, distribución geográfica, descripción del tipo polínico. Se acompañan estos datos con fotografías de las plantas y fotografías de microscopio óptico de los granos de polen que ilustran las descripciones y los calendarios de cada tipo polínico.
Allergic rhinitis is an IgE-mediated immune reaction of the nasal mucosa to foreign substances (allergens) characterized by sneezing, nasal congestion, rhinorrhea, and nasal itching often accompanied by red, watery, itchy eyes, thus the term rhinoconjunctivitis. For these symptoms to occur, various key pathophysiologic responses must be present and will be described briefly. Initially, the nasal mucosa is exposed to an allergen of which there are many varieties. The allergen is processed by antigen-presenting cells (such as macrophages, dendritic cells, and Langerhans cells), and portions of it are then presented to helper T cells as well as class II MHC molecules [1,2]. Helper T cells then secrete cytokines promoting growth and differentiation of other immune cells involved in the allergic response. The helper T cells are of the TH2 CD4+ variety and are responsible for secretion of cytokines such as IL-4, IL-5, and IL-13 [3]. IL-4 and IL-13 are key molecules involved in the upregulation of production of allergen-specific IgE by plasma cells, and IL-5 is important in the recruitment and survival of eosinophils, key cells in the allergic response [3–5]. Allergen-specific IgE attaches to high-affinity receptors on mast calls and basophils as well as low-affinity receptors on other cell types creating a sensitized nasal mucosa [6].
Atopic dermatitis, or eczema, is chronic inflammatory pruritic skin disorder, affecting both children and adults. Patients with atopic dermatitis often experience sleep disturbance, especially during flares of their skin disease. Sleep disturbances in atopic dermatitis range from difficulty falling asleep, shorter sleep duration, nighttime awakenings, and daytime sleepiness and fatigue. In addition, atopic dermatitis has also been associated with parasomnias and sleep-related breathing disorders. In children with atopic dermatitis, sleep disturbance may extend from the child to adult caregiver. The effects of sleep disruption in this setting are widespread including increased risk of mood disorders, impaired ability to perform activities of daily living, and decreased quality of life.
In most children elevated blood pressure measurements are transient and due to situational anxiety. When the blood pressure elevations persist, most children are found not to have an identifiable cause for the hypertension. In the minority of children, hypertension is due to an identifiable cause which may include a variety of medications and illicit substances. Substance-induced hypertension can be associated with unexpected and severe blood pressure elevations and should be considered in such circumstances. Fortunately, the blood pressure typically returns to normal values soon after stopping the offending agent, and usually pharmacologic intervention is not required.
In most children elevated blood p
ressure measurements are transient and due to situational anxiety. When the blood pressure elevations persist, most children are found not to have an identifiable cause for the hypertension. In the minority of children, hypertension is due to an identifiable cause which may include a variety of medications and illicit substances. Substance-induced hypertension can be associated with unexpected and severe blood pressure elevations and should be considered in such circumstances. Fortunately, the blood pressure typically returns to normal values soon after stopping the offending agent, and usually pharmacologic intervention is not required.
Chronic nonallergic rhinitis (NAR) is a syndrome rather than a specific disease. A lack of understanding of the pathogenesis of this condition has led to imprecise terminology with several alternate names for the condition, including vasomotor rhinitis, nonallergic rhinopathy, and idiopathic rhinitis. The therapy for NAR is best based on the underlying pathology, which typically exists in a form whereby an abnormality of the autonomic nervous system is dominant or a form in which inflammation seems to be the cause of symptoms. In general the most effective therapy is the combination of an intranasal antihistamine and an intranasal corticosteroid.
Background
Common colds are a major reason for physician visits. Being mainly of viral origin, treatment is symptomatic and antibiotics should be avoided.
Objectives
To review the evidence for conventional and alternative treatments of the common cold.
Material and Methods
Medline, eMbase, and the Cochrane database were searched from January 1985 to December 2015 combining the keywords “common cold” or “acute respiratory tract infection” with “treatment”.
