Efficacy Of Decongestants Research Articles

Is acupuncture effective in reducing overall symptomatology in chronic rhinosinusitis?

Is acupuncture effective in reducing overall symptomatology in chronic rhinosinusitis?

CURRENT ASPECTS OF USE OF NASAL VASOCONSTRICTORS AND ADJUNCTIVE AGENTS IN PEDIATRIC PRACTICE

Nasal forms of vasoconstrictor agents (decongestants) are one of the most frequently prescribed groups of drugs in the therapy of inflammatory diseases of the nasal cavity. The article provides an overview of the mechanisms of action of decongestants, safety and the evidence base for the efficacy of decongestants in various upper respiratory tract diseases. It is concluded that when choosing a nasal agent, the preference should be given to decongestants with a higher level of safety – modern imidazolines (primarily xylometazoline) over the “first generation” decongestants (naphazoline).

Decongestants, antihistamines and nasal irrigation for acute sinusitis in children.

The efficacy of decongestants, antihistamines and nasal irrigation in children with clinically diagnosed acute sinusitis has not been systematically evaluated. To determine the efficacy of decongestants, antihistamines or nasal irrigation in improving symptoms of acute sinusitis in children. We searched CENTRAL (2014, Issue 5), MEDLINE (1950 to June week 1, 2014) and EMBASE (1950 to June 2014). We included randomized controlled trials (RCTs) and quasi-RCTs, which evaluated children younger than 18 years of age with acute sinusitis, defined as 10 to 30 days of rhinorrhea, congestion or daytime cough. We excluded trials of children with chronic sinusitis and allergic rhinitis. Two review authors independently assessed each study for inclusion. Of the 662 studies identified through the electronic searches and handsearching, none met all the inclusion criteria. There is no evidence to determine whether the use of antihistamines, decongestants or nasal irrigation is efficacious in children with acute sinusitis. Further research is needed to determine whether these interventions are beneficial in the treatment of children with acute sinusitis.

Analgesic and Decongestant Efficacy of the Combination of Aspirin with Pseudoephedrine in Patients With Symptoms of Upper Respiratory Tract Infection.

The study investigated the efficacy and safety of a combination therapy of 1,000 mg aspirin (ASA) and 60 mg pseudoephedrine (PSE) on the symptoms of pain (combined score for headache and sore throat) and nasal congestion in 833 patients with acute upper respiratory tract viral infection (URTI), over 4 hours after a single dose in the clinic and over 3 days with multiple doses at home. The study demonstrated that over 4 hours in the clinic the combination ASA plus PSE was superior to PSE or placebo for relief of pain symptoms measured subjectively with pain scores, and was superior to ASA or placebo for relief of nasal congestion as measured objectively with rhinomanometry and subjectively with congestion scores. After 3 days of treatment, ASA plus PSE was superior to PSE but not to placebo or ASA for global pain assessments, and ASA plus PSE was superior to ASA and placebo but not to PSE for congestion assessments. No unexpected adverse events occurred and no serious adverse events were attributed to study medicines. This study demonstrates that a combination therapy of ASA plus PSE provides safe and effective relief of both common cold pain related symptoms and nasal congestion.

Loratadine and Montelukast Administered in Combination Produce Decongestion in an Experimental Feline Model of Nasal Congestion

Histamine and leukotrienes act to exert numerous local and systemic effects that contribute to the pathophysiology of allergic rhinitis. The aim of these experiments was to evaluate the nasal decongestant effects of loratadine and montelukast alone and in combination in a feline model of nasal congestion. We also studied the decongestant actions of the alpha-agonist adrenergic agonist D-pseudoephedrine with and without desloratadine. Acoustic rhinometry was used to determine nasal cavity dimensions after intranasal compound 48/80. Cats were given D-pseudoephedrine (0.3 mg/kg) alone or in combination with desloratadine (5 mg/kg) 1 hour before nasal provocation with compound 48/80 (1%, 75 microliters) to either the left or right nasal passageway. Using a similar design, the nasal decongestant effects of montelukast (1 mg/kg) and loratadine (10 mg/kg) were studied alone and in combination. The addition of desloratadine to D-pseudoephedrine did not improve decongestant efficacy compared with each drug given individually. In contrast, when montelukast (1 mg/kg) was given in combination with loratadine (10 mg/kg), the decongestant activity was greater than when these drugs were administered separately. Sixty minutes after compound 48/80 provocation the nasal cavity volume ratio (volume ratio of the compound 48/80 treated/untreated nasal passageway) for the control, montelukast alone, loratadine alone, and the montelukast plus loratadine-treated groups were 0.20 +/- 0.03, 0.24 +/- 0.01, 0.28 +/- 0.03, and 0.50 +/- 0.03. Concomitant montelukast plus loratadine produces a greater degree of nasal decongestion compared with montelukast or loratadine alone in an experimental model of nasal congestion.

