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Clinical Pharmacy Nov 1990The use of beta-adrenergic blocking agents in patients with congestive heart failure (CHF) is reviewed. The sympathetic nervous system plays an important compensatory... (Review)
Review
The use of beta-adrenergic blocking agents in patients with congestive heart failure (CHF) is reviewed. The sympathetic nervous system plays an important compensatory role in maintaining inotropic support of the failing heart; therefore, beta blockers have long been considered contraindicated in CHF patients. However, prolonged excessive activation of the sympathetic nervous system may be detrimental. Several clinical trials have shown improved functional status and hemodynamic indices in some patients with dilated cardiomyopathy who received beta blockers. The maximum effect required up to 12 months. Two studies also showed trends toward improved survival. Aspects of study design that appear to be associated with the observation of a favorable response to beta blockade in CHF patients are a low initial dosage, gradual adjustment of the dosage, and a sufficient duration of therapy. Trials with unfavorable results lacked one or more of those design characteristics. Mechanisms proposed to underlie the beneficial effects of beta blockers in CHF patients include up-regulation of beta-receptors, reduction in cardiac energy requirements, protection of the myocardium against norepinephrine toxicity, and anti-arrhythmic effects. Most studies were conducted in patients with idiopathic dilated cardiomyopathy; it is unknown whether beta-blocker therapy is equally beneficial in patients with CHF arising from other causes. Metoprolol is the agent for which there is the most experience; comparative efficacy trials have not been conducted. Beta-adrenergic blockers appear to be beneficial in some patients with CHF. Further trials are needed to identify the patients most likely to respond and the drugs most likely to work.
Topics: Adrenergic beta-Antagonists; Heart Failure; Humans; Research Design
PubMed: 1980240
DOI: No ID Found -
American Heart Journal May 1987The beta blockers exhibit clinically significant differences in beta-receptor selectivity, intrinsic sympathomimetic activity, and alpha-adrenergic blocking activity.... (Review)
Review
The beta blockers exhibit clinically significant differences in beta-receptor selectivity, intrinsic sympathomimetic activity, and alpha-adrenergic blocking activity. These agents also show important differences in their pharmacokinetic profiles, including gastrointestinal absorption, first-pass hepatic metabolism, lipid solubility, protein binding, hepatic biotransformation, pharmacologic activity of metabolites, and renal clearance of unchanged drug and metabolites. These many differences determine the appropriateness of administering a given beta blocker in a given clinical situation. The selection of beta blockers must also take into account concurrent therapy with other agents. Concurrent administration of beta blockers with drugs that alter gastric, hepatic, or renal function may affect blood levels, duration of action, or efficacy of beta-blocker action. The beta blockers vary in the extent to which their action is altered when they are given with other agents, and therapeutic substitution may produce unwanted side effects and toxicity. Elderly patients should be carefully monitored following interchange among beta blockers, since the probability of drug interaction, impact of adverse effects, unpredictability of response, and physiologic variability of renal and liver function is greater than for younger individuals. Therapeutic substitution among beta blockers in patients already stabilized on a given agent will require careful monitoring. Retitration with the new beta blocker will be required in many cases to assure therapeutic equivalence. Beta blockers are currently used for over 20 medical conditions. There is wide variation in the strength of the clinical evidence supporting the use and efficacy of specific beta blockers for specific conditions.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Adrenergic beta-Antagonists; Chemical Phenomena; Chemistry; Heart Diseases; Humans
PubMed: 2883867
DOI: 10.1016/0002-8703(87)90933-1 -
Acta Anaesthesiologica Scandinavica.... 1982The present paper reviews some recent experiments with relevance to the functional significance of brain noradrenergic systems with bearing on three clinically relevant... (Review)
Review
The present paper reviews some recent experiments with relevance to the functional significance of brain noradrenergic systems with bearing on three clinically relevant topics: 1. The withdrawal and abstinence reactions after the antihypertensive agent clonidine as well as after opiates. 2. The mental reactions associated with alterations in blood volume and acid-base balance. 3. The central actions and side-effects of beta-adrenoceptor blocking agents. The available evidence indicates that central NA neurons may serve a function within the CNS analogous to that of the peripheral sympathetic nerves, i.e. to alert and alarm the individual to significant events in the external and internal environment. Thus, the largest brain NA system, which emanates from locus coeruleus and innervates vast regions of the neuroaxis, is largely activated in the same situations and by the same mechanisms (e.g. blood-volume and chemoreceptors) as the sympathetic system, and may provide part of the central machinery for the anxiety reaction associated with hypercapnia as well as the withdrawal reactions after clonidine or morphine. Some, but not all centrally active beta-adrenoreceptor blocking agents were found to affect the activity of brain NA systems. This result suggests that there may be significant differences with respect to the clinical, central side effects of these drugs.
