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.

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.

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.

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.

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.

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.

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.

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.

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.

Female clitoral priapism: an over-the-counter option for management.

INTRODUCTION: Female priapism is a rare condition that is not commonly described in the literature. There are many treatment strategies for the management of priapism, including conservative and safe over-the-counter options. AIM: To describe a case of a woman who presented with clitoral priapism, who was managed conservatively with a simple over-the-counter treatment plan. METHODS: A 29-year-old gravida 0 para 0 presented to the emergency room with painful clitoral priapism lasting for 5 days. Despite cessation of the suspected causal agents, trazodone and wellbutrin, her symptoms persisted. RESULTS: The patient was managed conservatively with analgesics and around-the-clock oral pseudoephedrine and experienced complete resolution of her symptoms. CONCLUSIONS: Oral pseudoephedrine may be a reasonable option for certain patients, and may be considered as a first-line therapy and adjunct to conservative measures.

Kentucky pharmacists' opinions of the potential reclassification of pseudoephedrine as a legend drug.

OBJECTIVES: To collect and analyze Kentucky pharmacists' opinions of the effectiveness of current methamphetamine precursor controls, to analyze proposed legislation to make pseudoephedrine (PSE) a legend drug, and to analyze the potential impact of such legislation on pharmacy practice and patients. DESIGN: Descriptive, nonexperimental survey study. SETTING: Kentucky; June through October 2012. PARTICIPANTS: 431 Kentucky community pharmacists. INTERVENTION: Mailed survey. MAIN OUTCOME MEASURES: Perceived efficacy of current methamphetamine precursor controls, anticipated impact on individual pharmacy practices and patients of proposed legislation to make PSE available by prescription only, and current opinions about the proposed legislation. RESULTS: Analysis of 431 community pharmacists showed that approximately 77% believed proposed legislation to make PSE available by prescription only would be effective in reducing methamphetamine abuse and methamphetamine-related laboratory incidents, with 56.2% indicating support for the proposed legislation. Pharmacists practicing in chain pharmacies were 2.9 times more likely to support the legislation than pharmacists practicing in independent pharmacies. Additional factors influencing pharmacist support included Kentucky region of practice, anticipated impact on time spent on PSE activities, pharmacy profit, methamphetamine abuse, and methamphetamine-related laboratory incidents. Pharmacists practicing in regions of Kentucky associated with higher methamphetamine abuse appear to more strongly support the proposed legislation. CONCLUSION: Pharmacists are at the frontline of PSE distribution. Gaining a better understanding of issues surrounding the distribution of PSE will enhance the likelihood that future legislation may be crafted to reduce methamphetamine production, laboratory incidents, and abuse while minimizing inconvenience and cost.

Priapism, an emerging complication in ß-thalassemia intermedia patients.

The increase in survival rate of ß-thalassemia (ß-thal) patients allowed for the appearance and manifestation of several complications in almost every organ system. Priapism in ß-thal patients is rarely reported in the literature. We herein report and investigate the occurrence of two cases of priapism in two young patients with ß-thal intermedia (ß-TI). The potential mechanisms are due to either a cellular mechanism involving a thrombus obstructing the efferent venules of the corpora cavernosa leading to priapism, or a recently elucidated functional mechanism that causes alteration of nitric oxide (NO) response of the penis, ultimately causing priapism. This should incite clinicians for a close follow-up and monitoring of high risk patients who are susceptible to developing priapism.

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.

Outcomes of the management of post-chemotherapy retroperitoneal lymph node dissection-associated anejaculation.

UNLABELLED: What's known on the subject? and What does the study add? Modern surgical techniques have allowed preservation of fertility in most patients after post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND), but some patients still have infertility after surgery. We reviewed our experience treating infertility in 26 men after PC-RPLND. Using a structured clinical pathway we obtained sperm in 81% of men for use in assisted reproduction. OBJECTIVE: To evaluate the effectiveness of a clinical pathway on sperm retrieval outcomes in patients presenting with infertility after post-chemotherapy (PC) retroperitoneal lymph node dissection (RPLND). PATIENTS AND METHODS: We carried out a retrospective review of patients with advanced testicular cancer, presenting with infertility after PC-RPLND in a large reproductive urology practice. We implemented a clinical pathway where pseudoephedrine was first administered. If this medication failed, electroejaculation (EEJ) and/or testicular sperm extraction (TESE) was carried out. The primary outcome was retrieval of sperm for use in assisted reproduction. RESULTS: Four men had retrograde ejaculation, of whom two converted to antegrade ejaculation with medical therapy. In all, 22 patients had failure of emission (FOE) and, of these, no patient converted to antegrade ejaculation with medication. In patients with FOE, sperm was found in 15/20 of those experiencing a successful EEJ. Seven patients underwent TESE for azoospermia on EEJ or no ejaculate on EEJ, three of whom had sperm found on TESE. Sperm was found for assisted reproduction in 81% (21/26) patients. CONCLUSIONS: There appears to be no role for the use of pseudoephedrine therapy in patients with FOE after PC-RPLND. The use of a structured clinical pathway may optimize patient care.

