Current Drug Therapy - Volume 5, Issue 2, 2010

Type 2 diabetes mellitus (T2DM) is a highly prevalent and progressive metabolic disease associated with significant morbidity and mortality. While glycemic control remains the cornerstone of disease treatment, successful T2DM management requires consideration of several comorbid risk factors including overweight/obesity, dyslipidemia, and hypertension. Early and aggressive treatment of patients with T2DM should be implemented to slow disease progression and prevent long-term complications. This necessitates the selection of antidiabetes agents that effectively lower hyperglycemia and target the other fundamental defects of T2DM. Treatment regimens should be individualized according to patient profiles and risk factors. This is especially germane for overweight/obese patients with T2DM, who have an even higher risk for complications. Several newer antidiabetes agents, in particular, incretin-based therapies, target the underlying defects of T2DM, provide glycemic control with beneficial effects on cardiovascular risk factors including lipids and blood pressure while avoiding weight gain. These represent important therapeutic options for the management of patients with T2DM.

Despite the availability of a range of treatments, a majority of patients with Generalized Anxiety Disorder (GAD) report lack of functional recovery, and newer agents are needed for this unmet therapeutic need. This is a systematic review of newer agents in development for GAD, grouped by primary pharmacological activity, including clinical and late preclinical agents. The analysis also includes dose-response analysis for established drugs with substantial additional recently published data. Newer agents can be clustered in three groups: (i) ligands for novel pharmacological targets (e.g. specific glutamate receptor agonists; mitochondrial transporter protein ligands; beta-3-adrenoceptor agonists); (ii) refinements of ligands for established targets (e.g. subtype-selective benzodiazepine positive allosteric modulators); and (iii) new molecules that target established pharmacology (e.g. 5HT1A partial agonists; 5HT2A/2C antagonists; new formulations of or single enantiomers of approved drugs). Most agents in clusters (i) and (ii) have not yet been tested in patients with GAD, and despite their promising nature, still have a high risk of development failure. Agents in cluster (iii) have reported that positive clinical results do not appear to differentiate from earlier agents with the same mechanisms of action. Analysis of pregabalin and quetiapine dose-response data suggests these are flatter than previously reported. At this time, the prospects for availability of novel drugs for GAD with improved efficacy or safety profiles over current treatments are at best modest.

The vagina, in addition to being a genital organ with functions related to conception, serves as a potential route for drug administration. Mainly used for local action in the cervico-vaginal region, it has the potential of delivering drugs for systemic effects and uterine targeting. Within recent years the level of interest in both local and systemic vaginal drug delivery systems has increased considerably. The vagina offers numerous advantages as a site for drug delivery, such as convenient access, prolonged retention of formulations, a great permeation area, high vascularization, relatively low enzymatic activity, and the avoidance of first-pass metabolism. Currently available vaginal dosage forms have several limitations, such as leakage and messiness necessitating the need to develop novel drug delivery systems. The purpose of writing this review was to compile the recent literature on novel vaginal drug delivery systems.

Drug delivery to brain or brain targeting is one of the most challenging research areas in pharmaceutical sciences. The blood-brain barrier (BBB) represents an insurmountable obstacle for a large number of drugs, including antibiotics, antineoplastic agents, and a variety of central nervous system (CNS)-active drugs, especially neuropeptides and drugs which do not pass the blood brain barrier. Therefore, various strategies have been proposed to improve the delivery of different drugs to this tissue which includes liposomes, colloidal drug carriers, micelles, chimeric peptide technology, intranasal and olfactory route of administration and nano technology. This review deals in brief about the status of the BBB, different pathologies of brain like neurodegenerative, cerebrovascular and inflammatory diseases. The first part of this article aims to review the strategies developed to circumvent the BBB and deliver drugs into the brain. The use of nano technology and liposomes are discussed which are crucial part of this article as mainly used to target various CNS disorders. The later part of this article contains future aspects of brain drug targeting.

