Prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017.

OBJECTIVE: To evaluate the prescribing trends of glaucoma drugs in six major cities of China from 2013 to 2017. METHODS: A descriptive analysis using pharmacy prescription data was conducted. Outpatient prescription data was extracted from the Hospital Prescription Analysis Cooperative Project. Prescribing patterns, trends of visits, and corresponding expenditures for glaucoma medications were analyzed. RESULTS: A total of 84297 ambulatory prescriptions were included in the current study. Visits by glaucoma patients increased from 13808 in 2013 to 20060 in 2017. Over the same period, the yearly expenditure for glaucoma drugs increased from 2.33 million to 3.95 million Chinese Yuan (CNY). Among all the six classes of glaucoma drugs (prostaglandin analogues, carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, cholinergic agonists and fixed combinations), ß-receptor antagonists were the most commonly prescribed in 2013, accounting for 34.3% of patients, but gradually decreased to 27.1% in 2017. Prostaglandin analogues became the most frequently prescribed drugs in 2017, accounting for 30.2% of the visits. Prostaglandin analogues are the most expensive and yielded a total expenditure of 2.34 million CNY in 2017, followed by carbonic anhydrase inhibitors, α-receptor agonists, ß-receptor antagonists, fixed combinations, and cholinergic agonists. Combination therapy became increasingly prescribed in 2017. CONCLUSION: Glaucoma prescribing practices exhibited substantial changes over the study period. The number of glaucoma prescriptions continuously increased from 2013 to 2017, leading to increased prescription costs. These findings implied a similar trend observed in previous studies, as well as recommendations in the appropriate guidelines.

Tizanidina para o tratamento do espasmo muscular doloroso / Tizanidine for the treatment of painful muscle spasm

TECNOLOGIA: Tizanidina (Sirdalud®). INDICAÇÃO NA BULA: Espasmo muscular doloroso associado à distúrbios estáticos e funcionais da coluna (síndromes cervical e lombar) e após cirurgia, como por exemplo, de hérnia de disco intervertebral ou de osteoartrite do quadril. Também é indicado para a espasticidade decorrente de distúrbios neurológicos, tais como: esclerose múltipla, mielopatia crônica, doenças degenerativas da medula espinhal, acidentes cerebrovasculares e paralisia cerebral. PERGUNTA: Tizanidina é eficaz e segura para o tratamento do espasmo muscular doloroso? EVIDÊNCIAS: Foram incluídas duas revisões sistemáticas e um ensaio clínico randomizado. Uma revisão sistemática sugere que baclofeno e tizanidina têm eficácia semelhante em pacientes com espasticidade e que tizanidina está associada a maior frequencia de boca seca, enquanto baclofeno com maior fraqueza. Além disso, tizanidina foi eficaz em comparação com o placebo em pacientes com espasticidade (principalmente associada a esclerose múltipla, dor nas costas ou dor no pescoço). Outra revisão sistemática indicou que tizanidina não apresenta diferença na eficácia para baclofeno e diazepam. Em comparação com placebo, tizanidina reduziu o tônus muscular em até 34%. Os eventos adversos associados à tizanidina (que ocorreram em 60 a 88% dos pacientes) foram principalmente sonolência e boca seca, e com menor frequência, alteração nas enzimas hepáticas. O ensaio clínico randomizado demonstrou que tizanidina é eficaz contra placebo e possui eficácia comparável a tiocolchicósido no tratamento da dor lombar aguda associada a espasmos musculares. CONCLUSÕES: Com base em evidências derivadas de estudos de baixa qualidade, tizanidina demonstrou ser eficaz em comparação com o placebo e não apresenta diferença em termos de eficácia para outros comparadores ativos, como baclofeno e diazepam. O principal evento adverso associado ao medicamento foi boca seca. O medicamento não apresenta registro na EMA. Estudos mais robustos são necessários para confirmar a eficácia da tizanidina dentro da sua indicação clínica.(AU)

Noradrenaline is as Effective as Terlipressin in Hepatorenal Syndrome Type 1: A Prospective, Randomized Trial.

