Drugs

Ciurleo, Rosella; Bramanti, Placido; Calabrò, Rocco

doi: 10.1007/s40265-013-0138-8pmid: 24170667

Disorders of consciousness, including the coma state, vegetative state and minimally conscious state, are among the least understood and least curable conditions in modern neurology. Structural or functional injuries may produce impairments in the neuronal circuits (the ascending reticular activating system and thalamocortical loops) responsible for maintaining the wakefulness state and awareness, associated with a change in neurotransmitter concentrations. Pharmacological agents that are able to restore the levels of neurotransmitters and, consequently, neural synaptic plasticity and functional connectivity of consciousness networks, may play an important role as drugs useful in improving the consciousness state. Currently, there is growing interest in the scientific community with regard to pharmacological agents that act on the gamma amino-butyric acid (GABA) system, such as zolpidem and baclofen, and monoamine systems, such as dopaminergic agents and some antidepressants. The purpose of this article is to provide a comprehensive overview of these potential ‘awakening’ drugs in patients with disorders of consciousness. The possible mechanisms by which these drugs may exert their effects in promoting recovery of consciousness are discussed, highlighting how many findings are often the result of sporadic events rather than prospective controlled trials or implementation of standard treatment guidelines.

Monge-Maillo, Begoña; López-Vélez, Rogelio

doi: 10.1007/s40265-013-0133-0pmid: 24170666

Visceral leishmaniasis (VL), also known as Kala-Azar, is a disseminated protozoal infection caused principally by Leishmania donovani and Leishmania infantum (known as Leishmania chagasi in South America). The therapeutic options for VL are diverse and depend on different factors, such as the geographical area of the infection, development of resistance to habitual treatments, HIV co-infection, malnourishment and other concomitant infections. This article provides an exhaustive review of the literature regarding studies published on the treatment of VL, and gives therapeutic recommendations stratified according to their level of evidence, the species of Leishmania implicated and the geographical location of the infection.

Monge-Maillo, Begoña; López-Vélez, Rogelio

doi: 10.1007/s40265-013-0132-1pmid: 24170665

Estimated worldwide incidence of tegumentary leishmaniasis (cutaneous leishmaniasis [CL] and mucocutaneous leishmaniasis [MCL]) is over 1.5 million cases per year in 82 countries, with 90 % of cases occurring in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria. Current treatments of CL are poorly justified and have sub-optimal effectiveness. Treatment can be based on topical or systemic regimens. These different options must be based on Leishmania species, geographic regions, and clinical presentations. In certain cases of Old World CL (OWCL), lesions can spontaneously heal without any need for therapeutic intervention. Local therapies (thermotherapy, cryotherapy, paromomycin ointment, local infiltration with antimonials) are good options with less systemic toxicity, reserving systemic treatments (azole drugs, miltefosine, antimonials, amphotericin B formulations) mainly for complex cases. The majority of New World CL (NWCL) types require systemic treatment (mainly with pentavalent antimonials), either to speed the healing or to prevent dissemination to oral-nasal mucosa as MCL (NWMCL). These types of lesions are potentially serious and always require systemic-based regimens, mainly antimonials and pentamidine; however, the associated immunotherapy is promising. This paper is an exhaustive review of the published literature on the treatment of OWCL, NWCL and NWMCL, and provides treatment recommendations stratified according to their level of evidence regarding the species of Leishmania implicated and the geographical location of the infection.

Gutiérrez-Chico, Juan; Mehilli, Julinda

doi: 10.1007/s40265-013-0135-ypmid: 24155117

The epidemiology of coronary artery disease (CAD) differs between women and men: female cardiac patients are older and have poorer risk profiles than their male counterparts. This results in a preferential exclusion of women from participation in clinical trials, reducing their power to detect differences in performance of cardiovascular therapies in women. In general, all the antiplatelet and anticoagulant medications used in cardiac patients are equally effective in men and women, although women tend to experience a higher relative benefit due to their poorer risk profile. In particular, women with CAD benefit the most from interventional treatment combined with modern antithrombotic drugs. No gender-related differences in the reduction of thromboembolic risk with more potent antithrombotic drugs have been reported. On the other hand, a clear trend to a higher incidence of bleeding complications has been consistently reported in women, which might be related to a more frequent over-dosage of antithrombotic treatment in women than in men. Women are therefore one of the subgroups that might benefit the most from careful dose adjustment of available antithrombotic drugs. However, the development of a gender-based dosage guideline remains an unmet need in cardiology.

