Expert opinion on pharmacotherapy
-
Centrally acting opioids are well established in the treatment of acute, surgical and cancer pain. However, their use in chronic noncancer pain (CNCP) is controversial because of side effects such as tolerance, somnolence, respiratory depression, confusion, constipation and addiction. Chronic arthritis and other musculoskeletal diseases are among the leading causes of CNCP. ⋯ Aims in drug development include the design of peripherally restricted opioid agonists, selective targeting of endogenous opioids to sites of painful injury and the augmentation of peripheral ligand and receptor synthesis, for example, by gene therapy. Although a large number of peripherally acting opioid compounds have been developed, clinical Phase III studies have not been published so far. Another strategy is to augment the effects of endogenously released opioid peptides by the inhibition of their degrading enzymes. Technology-oriented research is needed to find novel ways of peripheral restriction of opioids. Such analgesics would be desirable for their lack of central side effects and of adverse effects typical of nonsteroidal anti-inflammatory drugs (gastrointestinal ulcers, bleeding, myocardial infarction and stroke).
-
Expert Opin Pharmacother · Feb 2014
ReviewPirfenidone for the treatment of idiopathic pulmonary fibrosis.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and lethal fibrosing interstitial pneumonia. The median survival from the onset of the symptoms is 2.8 - 4.2 years and the 5-year survival rate is 20%. Its poor prognosis, combined with the scarcity of treatment options, provides a strong rationale for the development of novel therapeutic strategies. During the past decade there has been a huge rise in clinical trials with anti-fibrotic drugs, although only pirfenidone (Esbriet) has shown a beneficial effect. ⋯ Pirfenidone is the only anti-fibrotic drug approved for the treatment of IPF. Pirfenidone provides a meaningful clinical effect on reductions in the decrease in forced vital capacity (FVC), six-minute walk test (6MWT) distance and mortality, and it improves the progression-free survival in IPF patients with mild-to-moderate disease. Pirfenidone is well tolerated, with the most common side-effects being gastrointestinal discomfort and photosensitivity. Pirfenidone has a favorable benefit-risk profile and represents a suitable treatment option for patients with mild-to-moderate IPF.
-
Expert Opin Pharmacother · Feb 2014
CommentCanagliflozin - something new for type 2 diabetes, but is it safe and efficacious?
Inhibition of the sodium-glucose cotransporter 2 (SGLT2), to promote the excretion of glucose, is a new paradigm in the treatment of type 2 diabetes. ⋯ Studies with canagliflozin, in subjects with type 2 diabetes, have shown that its use is associated with reductions in HbA1c and body weight and small reductions in blood pressure and triglycerides, while increasing high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. As monotherapy in Japanese subjects, or in comparison with glimepiride in CANTATA-SU (CANagliflozin Treatment and Trial Analysis versus SUlphonylurea), canagliflozin causes a low incidence of hypoglycemia, and this is an advantage over glimepiride. However, one of the disadvantages with canagliflozin, which was also highlighted in CANTATA-SU, is that canagliflozin can cause urogenital infections, which are not observed with other antidiabetic drugs. The Federal Drug Administration has recently approved canagliflozin for use in type 2 diabetes, while directing that a clinical outcome safety trial be undertaken. We are concerned that canagliflozin has been approved for use in type 2 diabetes prior to a clinical outcome study of efficacy being undertaken and without the outcome of further safety testing.
-
Expert Opin Pharmacother · Jan 2014
ReviewTargeting the Janus kinases in rheumatoid arthritis: focus on tofacitinib.
Treatment of rheumatoid arthritis (RA) has markedly advanced by the advent of biologic disease-modifying antirheumatic drugs (DMARDs). However, they require special storage and transportation and remission is observed in ∼ 30%. Tofacitinib inhibits the nonreceptor tyrosine kinase family Janus kinase (JAK), which is activated immediately after cytokines bind to their receptor within the cytoplasmic membrane. ⋯ Tofacitinib is a new class of DMARDs orally available with a new mechanism of action and with strong clinical efficacy similar to biologic DMARDs. Multiple cytokines and signaling pathways are partially inhibited at clinical doses that are in contrast to biological DMARDs. Further investigation is necessary to come to a conclusion on risk-benefit ratio and selection of patients.
-
Expert Opin Pharmacother · Jan 2014
Randomized Controlled Trial Multicenter StudyCombined long-acting bronchodilator single therapy for COPD.
In COPD, the long-acting bronchodilators are not always able to provide an appropriate bronchodilator effect in terms of amplitude and duration and this can result in increased severity of respiratory symptoms and in worsening of health status. Combined long-acting bronchodilators can address this limitation. ⋯ Such a combination can provide a superior and sustained bronchodilator effect and can minimize the respiratory symptoms resulting from a suboptimally inhibited bronchoconstriction.