Cns Drugs
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The CNS is the second most commonly affected organ in patients with AIDS. Many opportunistic infections may involve the brain, but the four most frequent conditions are toxoplasmosis, progressive multifocal leukoencephalopathy (PML), cryptococcosis and cytomegalovirus infection. Although the incidence of these infections among patients with AIDS has decreased in the past years as a consequence of the introduction of highly active antiretroviral therapy (HAART), they remain a major cause of morbidity and mortality in this patient group. ⋯ HAART has improved the outcome of patients with AIDS who have infections of the CNS, and the initiation of this therapy is mandatory for all patients with such infections, particularly in those conditions for which effective therapy is not available. Lifelong secondary prophylaxis with agents for the opportunistic infections was necessary before the HAART era because the risk of recurrence was very high if only induction therapy was administered. However, today, the discontinuation of secondary prophylaxis in patients treated with HAART who have stably reached a certain immune reconstitution is possible.
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Review Historical Article
Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience.
Thirty-five years since its introduction into clinical use, valproate (valproic acid) has become the most widely prescribed antiepileptic drug (AED) worldwide. Its pharmacological effects involve a variety of mechanisms, including increased gamma-aminobutyric acid (GABA)-ergic transmission, reduced release and/or effects of excitatory amino acids, blockade of voltage-gated sodium channels and modulation of dopaminergic and serotoninergic transmission. Valproate is available in different dosage forms for parenteral and oral use. ⋯ Other notable adverse effects include encephalopathy symptoms (at times associated with hyperammonaemia), platelet disorders, pancreatitis, liver toxicity (with an overall incidence of 1 in 20,000, but a frequency as high as 1 in 600 or 1 in 800 in high-risk groups such as infants below 2 years of age receiving anticonvulsant polytherapy) and teratogenicity, including a 1 to 3% risk of neural tube defects. Some studies have also suggested that menstrual disorders and certain clinical, ultrasound or endocrine manifestations of reproductive system disorders, including polycystic ovary syndrome, may be more common in women treated with valproate than in those treated with other AEDs. However, the precise relevance of the latter findings remains to be evaluated in large, prospective, randomised studies.
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Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan'). Its efficacy and tolerability have been assessed in a number of randomised, controlled trials in over 4800 adults with moderate or severe attacks of migraine. Oral almotriptan has a rapid onset of action (significant headache relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy is sustained in most patients who respond by 2 hours. The drug is significantly more effective than placebo as measured by a number of parameters including 2-hour headache response and pain-free response rates. Other symptoms of migraine, including nausea, photophobia and phonophobia, are also alleviated by almotriptan. The efficacy of oral almotriptan appears to be maintained over repeated doses for multiple attacks of migraine treated over a long period (up to 1 year). High headache response rates were reported over all attacks without tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan 12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan report less concern with adverse effects than patients given sumatriptan. The lower incidence of chest pain following treatment with almotriptan than with sumatriptan may lead to a reduction in direct costs, with fewer patients requiring management of chest pain. Almotriptan is well tolerated. Most adverse events were of mild or moderate intensity, transient and generally resolved without intervention or the need for treatment withdrawal. The most common adverse events associated with oral almotriptan 12.5mg treatment were dizziness, paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and chest symptoms. The incidence of adverse events did not differ from placebo and decreased in the longer term. Almotriptan can be coadministered with drugs that share a common hepatic metabolic path; in addition, dosage reduction is required only in the presence of severe renal or hepatic impairment. ⋯ Almotriptan is an effective drug for the acute treatment of moderate or severe attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown greater efficacy than placebo; current data indicate that efficacy is similar to that of oral sumatriptan 50mg, and is maintained in the long term (< or = 1 year). Almotriptan has a good adverse event profile and a generally similar overall tolerability profile to sumatriptan; of note, almotriptan is associated with a significantly lower incidence of chest pain than sumatriptan. However, further clinical experience is required to clearly define the place of almotriptan among the other currently available triptans. Nevertheless, because triptans have an important place in various management regimens, and because the nature of individual patient response to triptans is idiosyncratic, almotriptan is likely to become a useful treatment option in the management of adults with moderate or severe migraine headaches.
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The category of common sleep disorders known as parasomnias includes disorders of arousal, rapid eye movement (REM) sleep behaviour disorder (RBD), nocturnal seizures, rhythmic movement disorder, and tooth grinding or 'bruxism'. Parasomnias are all characterised as undesirable physical or behavioural phenomena occurring during the sleep period. Although these conditions can be distressing and, in some cases, hazardous to the sleeper and his or her bed partner, it is important to recognise that parasomnias are diagnosable and treatable in the vast majority of patients. ⋯ Relaxation training and guided imagery may be helpful strategies for some patients, especially those with disorders of arousal or rhythm movement disorders. There is no evidence of any association between parasomnias and psychiatric illness. Demystification of these conditions and reassurance, particularly for parents of paediatric patients, is an important aspect of clinical intervention.
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Review Historical Article
Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy.
Since its first marketing as an antiepileptic drug (AED) 35 years ago in France, valproate has become established worldwide as one of the most widely used AEDs in the treatment of both generalised and partial seizures in adults and children. The broad spectrum of antiepileptic efficacy of valproate is reflected in preclinical in vivo and in vitro models, including a variety of animal models of seizures or epilepsy. There is no single mechanism of action of valproate that can completely account for the numerous effects of the drug on neuronal tissue and its broad clinical activity in epilepsy and other brain diseases. ⋯ Although it is often proposed that blockade of voltage-dependent sodium currents is an important mechanism of antiepileptic action of valproate, the exact role played by this mechanism of action at therapeutically relevant concentrations in the mammalian brain is not clearly elucidated. By the experimental observations summarised in this review, most clinical effects of valproate can be explained, although much remains to be learned at a number of different levels about the mechanisms of action of valproate. In view of the advances in molecular neurobiology and neuroscience, future studies will undoubtedly further our understanding of the mechanisms of action of valproate.