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Archives of Ophthalmology (Chicago,... Apr 2009To review the available evidence for the neuroprotective qualities of brimonidine tartrate in optic nerve and retinal injury. (Review)
Review
OBJECTIVE
To review the available evidence for the neuroprotective qualities of brimonidine tartrate in optic nerve and retinal injury.
METHODS
References for this study were obtained by running a search of the PubMed database using keywords brimonidine, neuroprotection, ischemic optic neuropathy, and alpha2-adrenergic agonists. References focusing on ocular hypertension were excluded.
RESULTS
Forty-eight articles addressing 1 of 4 criteria for neuroprotection were included. The literature confirms that brimonidine therapy meets the first 3 criteria for neuroprotection: receptors on its target tissues, adequate penetration into the vitreous and retina at pharmacologic levels, and induction of intracellular changes that enhance neuronal resistance to insults or interrupt apoptosis in animal models. Brimonidine did not meet the final neuroprotective criterion of success in humans.
CONCLUSIONS
Experimental evidence has demonstrated that brimonidine is a potential neuroprotective agent. However, to date, clinical trials have failed to translate into similar efficacy in humans.
Topics: Adrenergic alpha-Agonists; Animals; Brimonidine Tartrate; Humans; Neuroprotective Agents; Optic Neuropathy, Ischemic; Quinoxalines; Retina; Retinal Diseases; Vitreous Body
PubMed: 19365015
DOI: 10.1001/archophthalmol.2009.9 -
Cardiology in Review 2006Nebivolol is a beta-blocker under U.S. Food and Drug Administration review for the treatment of hypertension. The unique pharmacologic properties of nebivolol include... (Review)
Review
Nebivolol is a beta-blocker under U.S. Food and Drug Administration review for the treatment of hypertension. The unique pharmacologic properties of nebivolol include high specificity for the beta-1 receptor and a nitric oxide-mediated vasodilatory effect. The agent provides significant blood pressure reduction from baseline values as compared with placebo. Clinical trials have demonstrated that nebivolol reduces blood pressure similarly to atenolol, bisoprolol, amlodipine, nifedipine, lisinopril, and hydrochlorothiazide. The tolerability of nebivolol is similar to or better than that of these agents. In elderly patients (> or = 70 years of age) with clinically stable congestive heart failure, the addition of nebivolol to the treatment regimen improved the time to all-cause mortality and cardiovascular hospital admissions over that of placebo. If approved, nebivolol would likely be a viable alternative therapy for hypertension and heart failure; however, additional studies are needed in patients having coronary artery disease.
Topics: Adrenergic beta-Antagonists; Benzopyrans; Blood Pressure; Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Interactions; Ethanolamines; Heart Failure; Humans; Hypertension; Nebivolol; Vasodilation
PubMed: 16924166
DOI: 10.1097/01.crd.0000223651.03023.8e -
The European Respiratory Journal Sep 2009Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent... (Review)
Review
Bronchodilators remain central to the symptomatic management of chronic obstructive pulmonary disease and asthma, and, for this reason and also because the patent protection of many bronchodilators has expired, several companies have reinitiated research into the field. The only limits set for the development of a long-lasting bronchodilator with a new product profile are medical needs and marketing opportunities. The incorporation of once-daily dose administration is an important strategy for improving adherence and is a regimen preferred by most patients. A variety of beta(2)-agonists and antimuscarinic agents with longer half-lives and inhalers containing a combination of several classes of long-acting bronchodilator are currently under development. The present article reviews all of the most important compounds under development, describing what has been done and discussing their genuine advantage.
Topics: Administration, Inhalation; Adrenergic Agents; Asthma; Bronchodilator Agents; Drug Administration Schedule; Humans; Pulmonary Disease, Chronic Obstructive
PubMed: 19720811
DOI: 10.1183/09031936.00013109 -
Dental Clinics of North America Jul 1995Allergic and pseudoallergic reactions can be associated with all drug classes used in dental practice. A thorough medical history is essential to avoid challenging a... (Review)
Review
Allergic and pseudoallergic reactions can be associated with all drug classes used in dental practice. A thorough medical history is essential to avoid challenging a patient with an agent for which they have proven intolerance. Despite this precaution, the dentist must be prepared to manage an immediate reaction, should it occur. In all cases, management should begin with standard ABC assessment and oxygen supplementation. The administration of either diphenhydramine or epinephrine is predicated on the severity of the reaction. Suggestions regarding dosages and routes of administration are summarized in Table 4. The duration of action for epinephrine is relatively brief (10 to 30 minutes), and dosages may need to be repeated if symptoms recur. Following stabilization, patients who have experienced anaphylactoid reactions should be transported by EMS to the closest emergency room for definitive management. A treatment algorithm summarizing management of allergic reactions is presented in Figure 1.
