Trends in Phenylephrine and Pseudoephedrine Sales in the US.

This study examines purchasing patterns regarding oral decongestants, concerns about their efficacy, and the need for timelier postmarket evaluation.

Effects of pseudoephedrine on rat fetal bone development: evaluation by three different methods.

Pseudoephedrine (PSE) is an agent that is contained in common cold medications. The agent, which is used to treat cold and cough, is the fourth most prescribed drug group in some countries. During pregnancy, expectant mothers use PSE for colds and other reasons. One out of every four expectant mothers use PSE alone or in combination with other medicines for various reasons. This study was aimed to investigate effects of PSE on long bones development in rat during fetal growth. Pregnant rats were divided into five groups: control and four experimental groups (25 mg/kg, 50 mg/kg, 100 mg/kg, 200 mg/kg PSE). Between 1 and 20 days of pregnancy, PSE was given to them by gavage. Weights and heights of fetuses isolated by cesarean on the 21st day were measured. Ossification of femur and humerus was examined by three different methods mentioned earlier. Depending on the dose increase, all morphometric data, ossification rate and bone length of the fetuses were decreased. Besides, it was determined that the amount of Calcium in the bone tissue decreased in the analyzes made with SEM-EDX Analysis. The data obtained from this study reveal that the use of PSE during pregnancy disrupts the existing balance in the bone and negatively affects ossification due to the dose increase. In conclusion, we present descriptive and novel data on the effects of PSE use during pregnancy on the bone development of rat fetal long bones.

Seizures provoked by over-the-counter cough and cold medications in an elderly patient: a case report.

BACKGROUND: Seizures are common neurological emergencies in the elderly that are frequently provoked. Geriatrics have higher rates of neurological disorders and other comorbidities that could affect seizure threshold. CASE PRESENTATION: An 83-year-old male Arabic patient presented to the emergency department with an acute confusional state and urinary incontinence followed by a witnessed tonic-clonic seizure in the hospital. Thorough investigations and imaging were positive only for nonspecific magnetic resonant imaging findings with a negative electroencephalogram. The patient was diagnosed with provoked seizure due to over-the-counter cold medications that included pseudoephedrine and caffeine. He was not prescribed antiepileptic medications at discharge and did not develop subsequent seizures up to this date. CONCLUSION: Over-the-counter cough and cold medications with sympathomimetic ingredients can be associated with provoked seizures in the elderly. Physicians should be aware of the potentially serious adverse events associated with commonly used nonprescription sympathomimetics such as pseudoephedrine and caffeine in elderly patients.

Pseudoephedrine-Benefits and Risks.

Pseudoephedrine (PSE) is a drug with a long history of medical use; it is helpful in treating symptoms of the common cold and flu, sinusitis, asthma, and bronchitis. Due to its central nervous system (CNS) stimulant properties and structural similarity to amphetamine, it is also used for non-medical purposes. The substance is taken as an appetite reducer, an agent which eliminates drowsiness and fatigue, to improve concentration and as a doping agent. Due to its easier availability, it is sometimes used as a substitute for amphetamine or methamphetamine. Pseudoephedrine is also a substrate (precursor) used in the production of these drugs. Time will tell whether legal restrictions on the sale of this drug will reduce the scale of the problem associated with its misuse.

In search of an ideal drug for safer treatment of obesity: The false promise of pseudoephedrine.

Obesity is a major public health problem worldwide. Only relatively few treatment options are, at present, available for the management of obese patients. Furthermore, treatment of obesity is affected by the widespread misuse of drugs and food supplements. Ephedra sinica is an old medicinal herb, commonly used in the treatment of respiratory tract diseases. Ephedra species contain several alkaloids, including pseudoephedrine, notably endowed with indirect sympathomimetic pharmacodynamic properties. The anorexigenic effect of pseudoephedrine is attributable primarily to the inhibition of neurons located in the hypothalamic paraventricular nucleus (PVN), mediating satiety stimuli. Pseudoephedrine influences lipolysis and thermogenesis through interaction with ß3 adrenergic receptors and reduces fat accumulation through down-regulation of transcription factors related to lipogenesis. However, its use is associated with adverse events that involve to a large extent the cardiovascular and the central nervous system. Adverse events of pseudoephedrine also affect the eye, the intestine, and the skin, and, of relevance, sudden cardiovascular death related to dietary supplements containing Ephedra alkaloids has also been reported. In light of the limited availability of clinical data on pseudoephedrine in obesity, along with its significantly unbalanced risk/benefit profile, as well as of the psychophysical susceptibility of obese patients, it appears reasonable to preclude the prescription of pseudoephedrine in obese patients of any order and degree.