Efficacy of phenylephrine

In his recent article, Dr Eccles' commented on the lack of studies in the public domain supporting the efficacy of oral phenylephrine (PE) as a nasal decongestant [1]. In 1976 the US Food & Drug Administration (FDA) reviewed 12 unpublished studies provided by pharmaceutical companies for the Monograph [2]. Although tedious to obtain, the information can be retrieved from the FDA's archives by utilizing the Freedom of Information Act (FOIA) by various means. First, one can request the information directly from the FDA. Secondly, one can view this information in the FDA reading rooms. Finally, third parties, for a cost, will obtain this information for clients. We were able to obtain all of the studies cited in the 1976 Monograph via the FOIA. At that time, the FDA reviewed 12 unpublished studies and two published studies. We undertook our own review of these studies. We rejected two of the studies because one was a methodological paper that tested an oral combination product whose specific ingredients were unknown and the other was an abstract without any clinical data. Five studies were reported to be negative with respect to PE efficacy. However closer examination showed that only one of these was a well-conducted study which failed to confirm efficacy of PE. In the other four, the ‘active’ controls also failed to show benefit bringing into question the sensitivity of the rhinometric assay performed in these studies. On the other hand, seven double-blind, randomized trials were positive, i.e. PE demonstrated a significant reduction in nasal airway resistance (NAR) compared with placebo at doses ranging from 5 to 25 mg. In each study a clinically significant reduction in NAR (20% or greater peak effect) was achieved at the 5 and 10 mg doses. Recently Hendeles & Hatton [3] questioned the oral efficacy of PE as a nasal decongestant. This article cited three studies which examined PE efficacy. One was conducted by McLaurin [4]. As noted by Dr Eccles neither PE nor pseudoephedrine were different from placebo in this study. In addition, there is a positive study conducted by Cohen published in 1972 [5]. The effects of PE on NAR and subjective improvement of nasal symptoms were evaluated in 48 subjects with nasal congestion due to colds in a double-blind, randomized, placebo controlled, crossover study. All doses of PE tested (10–25 mg) showed a significant reduction in NAR and subjective scores of nasal congestion. Finally, Hendeles cited a study by Bickerman which failed to show efficacy of PE whereas it demonstrated efficacy for pseudoephedrine [6]. In a letter to Congressman Waxman, who had requested that the FDA look into PE efficacy, the US FDA stands by their 1976 decision to approve PE at a dose of 10 mg. In their correspondence to Mr Waxman they noted ‘The conclusion about the effect of an active ingredient in light of both positive and negative trials is made based on the totality of findings and the quality of the data. The number of each type of study outcome is not generally a major factor in this determination’ [7]. We recently submitted to the FDA our company's analysis of the studies reviewed by the FDA in 1976, studies cited by Dr Hendeles in his letter to the editor, and three additional studies that had been sponsored by our company in the 1960s and 1980s. Of the latter, two showed statistically significant benefits of 10 mg PE and the third was supportive. This summary should be accessible soon through the FOIA or on the FDA website at http://www.fda.gov/ohrms/dockets/dailys/06/nov06/112006/112006.htm. In conclusion, we concur with the FDA opinion that the totality of the scientific evidence supports the nasal decongestant efficacy of PE based upon 12 studies of PE efficacy in the public domain in 1976. Seven of those studies supported the efficacy of oral PE, one was negative and four lacked sensitivity because the positive control failed. We also draw your attention to two additional published studies by Cohen (supportive of PE efficacy) and Bickerman (not supportive of PE) andthree previously unpublished studies that had been sponsored by our company which also supported the efficacy of PE 10 mg.

