Rizatriptan 10 mg PO is efficacious and generally well tolerated in acute migraine. Its efficacy is maintained throughout the treatment of multiple, discrete migraine attacks.

A 45-yr-old man with limb girdle muscular dystrophy, bilateral diaphragmatic paralysis, chronic carbon dioxide retention, and hypersomnolence was studied to determine the causes of hypoventilation during wakefulness and during sleep. Awake hypoventilation was associated with an insufficient inspiratory effort in the presence of inefficient respiratory muscles and a shortened inspiratory time. During sleep, severe hypoventilation and oxygen desaturation occurred only during REM-induced intercostal and accessory muscle inhibition.

Most pain information begins at simple, naked nerve endings called nociceptors that form a functional pain unit with nearby tissue capillaries and mast cells. Tissue injury causes these nerve terminals to depolarize, an event that is propagated along the entire afferent fiber eventuating in sensory impulses reaching the spinal cord. This firing of primary afferent fibers at the site of tissue injury causes axonal release of vesicles containing neuropeptides such as substance P, which acts in an autocrine and paracrine manner to sensitize the nociceptor and increase its rate of firing. Cellular damage and inflammation increase concentrations of other chemical mediators such as histamine, bradykinin, and prostaglandins in the area surrounding functional pain units. These additional mediators act synergistically to augment the transmission of nociceptive impulses along sensory afferent fibers. Primary fibers travel from the periphery to the dorsal horn where they synapse on secondary neurons and interneurons. When activated, interneurons exert inhibitory influences on further pain signal trafficking. Efferent supraspinal influences, in turn, determine the activity of interneurons by releasing a variety of neurotransmitter substances, thus resulting in a high degree of modulation of nociception within the dorsal horn. Events occurring in the periphery and in the dorsal horn can cause a dissociation of pain perception from the presence or degree of actual tissue injury. These phenomena involve many chemical mediators and receptor systems, and can increase pain experience qualitatively, quantitatively, temporally, and spatially. The complexity and plasticity of the nociceptive system can make clinical management of pain difficult. Undestanding the structure and chemical signals associated with this system can improve the use of existing analgesics and provide targets for development of newer and more specific pain-fighting drugs.

There is growing evidence that the metabolites of valproic acid (VPA) may be pharmacologically active and could contribute to both the therapeutic and toxic effects of the drug. The accumulation and washout kinetics of VPA and its oxidative metabolites were, therefore, examined in five healthy volunteers. Valproic acid (250-mg capsules) was administered bid for 15 days. Blood samples were obtained periodically during the 15 days of drug administration and for seven days following termination of treatment. Urine was also collected over the final dosing interval. Steady-state serum concentrations of VPA were achieved within three to four days of treatment. The accumulation of all metabolites in serum lagged behind that of the parent compound, with the mono-desaturated metabolites accumulating more slowly than the hydroxylated species. Furthermore, the apparent washout half-life of each metabolite was longer than the elimination half-life of VPA. In general, the unsaturated metabolites were eliminated more slowly than the hydroxylated metabolites. The serum and urinary metabolite profiles of VPA observed in the healthy volunteers were comparable with those reported for epileptic patients. The differences in the disposition kinetics of VPA and of its potentially active metabolites may explain the previously observed dissociation between the pharmacokinetics and pharmacodynamics of the drug in epileptic patients.

The first purpose of this article is to examine general signaling transduction processes that become deranged in diabetes and the means by which they damage cells. However, among the cells that can be damaged by diabetes, the primary sensory neurons, also known as dorsal root ganglion (DRG) neurons, are uniquely sensitive. Damage to these cells results in diabetic peripheral neuropathy (DPN), one of the costliest and most common diabetic complications. Therefore, the second purpose of this article is to focus attention on factors that make these cells particularly vulnerable to hyperglycemic damage. Some clinical inferences are drawn from these considerations. Finally, limitations in our knowledge about the effects of diabetes on signaling in DRG neurons are illustrated in an overview of the basic research literature.