Results
In children, commonly used medications such as cough syrups or Echinacea have not consistently been proven to be efficacious as treatment for the common cold. Products that potentially improve symptoms in children include vapour rub, zinc sulphate, pelargonium sidoides extract, and buckwheat honey. For adults, antihistamines, intranasal corticosteroids, codeine, nasal saline irrigation, and steam inhalation could not consistently proove efficacy at relieving cold symptoms. Topical decongestants, intranasal ipratropium, and zinc modestly reduced symptom severity and duration. NSAIDs and some herbal preparations slightly improved symptoms. Hand hygiene reduces the spread of viruses that cause cold illnesses.
Conclusions
In children, there is a potential for harm and no benefits with over-the-counter cough and cold medications; therefore, they should not be used, especially in the young. Beneficial effects exist for paracetamol and NSAIDS and potentially for antihistamine-decongestive combinations and intranasal ipratropium. Ibuprofen seems to be stronger antipyretic than paracetamol in paediatric patients. Among holistic strategies, there is moderate evidence for beneficial effects of zinc and probiotics in adults. In children, probiotics are also beneficial and – beyond the first year of life – honey at night. Commonly used strategies (e. g., garlic, gargling) warrant further research.
Comparable to other medicinal classes, many cardiovascular products used currently in children have not been tested adequately, but are given on an "off-label" or "unlicensed" basis, in doses extrapolated from adult data. Developmental changes in the cardiovascular system could have an important impact on the goals of efficacy and safety, including the development of adverse events related to the differences in the pharmacokinetic (PK) and pharmacodynamic (PD) properties of individual drugs. This chapter discusses the important implications for pediatric drug development. It talks about measurement of the QT interval and correction to heart rate. The chapter focuses on problems related to recording quality, measurement methodology, T wave morphology and U wave presence, HR variability and diurnal change of heart rate. Due to important developmental cardiovascular changes care should be taken to not extrapolate data from adults in both cardiovascular and non-cardiovascular drug studies.
Anesthesiologists prescribe, prepare, and administer medications during the perioperative period to facilitate patient safety while optimizing surgical conditions. The vast majority of these medications, unfortunately, have significant and potentially life-threatening side effects. Comprehension of these concepts can facilitate and impact operating conditions for the otolaryngologist, improve turnover efficiency in the operating room, and help to prevent surgical complications. Therefore, it is of paramount importance for the otolaryngologist to have a working understanding of the agents administered by anesthesiologists while they operate. © 2013 Springer Science+Business Media New York. All rights reserved.
Background:
Over-the-counter phenylephrine hydrochloride (PEH) is used for relief of nasal congestion caused by allergic rhinitis; however, data to support its efficacy are lacking. The US Food and Drug Administration recommended clinical trials to evaluate the efficacy and safety of PEH in patients with this condition.
Objective:
To evaluate the efficacy and safety of PEH 30-mg modified-release (MR) tablets in patients with nasal congestion caused by allergic rhinitis in a multicenter, randomized, double-blinded, placebo-controlled, 2-arm, parallel-group study.
Methods:
Eligible adults at least 18 years old with documented hypersensitivity to fall pollen allergens were randomized to PEH-MR or placebo every 12 hours for 7 days from August 30 to October 12, 2011. The primary end point was mean change from baseline during the entire treatment period in daily reflective nasal congestion score. Secondary end points included changes in other symptom score assessments, time to maximal effect, duration of effect, and quality of life. Safety assessments included adverse events, serious adverse events, vital signs, physical examination, and electrocardiograms.
Results:
Of 575 patients, 288 received PEH-MR and 287 received placebo. No significant beneficial difference was detected between PEH-MR and placebo for the primary end point (PEH-MR, mean -0.394, SD 0.4880; placebo, mean -0.412, SD 0.5383; P = .2655). Likewise, no significant differences were observed for most secondary end points or quality of life. Overall, 89 of 575 patients (15.5%), equally distributed between the PEH-MR and placebo groups, experienced at least 1 treatment-emergency adverse event.
Conclusion:
PEH-MR 30-mg tablets taken orally every 12 hours for 7 days is not more efficacious than placebo in relieving nasal congestion caused by allergic rhinitis.
Trial registration:
clinicaltrials.gov, identifier NCT01413958, protocol CL2011-06.