Anti-rheumatic activity of pseudoephedrine (a substituted phenethylamine) in complete Freund's adjuvant-induced arthritic rats by down regulating IL-1ß, IL-6 and TNF-α as well as upregulating IL-4 and IL-10.

Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1ß and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.

Pseudoephedrine alleviates atopic dermatitis-like inflammatory responses in vivo and in vitro.

AIMS: Atopic dermatitis is a chronic inflammatory disease characterized by eczematous lesions and has become a serious health problem worldwide. Pseudoephedrine (PSE) is a nasal decongestant to treat the common cold. PSE has been reported that is beneficial to allergic diseases. However, whether PSE has the potential in atopic dermatitis remains to be elucidated. MAIN METHODS: Male BALB/c mice were challenged with 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like lesion and orally administrated with PSE for two weeks. The skin hydration and the scratching behavior were detected. The skin lesions and histopathological changes were evaluated and inflammatory factors levels were detected. Human Keratinocytes (HaCaT cells) were stimulated by TNF-α/IFN-γ after PSE-pretreatment. The transcriptions of inflammatory factors were detected. KEY FINDINGS: PSE decreased skin lesion area and skin thickness in atopic dermatitis mice. PSE improved skin hydration and scratching. Histologically, PSE reduced mast cell and CD4+ cell infiltration. PSE suppressed serum TNF-α and IgE levels, reducing cytokines (IL-1ß, IL-4, IL-6, IL-13, IL-33, TSLP, and IL-23) and neutrophil migration factors (CCL2 and MMP-9) in skin tissues. In addition, PSE inhibited TNF-α/IFN-γ-induced release of inflammatory factors (TNF-α, IL-1ß, and IL-23) in HaCaT cells. Furthermore, PSE suppressed the activation of MAPKs and NF-κB signaling pathways in vivo and in vitro. SIGNIFICANCE: These results demonstrate that PSE could inhibit inflammatory responses in atopic dermatitis models. PSE may serve as a viable alternatives drug for the treatment of atopic dermatitis.

Analgesic Effects of Ephedra Herb Extract, Ephedrine Alkaloids-Free Ephedra Herb Extract, Ephedrine, and Pseudoephedrine on Formalin-Induced Pain.

The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids-free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0-5 min; second phase, 10-45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, "authentic" EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse-and at 4 to 6 h after administration of EHE-Ts-only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4-6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.

A Multicenter, Randomized, Placebo-Controlled Study of Pseudoephedrine for the Temporary Relief of Nasal Congestion in Children With the Common Cold.

This multicenter, double-blind, placebo-controlled, randomized study was designed to evaluate the efficacy and safety of pseudoephedrine hydrochloride 30-mg tablets in children aged 6 to 11 years for the temporary relief of nasal congestion due to the common cold. The primary efficacy end point was the weighted sum of the change from baseline in instantaneous nasal congestion severity score over the period from 1 to 8 hours following the first dose of study drug on day 1. Safety assessments included adverse events, sleepiness ratings, and vital signs. Pseudoephedrine was superior to placebo in reducing instantaneous nasal congestion severity in pediatric children over the first 8 hours after dosing on day 1 (least squares mean difference between treatment groups was 1.2; P = .029). Overall, secondary end points associated with nasal congestion were supportive on day 1, whereas secondary end points on day 2 were only numerically favorable. Somnolence was reported in a greater percentage of children on pseudoephedrine compared to placebo (71.9% vs 63.9%), while similar percentages of children in the same respective groups reported insomnia (34.4% and 38.9%) and nervousness (20.0% and 23.6%).Pseudoephedrine provides temporary relief of nasal congestion associated with the common cold in children 6 to <12 years of age at the current over-the-counter monograph dose. Multiple dosing of pseudoephedrine for up to 7 days, when given as needed for symptom relief, was generally safe in this population of children with the common cold.

