Access to affordable medicines and diagnostic tests for asthma and COPD in sub Saharan Africa: the Ugandan perspective.

BACKGROUND: Equitable access to affordable medicines and diagnostic tests is an integral component of optimal clinical care of patients with asthma and chronic obstructive pulmonary disease (COPD). In Uganda, we lack contemporary data about the availability, cost and affordability of medicines and diagnostic tests essential in asthma and COPD management. METHODS: Data on the availability, cost and affordability of 17 medicines and 2 diagnostic tests essential in asthma and COPD management were collected from 22 public hospitals, 23 private and 85 private pharmacies. The percentage of the available medicines and diagnostic tests, the median retail price of the lowest priced generic brand and affordability in terms of the number of days' wages it would cost the least paid public servant were analysed. RESULTS: The availability of inhaled short acting beta agonists (SABA), oral leukotriene receptor antagonists (LTRA), inhaled LABA-ICS combinations and inhaled corticosteroids (ICS) in all the study sites was 75%, 60.8%, 46.9% and 45.4% respectively. None of the study sites had inhaled long acting anti muscarinic agents (LAMA) and inhaled long acting beta agonist (LABA)-LAMA combinations. Spirometry and peak flow-metry as diagnostic tests were available in 24.4% and 6.7% of the study sites respectively. Affordability ranged from 2.2 days' wages for inhaled salbutamol to 17.1 days' wages for formoterol/budesonide inhalers and 27.8 days' wages for spirometry. CONCLUSION: Medicines and diagnostic tests essential in asthma and COPD care are not widely available in Uganda and remain largely unaffordable. Strategies to improve access to affordable asthma and COPD medicines and diagnostic tests should be implemented in Uganda.

Glycopyrrolate: It's time to review.

Medication shortages have become an all-too-common inconvenience that has forced anesthesia providers to examine our administering practices. Because of these shortages, commonly used medications are at the greatest risk. Glycopyrrolate (Robinul), which has been in short supply in recent years, is one of the most widely used anticholinergic agents, especially in conjunction with the anticholinesterase neostigmine, for reversal of neuromuscular blockade (NMB) drugs. Here we review multiple studies from 1972 through 1986 that used varying methods of patient selection and dosage and drug combination criteria, and which noted that glycopyrrolate had a superior efficacy and adverse effect profile when compared with atropine in NMB reversal. Meta-analysis from these studies indicated that the dosage of 0.2 mg of glycopyrrolate for every 1 mg of neostigmine, given concomitantly (maximum 1 mg glycopyrrolate and 5 mg neostigmine), demonstrated the greatest efficacy with the lowest incidence of unwanted adverse effects. It has now become common practice to use a dosage ratio of 0.2 mg glycopyrrolate to 1.0 mg neostigmine for NMB reversal. Yet since 1986, there have been no studies on reversal with glycopyrrolate and neostigmine. Frequent medication shortages and good medical practice should be an impetus for clinicians to reevaluate dosing practices of critical medications and revisit these drugs, such as glycopyrrolate, with more current studies.

Perfil del paciente con vejiga hiperactiva tratado con dosis flexible de antimuscarínicos en la práctica clínica diaria / Profile of oab patient on treatment with flexible-dose antimuscarinic drugs in daily clinical practice