Phenylephrine hydrochloride (PE HCl) is widely used for the treatment of nasal congestion, but efficacy at the 10-mg dose is not known for certain. The Food and Drug Administration has requested that sufficiently powered, multicenter, dose-ranging studies be conducted to assess the efficacy and safety of PE HCl.
To evaluate subjective nasal congestion symptom relief and safety of 4 different doses of PE HCl immediate-release 10-mg tablets and placebo in adults with seasonal allergic rhinitis (SAR).
This multicenter, phase 2, parallel, open-label trial randomized 539 adults with SAR (but otherwise healthy) to 7 days of treatment with either PE HCl 10-mg tablets at fixed doses of 10, 20, 30, or 40 mg or placebo. The primary efficacy end point was the mean change from baseline over the entire treatment period in daily reflective nasal congestion score. Other efficacy end points and safety were also evaluated.
None of the PE HCl treatment groups had a statistically significant change from baseline in instantaneous or reflective nasal congestion scores compared with the placebo group. PE HCl was well tolerated at doses of up to 30 mg. At least 1 treatment-emergent adverse event was experienced by 18.4% of the participants, the most common being headache (3.0%).
PE HCl, at doses of up to 40 mg every 4 hours, is not significantly better than placebo at relieving nasal congestion in adults with SAR. The phenylephrine section of the Food and Drug Administration monograph on over-the-counter cold, cough, allergy, bronchodilator, and antiasthmatic products should be revised accordingly.
Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Asymmetric hydrogenation is the simplest way of creating new chiral centers, and the technology is continuing to be an industrial flagship for chiral synthesis. In particular, stereoselective hydrogenation of ketones and imines are of a great importance as it is providing an efficient access to the optically active alcohols and amines.
This chapter is focused on a practical approach to homogeneous hydrogenations of CO and CN bonds to provide a variety of valuable, biologically active compounds and natural products under mild reaction conditions with high enantio‐ and diastereoselectivity and excellent atom economy. Asymmetric hydrogenation is a highly application‐oriented method, and therefore, examples of industrial applications of the relevant technologies are appropriately illustrated throughout the text.
Previous studies had demonstrated that sulfation constituted a major pathway for the metabolism of phenylephrine in vivo. The current study was designed to identify the major human SULT(s) responsible for the sulfation of phenylephrine. Of the twelve human SULTs analyzed, SULT1A3 displayed the strongest sulfating activity toward phenylephrine. The enzyme exhibited a pH optimum spanning 7 – 10.5. Kinetic analysis revealed that SULT1A3- mediated sulfation of phenylephrine occurred in the same order of magnitude compared with that previously reported for SULT1A3-mediated sulfation of dopamine. Moreover, sulfation of phenylephrine was shown to occur in HepG2 cells under metabolic setting. Collectively, these results provided useful information concerning the biochemical basis underlying the metabolism of phenylephrine in vivo as previously reported.
Over-the-counter combinations containing acetaminophen and phenylephrine for treatment of the common cold and influenza are widespread, but there are few data about pharmacokinetics of these two drugs used in combination. We aimed to investigate pharmacokinetic interactions between acetaminophen and phenylephrine.
A series of four randomised, open-label, crossover studies investigating phenylephrine and acetaminophen combination pharmacokinetics were undertaken (n = 28, 30, 6 and 26) using standard non-compartmental analyses. Time-concentration observations from these four studies were pooled to examine the interaction between these two compounds. Data were analysed using non-linear mixed effects models.
Non-compartmental analyses showed an approximate doubling of phenylephrine plasma concentration when the standard 10-mg dose was administered in combination with acetaminophen. Population analysis was based on data from 90 subjects with 2050 observations. The relative bioavailability of phenylephrine 10 mg was doubled (Fbio 2.11, 95%CI 1.89, 2.31) when combined with acetaminophen 1000 mg, while the absorption half-time was reduced by 50 %. When combined with 500 mg of acetaminophen, bioavailability increased by 64 % (Fbio 1.64). Phenylephrine 5 mg in combination with acetaminophen 1000 mg produced a phenylephrine plasma time-concentration profile similar to that seen with phenylephrine 10 mg administered alone.