IPADAM "Pharmaceutical interventions on the issue of pharmaceutical records and self-medication" quanti survey in 482 French pharmacies.

OBJECTIVES: This study aims to: (i) quantify the number of pharmaceutical interventions (PIs) linked to spontaneous requests for the two oral target molecules, ibuprofen and pseudoephedrine (ii) analyse the causes and proposed solutions (iii) quantify the number of registrations in the patient's pharmaceutical record and identify the various causes of non-registration. METHODS: The study was conducted over a 2 weeks' period in the months of February and April 2014 in 482 pharmacies affiliated to the training supervisor associations of 8 French Faculties of Pharmacy. Data regarding spontaneous requests for the target molecules was collected, with due respect to a patient care flow chart at the pharmacy, by incorporating the systematic proposal for registration of the medication in the patient's pharmaceutical record. Each PI was the subject of a notification made with reference to a standardized grid. RESULTS: A total of 12,160 dispensations were made over the two weeks of the study. Overall 815 of them gave rise to an PI (6.7%), justified in almost half of the cases by a contraindication. The alternative proposed by the dispensing pharmacist was accepted in more than 9 out of 10 cases. In half of the cases, the dispensing pharmacist had access to the patient's French healthcare card; more than 2/3 of the dispensations thus led to the registration of the medication in the patient's pharmaceutical record. CONCLUSION: The pairing of the two tools, these being the notification grid and the pharmaceutical record, aims to maximize dispensation security while patients are being guided in their approach to self-medication.

[IPADAM quali study. Intervention of the Pharmacist in the Issue of Self-medication: Experience of pharmacy team focus groups and patients' perceptions]. / IPADAM quali « Interventions Pharmaceutiques À propos du Dossier pharmaceutique et de l'AutoMédication ¼ : expérience des équipes officinales et ressenti des patients.

OBJECTIVES: This study had two main aims: (i) document the experience of community pharmacists receiving a spontaneous request for ibuprofen and oral pseudoephedrine, and their use of pharmaceutical records, and (ii) explore patients' perceptions of pharmaceutical records and pharmaceutical interventions. METHODS: The study was conducted over two weeks between February and April 2014 in 482 community pharmacies and 8 French faculties of pharmacy. It was based on data collected by pharmacy team focus groups during patient telephone interviews using standardized question grids. Textual and thematic analyses were made of the patient responses. RESULTS: Four pharmacy team focus groups carried out 49 telephone interviews. Examination of the practice of the groups showed that pharmaceutical interventions, although incompletely registered, are performed on a daily basis and enhance the value of the pharmacist's function. Analysis of the telephone interviews also showed the importance of the advisory role of the pharmacist in dispensing an optional medical prescription. The thematic analysis of the results identified a positive response of patients to pharmaceutical interventions if made by their regular pharmacist and accompanied by explanatory information. The focus groups and patients agreed that pharmaceutical records were not consulted often enough. CONCLUSION: This study underlines the need for greater safety in the use of optional medical prescription drugs. Promoting responsible self-medication in compliance with proper use should include systematic reference to a PR and informed dialogue with the patient.

Cistitis intersticial y embarazo / Interstitial cystitis and pregnancy

La etiopatogenia multifactorial de la cistitis intersticial hace que las modificaciones que se producen durante el embarazo puedan desenmascarar un cuadro de cistitis intersticial o producir el agravamiento del mismo (AU)

The multifactorial etiopathogenesis of interstitial cystitis causes changes that occur during pregnancy to unmask an interstitial cystitis or to worsen it (AU)

Clinical Inquiry: Do oral decongestants have a clinically significant effect on BP in patients with hypertension?