OBJECTIVES: Hepatorenal syndrome (HRS) is a functional renal failure occurring in end stage liver disease, which is associated with poor prognosis. Terlipressin has been shown to be effective in treatment of HRS. More recently, it was suggested that noradrenaline, an alpha-adrenergic drug may be also effective in HRS. We aimed to compare the efficacy of noradrenaline versus terlipressin in treatment of HRS type 1. METHODS: Consecutive patients with cirrhosis and HRS type 1 were enrolled and randomised into 2 groups- Group A received intravenous noradrenaline infusion (0.5-3 mg/h) and group B received intravenous terlipressin (0.5-2 mg/6h) for 2 weeks. Intravenous albumin (20 g/day) was given to both groups. RESULTS: Out of 55 cirrhotics screened, 41 were randomised into group A (n=21) or group B (n=20). Baseline characteristics of the two groups were similar. HRS reversal was seen in 47.6%(10/21) patients in group A, and 45% (9/20) patients in group B (p=1.00). In both groups, there was a significant decrease in serum creatinine from baseline (group A- 3.1±1.4 mg/dl to 2.2±1.3 mg/dl, p=0.028; group B- 3.4±1.6 mg/dl to 2.3±1.3 mg/dl, p=0.035). Both the groups showed a significant increase in mean arterial pressure (group A- 77.3±8.6 mmHg to 103.4±8.3 mmHg, p=0.0001; group B- 76.8±11.6 mmHg to 100±9.4 mmHg, p=0.0001). Noradrenaline was associated with fewer adverse events and was significantly cheaper than terlipressin. Lower baseline MELD score was an independent predictor of response to treatment. CONCLUSIONS: Noradrenaline is as effective and safe as terlipressin in the treatment of HRS type 1.

Neonatal abstinence syndrome: Pharmacologic strategies for the mother and infant.

Opioid use in pregnancy has increased dramatically over the past decade. Since prenatal opioid use is associated with numerous obstetrical and neonatal complications, this now has become a major public health problem. In particular, in utero opioid exposure can result in neonatal abstinence syndrome (NAS) which is a serious condition characterized by central nervous system hyperirritability and autonomic nervous system dysfunction. The present review seeks to define current practices regarding the approach to the pregnant mother and neonate with prenatal opiate exposure. Although the cornerstone of prenatal management of opioid dependence is opioid maintenance therapy, the ideal agent has yet to be definitively established. Pharmacologic management of NAS is also highly variable and may include an opioid, barbiturate, and/or α-agonist. Genetic factors appear to be associated with the incidence and severity of NAS. Establishing pharmacogenetic risk factors for the development of NAS has the potential for creating opportunities for "personalized genomic medicine" and novel, individualized therapeutic interventions.

Assessment and treatment of attention-deficit/hyperactivity disorder: part 2.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. In part 1 of this article, information regarding primary care assessment of ADHD was presented. Part 2 focuses on best practice guidelines for treatment once the diagnosis has been established. For most children, successful treatment of ADHD requires a multicomponent approach comprised of patient and family psychoeducation, use of medications approved by the US Food and Drug Administration (eg, stimulants) and/or behavioral interventions, and management of any psychiatric comorbid conditions. Furthermore, as ADHD is a chronic illness, primary care physicians will need to frequently reassess their patients and make treatment adjustments as needed.

[Dexmedetomidine]. / Dexmedetomidin.

Dexmedetomidine is a highly selective α2-receptor agonist with sedative, analgetic and anxiolytic effects. It is chemically related to clonidine and has been an authorized drug in Europe since September 2011. Dexmedetomidine enables a level of sedation in which mechanically ventilated patients may be woken by verbal stimulation (Richmond agitation sedation scale RASS 0--3). In this respect dexmedetomidine achieves the same desired effect as propofol and midazolam; however, in direct comparison to a sedation regime with benzodiazepines, dexmedetomidine reduces the prevalence, duration and severity of delirium in intensive care. Patients sedated by dexmedetomidine can statistically be extubated earlier and an influence on duration of stay in the intensive care unit (ICU) has not been shown. Daily therapy costs are approximately 5 times higher than those of propofol but an objective standpoint in relation to clinical cost efficiency is unattainable.

Update on the role of alpha-agonists in glaucoma management.

Glaucoma is the second most common cause of world blindness (following cataract) with estimated cases reaching 79.6 million by 2020. Although the etiology of glaucoma is multi-factorial, intraocular pressure (IOP) is the only modifiable factor in glaucoma management proven to alter the natural course of the disease. Among various classes of IOP-lowering medications currently available, alpha-adrenergic receptor agonists are used either as monotherapy, as second-line therapy, or in fixed combination with beta-blockers. Non-selective adrenergic agonists such as epinephrine and dipivefrin are infrequently used today for the treatment of glaucoma or ocular hypertension, and have been replaced by the alpha-2-selective agonists. The use of apraclonidine for IOP reduction in glaucoma or OHT is limited due to a high rate of follicular conjunctivitis. The alpha-2-selective agonist in use today is brimonidine. The brimonidine-purite formulations are preferred to brimonidine-benzalkonium chloride (BAC) formulations due better tolerability while maintaining similar efficacy. Brimonidine is also effective when used in combination with a beta-blocker. Using brimonidine-timolol fixed combination (BTFC) as first-line therapy has an added potential for neuroprotection. This would be a valuable strategy for glaucoma treatment, for patients who are intolerant of prostaglandin analogs, or for patients where prostaglandin analogues are contraindicated as first-line therapy, such as in patients with inflammatory glaucoma.