Efficacy of phenylephrine

In his recent article, Dr Eccles' commented on the lack of studies in the public domain supporting the efficacy of oral phenylephrine (PE) as a nasal decongestant [1]. In 1976 the US Food & Drug Administration (FDA) reviewed 12 unpublished studies provided by pharmaceutical companies for the Monograph [2]. Although tedious to obtain, the information can be retrieved from the FDA's archives by utilizing the Freedom of Information Act (FOIA) by various means. First, one can request the information directly from the FDA. Secondly, one can view this information in the FDA reading rooms. Finally, third parties, for a cost, will obtain this information for clients. We were able to obtain all of the studies cited in the 1976 Monograph via the FOIA. At that time, the FDA reviewed 12 unpublished studies and two published studies. We undertook our own review of these studies. We rejected two of the studies because one was a methodological paper that tested an oral combination product whose specific ingredients were unknown and the other was an abstract without any clinical data. Five studies were reported to be negative with respect to PE efficacy. However closer examination showed that only one of these was a well-conducted study which failed to confirm efficacy of PE. In the other four, the ‘active’ controls also failed to show benefit bringing into question the sensitivity of the rhinometric assay performed in these studies. On the other hand, seven double-blind, randomized trials were positive, i.e. PE demonstrated a significant reduction in nasal airway resistance (NAR) compared with placebo at doses ranging from 5 to 25 mg. In each study a clinically significant reduction in NAR (20% or greater peak effect) was achieved at the 5 and 10 mg doses. Recently Hendeles & Hatton [3] questioned the oral efficacy of PE as a nasal decongestant. This article cited three studies which examined PE efficacy. One was conducted by McLaurin [4]. As noted by Dr Eccles neither PE nor pseudoephedrine were different from placebo in this study. In addition, there is a positive study conducted by Cohen published in 1972 [5]. The effects of PE on NAR and subjective improvement of nasal symptoms were evaluated in 48 subjects with nasal congestion due to colds in a double-blind, randomized, placebo controlled, crossover study. All doses of PE tested (10–25 mg) showed a significant reduction in NAR and subjective scores of nasal congestion. Finally, Hendeles cited a study by Bickerman which failed to show efficacy of PE whereas it demonstrated efficacy for pseudoephedrine [6]. In a letter to Congressman Waxman, who had requested that the FDA look into PE efficacy, the US FDA stands by their 1976 decision to approve PE at a dose of 10 mg. In their correspondence to Mr Waxman they noted ‘The conclusion about the effect of an active ingredient in light of both positive and negative trials is made based on the totality of findings and the quality of the data. The number of each type of study outcome is not generally a major factor in this determination’ [7]. We recently submitted to the FDA our company's analysis of the studies reviewed by the FDA in 1976, studies cited by Dr Hendeles in his letter to the editor, and three additional studies that had been sponsored by our company in the 1960s and 1980s. Of the latter, two showed statistically significant benefits of 10 mg PE and the third was supportive. This summary should be accessible soon through the FOIA or on the FDA website at http://www.fda.gov/ohrms/dockets/dailys/06/nov06/112006/112006.htm. In conclusion, we concur with the FDA opinion that the totality of the scientific evidence supports the nasal decongestant efficacy of PE based upon 12 studies of PE efficacy in the public domain in 1976. Seven of those studies supported the efficacy of oral PE, one was negative and four lacked sensitivity because the positive control failed. We also draw your attention to two additional published studies by Cohen (supportive of PE efficacy) and Bickerman (not supportive of PE) andthree previously unpublished studies that had been sponsored by our company which also supported the efficacy of PE 10 mg.

Efficacy and Safety of Single and Multiple Doses of Pseudoephedrine in the Treatment of Nasal Congestion associated with Common Cold

Pseudoephedrine (60 mg) is widely used as an oral decongestant taken in tablet or syrup formulations every 4-6 hours for the treatment of nasal congestion associated with common cold and allergy. However, there are relatively few studies in the literature that have used objective measures of nasal airway resistance (NAR) to assess the efficacy of pseudoephedrine, and most studies use only a single dose of medication. The present study has the aims of studying the safety and efficacy of a new pseudoephedrine formulation after single and multiple doses in patients with URTI. The study was a double-blind, randomized, parallel-group, placebo-controlled trial conducted over three study days at a single center. Patients suffering from nasal congestion associated with common cold were recruited and total NAR was measured by the technique of posterior rhinomanometry. NAR and subjective scores of nasal congestion were measured at baseline and after dosing with study medication, every hour over a four-hour period on day 1 after a single dose, and on day 3 after multiple doses of medication. Subjective scores of congestion/stuffiness were also made as a summary score at the end of each day of treatment. Two hundred and thirty-eight patients with nasal congestion associated with acute upper respiratory tract infection (URTI), mean age 20 years, were recruited to the study and received treatment. After a single dose on day 1 the pseudoephedrine group had a statistically significant lower area under the NAR curve than placebo (p = 0.006) for the primary efficacy variable area under the NAR curve from 0-3 hours (NAR AUC 0-3h), and similarly for the secondary efficacy variable NAR AUC 0-4h (p = 0.001). On day three after multiple doses, the pseudoephedrine group had a statistically significant lower NAR AUC 0-3h and AUC 0-4h than placebo (p < 0.001), On day 1, the pseudoephedrine group had significantly lower subjective scores for congestion than placebo visual analog scale (VAS) AUC 0-3h (p = 0.029) and similarly for VAS AUC 0-4h (p = 0.021). On day 3, the differences in subjective scores were not significantly different. The mean decrease from baseline of the summary score for congestion/stuffiness over the duration of the study was greater in the pseudoephedrine group compared to the placebo group (p = 0.016). On average, heart rate was between two and four beats per minute greater in the pseudoephedrine group compared to placebo. Five adverse events were reported in both treatment groups and these were deemed to be unrelated to treatment. The results demonstrate that pseudoephedrine is a safe and effective treatment for nasal congestion associated with URTI. The results from the laboratory study on day 1 demonstrate by both objective and subjective measures of nasal congestion that a single dose of 60 mg pseudoephedrine is superior to placebo treatment. Support for the decongestant efficacy of multiple doses of pseudoephedrine is provided by objective measures on day 3 and subjective measures made over three days, but not by the VAS scores on day 3.