It is unclear. Pseudoephedrine causes an average increase of 1.2 mm Hg in systolic blood pressure (BP) in patients with controlled hypertension. However, the studies are not adequately powered to provide evidence about whether this rise in systolic BP is linked to patient-oriented outcomes (strength of recommendation: C, multiple randomized controlled trials supporting disease-oriented evidence). Significant variations in BP are defined differently among studies. In addition, we do not have data on chronic use of oral decongestants; the longest time on medication in these trials was 4 weeks.

Recurrent Priapism Gone Wrong: ST-Elevation Myocardial Infarction and Cardiogenic Shock After Penile Corporal Phenylephrine Irrigation.

BACKGROUND: Recurrent priapism secondary to sickle cell trait in an African-American male has been reported in the literature. A common treatment for these low-flow priapism cases is aspiration and injection of the corpus cavernosum with a sympathomimetic agent. We report a rare complication not described previously in the literature of ST-elevation myocardial infarction (STEMI) and cardiogenic shock in a 29-year-old male with sickle cell trait undergoing a routine detumescence procedure. CASE REPORT: A 29-year-old African-American male with a history of sickle cell trait and recurrent low-flow/ischemic priapism presented with a painful erection for 8 h. Corporal aspiration and irrigation with phenylephrine was performed. After phenylephrine injection, the patient experienced hypertensive emergency, flash pulmonary edema, STEMI, and subsequent cardiogenic shock. He required intubation, ionotropic support, cardiac catheterization, and admission to the cardiac care unit. History taken from the patient's wife on the following day revealed that he was taking high doses of pseudoephedrine at home to treat symptoms. The patient was subsequently discharged after 3 days with normalization of ejection fraction and negative troponin. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Intracavernosal injection of phenylephrine is a common emergency department treatment utilized in management of priapism, but emergency physicians should be aware of the potential severe systemic complications resulting from this procedure. Providers should take a careful history, including over-the-counter medication use; consider comorbid medical history; standardize phenylephrine mixing instructions with pharmacy; and perform the procedure in a monitored setting with a brief observation after complete detumescence.

Acetylcysteine in the treatment of subacute sinusitis: A double-blind placebo-controlled clinical trial.

Sinusitis is a common disease with harmful effects on the health and finances of patients and the economy of the community. It is easily treated in most of its acute stages but is associated with some management difficulties as it goes toward chronicity. Therefore, we tried to improve the treatment of subacute sinusitis by using acetylcysteine, which is a safe mucolytic and antioxidant agent. Thirty-nine adult patients with subacute sinusitis proved by computed tomography (CT) were enrolled in a double-blind, placebo-controlled trial. They received oral amoxicillin-clavulanic acid and normal saline nasal drops for 10 days and oral pseudoephedrine for 7 days. In addition, the patients received acetylcysteine (600 mg orally, once daily) in the intervention group or placebo in the control group for 10 days. A paranasal CT scan was taken at baseline and 30 days after patients finished the treatment and was evaluated quantitatively by Lund-Mackay (LM) score. Symptoms and some aspects of quality of life also were assessed at baseline and 14 days after initiation and 30 days after termination of the treatment via the Sino-Nasal Outcome Test questionnaire. The groups showed no significant difference in LM score after treatment. A positive correlation was observed between the LM and SNOT-20 scores. We concluded that adding oral acetylcysteine to amoxicillin-clavulanic acid, pseudoephedrine, and intranasal normal saline has no benefit for the treatment of subacute sinusitis.

Factors associated with efficacy of an ibuprofen/pseudoephedrine combination drug in pharmacy customers with common cold symptoms.