Topics: Adrenergic Agonists; Anaphylaxis; Anti-Allergic Agents; Dental Care; Dental Offices; Diphenhydramine; Drug Hypersensitivity; Emergencies; Epinephrine; Humans; Hypersensitivity, Immediate; Resuscitation
PubMed: 7556791
DOI: No ID Found -
Circulation Jul 1973
Clinical Trial Comparative Study Randomized Controlled Trial
Topics: Administration, Oral; Adrenergic beta-Antagonists; Amino Alcohols; Antihypertensive Agents; Blood Pressure; Butylamines; Cardiac Output; Heart Rate; Hemodynamics; Humans; Hypertension; Male; Middle Aged; Morpholines; Propranolol; Thiadiazoles; Valsalva Maneuver; Vascular Resistance
PubMed: 4150000
DOI: 10.1161/01.cir.48.1.118 -
Journal of Clinical Hypertension... Feb 2012Hypertension is a major cardiovascular (CV) risk factor, but several other common conditions, including chronic obstructive pulmonary disease (COPD), osteoporosis, and... (Review)
Review
Hypertension is a major cardiovascular (CV) risk factor, but several other common conditions, including chronic obstructive pulmonary disease (COPD), osteoporosis, and peripheral arterial disease (PAD), have been shown to independently increase the risk of CV events and death. The physiological basis for an increased CV risk in those conditions probably lies in the augmentations of oxidative stress, endothelial dysfunction, systemic inflammation, and arterial stiffness, which all are also hallmarks of hypertension. β-Blockers have been used for the treatment of hypertension for more than 40 years, but a number of meta-analyses have demonstrated that treatment with these agents may be associated with an increased risk of CV events and mortality. However, the majority of primary prevention β-blocker trials employed atenolol, an earlier-generation β(1) -selective blocker whose mechanism of action is based on a reduction of cardiac output. Available evidence suggests that vasodilatory β-blockers may be free of the deleterious effects of atenolol. The purpose of this review is to summarize pathophysiologic mechanisms thought to be responsible for the increased CV risk associated with COPD, osteoporosis, and PAD, and examine the possible benefits of vasodilatory β-blockade in those conditions. Our examination focused on nebivolol, a β(1) -selective agent with vasodilatory effects most likely mediated via β(3) activation.
Topics: Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-Antagonists; Animals; Benzopyrans; Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Comorbidity; Endothelium, Vascular; Ethanolamines; Humans; Nebivolol; Osteoporosis; Peripheral Arterial Disease; Pulmonary Disease, Chronic Obstructive; Vascular Stiffness; Vasodilator Agents
PubMed: 22277144
DOI: 10.1111/j.1751-7176.2011.00553.x -
Cardiovascular Research Feb 1996In summary, there are marked age-dependent alterations in the myocardial alpha 1-adrenergic, beta-adrenergic and muscarinic signal transduction cascades. With... (Review)
Review
In summary, there are marked age-dependent alterations in the myocardial alpha 1-adrenergic, beta-adrenergic and muscarinic signal transduction cascades. With maturation, an inhibitory alpha 1-adrenergic response appears, which differs from the pre-existing excitatory response both with respect to the specific receptor subtype involved and its G protein coupling. Neurally released NPY appears to play a critical role in regulating the expression of the inhibitory alpha 1-adrenergic response. Likewise, sympathetic innervation appears involved in the loss of an excitatory muscarinic response during development. Again, this response, which is M1 mediated, differs in receptor subtype from that of the M2 inhibitory response characteristic of the adult. Both responses are PT-sensitive, which suggests the involvement of a PT-sensitive G protein in each case, although not necessarily the identical G protein. The role of innervation in developmental regulation of the beta-adrenergic response is unknown. While a distinct beta 1-adrenergic response exists through development, and appears to change predominantly only with respect to magnitude, the beta 2-adrenergic cascade would seem to have somewhat more complex regulation. Not only is the adult normally far less sensitive to beta 2-agonists than the neonate, but the classical beta-adrenergic effect to enhance relaxation along with the increase in force is absent in the adult when the beta 2 (but not beta 1) receptors are activated. It is apparent from the above summary that in the case of all three autonomic receptor systems, the functional signal transduction cascades in the neonate seem designed to favor excitation (chronotropic and/or inotropic) over inhibition. The alpha 1-adrenergic system is exclusively excitatory in the newborn, with an opposing inhibitory cascade only becoming evident after the onset of sympathetic innervation. Similarly, prior to sympathetic innervation the muscarinic system exhibits both excitatory and inhibitory effects, with the excitatory response being lost with development. Finally, while the beta-adrenergic system appears exclusively excitatory at all ages, in the neonate the beta 1- and beta 2-cascades both contribute to the total positive inotropic response to low concentrations of agonist, while in the adult the beta 2-component