OBJETIVO: Describir en el entorno de la práctica clínica diaria, el perfil del paciente con vejiga hiperactiva (VH) tratado con dosis flexible de antimuscarícos. MÉTODOS: Estudio observacional, retrospectivo y multicéntrico llevado a cabo en 88 Hospitales públicos y privados. Se incluyeron pacientes adultos, diagnosticados de VH que iniciaron tratamiento con algún antimuscarínico a dosis flexible. Se recogió tipo de antimuscarínico, dosis, tratamientos concomitantes, beneficio aportado y cumplimiento terapéutico. RESULTADOS: Población constituida por 846 pacientes mayores de 60 años, pluripatológica (83,5%) y polimedicada (73,4%), formada mayoritariamente por mujeres (74,5%) y con más de un año de evolución de la VH. Principales antimuscarínicos inicialmente prescritos: fesoterodina (66,9%) y solifenacina (31,0%). El 68,2% de los pacientes iniciaron el tratamiento con la dosis baja. En la visita de seguimiento, el 47,0% modificó dosis (84,2% aumentaron la dosis, 15,8% disminuyeron la dosis). Los grupos que tuvieron que modificar dosis presentaron significativamente mayor morbilidad, peor sintomatología, mayor empleo de recursos sanitarios y peor cumplimiento terapéutico que el grupo de pacientes tratados siempre a dosis alta. CONCLUSIÓN: En determinados pacientes, el empleo desde el inicio del tratamiento antimuscarínico de dosis- flexible a la dosis más alta, podría proporcionar mayor beneficio terapéutico, adherencia y menor empleo de recursos sanitarios que el escalado de dosis

OBJECTIVE: To describe the profile of the overactive bladder (OAB) patient on treatment with flexible-dose antimuscarinic treatment in daily clinical practice. METHODS: This was an observational, retrospective and multicenter study, carried out at 88 public and private hospitals. Adult patients diagnosed with OAB who initiated flexible-dose antimuscarinic treatment. Type of antimuscarinic, dose, concomitant treatments, treatment benefit and treatment adherence were recorded. RESULTS: This was a pluripathological (83.5%) and polymedicated (73.4%) population, comprised of 846 patients, mostly women (74.5%) with a mean (SD) age of 61.3 (12.1) years and more than one year of OAB evolution. Main initially prescribed antimuscarinics were fesoterodine (66.5%) and solifenacine (30.0%). Overall, 68.2% of the patients started treatment with the low dosage; at the follow-up visit 47.0% changed the dosage (84.2% increased the dosage, 15.8% decreased the dosage). Patients who changed the dosage showed a significantly greater morbidity, worse OAB symptoms, greater health resources use, and worse adherence to treatment compared with those that maintained the high dosage all the time. CONCLUSION: No differences were found regarding the demographic or clinical characteristics that allow us to identify which patients should receive the different options of available dose of antimuscarinic drugs, although greater benefits seem to be achieved with the use of the highest or the lowest dose from the outset than with the change of dose

Fluoxetine induces vasodilatation of cerebral arterioles by co-modulating NO/muscarinic signalling.

Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose-dependent vasodilatation (by 1.2 to 1.6-fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG-nitro-l-arginine methyl ester (l-NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10-30 min. following experimental vascular photo-thrombosis increased arterial diameter (1.3-1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor-dependent increases in intracellular [Ca(2+) ] and promoted albumin- and eNOS-dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co-promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin-dependent inhibition of serum AChE.

Elevating our therapeutic expectations in overactive bladder.

Drug therapy for overactive bladder (OAB) most commonly includes antimuscarinic agents, which work by relaxing bladder smooth muscle through inhibition of acetylcholine receptors in the bladder. The major adverse effects with existing antimuscarinic agents are anticholinergic in nature (e.g., dry mouth, constipation, blurred vision). Oxybutynin and tolterodine have been used for several years for treatment of OAB; both are available in immediate- and extended-release formulations. Fewer or less severe adverse effects are reported with the extended- versus the immediate-release formulations, with little or no difference in efficacy. Oxybutynin is also available as a transdermal patch. Trospium, which was recently approved for use in the United States, has efficacy and an incidence of dry mouth similar to existing agents but does not cross the blood-brain barrier. It requires twice-daily dosing. Two new antimuscarinic agents--darifenacin and solifenacin--are in development. Both show significantly better efficacy compared with placebo for key symptoms of OAB, including urgency. The incidence of dry mouth at the lowest effective dose is 19% for darifenacin and 8% and 14% for solifenacin (2 studies).