An updated focused review of dexmedetomidine in adults.

OBJECTIVE: To evaluate recent comparative studies regarding the safety and efficacy of dexmedetomidine in adults. DATA SOURCES: Articles evaluating safety and efficacy of dexmedetomidine were identified from an English-language MEDLINE search (1996-July 2009), with a focus on data published since our previous review in 2007 to the present. MeSH terms included dexmedetomidine, medetomidine, alpha2-agonist, and sedation. References from selected articles were also reviewed for additional material. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational English-language studies that focused on the efficacy, safety, and pharmacoeconomics of dexmedetomidine in humans were selected. DATA SYNTHESIS: Dexmedetomidine is an 2-agonist used for sedation during procedures and in critical illness. Compared with placebo, use of dexmedetomidine during procedures was associated with decreased use of rescue midazolam and a similar degree of sedation compared with various agents used during surgery or for procedures. Use of long-term (>24 h) dexmedetomidine sedation is comparable to sedation with benzodiazepines in critically ill patients. In a Phase 4 study, dexmedetomidine was safe in dosages up to 1.4 microg/kg/hour for greater than 24 hours and did not produce rebound tachycardia or hypertension when abruptly discontinued. One small randomized controlled trial demonstrated decreased incidence of delirium, the primary endpoint, with dexmedetomidine compared with midazolam or propofol for sedation after cardiac valve surgery. Many, but not all, studies suggest that dexmedetomidine has a promising role in prevention and treatment of delirium in critically ill patients when delirium was studied as a secondary endpoint. CONCLUSIONS: Dexmedetomidine is an alternative for procedural sedation and can be used long-term (>24 h) in critically ill patients, in dosages up to 1.5 microg/kg/hour. More studies are needed to better define the role of dexmedetomidine in preventing and treating delirium.

Randomised controlled study-efficacy of clonidine versus carbamazepine in children with ADHD.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common childhood psychiatric disorder with a prevalence of 8-12%. Even though psychostimulants remain the treatment of choice, its cost and availability in developing countries limits the usage of the drug. In view of free availability and low cost, a Randomized controlled study was carried out using two second line drugs (clonidine and carbamazepine) in a tertiary care hospital, Pondicherry, South India. OBJECTIVE: To compare the efficacy of clonidine and carbamazepine in children with ADHD. METHOD: With approval of ethics committee, a prospective, Double-blind, Randomized controlled study of clonidine and carbamazepine was conducted with 50 children with ADHD (age group 4-12 years), over a period of 2 years (2005-07) in a tertiary care hospital, Pondicherry, South India. RESULTS: Clonidine was effective in improving the hyperactivity and impulsivity symptoms in children with ADHD as compared to carbamazepine. Statistical significant improvement was not noted with respect to inattention symptoms and other comorbid conditions. CONCLUSION: Clonidine can be a safer and cheaper alternative in treatment of children with ADHD, with a predominant effect on their hyperactivity and impulsivity symptoms.

Silodosin: a selective alpha1A-adrenergic receptor antagonist for the treatment of benign prostatic hyperplasia.

