Current pharmaceutical design
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Management of pain, agitation, and delirium is a complex process requiring a multimodal approach to optimize patient outcomes. Dexmedetomidine is a centrally acting alpha-2 agonist with sedative and analgesic properties that has demonstrated efficacy in managing pain, agitation, and delirium in a variety of critically ill patient populations. ⋯ However, dexmedetomidine therapy has also been associated with adverse cardiovascular events including hypotension, bradycardia, and asystole. The clinical pharmacology, therapeutic efficacy, safety considerations, controversies, and future directions of dexmedetomidine therapy in the ICU setting will be discussed.
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Spinal cord injury (SCI) often results in permanent paralysis because there is little spontaneous repair. Neuronal injury in the central nervous system (CNS) causes breakage of axonal connections, release of myelin, inflammation and cell death at the lesion site. Many factors contribute to the failure of spontaneous repair after SCI, including the presence of growth inhibitory proteins in myelin, the inflammatory environment of the injured CNS, and the resulting signaling cascades that result in over-activation of Rho, a signaling switch in neurons and axons. ⋯ We review the preclinical evidence that targeting Rho is an effective way to stimulate axon regeneration and functional recovery in preclinical animal models. In the last part of the review, we describe the creation of Cethrin, a new investigational drug, and summarize the results of the Phase I/IIa clinical study to examine the safety, tolerability and efficacy of Cethrin in patients with acute SCI. We conclude with some insight for future clinical studies.
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The amphetamine derivative 3, 4 Methylenedioxymethanphetamine (MDMA) is a powerful central nervous system stimulant that displays numerous pharmacological effects, including neurotoxicity. MDMA, or ecstasy, acts by inducing the release of different neurotransmitters depending on the animal species and, in particular, it produces the release of serotonin and dopamine. MDMA induces rewarding and reinforcing effects in rodents, primates and humans, and is currently consumed as an illicit psychostimulant among young people. ⋯ This paper represents a brief overview of the pharmacological interaction between MDMA and cannabis derivatives acting in the endocannabinoid system. We have evaluated recent findings in the literature of the most representative pharmacological effects displayed by both types of drugs. We analyze both, the synergic and opposite effects produced by these two compounds and we have found a gap regarding the negative consequences of long-term human consumption of MDMA alone or in combination with cannabis.
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Cardiac events occur in 1% to 5% of patients undergoing non-cardiac surgery. Myocardial ischemia and nonfatal myocardial infarction constitute the most significant risk factors for mortality and cardiovascular morbidity, in patients with coronary artery disease. Perioperative b- blockade has been reported to reduce the risk of perioperative cardiac complications. ⋯ However, patients with extensive preoperative ischemia were at high risk of perioperative cardiac complications, despite b-blocker therapy. Conversely, perioperative b-blocker therapy did not reduce the incidence of cardiac complications in patients without clinical risk factors. While, the safety and effectiveness of perioperative b-blockers in intermediate-risk patients, still remain a debatable issue.
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Dyslipidemia is one of the main risk factors leading to cardiovascular disease (CVD). The standard of therapy, administration of statins, in conjunction with lifestyle and habit changes, can improve high cholesterol levels in the majority of patients. However, some patients with familial hypercholesterolemia (FH) need low-density-lipoprotein cholesterol (LDL-C) apheresis, as the available medications fail to reduce LDL-C levels sufficiently even at maximum doses. ⋯ Mipomersen has been investigated in different indications including homozygous and heterozygous FH, as well as in high-risk hypercholesterolemic patients. Recent phase II and III clinical studies have shown a 25-47% reduction in LDL-C levels in mipomersen-treated patients. If future studies continue to show such promising results, mipomersen would likely be a viable additional lipid-lowering therapy for high-risk populations.