The relative bioavailability of phenylephrine was increased when co-administered with acetaminophen.
Objective: Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses. Design: Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30
Funnel plots (plots of effect estimates against sample size) may be useful to detect bias in meta-analyses that were later contradicted by large trials. We examined whether a simple test of asymmetry of funnel plots predicts discordance of results when meta-analyses are compared to large trials, and we assessed the prevalence of bias in published meta-analyses.
Medline search to identify pairs consisting of a meta-analysis and a single large trial (concordance of results was assumed if effects were in the same direction and the meta-analytic estimate was within 30% of the trial); analysis of funnel plots from 37 meta-analyses identified from a hand search of four leading general medicine journals 1993-6 and 38 meta-analyses from the second 1996 issue of the Cochrane Database of Systematic Reviews.
Degree of funnel plot asymmetry as measured by the intercept from regression of standard normal deviates against precision.
In the eight pairs of meta-analysis and large trial that were identified (five from cardiovascular medicine, one from diabetic medicine, one from geriatric medicine, one from perinatal medicine) there were four concordant and four discordant pairs. In all cases discordance was due to meta-analyses showing larger effects. Funnel plot asymmetry was present in three out of four discordant pairs but in none of concordant pairs. In 14 (38%) journal meta-analyses and 5 (13%) Cochrane reviews, funnel plot asymmetry indicated that there was bias.
A simple analysis of funnel plots provides a useful test for the likely presence of bias in meta-analyses, but as the capacity to detect bias will be limited when meta-analyses are based on a limited number of small trials the results from such analyses should be treated with considerable caution.
Phenylpropanolamine is commonly found in appetite suppressants and cough or cold remedies. Case reports have linked the use of products containing phenylpropanolamine to hemorrhagic stroke, often after the first use of these products. To study the association, we designed a case-control study.
Men and women 18 to 49 years of age were recruited from 43 U.S. hospitals. Eligibility criteria included the occurrence of a subarachnoid or intracerebral hemorrhage within 30 days before enrollment and the absence of a previously diagnosed brain lesion. Random-digit dialing identified two matched control subjects per patient.
There were 702 patients and 1376 control subjects. For women, the adjusted odds ratio was 16.58 (95 percent confidence interval, 1.51 to 182.21; P=0.02) for the association between the use of appetite suppressants containing phenylpropanolamine and the risk of a hemorrhagic stroke and 3.13 (95 percent confidence interval, 0.86 to 11.46; P=0.08) for the association with the first use of a product containing phenylpropanolamine. All first uses of phenylpropanolamine involved cough or cold remedies. For men and women combined, the adjusted odds ratio was 1.49 (95 percent confidence interval, 0.84 to 2.64; P=0.17) for the association between the use of a product containing phenylpropanolamine and the risk of a hemorrhagic stroke, 1.23 (95 percent confidence interval, 0.68 to 2.24; P=0.49) for the association with the use of cough or cold remedies that contained phenylpropanolamine, and 15.92 (95 percent confidence interval, 1.38 to 184.13; P=0.03) for the association with the use of appetite suppressants that contained phenylpropanolamine. An analysis in men showed no increased risk of a hemorrhagic stroke in association with the use of cough or cold remedies containing phenylpropanolamine. No men reported the use of appetite suppressants.
The results suggest that phenylpropanolamine in appetite suppressants, and possibly in cough and cold remedies, is an independent risk factor for hemorrhagic stroke in women.
Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading. One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included. This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta-analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction. Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses.* This paper was presented at a meeting on Systematic Reviews organised jointly by the BMJ and the UK Cochrane Centre and held in London in July 1993; it is the last in this seriesThe purpose of a meta-analysis of a set of clinical trials is rather different from the specific aims of an individual trial. For example, a particular clinical trial investigating the effect of serum cholesterol reduction on the risk of ischaemic heart disease tests a particular treatment regimen, given for a specified duration to participants fulfilling certain selection criteria, using a particular definition of outcome measures. The purpose of a meta-analysis of cholesterol lowering trials is broader - that is, to estimate the extent to which serum cholesterol reduction, achieved by a variety of means, generally influences the risk of ischaemic heart disease. A meta- analysis also attempts to gain greater objectivity, generalisability, and precision by including all the available evidence from randomised trials that pertain to the issue.1 Because of the broader aims of a meta- analysis, the trials included usually encompass a substantial variety of specific …
This chapter contains section titled:
Although nasal airways flow/resistance (R
n) measurements distinguish drug-induced changes in nasal patency better than investigator observations, it has not been shown that these alterations reflect useful clinical effects. Forty-eight patients with elevatedR
n values from colds were studied for their responses to 10.0, 15.0 and 25.0 mg single doses of phenylephrine, and to placebo, given orally in a double-blind crossover protocol. Nasal flow/resistance was determined by electronic posterior rhinometry, and subjective estimates of nasal congestion using a five-ranked scale, before and over 120 min after, therapy each day. The meanR
n changes observed for all three drug doses were significantly better than those following placebo at 14 of 15 time periods, with like significance for the mean subjective scores. Mean per cent changes inR
n separated the effects of 25.0 mg from 10.0 and 15.0 mg doses of phenylephrine, and distinguished all three active tablet doses from placebo, whereas the subjective estimates could only differentiate the three phenylephrine doses from placebo, but not from one another. While these data confirm the sharp ranking of nasal decongestant potency possible withR
n recording, contrasted with more blurred patient impressions, they suggest that statistically valid changes in nasal airways flow/resistance commonly imply favorable clinical activity as well as increased nasal passage patency.
7-3H-phenylephrine was given to 15 volunteers by a short-infusionn=4) or p.o. (10 volunteers, 1 patient with porto-caval anastomosis). Analysis of serum for free3H-phenylephrine and fractionation of urinary radioactivity was performed by ion-exchange and thin-layer chromatography. As almost the same3H-activity was excreted in urine after i.v. and p.o. administration, 86% and 80% of the dose respectively, complete enteral absorption can be assumed. A considerable difference was seen in the fraction of free phenylephrine, i.v. 16% of the dose versus p.o. 2.6%, which suggested reduced bioavailability. This was confirmed by comparison of the areas under the serum curve, which showed a bioavailability factor of 0.38. The result for the patient with porto-caval anastomosis was comparable to that in the normal volunteers. The biological half-life of 2 to 3h was comparable to that of structurally related amines, as were the total clearance of 2 1/h, and the volume of distribution of 340l. Metabolism to phenolic conjugates mainly after oral ingestion, and tom-hydroxymandelic acid after i.v. injection, again demonstrated thatm-hydroxylated amines are predominantly conjugated during the first-pass metabolism.
In recent years, considerable attention has been focused on the pressor effects of nonprescription sympathomimetic agents. The impact and usage of these agents especially ephedrine, pseudoephedrine, phenylpropanolamine and phenylephrine, in hypertensive patients has been the topic of constant debates. The present review is an attempt to report and evaluate all the clinical trials and cases of pressor reactions associated with these 4 agents. The study protocols used in these clinical trials are examined and comments made on any diversion from the standard design. Many factors are found to cause the discrepancies in the data available. It is concluded that ephedrine and phenylpropanolamine are best avoided by hypertensive patients due to higher probability of causing pressor reactions. Data on pseudoephedrine and phenylephrine appear to indicate non-significant effects on blood pressure of normotensive subjects when used at the recommended oral dose as nasal decongestants. Phenylephrine is also commonly employed in nasal and eye drops and the limited data available appear to support its usage in hypertensive patients. However, it is noted that most of the clinical trials involve normotensive subjects and the majority of the results could not be verified due to inadequacies in the study design. This paucity and inconclusive information on hypertensive patients warrants further investigations with emphasis on the study protocols used.
This paper examines eight published reviews each reporting results from several related trials. Each review pools the results from the relevant trials in order to evaluate the efficacy of a certain treatment for a specified medical condition. These reviews lack consistent assessment of homogeneity of treatment effect before pooling. We discuss a random effects approach to combining evidence from a series of experiments comparing two treatments. This approach incorporates the heterogeneity of effects in the analysis of the overall treatment efficacy. The model can be extended to include relevant covariates which would reduce the heterogeneity and allow for more specific therapeutic recommendations. We suggest a simple noniterative procedure for characterizing the distribution of treatment effects in a series of studies.