BACKGROUND: Silodosin is a new alpha(1)-adrenergic receptor antagonist that is selective for the alpha(1A)-adrenergic receptor. It was approved by the US Food and Drug Administration (FDA) in 2008 for the treatment of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). OBJECTIVE: This article reviews the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of silodosin in adult male patients with BPH. METHODS: A search of MEDLINE (1950-October 8, 2009), International Pharmaceutical Abstracts (1970-October 8, 2009), and the Iowa Drug Information Service database (1966-October 8, 2009) was conducted using the terms silodosin, KMD-3213, benign prostatic hyperplasia, and alpha(1)-adrenergic receptor antagonist. Reports of research and review articles published in English were identified and evaluated, and the bibliographies of these articles were reviewed for additional relevant publications. A search of the FDA Web site was performed, and abstracts and posters presented at scientific meetings of the American Urological Association were reviewed. RESULTS: By antagonizing alpha(1A)-adrenergic receptors in the prostate and urethra, silodosin causes smooth muscle relaxation in the LUT. Silodosin has greater affinity for the alpha(1A)-adrenergic receptor than for the alpha(1B)-adrenergic receptor (by a factor of 583), minimizing the propensity for blood pressure-related adverse effects mediated by alpha(1B) blockade. In 3 controlled clinical studies in patients with BPH-related LUTS (1 published; 2 presented in the prescribing information and published in a pooled analysis), patients receiving silodosin at a total daily dose of 8 mg had significant improvements in the International Prostate Symptom Score (IPSS) and maximum urinary flow rate (Q(max)) compared with those receiving placebo (both, P < 0.05). The most commonly reported adverse effect was abnormal or retrograde ejaculation (>22%), and the incidence of orthostatic hypotension was low (<3%). CONCLUSIONS: In the small number of clinical trials reviewed, silodosin was associated with significant reductions in IPSS and Q(max) compared with placebo. To determine whether silodosin's selectivity for the alpha(1A)-adrenergic receptor translates into a clinical advantage relative to other available agents, long-term studies evaluating the comparative efficacy and tolerability of silodosin and other alpha(1)-blockers (specifically tamsulosin) are necessary.

Costs and persistence of brimonidine versus brinzolamide in everyday glaucoma care: an analysis conducted on the UK General Practitioner Research Database.

OBJECTIVE: To compare the persistence and costs of brimonidine versus brinzolamide therapy according to data collected by the UK General Practitioner Research Database (GPRD). METHODS: Patients with diagnoses of ocular hypertension or glaucoma, or treated for glaucoma by surgery or laser therapy were identified. Selected patients were prescribed either brimonidine or brinzolamide as monotherapy. Treatment failure was defined as a glaucoma prescription change (adding, removing or replacing a drug, or initiating surgery or laser therapy). Times to treatment failure were compared with an adjusted Cox model using a propensity score method. RESULTS: A total of 2,172 patients received brimonidine and 485 brinzolamide. Mean age was 69.5 years and 46.4% were male. Age and gender did not differ significantly whereas disease duration was longer with brinzolamide. Treatment failure at 1 year was experienced by 47.7% of patients given brinzolamide and by 55.9% given brimonidine (p<0.001). The hazard ratio for failure was less with brinzolamide (0.79: p<0.001) compared to brimonidine, after adjusting for age, gender, comorbidities and duration of follow-up. Adjusted annual costs of glaucoma management (in pound2005) were significantly (p<0.0042) lower with brinzolamide (pound196) than brimonidine (pound230). CONCLUSIONS: According to data from everyday practice collected by the UK GPRD, brinzolamide was found to be more persistent than brimonidine when given as glaucoma monotherapy. Patients continued longer with brinzolamide treatment at a lower cost.

Persistency rates for prostaglandin and other hypotensive eyedrops: population-based study using pharmacy claims data.

BACKGROUND: Effective management of ocular hypertension requires patients to be persistent with their treatment regimen. We evaluated patients' persistency with hypotensive eyedrops commonly used to treat glaucoma and ocular hypertension. METHODS: This large, population-based, retrospective, cohort study used pharmacy claims data for concessional patients from the Australian Pharmaceutical Benefits Scheme (July 1999-June 2005). Resupply rates for prostaglandins, beta-blockers, alpha-agonists and carbonic anhydrase inhibitors were analysed using life tables and Cox regression. Two populations, based on patients' supply histories, were examined: (i) 'new to this eyedrop'- patients who had used other hypotensive eyedrops before (presumably, previously diagnosed with glaucoma or ocular hypertension); and (ii) 'new to any eyedrop'- patients who were using their first hypotensive eyedrop (presumably, newly diagnosed with glaucoma or ocular hypertension). RESULTS: Data were obtained for 14,359,618 supplies of commonly used hypotensive eyedrops to 357,099 concessional patients. For both populations, resupply rates were highest for prostaglandins or the dorzolamide-timolol combination eyedrops, compared with beta-blockers, alpha-agonists or carbonic anhydrase inhibitors. Among the prostaglandins, there was no significant difference in the risk of ceasing supply between latanoprost and bimatoprost, but the risk was significantly higher for travoprost. CONCLUSIONS: Based on resupply rates from a national pharmacy claims database, patients supplied with ocular hypotensive eyedrops were most persistent with prostaglandin (bimatoprost, latanoprost and travoprost) and dorzolamide-timolol combination eyedrops. Among the prostaglandins, persistency was highest with, and similar between, bimatoprost and latanoprost. Persistency should be taken into account when selecting the most appropriate eyedrop to treat glaucoma and ocular hypertension.

