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Boster, Aaron; Ankeny, Daniel; Racke, Michael
doi: 10.2165/11585230-000000000-00000pmid: 21142258
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Until recently, most therapeutic interventions have targeted T cells in the treatment of MS. Recent data show that B cells also have a role in the pathogenesis of MS. The cerebrospinal fluid and CNS of MS patients contain B cells, plasma cells and immunoglobulins, and recent data indicate that B cells are involved in antigen presentation and T-cell activation, cytokine production, antibody secretion, demyelination and remyelination in MS. These advances in the understanding of B cells and their role in the pathophysiology of MS provide a strong rationale for B cell-targeted therapies. Recent clinical trials with rituximab highlight the possibility that B cells should be an important therapeutic target in patients with MS.
doi: 10.2165/11538190-000000000-00000pmid: 21142259
Tobacco use is the leading cause of preventable death and disability in the world. Although gradually declining in most developed countries, the prevalence of tobacco use has increased among developing countries. Treatment for tobacco use and dependence is effective, although long-term abstinence rates remain disappointingly low. In response, new treatments continue to be developed. In addition, many of the pharmacotherapies that have been available for years have found new applications with the use of medication combinations, higher doses and a longer duration of therapy for approved medications.
Seden, Kay; Dickinson, Laura; Khoo, Saye; Back, David
doi: 10.2165/11585250-000000000-00000pmid: 21142260
Grapefruit juice and grapefruit product consumption have potential health benefits; however, their intake is also associated with interactions with certain drugs, including calcium channel blockers, immunosuppressants and antihistamines. The primary mechanism through which interactions are mediated is mechanism-based intestinal cytochrome P450 3A4 inhibition by furanocoumarins resulting in increased bioavailability of administered medications that are substrates. Grapefruit products have also been associated with interactions with P-glycoprotein (P-gp) and uptake transporters (e.g. organic anion-transporting polypeptides [OATPs]). Polyphenolic compounds such as flavonoids have been proposed as the causative agents of the P-gp and OATP interactions. The mechanisms and magnitudes of the interactions can be influenced by the concentrations of furanocoumarins and flavonoids in the grapefruit product, the volume of juice consumed, and the inherent variability of specific enzymes and transporter components in humans. It is therefore challenging to predict the extent of grapefruit product-drug interactions and to compare available in vitro and in vivo data. The clinical significance of such interactions also depends on the disposition and toxicity profile of the drug being administered. The aim of this review is to outline the mechanisms of grapefruit-drug interactions and present a comprehensive summary of those agents affected and whether they are likely to be of clinical relevance.
Karst, Matthias; Wippermann, Sonja; Ahrens, Jörg
doi: 10.2165/11585260-000000000-00000pmid: 21142261
Both the discovery of the endocannabinoid system (ECS) and its role in the control of pain and habituation to stress, as well as the significant analgesic and antihyperalgesic effects in animal studies, suggest the usefulness of cannabinoids in pain conditions. However, in human experimental or clinical trials, no convincing reduction of acute pain, which may be caused by a pronociceptive, ECS-triggered mechanism on the level of the spinal cord, has been demonstrated. In contrast, in chronic pain and (painful) spasticity, an increasing number of randomized, double-blind, placebo-controlled studies have shown the efficacy of cannabinoids, which is combined with a narrow therapeutic index. Patients with unsatisfactory response to other methods of pain therapy and who were characterized by failed stress adaptation particularly benefited from treatment with cannabinoids. None of the attempts to overcome the disadvantage of the narrow therapeutic index, either by changing the route of application or by formulating balanced cannabinoid preparations, have resulted in a major breakthrough. Therefore, different methods of administration and other types of cannabinoids, such as endocannabinoid modulators, should be tested in future trials.
Muir, Victoria; Keating, Gillian
doi: 10.2165/11206310-000000000-00000pmid: 21142262
Olmesartan medoxomil is an orally administered angiotensin II receptor antagonist, selective for the angiotensin II type 1 receptor, which has established antihypertensive efficacy in adults.
doi: 10.2165/11204920-000000000-00000pmid: 21142263
Quadrivalent human papilloma virus (HPV) [types 6, 11, 16, 18] recombinant vaccine (Gardasil®; Silgard®) is composed of virus-like particles (VLPs) formed by self-assembly of recombinant L1 capsid protein from each of HPV types 6,11, 16 and 18. The VLPs are noninfectious, containing no DNA, and are highly immunogenic, inducing high levels of neutralizing antibodies against the particular HPV types when administered to animals or humans. Quadrivalent HPV vaccine is indicated for use from the age of 9 years for the prevention of premalignant genital lesions (cervical, vulvar and vaginal), cervical cancer and external genital warts (condyloma acuminata) causally related to certain oncogenic or specific HPV types.
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