Related Articles

Febuxostat: a new agent for lowering serum urate.

Drugs Today (Barc). 2009 Apr;45(4):247-60

Authors: Keenan RT, Pillinger MH

The prevalence of gout has been increasing in epidemic proportions over the last several decades. Hyperuricemia has been shown to be associated with metabolic syndrome and to be an independent risk factor for cardiovascular disease. Associations between hyperuricemia, obesity and aging have provided an impetus in recent years to develop alternative methods of treating hyperuricemia and gout. Febuxostat is a new non-purine xanthine oxidase inhibitor indicated for chronic gout. Febuxostat has been shown to quickly and effectively lower serum urate levels in patients with chronic gout. This manuscript will review febuxostat, its pharmacokinetics and pharmacodynamics, efficacy and adverse events and use in patients with comorbid conditions. The review will also summarize the phase III trials leading up to the drug’s approval by both the European Commission in 2008 and the U.S. FDA in 2009. Possible implications the medication may have in the future on gout and hyperuricemia will also be discussed.

PMID: 19499090 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Prasugrel for arterial coronary thrombosis.

Drugs Today (Barc). 2009 Feb;45(2):83-91

Authors: Serebruany V, Makarov L

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndrome undergoing percutaneous coronary intervention. Clopidogrel, in combination with aspirin, is associated with improvement in longterm vascular clinical outcomes in these patients and is currently the antiplatelet standard of care. However, a significant number of patients still experience secondary ischemic thrombotic events due to potential insufficient platelet inhibition or noncompliance. Therefore, the development of better and safer antiplatelet agents is of the utmost priority. Indeed, oral antiplatelet agents, such as aspirin in the ISIS-2 study and clopidogrel in the COMMIT mega trial, in moderate doses are among the very few classes of drugs that reduce absolute mortality in patients after acute vascular thrombotic events. Prasugrel (CS-747; LY-640315), an experimental third-generation oral thienopyridine, is a specific, irreversible antagonist of the platelet adenosine diphosphate P2Y(12) receptor. Preclinical and early phase clinical studies have shown that prasugrel has greater antiplatelet potency, lower variability in platelet response and faster onset of inhibition than clopidogrel. However, the doses of the drug chosen for further prasugrel developments are much higher (about 2.5-2.7 times higher) than those of conventional clopidogrel regimen(s). The recent TRITON trial assessed head-to-head prasugrel versus clopidogrel, both in addition to aspirin, and led to numerous controversies with regard to the fairness of the trial design, interpretation of its results, and the suitability of the high maintenance prasugrel dose for chronic preventive human use. We critically review various aspects of prasugrel development, focusing on the discrepancies between the official interpretation of the results and actual findings. We conclude that the benefits of prasugrel are exaggerated and that the risks are underestimated. Very careful maintenance dose selection and a flawless long-term safety profile for the new agents will become the keys to the success of future oral antiplatelet drug development.

PMID: 19343228 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Liraglutide: a new treatment for type 2 diabetes.

Drugs Today (Barc). 2009 Feb;45(2):101-13

Authors: Vilsboll T

Liraglutide is a novel glucagon-like peptide-1 (GLP-1) receptor agonist with 97% amino acid sequence identity to native GLP-1. An amino acid substitution and fatty acid side chain enable a more protracted pharmacokinetic profile of over 24 hours. These modifications make liraglutide suitable for once-daily dosing. Liraglutide use exploits the incretin effect to glucose-dependently stimulate insulin secretion. The LEAD (Liraglutide Effect and Action Diabetes) program evaluated the safety and efficacy of liraglutide and demonstrated an improved level of glycemic control relative to currently used oral antidiabetic drugs, including other GLP-1-based therapies. In these trials, liraglutide was shown to enable many patients to achieve hemoglobin A1c (HbA1c) targets and to improve several morbidities commonly associated with type 2 diabetes; liraglutide induced weight loss, reduced systolic blood pressure and improved beta-cell function. Liraglutide was well tolerated, although an increased incidence of mild nausea was observed. Since liraglutide mimics the glucose-sensitive action of native GLP-1, it does not induce hypoglycemia. Liraglutide offers an interesting alternative therapy to control blood glucose levels in patients with type 2 diabetes, who commonly present with hypertension and overweight. It is expected to be approved by the U.S. Food and Drug Administration and the European Medicines Agency in Europe for use in 2009.

