domingo, 28 de junio de 2015


El receptor H4 de histamina: del huérfano a la clínica.
The histamine H4 receptor: from orphan to the clinic.
Thurmond RL.
Front Pharmacol. 2015 Mar 31;6:65. doi: 10.3389/fphar.2015.00065. eCollection 2015.
The histamine H4 receptor (H4R) was first noted as a sequence in genomic databases that had features of a class A G-protein coupled receptor. This putative receptor was found to bind histamine consistent with its homology to other histamine receptors and thus became the fourth member of the histamine receptor family. Due to the previous success of drugs that target the H1 and H2 receptors, an effort was made to understand the function of this new receptor and determine if it represented a viable drug target. Taking advantage of the vast literature on the function of histamine, a search for histamine activity that did not appear to be mediated by the other three histamine receptors was undertaken. From this asthma andpruritus emerged as areas of particular interest. Histamine has long been suspected to play a role in the pathogenesis of asthma, but antihistamines that target the H1 and H2 receptors have not been shown to be effective for this condition. The use of selective ligands in animal models of asthma has now potentially filled this gap by showing a role for the H4R in mediating lung function and inflammation. A similar story exists for chronicpruritus associated with conditions such as atopic dermatitis. Antihistamines that target the H1 receptor are effective in reducing acute pruritus, but are ineffective in pruritus experienced by patients with atopic dermatitis. As for asthma, animal models have now suggested a role for the H4R in mediating pruritic responses, with antagonists of the H4R reducing pruritus in a number of different conditions. The anti-pruritic effect of H4R antagonists has recently been shown in human clinical studies, validating the preclinical findings in the animal models. A selective H4R antagonist inhibited histamine-induced pruritus in health volunteers and reduced pruritus in patients with atopic dermatitis. The history to date of the H4R provides an excellent example of the deorphanization of a novel receptor and the translation of this into clinical efficacy in humans.
KEYWORDS: arthritis; asthma; atopic dermatitis; histamine; pruritus
Hidrocloruro de Nalfurafina para tratar el prurito. Una revisión
Nalfurafine hydrochloride to treat pruritus: a review.
Inui S.
Clin Cosmet Investig Dermatol. 2015 May 11;8:249-55. doi: 10.2147/CCID.S55942. eCollection 2015.
Uremic pruritus has a great negative influence on quality of life in hemodialysis (HD) patients and, importantly, negatively affects mortality risk. Recently, nalfurafine hydrochloride, an opioid κ-selective agonist, has been officially approved for resistant pruritus in HD patients on the basis of a well-evidenced clinical trial in Japan. From clinical observation, it has been suggested that the upper neuron system plays a role in its pathogenesis. According to previous experimental results, using mice injected with opioids, dynorphin suppresses itch through binding κ-opioid receptors, suggesting that κ-opioid opioid receptor agonists act as potential therapeutic reagents for pruritus in HD patients. In Japan, a large-scale placebo-controlled study was performed to examine the efficacy and safety of oral nalfurafine hydrochloride for intractable pruritus in 337 HD patients. Two daily doses of 2.5 or 5 μg nalfurafine or placebo were orally administered for 2 weeks, and clinical responses were analyzed. The results showed that the mean decrease in the visual analog scale for pruritus from baseline was 22 mm in the 5 μg nalfurafine hydrochloride group (n=114) and 23 mm in the 2.5 μg group (n=112). These reductions were statistically significant compared with 13 mm, which is the mean decrease of visual analog scale in the placebo group (n=111), demonstrating that nalfurafine is an effective and safe drug for uremic pruritus in HD patients. Moreover, another open-label trial (n=145) examining the long-term effect of 5 μg oral nalfurafine revealed the maintenance of the antipruritic effect of nalfurafine for 52 weeks. In addition, on the basis of recent data showing κ-opioid receptor expression in the epidermis of atopic dermatitis and psoriasis, nalfurafine hydrochloride also can be potentially used for these two skin diseases.
KEYWORDS: hemodialysis; nalfurafine hydrochloride; opioid κ-selective agonist; uremic pruritus
Tratamiento del prurito en hepatopatias crónicas
Management of pruritus in chronic liver disease.
Bhalerao A, Mannu GS.
Dermatol Res Pract. 2015;2015:295891. doi: 10.1155/2015/295891. Epub 2015 Mar 10.
Background. There continues to be uncertainty on the ideal treatment of pruritus in chronic liver disease. The aim of this study was to gather the latest information on the evidence-based management of pruritus in chronic liver disease. Methodology. A literature search for pruritus in chronic liver disease was conducted using Pubmed and Embase database systems using the MeSH terms "pruritus," "chronic liver disease," "cholestatic liver disease," and "treatment." Results. The current understanding of the pathophysiology of pruritus is described in addition to detailing research into contemporary treatment options of the condition. These medical treatments range from bile salts, rifampicin, and opioid receptor antagonists to antihistamines. Conclusion. The burden of pruritus in liver disease patients persists and, although it is a common symptom, it can be difficult to manage. In recent years there has been greater study into the etiology and treatment of the condition. Nonetheless, pruritus remains poorly understood and many patients continue to suffer, reiterating the need for further research to improve our understanding of the etiology and treatment for the condition.
Medicamentos para el tratamiento del adulto en cuidado paliativo
Drug treatments for pruritus in adult palliative care.
Siemens W, Xander C, Meerpohl JJ, Antes G, Becker G.
Dtsch Arztebl Int. 2014 Dec 12;111(50):863-70. doi: 10.3238/arztebl.2014.0863.
BACKGROUND: Pruritus is a rare but troublesome symptom in palliative-care patients with a variety of underlying diseases. The pharmacotherapy ofpruritus is often off-label, and an evidence-based evaluation is needed. METHODS: A Cochrane Review published in 2013 was updated with a systematic literature search up to January 2014. Randomized and controlled trials (RCTs) with adult palliative-care patients were included. RESULTS: In the 43 RCTs that were analyzed, three of which were more recent than the Cochrane Review, 8 clinically relevant active substances were investigated in a total of 19 RCTs. Effective drugs for pruritus in palliative-care patients included paroxetine for pruritus of diverse origins (1 RCT; strong effect) and indomethacin for HIV-induced prutitus (1 RCT; median effect = moderate reduction). Effective drugs for pruritus in uremia were gabapentin (2 RCTs; strong effect), nalfurafin (3 RCTs; moderate effect), naltrexone (3 RCTs; heterogeneous effects, ranging from weak to strong), and cromoglicic acid (2 RCTs; moderate to strong effect). Effective drugs for cholestatic pruritus were rifampicin (3 RCTs; moderate effect), flumecinol (2 RCTs; weak to moderate effect), and naltrexone (2 RCTs; moderate to strong effect). Undesired effects were most common with naltrexone (dizziness: 0% -50% , nausea: 0% -50% ) and nalfurafin (nasopharyngitis: 8% -12% , insomnia: 7% -15%). CONCLUSION: In view of the diverse etiologies of pruritus in palliative-care patients, careful consideration should be given to the choice of drug used to treat it. The substances listed here have moderate to strong antipruritic effects and merit further study in RCTs of high methodological quality.
Anestesia y Medicina del Dolor
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