AIM: The aim of this study was to explore factors affecting efficacy of treatment of common cold symptoms with an over-the-counter ibuprofen/pseudoephedrine combination product. METHODS: Data from an anonymous survey among 1770 pharmacy customers purchasing the combination product for treatment of own common cold symptoms underwent post-hoc descriptive analysis. Scores of symptoms typically responsive to ibuprofen (headache, pharyngeal pain, joint pain and fever), typically responsive to pseudoephedrine (congested nose, congested sinus and runny nose), considered non-specific (sneezing, fatigue, dry cough, cough with expectoration) and comprising all 11 symptoms were analysed. Multiple regression analysis was applied to explore factors associated with greater reduction in symptom intensity or greater probability of experiencing a symptom reduction of at least 50%. RESULTS: After intake of first dose of medication, typically ibuprofen-sensitive, pseudoephedrine-responsive, non-specific and total symptoms were reduced by 60.0%, 46.3%, 45.4% and 52.8%, respectively. A symptom reduction of at least 50% was reported by 73.6%, 55.1%, 50.9% and 61.6% of participants, respectively. A high baseline score was associated with greater reductions in symptom scores but smaller probability of achieving an improvement of at least 50%. Across both multiple regression approaches, two tablets at first dosing were more effective than one and (except for ibuprofen-sensitive symptoms) starting treatment later than day 2 of the cold was generally less effective. DISCUSSION AND CONCLUSIONS: Efficacy of an ibuprofen/pseudoephedrine combination in the treatment of common cold symptoms was dose-dependent and greatest when treatment started within the first 2 days after onset of symptoms.

Stevens-Johnson Syndrome/Toxic epidermal necrolysis overlap induced by fexofenadine

No disponible

Voiding dysfunction in patients with nasal congestion treated with pseudoephedrine: a prospective study.

BACKGROUND: Pseudoephedrine is a sympathomimetic drug widely used as a nasal decongestant. However, it can cause adverse effects, such as voiding dysfunction. The risk of voiding dysfunction remains uncertain in patients without subjective voiding problems. METHODOLOGY: We prospectively enrolled patients with nasal congestion who required treatment with pseudoephedrine from May to August 2015. All patients denied concomitant subjective voiding problem. The International Prostate Symptom Score (IPSS) questionnaire was used to evaluate voiding function before and 1 week after the pseudoephedrine treatment. The results of the IPSS questionnaire were analyzed as the total (IPSS-T), voiding (IPSS-V), storage (IPSS-S), and quality of life due to urinary symptom scores. RESULTS: We enrolled 131 males with a mean age of 42.0±14.3 years. The IPSS-T, IPSS-V, and IPSS-S scores slightly increased after the medication (IPSS-T increased from 6.49 to 6.77, IPSS-V from 3.33 to 3.53, and IPSS-S from 3.17 to 3.24). The quality of life due to urinary symptom score nonsignificantly decreased from 2.02 to 1.87. We observed that older age and a higher premedication IPSS-V score yielded significant differences (P<0.05) for subclinical voiding dysfunction and unchanged voiding function. In patients aged ≥50 years, the IPSS-T, IPSS-V, and IPSS-S scores significantly increased after the pseudoephedrine treatment (IPSS-T increased from 9.95 to 11.45, IPSS-V from 5.38 to 6.07, and IPSS-S 4.57 to 5.38), whereas the quality of life due to urinary symptom score nonsignificantly decreased from 2.71 to 2.48 (P=0.057). In patients aged <50 years, all scores did not significantly differ. CONCLUSION: Pseudoephedrine treatment for nasal congestion requires extra precautions in males >50 years, even without subjective voiding symptoms.

Methylene blue, midodrine, and pseudoephedrine: a review of alternative agents for refractory hypotension in the intensive care unit.

Hypotensive episodes are common among patients in the intensive care unit and can lead to multiorgan failure if uncontrolled. Fluid administration and continuous infusion of vasoactive agents are frequently used for management of hypotension; however, both therapies may be associated with adverse effects including pulmonary edema and tissue necrosis. In addition, availability of these first-line agents has been impacted by the increasing occurrence of drug shortages. Methylene blue, pseudoephedrine, and midodrine have been considered potential alternatives to standard therapy. These agents may not only be used when first-line agents are unavailable due to shortages, but they may also aid in reducing the cumulative dose of other vasoactive agents used. The purpose of this review was to discuss strategies for the safe and effective use of methylene blue, pseudoephedrine, and midodrine for the treatment of hypotension in the critically ill.