The antidiabetic effect of the dipeptidyl peptidase 4 (DPP-4) inhibitor saxagliptin depends on the prolongation of action of the 2 incretin hormones: glucagon like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) by preventing their rapid degradation by the enzyme DPP-4. The use of saxagliptin (5 mg/d) is associated with mean reduction in glycosylated hemoglobin (HbA1c) levels ranging from 0.5% to 0.9% compared with baseline and 0.6 to 0.8% compared with placebo after 24 weeks of therapy. The main advantages of saxagliptin are the low risk of hypoglycemia, the neutral effect on body weight, the simplicity of use, and reassuring short-term safety profile. However, its mild-to-moderate efficacy, the lack of long-term safety and efficacy data, and relatively high cost represent its major limitations. Overall, saxagliptin may be a useful second agent for patients with type 2 diabetes who are not optimally controlled on metformin. This drug can also be used as monotherapy in patients with mild hyperglycemia who cannot tolerate metformin or a sulfonylurea (SU).

HepatoCellular Carcinoma (HCC) is the fifth most common cancer and the third most common cause of cancer- related deaths. In unresectable disease, chemotherapy has modest response rates without a clear improvement in overall survival. Sorafenib is a multikinase inhibitor that recently demonstrated improved overall survival in two randomized clinical trials. This review paper outlines the basic treatment options for HCC by stage, followed by a discussion of key issues in the treatment and management of patients with HCC: the use of targeted therapies and/or chemotherapy in metastatic disease and in different ethnic groups; the potential use of combination therapies in earlier disease stages; and the role of imaging in the era of targeted therapy and the associated challenges.

Not all sarcoidosis patients need treatment. In about 40% of cases, disease will subside spontaneously. For the rest who need to be treated, older drugs like corticosteroids, methotrexate and hydroxychloroquine, as well as the more recent anti-TNF agents, will be effective in suppressing granulomatous inflammation in every organ involved in about 30% of cases. In 20% of the patients, disease will relapse upon discontinuation or tapering of treatment, and in 10% will progress (these two categories constituting chronic disease). In these cases, reinstitution of the same or alternative medication or a combination regimen is warranted. Drugs' side-effects and patients' comorbidities should be taken in consideration during the selection of the appropriate regimen.

It has been over 50 years since the discovery of interferon. While initially touted as “the wonder drug” for cancer therapy, the reality of interferon use as a treatment for cancer has been far different. Today, interferon is used predominantly as adjuvant therapy in renal cell carcinoma and melanoma and is being evaluated for potential new applications in other malignancies, including leukemias, lymphomas, ovarian and prostate cancer, and tumors of the central nervous system. In this review we will discuss the outcome and challenges of interferon administration in malignancies and the future of this first “cytokine” in cancer therapy.

Background: The various patient-, parent-, and physician-related factors that influence the choice of a particular medication for attention-deficit/hyperactivity disorder (ADHD) have been insufficiently investigated. The physician-reported reason for choice of medication was one factor assessed in this observational study on compliance with ADHD medication. Methods: This is a baseline data analysis of a multicenter, prospective, 12-month observational study in children and adolescents with ADHD. Among other factors, the physician's reason for choice of medication was captured at baseline.The two largest medication groups (non-stimulants vs. stimulants) were compared in terms of reasons for choice of medication. Correlations were explored by Pearson's correlation coefficient, Cohen's Kappa, and cluster analyses. Results: 504 patients with a mean age 9.6 years were included. Non-stimulant medication was prescribed in 50.0% and stimulant medication in 49.0% of patients (1% received both). There were no significant group differences in baseline ADHD symptom scores.Reasons for choosing non-stimulants over stimulants included: “duration of action” (73.4%/28.7%), “beneficial for compliance” (60.3%/40.1%), and “patient/parent decision” (33.7%/26.3%). Reasons for choosing stimulants over non-stimulants included: “good efficacy” (93.1%/73.0%), “good tolerability” (66.4%/44.1%), and “well-priced” (38.1%/2.8%). Conclusion: The reasons for choice of medication reported by physicians differed significantly between the two medication groups. Trial Registration Number: ClinicalTrials.gov Identifier: NCT00540826.