Cns Drugs
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Infections with fungi cause significant morbidity in the immunocompromised host and invasion of the CNS may lead to devastating consequences. Vulnerable individuals include those with haematological malignancies, transplant recipients, and those infected with HIV. Potential pathogens include yeasts, Aspergillus spp., other moulds of an increasing variety, and a range of dimorphic fungi, often associated with particular geographical locations. ⋯ Reliable treatment data are lacking for CNS infections with most of the non-aspergillus moulds; posaconazole holds promise for the zygomycetes and perhaps some of the rarer pigmented fungi, but amphotericin B preparations are still recommended. Oral fluconazole is effective for the CNS manifestations of coccidioides, while histoplasmosis and blastomycoses typically require amphotericin B therapy. Effective treatment requires a definitive diagnosis, which is often challenging in the population at risk of CNS fungal infections.
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Postoperative nausea and vomiting (PONV) is one of the most common and distressing complications following surgery, and understanding the mechanism(s) underlying PONV is essential to providing optimal prophylaxis and/or treatment of PONV. The knowledge base of PONV physiology has significantly expanded over the past decade. ⋯ NK(1) receptor antagonists, with their unique mechanism of action, are a particularly promising area of research as they appear to be efficacious in preventing PONV during both the early and the late postoperative periods. A successful PONV management strategy includes: (i) identifying patients at risk; (ii) keeping the baseline risk low; and (iii) using a combination of antiemetics acting on different receptors in moderate- to high-risk patients.
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Review
Acetyl-L-carnitine for the treatment of chemotherapy-induced peripheral neuropathy: a short review.
Peripheral neurotoxicity is a major complication associated with the use of chemotherapeutic agents such as platinum compounds, taxanes and vinca alkaloids. The neurotoxicity of chemotherapy depends not only on the anticancer agent(s) used, the cumulative dose and the delivery method, but also on the capacity of the nerve to cope with the nerve-damaging process. The sensory and motor symptoms and signs of neurotoxicity are disabling, and have a significant impact on the quality of life of cancer patients. ⋯ These results, plus the favourable safety profile of ALC in neuropathies of other aetiologies, have led to the effects of ALC on CIPN being investigated in cancer patients. Preliminary results have confirmed the reasonably good tolerability profile and the efficacy of ALC on CIPN. The present studies support the use of ALC in cancer patients with persisting neurotoxicity induced by paclitaxel or cisplatin treatment.
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Pramipexole is an oral, non-ergoline dopamine agonist with selectivity for the dopamine D(3) receptor, which was recently approved in the EU and the US for the treatment of idiopathic restless legs syndrome (RLS) in adults. In a polysomnographic study, pramipexole 0.125, 0.25, 0.50 or 0.75 mg once daily for 3 weeks significantly reduced from baseline the periodic limb movement index compared with placebo (-27 to -53 vs -3). ⋯ Treatment with pramipexole 0.25, 0.50 or 0.75 mg once daily for 12 weeks significantly reduced IRLS scores from baseline values (-13 to -14 vs -9) and produced significantly higher proportions of CGI-I responders (68-75% vs 51%) compared with placebo. Pramipexole was generally well tolerated, with most adverse events being transient and of mild to moderate severity.
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Peripheral neuropathies are extremely heterogeneous nosological entities. One of the most common symptoms is pain, the underlying mechanisms of which are numerous and complex. Inflammation, reparative processes, and anatomical and gene expression alterations lead to chronic pain, the persistence of which is sustained by peripheral and central sensitisation mechanisms. ⋯ Certain drugs are known to exert more than one action on different pathophysiological mechanisms. This is the case with acetyl-L-carnitine (ALC), which can be considered both a symptomatic therapy that can be used in any kind of painful neuropathy, and an aetiological therapy, at least in diabetic neuropathy and neuropathies induced by nucleoside reverse transcriptase inhibitors and cancer chemotherapeutic agents. ALC acts via several mechanisms, inducing regeneration of injured nerve fibres, reducing oxidative stress, supporting DNA synthesis in mitochondria, and enhancing nerve growth factor concentrations in neurons.