Triptans in the Treatment of Migraine

Migraine is a neurovascular disease, which pathogenesis is still unclear. It causes a severe headache and a substantial financial loss due to absenteeism, therefore, its effective treatment is particularly valuable. Triptans, selective 5HT1B and D receptor agonists, are effective treatment choices of acute migraine attacks. Migraine patients, who bear special conditions such as hypertension, hepatic or renal impairment, constitute a special subgroup of patients whose treatment with triptans has to be individually arranged. The review of Kalanuria and Peterlin, regarding the metabolism and efficacy of zolmitriptan in the abortive treatment of migraine, highlights many details of the use of zolmitriptan in migraine patients.

A Review of Enteric-coated Mycophenolate Sodium for Renal Transplant Immunosuppression

Mycophenolic acid inhibits an enzyme, inosine monophosphate dehydrogenase (IMPDH), blocking purine synthesis of lymphocytes and therefore functioning as an effective immunosuppressive agent in transplantation. Currently, there are two available forms of mycophenolic acid (MPA) available; mycophenolate mofetil (MMF) and enteric-coated, delayed-release mycophenolate sodium (EC-MPS). Both products are approved for prophylaxis of organ rejection in renal transplant recipients. The use of MPA may be associated with adverse gastrointestinal effects which can lead to a reduction of the dose or discontinuation of therapy. Enteric-coated MPS was developed to reduce the upper gastrointestinal side effects due to its delayed release in the small intestines. Similar systemic MPA exposure is provided by oral administration of MMF 1000 mg daily and EC-MPS 720 mg, which contain near equimolar MPA content. Clinical trials in renal transplant recipients have demonstrated that EC-MPS is therapeutically equivalent to MMF when used at the time of transplantation and when used for conversion for gastrointestinal complications. The available literature regarding the incidence and severity of gastrointestinal adverse effects and the impact on quality of life remains controversial. Prospective, randomized trials of the available MPA formulations are warranted to further explore the gastrointestinal adverse effect profiles.

A Review of the Pharmacokinetics, Pharmacodynamics and Efficacy of Zolmitriptan in the Acute Abortive Treatment of Migraine

Migraine is a common and often disabling neurovascular disorder. Changes in the metabolism and the central processing of serotonin, as well as abnormalities in the modulation of the central and peripheral trigeminal nociceptive pathways, have been shown to play significant roles in migraine pathophysiology. Recent evidence suggests that a low serotonin state facilitates activation of the trigeminal nociceptive pathways. In addition, several pharmacological agents that modulate serotonin are used in the treatment of migraine. Specifically there are seven FDA approved, 5-hydroxytryptamine (5-HT) 1B/1D receptor agonists, used for the acute abortive therapy of migraine. Zolmitriptan is one such triptan. Zolmitriptan is available as a tablet, orally disintegrating tablet and as a nasal spray. It is rapidly absorbed and detectable within the plasma, within 2 to 5 minutes for the nasal spray and within 15 minutes for the tablet. Zolmitriptan reaches peak plasma levels in 2-4 hours, with good levels maintained for up to 6 hours. Although the metabolism of zolmitriptan is predominantly hepatic, only 25% of zolmitriptan is bound to plasma proteins. Thus it is unlikely for drug interactions involving the displacement of highly protein-bound drugs. Zolmitriptan is very well tolerated with less than half of participants in clinical trials reporting adverse events, most of which were mild and transient. Although rare, serious cardiovascular events have been reported with all triptans. However, when patients are appropriately selected, zolmitriptan is both, a safe and effective acute migraine abortive agent. In this article, we will first briefly review the biological role of serotonin and the literature linking serotonin to migraine pathophysiology. This will be followed by a comprehensive review of the pharmacodynamics, pharmacokinetics and efficacy of zolmitriptan. Finally, the clinical application of the use of zolmitriptan in migraine therapy will be discussed.

Sitaxentan for the Oral Treatment of Pulmonary Arterial Hypertension: Benefits from Endothelin Receptor Subtype Selectivity?

Pulmonary arterial hypertension (PAH) is a deadly and underdiagnosed disease which causes right heart failure secondary to pressure overload resulting from the thickening of the pulmonary artery endothelium, associated with elevated levels of circulating endothelin-1. Sitaxentan was the first endothelin antagonist with high selectivity for receptor subtype A (over subtype ET-B) to gain regulatory approval for the treatment of PAH in major pharmaceutical markets. This review traces the development history of sitaxentan, summarizes the designs and results from its clinical studies, and relates the drug's profile to that of the two other broadly available endothelin receptor antagonists, bosentan and ambrisentan. All three drugs have comparable therapeutic efficacy in the 6-minute walk test–-a frequently employed standard–-during the first 3-4 months of therapy. Their performance might differ slightly in other clinically relevant outcome measures, especially in longer-term treatment where fully comparable data have not yet been reported. In clinical trials of up to one year duration the propensity of sitaxentan to induce elevation of liver transaminases and hepatic failure was significantly lower than that of bosentan. As a once-daily oral drug with good tolerability sitaxentan has become a crucial element in the treatment of PAH.