The role of pseudoephedrine on daytime somnolence in patients suffering from perennial allergic rhinitis (PAR).

BACKGROUND: Allergic rhinitis is one of several inflammatory diseases affecting the nasal mucosa. Cellular inflammation of nasal mucosa is a hallmark of this disease and is characterized by the accumulation of eosinophils and the release of various chemical messengers such as chemokines, cytokines, and histamine. This inflammation of the nose leads to nasal congestion and a reduction in sleep quality, resulting in daytime somnolence. OBJECTIVE: Drugs that significantly reduce the symptoms of nasal congestion also may help in alleviating sleep-related symptoms of allergic rhinitis. Pseudoephedrine is a sympathomimetic amine that is indicated for treatment of nasal congestion associated with allergic rhinitis. Despite relieving nasal congestion, we speculated that, because of pseudoephedrine's well-known stimulant profile, sleep would not be improved. METHOD: Fourteen subjects who met the inclusion criteria were enrolled into a double-blind, placebo-controlled, randomized study to either pseudoephedrine or placebo once per day in the morning, using the traditional crossover design. Skin testing test was performed to ensure a positive response to a relevant perennial allergen and a negative response to a seasonal allergen. Several questionnaires were used to evaluate the patients' sleep-related symptoms, allergic rhinitis symptoms, and quality of life. RESULTS: Our results showed that pseudoephedrine did not have a positive or negative effect on quality of sleep, daytime sleepiness, or daytime fatigue as compared with placebo. Pseudoephedrine did show a statistical significance in improving stuffy nose (P = .0172). With respect to quality of life, pseudoephedrine led to a statistically significant decrease in intimate relationships and sexual activity as compared with the placebo group (P = .0310). CONCLUSION: Our research suggests that sleep quality is not significantly affected by pseudoephedrine. As expected, congestion is reduced, but side effects such as a decline of intimate relationships and sexual activity may interfere with quality of life.

Decongestant use during pregnancy and its association with preterm delivery.

BACKGROUND: Despite the frequent intake of decongestants during pregnancy, only one study to date has evaluated the association of decongestants with preterm delivery, and it identified a reduced risk. We examined this association in more detail. METHODS: Using a population-based random sample of 3271 Massachusetts live-born births without major malformations, we categorized decongestant exposure according to timing, frequency of use, route, and indication. Preterm birth was defined as a gestational age of <37 completed weeks. We estimated hazard ratios and examined confounding by indication by examining various strata of women and through multivariate adjustment. RESULTS: Compared to nonexposed women, those who took decongestants during the second or third trimester only were less likely to experience preterm delivery (HR, 0.42; 95% CI, 0.21-0.84). This association was observed only for women without preeclampsia. CONCLUSIONS: A protective association between decongestant use and preterm delivery has now been observed in two studies; however, the possibility of confounding by underlying condition remains.

Impact of the voluntary withdrawal of over-the-counter cough and cold medications on pediatric ingestions reported to poison centers.

PURPOSE: To assess the impact of a voluntary withdrawal of over-the-counter cough and cold medications (OTC CCMs) labeled for children under age 2 years on pediatric ingestions reported to the American Association of Poison Control Centers. METHODS: Trend analysis of OTC CCMs ingestions in children under the age 6 years resulting from therapeutic errors or unintentional poisonings for 27 months before (pre-) and 15 months after (post-) the October 2007 voluntary withdrawal was conducted. The rates and outcome severity were examined. RESULTS: The mean annual rate of therapeutic errors involving OTC CCMs post-withdrawal, in children less than 2-years of age, 45.2/100,000 (95%CI 30.7-66.6) was 54% of the rate pre-withdrawal, 83.8/100,000 (95%CI 67.6-104.0). The decrease was statistically significant p < 0.02. In this age group, there was no difference in the frequency of severe outcomes resulting from therapeutic errors post-withdrawal. There was no significant difference in unintentional poisoning rates post-withdrawal 82.1/100,000 (66.0-102.2) vs. pre-withdrawal 98.3/100,000 (84.4-114.3) (p < 0.21) in children less than 2-years of age. There were no significant reductions in rates of therapeutic errors and unintentional poisonings in children ages 2-5 years, who were not targeted by the withdrawal. CONCLUSIONS: A significant decrease in annual rates of therapeutic errors in children under 2-years reported to Poison Centers followed the voluntary withdrawal of OTC CCMs for children under age 2-years. Concerns that withdrawal of pediatric medications would paradoxically increase poisonings from parents giving products intended for older age groups to young children are not supported.