Pharmacological characterization of the novel histamine H3-receptor antagonist N-(3,5-dichlorophenyl)-N'-[[4-(1H-imidazol-4-ylmethyl)phenyl]-methyl]-urea (SCH 79687).

We present the pharmacological and pharmacokinetic profiles of a novel histamine H3 receptor antagonist, N-(3,5-dichlorophenyl)-N'-[[4-(1H-imidazol-4-ylmethyl)phenyl]-methyl]-urea (SCH 79687). The H3-receptor binding Ki values for SCH 79687 were 1.9 and 13 nM in the rat and guinea pig (GP), respectively. The Ki values for SCH 79687 at histamine H1 and H2 receptors were greater than 1 microM. SCH 79687 showed a 41- and 82-fold binding selectivity for the H3 receptor over alpha 2A-adrenoceptors and imidazoline I2, and >500-fold H3 selectivity compared with over 60 additional receptors. The pA2 value for SCH 79687 in the GP ileum electrical field-stimulated (EFS) contraction was 9.6 +/- 0.3. Similar H3 antagonist activity was observed in the EFS cryopreserved and fresh tissue isolated human saphenous vein (HSV) assays (pKb = 9.4 +/- 0.3 and 10.1 +/- 0.4). SCH 79687 (30 nM) did not block clonidine-induced inhibition of EFS-induced contractions in HSV. SCH 79687 (ED50 = 0.3 mg/kg i.v.) attenuated (R)-alpha-methylhistamine inhibition of sympathetic hypertensive responses in the GP. At the time of activity evaluation, the GP plasma SCH 79687 concentration was 25 ng/ml at the dose of 0.3 mg/kg i.v. In feline nasal studies, combined administration of SCH 79687 (3 mg/kg i.v.) and the H1-antagonist loratadine (3 mg/kg i.v.), at individual doses that do not produce decongestion, inhibited the compound 48/80-induced congestion by 47%. The alpha-adrenergic agonist phenylpropanolamine (PPA; 1 mg/kg i.v.) also attenuated compound 48/80 nasal responses by 42%. Unlike the H3/H1 combination that did not affect blood pressure (BP), PPA (1 mg/kg i.v.) significantly increased BP compared with control animals by a maximum of 31 mm Hg. Orally, SCH 79687 (10 mg/kg) plus loratadine (10 mg/kg) also produced decongestion without effects on BP. In pharmacokinetic studies, oral dosing with SCH 79687 in the rat (10 mg/kg) and monkey (3 mg/kg) achieved plasma Cmax and area under the curve values greater than 1.5 and 12.1 microg. h/ml, respectively. SCH 79687 is an orally active H3 antagonist with a good pharmacokinetic profile that, in combination with an H1 antagonist, demonstrates decongestant efficacy comparable with oral sympathomimetic decongestants but without hypertensive liabilities.

Decongestant efficacy of desloratadine in patients with seasonal allergic rhinitis.

Recent advances in experimental immunologic approaches to seasonal allergic rhinitis (SAR) have led to a shift in the concepts of its pathogenesis. The conventional view of SAR as a local response to inhaled allergens has largely given way to a new view of this disorder as a systemic condition with local tissue manifestations. This concept, together with an increasing recognition of specific mediators' distinct roles in driving the early- and late-phase allergic responses, has opened multiple lines of therapeutic attack within the allergic cascade. Potent inhibition of inflammatory mediator release at distinct points in this cascade is conferred by desloratadine. In addition to the familiar range of SAR symptoms amenable to antihistamine therapy, desloratadine uniquely attenuates patient ratings of nasal congestion. This novel, nonsedating histamine H1-receptor antagonist is the only once-daily antiallergic product with a consistent decongestant effect that begins within hours of the first morning dose and is sustained for the entire treatment period.