Clinical review of treatment options for select nonmotor symptoms of Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is associated with a host of nonmotor symptoms, including psychosis, cognitive impairment, depression, sleep disturbance, swallowing disorders, gastrointestinal symptoms, and autonomic dysfunction. The nonmotor symptoms of PD have the potential to be more debilitating than the motor features of the disorder. OBJECTIVE: The aim of this article was to review treatment options for the nonmotor manifestations of PD, including pharmacologic and nonpharmacologic interventions. METHODS: The PubMed and MEDLINE databases were searched for articles published in English between January 1966 and April 2010, using the terms Parkinson's disease, nonmotor, psychosis, hallucination, antipsychotic, cognitive impairment, dementia, depression, sleep disturbance, sleepiness, REM (rapid eye movement) sleep behavior disorder, dysphagia, swallowing disorder, sialorrhea, gastrointestinal, constipation, autonomic dysfunction, orthostatic hypotension, gastroparesis, erectile dysfunction, sexual dysfunction, and urinary dysfunction. Articles were selected for review if they were randomized controlled trials (RCTs), meta-analyses, or evidence-based reviews of treatment of patients with PD, and/or expert opinion regarding the treatment of nonmotor symptoms of PD. RESULTS: A total of 148 articles, including RCTs, meta-analyses, and evidence-based reviews, were included in this review. The treatment of hallucinations or psychosis in PD should include a stepwise reduction in medications for motor symptoms, followed by the use of quetiapine or clozapine. Dementia may be treated with acetylcholinesterase inhibitors. Evidence is lacking concerning the optimal pharmacologic treatment for depression in PD, with expert opinions indicating selective serotonin reuptake inhibitors as the antidepressants of choice. However, the largest study to date found nortriptyline therapy to be efficacious compared with placebo, whereas paroxetine controlled release was not. A variety of sleep disturbances may plague a person with PD, and treatment must be individualized to the patient's specific sleep disturbance pattern and contributing factors. Swallowing disorders may lead to aspiration and pneumonia, and patients with dysphagia should be referred to a speech therapist for further evaluation and treatment. Orthostasis may be treated with nonpharmacologic interventions as well as pharmacologic treatments (eg, fludrocortisone, midodrine, indomethacin). Other autonomic symptoms are managed in a manner similar to that in patients without PD, although careful attention must be aimed at avoiding dopamine-blocking therapies in the treatment of gastrointestinal dysfunction and gastroparesis. CONCLUSIONS: Various pharmacologic and nonpharmacologic strategies are available for the management of the nonmotor symptoms of PD. The challenges associated with nonmotor symptoms must not be forgotten in light of the motor symptoms of PD, and treatment of nonmotor symptoms should be encouraged.

Nurse identified hospital to home medication discrepancies: implications for improving transitional care.

Care transitions are clinically dangerous times, particularly for older adults with complex health problems. This article describes the most common medication discrepancies identified by nurses during patients' (n = 101) hospital to home transition. Findings indicated that medication discrepancies were astoundingly widespread, with 94% of the participants having at least 1 discrepancy. The average number of medication discrepancies identified was 3.3 per participant. Medication discrepancies were identified in virtually all classes of medications, including those with high safety risks. Evidence-based best practices to reduce transition-related medication discrepancies are presented.

A review of inhaled technosphere insulin.