How is norepinephrine used in intensive care? A field study.

OBJECTIVE: To assess how norepinephrine (NE), an emergency treatment of cardiovascular collapse, is used in intensive care. METHODS: Nurses and physicians of 14 intensive care units of the Bordeaux University Hospital were given questionnaires on the way they say they use NE and on actual NE treatment of patients. RESULTS: The clinical monitoring parameters cited were blood pressure, heart rate and hourly urine flow. Only 25% of the prescribers indicated the systematic use of hemodynamic monitoring. All the prescribers indicated they adapted the treatment to clinical objectives and blood pressure, and 77.5% to hourly urine flow. Initial NE concentrations ranged from 0.5 to 2 mg/ml, diluted in saline or dextrose. Initial prescribed dose ranged from 0.1 to 1 microg/kg/min. Large differences were observed between services and even within units. CONCLUSION: These data clearly show the need for recommendations regarding the use of norepinephrine.

[Perioperative cardioprotection. Golden standard beta-blockade?]. / Perioperative Kardioprotektion. Goldstandard beta-Blockade?

Myocardial ischemia is a major cause of perioperative morbidity and mortality. Because of a growing expectancy of lives, the prevalence of cardiovascular diseases is increasing, and thus the number of surgical patients presenting with a cardiovascular risk profile. Based upon pathophysiological considerations, different interventions to lower perioperative cardiovascular risk have been evaluated. The mostly discussed intervention believed to prevent cardiovascular complications in the perioperative period is the use of beta-blockers. Although many authors agree that perioperative beta-blockade is effective in high-risk patients, less is known about the optimal timing, dosage and the identification of patients in whom the intervention would be beneficial. Based upon the available data we try to answer questions about timing and dosage, and we discuss possible side effects and economic questions. Another cardioprotective option is the use of statins. Besides their lipid-lowering properties, so called pleiotropic effects are believed to decrease cardiac risk. Furthermore, different interventions can be used in addition to or as an alternative to perioperative beta-blocker therapy, such as alpha-2 agonists, thoracic epidural analgesia or coronary revascularization.

Clonidine and modification of perioperative outcome.

PURPOSE OF REVIEW: Perioperative cardiac risk reduction using perioperative beta-blockade is being widely adopted. Recent research has identified a second-line agent, perioperative clonidine, that can be used to reduce the risk of perioperative cardiac mortality. Perioperative clonidine has some advantages over perioperative beta-blockers because it has less risk of bronchospasm in asthmatics and it comes in a transcutaneous form that can be used in patients who are not taking oral medications ('NPO'). RECENT FINDINGS: Clonidine has been used for many purposes, including reduction of blood pressure in hypertension, reduction in alcohol and drug withdrawal phenomena, reduction in nicotine withdrawal symptoms during smoking cessation, analgesia, reduction in stress response, and now as an anti-ischemic agent to reduce the risk of perioperative myocardial ischemia and perioperative mortality. SUMMARY: Administration of perioperative clonidine can reduce the risk of perioperative myocardial ischemia and mortality in patients undergoing non-cardiac surgery. Perioperative clonidine comes in a patch form that can be used in patients who are not taking medications by mouth, and can be used when beta-blockers are contraindicated (for asthmatics or patients with high-grade atrioventricular block).

Considerations in the long-term management of asthma in ambulatory patients.

PURPOSE: The goals of treatment and drug therapies used for long-term asthma control, classification of the disease by severity, and treatment based on severity are reviewed, with an emphasis on recent controversies in treatment approach and safety concerns. SUMMARY: Patient education and written asthma self-management and action plans are essential components of asthma treatment because of the need for patients to acquire substantial knowledge and skills in self-care. Inhaled corticosteroids are the most effective long-term-control therapy and usually suffice as monotherapy for mild persistent asthma. Adding a long-acting, inhaled beta2 agonist to the inhaled corticosteroid is preferred for moderate and severe persistent disease despite safety concerns. Omalizumab use is limited to selected patients with moderate-to-severe allergic asthma and an inadequate response to inhaled corticosteroids. CONCLUSION: The long-term control of asthma requires substantial patient knowledge and skill. Persistent disease is best managed by inhaled corticosteroids and if it is moderate or severe, long-acting, inhaled beta2 agonists in combination with inhaled corticosteroids.