Current Clinical Pharmacology - Volume 5, Issue 2, 2010

The association between hepatitis C virus (HCV) infection and B-cell non-Hodgkin's lymphomas has been demonstrated in epidemiological studies, in particular in highly endemic geographical areas such as Italy, Japan and southern parts of United States. Marginal zone lymphomas are the histotypes that are most frequently associated with HCV infection. The WHO classification comprises extranodal marginal zone B-cell lymphoma of MALT type, splenic marginal zone B-cell lymphoma and nodal marginal zone B-cell lymphoma. Recently, antiviral treatment has been proved to be effective in the treatment of HCV-positive patients with indolent lymphoma, prevalently of marginal zone origin. This is the strongest evidence of a causative link between HCV and lymphomas. Aim of this review is to illustrate the relationship between HCV infection and marginal zone lymphomas and to systematically summarize the data from the therapeutic studies where antiviral treatment with α-interferon with or without ribavirin was employed in patients with marginal zone lymphomas.

The peritoneum is a cavity which has been successfully utilized by nephrologists to perform peritoneal dialysis (PD) in patients with renal failure. The physiologic characteristic of the peritoneal cavity not only helps remove toxic metabolites from the body, but also provides a useful portal of entry in the body for several pharmacological agents. Several medications such as antibiotics are given via the intraperitoneal (IP) route in PD patients to treat episodes of peritonitis. More recently the IP route has been used for chemotherapy in patients with intra-abdominal malignancies, i.e. gynecological and gastrointestinal cancers and has shown very promising results. In patients with peritoneal surface malignancies, perioperative IP chemotherapy has been used with good results. The rate and amount of drug transfer in the peritoneum are dependent on several factors. Factors such as peritoneal inflammation, surface area, peritoneal blood flow, time of contact, etc, influence the drug transfer. This review discusses the usefulness of IP drug therapy and the factors influencing it, as well as strategies to increase the efficacy, and conclude that IP route is an alternate route to the more conventional drug delivery routes, and can be successfully used when the target is within the peritoneal cavity or adjacent tissue.

The cardiovascular disease continuum is a sequence of events, which begins with a host of risk factors consisting of diabetes mellitus, dyslipidemia, hypertension, smoking and visceral obesity. If left untreated, it will inexorably progress to atherosclerosis, CAD, myocardial infarction, left ventricular remodeling, LVH, left ventricular enlargement, and eventually end-stage heart failure and death. Treatment intervention at any stage of its course will prevent or delay its further progression. However, the best results are expected to be achieved when treatment is initiated at the beginning, or at an early stage of its course. A Pub-Med/MEDLINE search was conducted for relevant English language, randomized clinical trials and epidemiologic studies for the years 1995-2009 using the terms, cardiovascular continuum, obesity, hyperlipidemia, diabetes mellitus, hypertension, metabolic syndrome, renal disease, stroke, and blockers of the renin angiotensin system (RAS). A total of 34 pertinent studies were selected for review. This concise review will focus on prevention and the aggressive treatment of the existing cardiovascular risk factors with emphasis on the blockers of RAS, and demonstrate that RAS blockers are the best drugs for its treatment.

Failure of first-line chemotherapy to cure tuberculosis (TB) patients occurs, in part, because of the development of resistance to isoniazid (INH) and rifampicin (RIF) the two most sterilizing agents in the four-drug regimen used to treat primary infections. Strains resistant to both INH and RIF are termed multidrug-resistant (MDR). Treatment options for MDR patients involve a complex array of twenty different drugs only two classes of which are considered to be highly effective (fluoroquinolones and aminoglycosides). Resistance to these two classes results in strains known as extensively drug-resistant (XDR) and these types of infections are becoming increasingly common. Many of the remaining agents have poorly defined pharmacology but nonetheless are widely used in the treatment of this disease. Several of these agents are known to have highly variable exposures in healthy volunteers and little is known in the patients in which they must be used. Therapeutic drug monitoring (TDM) is infrequently used in the management of MDR or XDR disease yet the clinical pharmacokinetic studies that have been done suggest this might have a large impact on disease outcome. We review what is known about the pharmacologic properties of each of the major classes of second- and third-line antituberculosis agents and suggest where judicious use of TDM would have the maximum possible impact. We summarize the state of knowledge of drug-drug interactions (DDI) in these classes of agents and those that are currently in clinical trials. Finally we consider what little is known about the ability of TB drugs to reach their ultimate site of action - the interior of a granuloma by penetrating the diseased lung area. Careful consideration of the pharmacology of these agents is essential if we are to avoid further fueling the growing epidemic of highly drug-resistant TB and critical in the development of new antituberculosis drugs.