Ibandronate in the Management of Postmenopausal Osteoporosis

Oral daily and weekly bisphosphonates were considered, for several years, as the mainstay for the treatment of postmenopausal osteoporosis. However, the inconvenience of frequent dosing is known to negatively affect adherence to therapy in the long-term, hence outcomes. This has prompted the development of convenient oral bisphosphonate regimens that feature simple, less frequent dosing schedules. Ibandronate is a potent, nitrogen-containing bisphosphonate which, uniquely, can be administered either orally, monthly, or as an intravenous injection, every 3 months. A positive impact for adherence has been observed with a reduction in the bisphosphonate dosing frequency. Anti-fracture efficacy of the various currently available regimens of ibandronate is documented in randomized controlled clinical trials, non-inferiority studies, meta-analyses and real-life settings studies. The present paper summarizes the pharmacology, efficacy and tolerability of oral and intravenous ibandronate, when administered with extended dosing intervals, in postmenopausal osteoporosis.

Current Approaches to the Treatment of Gastrointestinal Infections: Focus on Nitazoxanide

Nitazoxanide is a broad-spectrum agent active against several protozoa, helminths, and bacteria, including C. difficile and H. pylori. It is available as an oral tablet and suspension, both with adequate bioavailability. Nitazoxanide is associated with minimal side effects, has an acceptable safety profile, and has been classified as a pregnancy category B agent. It is 99% protein bound, which could result in drug interactions. It is the preferred agent for the treatment of Cryptospordiosis and Giardiasis in immunocompetent patients and has shown promise for the treatment of rotavirus, mild to moderate initial C. difficile infection, refractory C. difficile infection, Amoebiasis, Blastocystosis, and Taenia saginata.

A Review on the Use of Eltrombopag in Patients with Advanced Liver Disease

Thrombocytopenia is the most common hematological abnormality in patients with chronic, advanced liver disease. In these patients, the presence of severe thrombocytopenia is an obstacle to the performance of invasive diagnostic and therapeutic procedures, and the current standard treatment for these patients is platelet transfusions, a remedy whose characteristics are far from being ideal. Furthermore, thrombocytopenia in patients with chronic hepatitis C virus infection may render the patients ineligible to antiviral treatment or may limit its efficacy because of premature discontinuation. Although the cause of thrombocytopenia in patients with chronic liver disease is likely multi-factorial, decreased thrombopoietin production by the liver undoubtedly plays a significant role. In this regard, eltrombopag, a non-peptide, orally bioavailable thrombopoietin receptor agonist has been shown to safely increase platelet count in a dose-dependent fashion in both healthy subjects and thrombocytopenic patients with chronic hepatitis C. Furthermore, in this latter group of patients, it has been shown to be superior to placebo in counteracting the myelosuppressive effect of short-term pegylated interferon treatment.

Pharmacotherapy of Bipolar I Disorder: Focus on Aripiprazole

Bipolar disorder is a common and complex condition, starting early in life and continuing throughout the life cycle. Most people suffering from bipolar disorder manifest other problems as well, including metabolic disturbances, cardiovascular disease, anxiety disorders, substance use disorders, attention deficit hyperactivity disorder, and borderline personality disorder, among others. The treatment of bipolar disorder needs to be conceptualized within this context of early onset, chronic course, and significant co-morbidity. Because of its unique mode of action, its efficacy and its good tolerability profile, aripiprazole is well placed among the different treatment options to benefit the patient with bipolar disorder. This article will focus on aripiprazole's pharmacology, efficacy, effectiveness, and tolerability from a clinical perspective, while considering the complexities of bipolar disorder.

A Re-assessment of the Safety and Efficacy of Interleukin-2 for the Treatment of Renal Cell Carcinoma

Interleukin-2 (IL-2) can provide long term durable remissions for patients with advanced or metastatic renal cell carcinoma. The perceived morbidity and the difficulties in delivering this treatment hampered its widespread use in these patients. This review aims to place IL-2 in the modern milieu by reviewing the pharmacology, efficacy and toxicity of this drug. These will be contrasted and compared with the new targeted-agents. The methodology of providing high dose IL-2 treatment, follow-up care and its impact on patient quality of life will be discussed. Importantly, the ability of these agents to provide durable, complete remissions for RCC patients will be placed in context. The goal is to provide the perspective and framework for the reader to balance the important attributes of each of these drugs during the clinical decision making process.

Malfunction in GABA and Glutamate as Pathways to Depression: A Review of the Evidence

With nearly one fifth of the population experiencing depression sometime during their lives, plus the recent finding that depression rivals smoking in its association with mortality, the search for effective pharmacological treatments for depression remains urgent. However, despite this heavy disease burden upon society, the various waves of antidepressants developed in the last 40 years have shown significant side effects and little specific efficacy over placebo. One potential treatment may be via re-establishment of glutamate and GABA neurotransmitter systems that have been shown to malfunction in depressed patients. The literature describing possible causal links between GABA and/or glutamate malfunction and depression is reviewed, plus those studies which provide experimental data to confirm this hypothesis. While there is plausible support for the links between malfunction of these neurotransmitters and depression, few data exist yet regarding development of effective antidepressant medications based upon these findings.