only contributes at high agonist concentrations. While the reasons for the favoring of excitation cascades in the neonate is not known, it is tempting to speculate on this point. In this respect it is worth noting that in the young, increasing heart rate, rather than stroke volume, is the primary mechanism by which cardiac output is increased [62]. In this situation, excitatory autonomic mechanisms may be advantageous. Also, at the time of birth in the rat (and at other times in different species) there is a period of potential autonomic imbalance when the parasympathetic innervation to the heart is established but the sympathetic innervation is not yet well developed. During this period, having a positive chronotropic component to muscarinic action, and a positive rather than negative alpha 1-adrenergic response, could serve to compensate for any imbalance between the two limbs of the autonomic nervous system. Finally, while the sympathetic innervation of the heart is not fully developed at birth, there can be circulating catecholamines from the adrenal medulla, and these would be primarily epinephrine rather than norepinephrine. Since epinephrine has a much higher affinity than norepinephrine for beta 2-adrenergic receptors, the presence of a strong beta 2-adrenergic cascade in the neonate could be designed to respond to the circulating, rather than neuronal, catecholamines. Lastly, one should not forget that the final physiologic response depends not only on the proximal events of receptor-effector coupling, but on more distal elements that provide the substrate for these autonomic agonists.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Adrenergic Agents; Animals; Autonomic Nervous System; Cholinergic Agents; Heart; Signal Transduction
PubMed: 8681348
DOI: No ID Found -
Neurology Nov 1994Pharmacologic and electrophysiologic studies over the past 20 years have shown tizanidine to be a potent, central-acting myotonolytic agent that principally affects... (Review)
Review
Pharmacologic and electrophysiologic studies over the past 20 years have shown tizanidine to be a potent, central-acting myotonolytic agent that principally affects spinal polysynaptic reflexes. This action arises from agonistic activity of the compound at noradrenergic alpha 2 receptors, resulting in both direct impairment of excitatory amino acid release from spinal interneurons and a concomitant inhibition of facilitatory coeruleospinal pathways. Similar alpha 2-receptor-mediated inhibition of interneuronal activity appears to underlie the additional antinociceptive and anticonvulsant activity of tizanidine reported in several species and test paradigms. Despite its structural and biochemical similarity to clonidine, the cardiovscular properties of tizanidine are mild and transitory in relation to its activity as a muscle relaxant. These findings, together with a possible greater separation between myotonolytic and general CNS depressant activity than with other agents, make tizanidine a valuable addition in the pharmacologic treatment of spasticity.
Topics: Adrenergic alpha-2 Receptor Agonists; Animals; Clonidine; Muscle Relaxants, Central; Spinal Cord; Synaptic Transmission
PubMed: 7970012
DOI: No ID Found -
Behavioural Neurology 2006Pharmacotherapy may contribute to the rehabilitation of persons with posttraumatic cognitive impairments. This article reviews first the neurobiological consequences of... (Review)
Review
Pharmacotherapy may contribute to the rehabilitation of persons with posttraumatic cognitive impairments. This article reviews first the neurobiological consequences of traumatic brain injury with a particular emphasis on acute and long-term posttraumatic neurochemical disturbances. Studies of pharmacotherapies for posttraumatic cognitive impairments are reviewed next, and are organized according to medication class and the neurotransmitter system they affect most. Based on the evidence provided by that review, augmentation of posttraumatic cerebral catecholaminergic and cholinergic function are suggested as potentially useful neurochemical targets for pharmacologic intervention in this population. More specifically, it is suggested that persons with posttraumatic impairments in arousal, speed of processing, and possibly attention may benefit most from treatment with an agent that augments cerebral catecholaminergic function, and that persons whose predominant posttraumatic impairment is in the domain of memory may benefit most from treatment with cholinesterase inhibitors. Practical considerations regarding the use of pharmacotherapies for posttraumatic cognitive impairments are offered, and the need for additional research in this area is highlighted.
Topics: Adrenergic Agents; Biogenic Amines; Brain Injuries; Central Nervous System Stimulants; Cholinesterase Inhibitors; Cognition Disorders; Dopamine Agents; Glutamic Acid; Humans; Neurotransmitter Agents
PubMed: 16720958
DOI: 10.1155/2006/460592 -
Proceedings of the Society For... Jun 1965
Topics: Adrenergic beta-Antagonists; Blood Pressure; Blood Pressure Determination; Heart; Isoproterenol; Pharmacology; Physiology; Propranolol; Research; Sympatholytics; Vasoconstrictor Agents; Vasodilator Agents
PubMed: 14328886
DOI: 10.3181/00379727-119-30177