Certain limitations of conventional spirometry1 imply that sophisticated appraisal of the presence and degree of physiologic dysfunction in patients with obstructive ventilatory disorders should include definition of the important pressure-volume-flow determinants of lower airway resistance. Macklem and Mead2 have analyzed the complexities inherent in the use of pulmonary function tests dependent upon a forced expiratory maneuver as an index of airway dynamics. The usefulness of the whole-body, volume-displacement plethysmograph as a source of more critical estimates of airway resistance and airway responsiveness3-8 has been documented beyond cavil. Payne and associates8 further suggest that estimates of bronchodilator drug potency, based upon spirometric changes alone, may be misleading in terms of locus of action by reflecting summation of various organ responses rather than the airway only.
Antihistamines and decongestants often are used interchangeably and in combination for a variety of upper respiratory illnesses ranging from allergic rhinitis to the common cold; yet, these two classes of drugs have distinct therapeutic actions. When administered alone, antihistamines are of no value in reducing nasal stuffiness. Therefore, many allergy products also contain decongestants. Conversely, cough-cold remedies often contain antihistamines despite their lack of efficacy in these conditions. Nasal congestion, on the other hand, regardless of its cause, responds quite well to decongestants. The topical route provides a faster and more intense decrease in nasal airway resistance, but has a shorter duration and the potential to produce rebound congestion in patients with allergic rhinitis, whereas oral agents do not. Phenylpropanolamine, pseudoephedrine, and phenylephrine are the most common decongestants. Although all are sympathomimetic amines, their efficacy varies. In particular, phenylephrine is subject to first-pass metabolism and therefore is not bioavailable in currently recommended doses. In addition, phenylpropanolamine and pseudoephedrine, but not phenylephrine, are effective decongestants. Slow-release formulations allow a longer dosing interval, especially during the night. However, most formulations available in the United States are manufactured and sold without Food and Drug Administration scrutiny. Since the in vitro dissolution of many of these products differs, it is possible that some of the generic formulations are not bioequivalent to established brand-name products. Therefore, pharmacists should not substitute formulations without discussing the matter with the prescriber.
Only three drugs are commonly used as oral decongestants--phenylpropanolamine (PPA), pseudoephedrine (PDE), and phenylephrine (PE). They are all chiral drugs that exist as stereoisomers. It is possible that each enantiomer can reflect significant enantioselective differences with regard to both pharmacokinetic and pharmacodynamic effects. Both PPA and PDE are readily and completely absorbed, whereas PE, with a bioavailability of only approximately 38%, is subject to gut wall metabolism and is thought to be absorbed erratically. Peak concentrations are reached between 0.5 and 2 hours after administration. All three drugs are extensively distributed into extravascular sites (apparent volume of distribution between 2.6 and 5.0 L/kg). No protein-binding data in humans are available. Whereas PPA and PDE are not substantially metabolized, PE undergoes extensive biotransformation in the gut wall and the liver. Elimination of PPA and PDE is predominantly renal, with urinary excretion being pH dependent. Half-lives are relatively short, approximately 2.5 hours for PE, 4 hours for PPA, and 6 hours for PDE. Elimination of PPA and PDE may be rapid in children, and the agents should be used with caution in patients with renal impairment. In addition, PPA increases caffeine plasma levels and decreases theophylline clearance. Reduced metabolism of PE occurs with concurrent administration of monoamine oxidase inhibitors. No direct relationship between nasal decongestant effect and plasma concentration has been established.
Although meta-analysis is now well established as a method of reviewing evidence, an uncritical use of the technique can be very misleading. One common problem is the failure to investigate appropriately the sources of heterogeneity, in particular the clinical differences between the studies included. This paper distinguishes between the concepts of clinical and statistical heterogeneity and exemplifies the importance of investigating heterogeneity by using published meta-analyses of epidemiological studies of serum cholesterol concentration and clinical trials of its reduction. Although not without some dangers of speculative conclusions, prompted by overzealous inspection of the data to hand, a sensible investigation of sources of heterogeneity should increase both the scientific and the clinical relevance of the results of meta-analyses.
The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity.
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