Keating, Gillian

doi: 10.1007/s40265-013-0140-1pmid: 24194435

The highly selective serotonin 5-HT4 receptor agonist prucalopride (Resolor®, Resotran®, Resotrans®) is indicated for the treatment of chronic constipation. In four randomized, double-blind, multicentre, 12-week trials in patients (predominantly women) with chronic constipation, oral prucalopride 2 mg once daily improved bowel function to a significantly greater extent than placebo, with a significantly greater proportion of prucalopride than placebo recipients achieving an average of ≥3 spontaneous, complete bowel movements per week (primary endpoint). Significantly greater improvements in health-related quality of life, patient satisfaction with treatment and bowel habit, and a range of constipation-related symptoms were also seen with prucalopride than with placebo. Satisfaction with treatment and bowel habit was maintained with prucalopride in the longer term. Prucalopride was generally well tolerated in patients with chronic constipation, with the most commonly reported adverse events (headache, nausea, abdominal pain, diarrhoea) primarily occurring on the first day of treatment. During the clinical trials, no cardiovascular safety issues have arisen in patients with chronic constipation receiving prucalopride. In conclusion, prucalopride is an important option for use in patients with chronic constipation who have not experienced adequate relief with laxatives.

Keating, Gillian

doi: 10.1007/s40265-013-0143-ypmid: 24202878

Fosfomycin trometamol (fosfomycin tromethamine) [Monuril®, Monurol®, Monural®] is approved in numerous countries worldwide, mainly for the treatment of uncomplicated urinary tract infections (UTIs). Fosfomycin has good in vitro activity against common uropathogens, such as Escherichia coli (including extended-spectrum β-lactamase-producing E. coli), Proteus mirabilis, Klebsiella pneumoniae and Staphylococcus saprophyticus, and the susceptibility of uropathogens to fosfomycin has remained relatively stable over time. A single oral dose of fosfomycin trometamol 3 g (the approved dosage) achieves high concentrations in urine. Results of recent randomized trials indicate that single-dose fosfomycin trometamol had similar clinical and/or bacteriological efficacy to 3- to 7-day regimens of ciprofloxacin, norfloxacin, cotrimoxazole or nitrofurantoin in women with uncomplicated lower UTIs. In addition, single-dose fosfomycin trometamol had similar bacteriological efficacy to a 5-day course of cefuroxime axetil or a 7-day course of amoxicillin/clavulanic acid in pregnant women with asymptomatic bacteriuria, and similar clinical and/or bacteriological efficacy to a 5-day course of cefuroxime axetil or amoxicillin/clavulanic acid or a 3-day course of ceftibuten in pregnant women with a lower UTI. Single-dose fosfomycin trometamol was generally well tolerated, with gastrointestinal adverse events (e.g. diarrhoea, nausea) reported most commonly. In conclusion, single-dose fosfomycin trometamol is an important option for the first-line empirical treatment of uncomplicated lower UTIs.

Conole, Daniel; Scott, Lesley

doi: 10.1007/s40265-013-0149-5pmid: 24218053

Riociguat (Adempas®), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). The drug directly stimulates sGC in a nitric oxide independent manner, thereby increasing the sensitivity of sGC to nitric oxide, leading to increased cyclic guanosine monophosphate generation (a key signalling molecule involved in regulating vascular tone, proliferation, fibrosis and inflammation). Riociguat is the world’s first approved pharmacotherapy for CTEPH, with its first global approval in this indication occurring in Canada. It has subsequently been approved in the USA for the treatment of patients with CTEPH and also received its first global approval in patients with PAH in the USA. It is undergoing regulatory review for these indications in Europe and for use in patients with CTEPH in Japan. This article summarizes the milestones in the development of riociguat, leading to its first global approvals in patients with CTEPH and PAH.

Patel, Trina; Dhillon, Sohita

doi: 10.1007/s40265-013-0152-xpmid: 24249649

A non-lacquer 10 % topical solution of efinaconazole, developed by Valeant Pharmaceuticals International, received its first global approval in Canada in October 2013 for the treatment of onychomycosis. The product is under regulatory review in the US and Japan. The mechanism of anti-fungal activity of efinaconazole, a small-molecule triazole compound, appears to be similar to that of other anti-fungal triazoles, namely ergosterol synthesis inhibition. In particular, it appears to inhibit 14α demethylase, an enzyme involved in the conversion of lanosterol to ergosterol, resulting in secondary degenerative changes. This article summarizes the milestones in the development of efinaconazole leading to this first approval for onychomycosis.