PMID: 19343230 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Future trends in the treatment of serious Gram-positive infections.

Drugs Today (Barc). 2009 Jan;45(1):33-45

Authors: Metzger R, Bonatti H, Sawyer R

Gram-positive organisms are the most common bacterial pathogens that cause diseases in humans, with streptococci and staphylococci occurring most frequently. Immunization has been extremely successful in eradicating some Gram-positive infections, such as diphtheria and tetanus, and relatively successful for pneumococci. Staphylococcus aureus vaccines are under investigation. In terms of antimicrobial susceptibility, some Gram-positive organisms have remained sensitive to most antimicrobials, whereas others, including staphylococci, pneumococci and enterococci, have developed clinically relevant resistance. Extensive exposure to antimicrobials in the hospital setting has caused the spread of clones mainly in the hospital environment, yet multiresistance is now also found in community-acquired diseases. Community-acquired methicillin-resistant S. aureus (CA-MRSA) and resistant pneumococci are the most important examples, but even viridans streptococci are becoming resistant to some antibiotics. Moreover, MRSA and vancomycin-resistant enterococci (VRE) are found in pets and farm animals. Because of these concerns, new antimicrobials have been developed during the past decade, including quinupristin/dalfopristin, linezolid, tigecycline, daptomycin and dalbavancin. Also under investigation are beta-lactams, streptogramins and quinolones with activity against MRSA, penicillin-resistant pneumococci and VRE. Finally, infection-control measures, including the identification of carriers of multiresistant organisms and appropriate isolation, must continue to be implemented.

PMID: 19271030 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Oral formulations of budesonide: a novel treatment for inflammatory bowel disease.

Drugs Today (Barc). 2008 Nov;44(11):857-63

Authors: Svoboda RP, Patel DH, Olden KW

Budesonide is a promising drug for a variety of documented applications and has potential in gastroenterology. Its unique local mechanism of delivery and efficient first-pass metabolism, resulting in fewer systemic adverse effects than with conventional glucocorticoids, makes this a desirable drug for clinical practice. This drug has shown promise in treating a wide spectrum of inflammatory diseases from inflammatory bowel disease and other colitides to autoimmune liver diseases. Future research should focus on ways to increase delivery methods to promote long-term usage for maintenance therapy for the disease entities listed above, as well as for other potential nongastrointestinal conditions.

PMID: 19180263 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Sitaxsentan sodium for pulmonary hypertension.

Drugs Today (Barc). 2008 Aug;44(8):585-600

Authors: MacIntyre IM, Dhaun N, Goddard J, Webb DJ

Sitaxsentan is the first oral endothelin receptor antagonist (ETRA) with high selectivity for the endothelin-A (ET(A)) receptor to be approved for clinical use by regulatory agencies in Europe for the treatment of pulmonary arterial hypertension (PAH). Clinical trials have shown it to be well tolerated and to improve exercise tolerance, functional class and pulmonary hemodynamics in PAH, results which appear to be at least as good as those for the mixed ETRA bosentan. Importantly, compared to bosentan, sitaxsentan has a lower incidence of liver toxicity and no interaction with sildenafil, a drug commonly used in the management of PAH. Furthermore, there is increasing evidence to suggest that ETRAs may play an important role in the future management of a wide variety of other conditions, from hypertension and renal disease to connective tissue disease and cancer. In some of these conditions, ET(A) selectivity may be an advantage.

PMID: 18846270 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Diastolic dysfunction: a link between hypertension and heart failure.