Galantamine is a reversible acetylcholinesterase inhibitor for the treatment of Alzheimer 's disease. Following oral administration, galantamine is rapidly absorbed and reaches Cmax in approximately one hour for immediate release (IR) tablets and four hours for extended-release (ER) capsules. Food has no clinically important effects on the absorption of galantamine. Galantamine displays dose-proportional pharmacokinetics over a dose range of 8 - 32 mg and 8 - 24 mg for IR and ER formulations, respectively. The elimination half-life of galantamine is about 7 - 8 hours. Galantamine has low protein binding (28.3 - 33.8%) and has an apparent steady-state volume of distribution (Vss) of 193 L. Approximately 20-25% of the galantamine dose administered is excreted unchanged in urine. No clinically significant effects of age, gender, and race have been observed on galantamine pharmacokinetics. The exposures to galantamine in patients with moderate and severe renal impairment are 37% and 67% higher, respectively than in healthy subjects, whereas the exposure to galantamine is approximately 30% higher in patients with moderate hepatic impairment. Co-administration of galantamine with ketoconazole (CYP 3A4 strong inhibitor) or paroxetine (CYP 2D6 strong inhibitor) leads to a 30% and 40% increase, respectively, in galantamine exposure compared to galantamine given alone.

Atherosclerosis leads to narrowing and occlusion of coronary arteries, resulting in inadequate oxygen supply for maintenance of normal oxidative metabolism. To avoid profound ischaemia and subsequent necrosis of cardiomyocytes, blood flow has to be restored by means of thrombolysis, percutaneous coronary intervention, or surgical revascularisation. Besides restoring oxygen supply to the cells, introduction of molecular oxygen to the ischaemic tissue results in a spectrum of unfavourable events, termed altogether as reperfusion injury. Exposure to hyperoxia for a limited time before ischaemia induces a low-grade oxidative stress and evokes an (ischaemic) preconditioning-like effect in the myocardium, which protects the heart from subsequent injury. This review addresses the effects of pretreatment by hyperoxia both in experimental and clinical setting.

People with metabolic syndrome (MetS) are at increased risk of type 2 diabetes and cardiovascular diseases, and often have increased triglyceride, reduced high-density lipoprotein cholesterol (HDL-C) and sometimes moderately increased low-density lipoprotein cholesterol (LDL-C) levels. Lifestyle intervention is critical for treating MetS, while pharmacotherapy of dyslipidemia in MetS remains controversial. Considering the specific lipid profile in MetS, fibrates are typically used as first-line treatment. Nevertheless, first-line therapy should be directed towards LDL-C, even in people with MetS, because of the evidence that lowering LDL-C has cardioprotective effects. Non-HDL-C is considered to be an alternative treatment target for people with moderately or severely elevated triglyceride (≥ 200mg/dl). Statins improve lipid profiles principally by lowering LDL-C and may exert anti-inflammatory and anti-atherothrombogenic effects, which ameliorate the fundamental pathophysiology of MetS. Fibrates also have pleiotropic effects that improve cardiometabolic risk factors, including insulin resistance, although they do not have clear cardioprotective effects. Omega- 3 fatty acids, niacin, pioglitazone and anti-obesity drugs are also candidates for the treatment of dyslipidemia and other complications in MetS. Another question is whether statins in combination with fibrates or other lipid-lowering drugs has greater cardioprotective properties than monotherapy. In this article, we discuss several issues in the pharmacotherapy of MetS.