Current pharmaceutical design
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The therapeutic action of opioid analgesics is compromised by peripheral adverse effects among which opioid-induced constipation (OIC) is the most disabling, with a prevalence reported to vary between 15 and 90 %. Although OIC is usually treated with laxatives, there is insufficient clinical evidence that laxatives are efficacious in this indication. In contrast, there is ample evidence from double- blind, randomized and placebo-controlled trials that peripheral opioid receptor antagonists (PORAs) counteract OIC. ⋯ While the addition of naloxone to oxycodone seems to act by preventing OIC, the intermittent dosing of methylnaltrexone every other day seems to stimulate defaecation by provoking an intestinal withdrawal response. The availability of PORAs provides a novel opportunity to specifically control OIC and other peripheral adverse effects of opioid analgesics (e.g., urinary retention and pruritus). The continuous dosing of a PORA has the advantage of few adverse effects, while intermittent dosing of a PORA can be associated with abdominal cramp-like pain.
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This review provides an overview of the immunological effects of commonly used analgesic opioid drugs, focusing mainly on two aspects: the mechanisms involved and the potential clinical relevance. The immunomodulatory effects of morphine have been characterized in animal and human studies. Morphine decreases the effectiveness of both natural and acquired immunity, interfering with intracellular pathways involved in immune regulation, both directly and indirectly via the activation of central receptors. ⋯ It is also emerging that not all opioids induce the same immunosuppressive effects and evaluating each opioid profile is important for appropriate analgesic selection. The impact of the opioid-mediated immune effects could be particularly dangerous in selective vulnerable populations, such as the elderly or immunocompromised patients. Indeed, it is evident that the possibility of reaching adequate and equivalent pain control by choosing either immunosuppressive drugs or drugs without an effect on immune responses may be an important consideration in opioid therapy.
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Review Randomized Controlled Trial
Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.
Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. ⋯ In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.
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Normal cognitive development depends on the timely formation of meaningful neuronal circuitries. These, in turn, depend on the proper formation and functioning of neuronal synapses, which control the flow of information between neurons. The time period when synapse formation is most intense is referred to as synaptogenesis, coinciding with the peak of brain development. ⋯ Although a direct causal link between disturbed synaptogenesis and behavioral development is not yet established, several animal studies have confirmed that cognitive development of rodents and non-human primates could be permanently impaired after a single exposure to clinically-relevant general anesthetics. Clinical evidence is now beginning to emerge suggesting that very young children may be susceptible to anesthesia-induced impairment of behavioral development, cognitive in particular. This review will summarize some of the presently available evidence regarding anesthesia-induced effects on developmental synaptogenesis and intellectual functioning.
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The vasoconstrictive and antidiuretic physiologic properties of vasopressin (antidiuretic hormone) have long been known. Until recently however, vasopressin was mostly used for diabetes insipidus and noctournal enuresis. This review summarizes the growing body of evidence regarding the perioperative use of vasopressin and its analogues in the management of certain forms of cardiovascular collapse. ⋯ Although there is yet no clear cut mortality benefit, vasopressin is now recommended as a second-line agent in septic shock for its catecholamine-sparing effect and as an alternative to epinephrine in cardiopulmonary resuscitation. It has also demonstrated efficacy in ameliorating vasoplegia after cardiopulmonary bypass as well as perioperative hypotension in patients on renin-angiotensin system antagionists preoperatively. In summary, accumulating clinical experience and formal studies indicate that vasopressin has a role in restoring vascular tone in refractory vasodilatory shock states with minimal adverse effects provided that euvolemia is assured.