Drugs Today (Barc). 2008 Jul;44(7):503-13

Authors: Lalande S, Johnson BD

Diastolic heart failure is characterized by the symptoms and signs of heart failure, a preserved ejection fraction and abnormal left ventricular (LV) diastolic function caused by a decreased LV compliance and relaxation. The signs and symptoms of diastolic heart failure are indistinguishable from those of heart failure related to systolic dysfunction; therefore, the diagnosis of diastolic heart failure is often one of exclusion. The majority of patients with heart failure and preserved ejection fraction have a history of hypertension. Hypertension induces a compensatory thickening of the ventricular wall in an attempt to normalize wall stress, which results in LV concentric hypertrophy, which in turn decreases LV compliance and LV diastolic filling. There is an abnormal accumulation of fibrillar collagen accompanying the hypertension-induced LV hypertrophy, which is also associated with decreased compliance and LV diastolic dysfunction. There are no specific guidelines for treating diastolic heart failure, but pharmacological treatment should be directed at normalizing blood pressure, promoting regression of LV hypertrophy, preventing tachycardia and treating symptoms of congestion. Preventive strategies directed toward an early and aggressive blood pressure control are likely to offer the greatest promise for reducing the incidence of diastolic heart failure.

PMID: 18806901 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Retapamulin: a new topical antibiotic for the treatment of uncomplicated skin infections.

Drugs Today (Barc). 2008 Feb;44(2):91-102

Authors: Parish LC, Parish JL

Retapamulin is the first agent in the new pleuromutilin class of antibacterials to become commercially available for clinical use in humans. Retapamulin acts as a potent inhibitor of bacterial protein synthesis and has a unique mode of antibiotic action. To date, retapamulin has not demonstrated any clinically relevant, target-specific crossresistance with other antibiotic classes, and has shown a low potential for resistance selection in vitro. In preclinical studies, retapamulin demonstrated pronounced in vitro activity against staphylococcal, streptococcal and anaerobic Gram-positive clinical isolates associated with skin and skin structure infections. Clinical pharmacology studies showed low systemic exposure with topical use of retapamulin, and a favorable tolerability profile. In clinical efficacy trials involving pediatric and adult patients who received retapamulin twice daily for five days, retapamulin was highly effective in the treatment of impetigo, secondarily infected traumatic lesions and secondarily infected dermatitis. Further, the clinical efficacy and safety profile of retapamulin was comparable to that of commonly used oral and topical antibiotics. Retapamulin was also clinically effective against isolates resistant to existing therapies. As a 1% ointment, retapamulin has been approved in the United States for the treatment of impetigo and in Europe for the shortterm treatment of impetigo and infected small lacerations, abrasions and sutured wounds.

PMID: 18389088 [PubMed - indexed for MEDLINE]

[Read more →]

Related Articles

Aliskiren.

Drugs Today (Barc). 2007 Dec;43(12):849-55

Authors: Anderson DL

Aliskiren (CGP-60536 or SPP100) is the first oral direct renin inhibitor and the first new class of antihypertensive agents to be introduced in more than a decade. Aliskiren taken once a day, alone or in combination with other antihypertensive agents, has been shown to be effective in reducing blood pressure and is generally well tolerated. Based on an extensive clinical trials program, aliskiren was approved for the treatment of hypertension in March 2007 (as Tekturna; Novartis Pharmaceuticals, East Hanover, NJ, USA) by the U.S. Food and Drug Administration and in August 2007 (as Rasilez, Enviage, Sprimeo, Tekturna and Riprazo, all from Novartis) for the treatment of essential hypertension by the European Commission. Although the indication for aliskiren is treatment of essential hypertension, benefits similar to those demonstrated with certain angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) are anticipated for aliskiren. Some of the 44 trials with aliskiren are listed in Table II. Inhibition of renin, which is the first and rate-limiting step in the renin-angiotensin pathway has theoretical advantages over either ACE inhibitors or ARBs.

PMID: 18174970 [PubMed - indexed for MEDLINE]

[Read more →]