OBJECTIVE: To review the pharmacology, pharmacokinetics, efficacy, safety, and clinical use of Technosphere insulin. DATA SOURCES: A MEDLINE search (1966-March 2010) was conducted for English-language articles using the terms AFREZZA, AFRESA, Technosphere insulin, pulmonary insulin, and inhaled insulin. Abstracts from the American Diabetes Association and European Association for the Study of Diabetes annual meetings, presented in 2004, 2005, 2006, 2007, 2008, and 2009 were also searched for relevant data. STUDY SELECTION AND DATA EXTRACTION: English-language articles pertinent to the pharmacology, pharmacokinetics, efficacy, and safety of Technosphere insulin were reviewed. DATA SYNTHESIS: Technosphere insulin is an inhaled insulin product with a pharmacokinetic profile suitable to meet prandial insulin needs in patients with diabetes. Technosphere insulin has demonstrated efficacy in terms of postprandial and overall glycemic control, with efficacy and safety outcomes maintained for up to 4 years in one study. The overall tolerability profile for Technosphere insulin in clinical trials published to date has demonstrated a relatively low risk of hypoglycemia and weight gain when compared with subcutaneous mealtime insulins. Clinical trials to date have demonstrated safety in terms of pulmonary function, and the absorption of Technosphere insulin is not significantly altered in patients with chronic obstructive pulmonary disease or in those who smoke. CONCLUSIONS: The Technosphere delivery system allows for the rapid absorption of Technosphere insulin via the lung, making this product a potential option for prandial insulin coverage in both type 1 and type 2 diabetes. The device to administer the insulin is well designed, small, and easy to use. Technosphere inhaled insulin may provide a useful treatment option for patients resistant to or fearful of initiating prandial insulin injections.

Clinical review and treatment of select adverse effects of dopamine receptor agonists in Parkinson's disease.

Dopamine receptor agonists provide a viable alternative or adjunct to levodopa therapy in Parkinson's disease and are associated with fewer motor complications and dyskinesia. However, all available dopamine agonists may cause profound adverse effects in some patients. In many cases, these adverse effects amplify non-motor symptoms that people with Parkinson's disease may already be experiencing. Nausea from dopamine agonists generally lessens with time and may be responsive to both antiemetic therapy and complementary remedies, such as ginger, peppermint and chamomile. Unfortunately, compulsive behaviours, as well as peripheral oedema caused by dopamine agonists, are poorly responsive to pharmacological therapy and require a reduction or discontinuation of agonist therapy. Somnolence and associated sleep attacks generally require elimination of the agonist or the use of a stimulating agent. The necessity of treatment for hallucinations and psychosis associated with dopamine agonists must be thoroughly evaluated prior to initiating therapy. If a medication is initiated for hallucinations or psychosis, quetiapine or clozapine are agents of choice. Orthostatic hypotension, though not always symptomatic, responds well to nonpharmacological strategies and medications, including indometacin, midodrine and fludrocortisone. Care must be taken to educate patients with Parkinson's disease about the common adverse effects of dopamine agonists and what can be done to lessen them.

Pharmacology, efficacy and safety of liraglutide in the management of type 2 diabetes.

Liraglutide is a glucagon-like peptide-1 analog with pharmacokinetic properties suitable for once-daily administration approved by the Food and Drug Administration for the treatment of patients with type 2 diabetes. Clinical trial data from large, controlled studies demonstrate the safety and efficacy of liraglutide in terms of hemoglobin A(1c) (HbA(1c)) reduction, reductions in body weight, and the drug's low risk for hypoglycemic events when used as monotherapy. Liraglutide has been studied as monotherapy and in combination with metformin, glimepiride, and rosiglitazone for the treatment of type 2 diabetes. Additionally, comparative data with insulin glargine and exenatide therapy are available from Phase III trials. Once-daily administration may provide a therapeutic advantage for liraglutide over twice-daily exenatide, with similar improvements in HbA(1c) and body weight observed when liraglutide was compared with exenatide. The glucose-dependent mechanism of insulin release with incretin analog therapy holds potential clinical significance in the management of postprandial hyperglycemic excursions, with minimal risk of hypoglycemia when used with non-secretagogue medications. Data to date on patient-reported outcomes with liraglutide treatment are encouraging. The most common adverse events associated with liraglutide therapy are dose-dependent nausea, vomiting, and diarrhea. Diligent postmarketing surveillance to elucidate the risk of pancreatitis and medullary thyroid carcinoma in a heterogeneous population are likely warranted.