Topics: Adrenergic beta-Antagonists; Animals; Norepinephrine; Rats; Sympathetic Nervous System
PubMed: 6152887
DOI: 10.1111/j.1399-6576.1982.tb01883.x -
Pharmacotherapy Sep 2000Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more... (Review)
Review
Clozapine is an effective atypical antipsychotic drug, but its use may be compromised by its side effects. Agranulocytosis may be fatal, but sialorrhea occurs more frequently and plays a major role in patients' noncompliance. A MEDLINE search from 1975-2000 revealed that treatment of clozapine-induced sialorrhea is predominantly based on case reports. Due to its elusive mechanism, physicians have attempted to treat this side effect with agents that counteract clozapine's adrenergic and muscarinic properties. We evaluated reported treatment options and other possible strategies from a pharmacologic standpoint. Antimuscarinic agents and alpha-receptor agonists are both viable options but must be administered and monitored cautiously in patients with psychiatric disorders. Although not yet available in the United States, pirenzepine, a selective muscarinic receptor antagonist, has the most promising mechanism. Other selective, peripherally acting agents must be investigated in controlled clinical trials to determine their efficacy as possible alternatives.
Topics: Adrenergic Agents; Antipsychotic Agents; Cholinergic Agents; Clozapine; Humans; Receptors, Adrenergic; Receptors, Muscarinic; Sialorrhea
PubMed: 10999502
DOI: 10.1592/phco.20.13.1092.35036 -
Anesthesiology Apr 2003The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock. (Comparative Study)
Comparative Study
BACKGROUND
The authors evaluated optimal adrenergic support using norepinephrine, dopamine, and dobutamine in a clinically relevant model of septic shock.
METHODS
Twenty-eight mature, female, anesthetized sheep (weight, 30.5 +/- 3.6 kg) underwent cecal ligation and perforation and were randomized into four groups of seven animals to be treated with norepinephrine, dopamine-norepinephrine, dobutamine-norepinephrine, or no adrenergic agent. In all groups, lactated Ringer's solution was administered to restore cardiac filling pressures to baseline. In the norepinephrine group, norepinephrine (0.5-5 microg. kg(-1). min(-1)) was titrated to maintain mean arterial pressure between 75-85 mmHg. In the dopamine-norepinephrine group, dopamine was given first, and norepinephrine was added only when mean arterial pressure remained below 75 mmHg despite the infusion of 20 microg. kg(-1). min(-1) dopamine. In the dobutamine-norepinephrine group, dobutamine was started at the same time as norepinephrine and titrated up to 20 microg. kg(-1). min(-1) to get a 15% increase in cardiac output.
RESULTS
The dobutamine-norepinephrine group had greater cardiac output; superior mesenteric blood flow, oxygen delivery (Do(2)), and oxygen consumption ([OV0312]o(2)); and lower blood lactate concentration and partial pressure of carbon dioxide (Pco(2)) gap than the controls did. Cumulative urine output was significantly higher in the dobutamine-norepinephrine group than in the other groups. Survival time was significantly longer in the dobutamine-norepinephrine (24 +/- 4 h), dopamine- norepinephrine (24 +/- 6 h), and norepinephrine (20 +/- 1 h) groups than the control group (17 +/- 2 h; P < 0.05 vs. other groups), and significantly longer in the combined dopamine-norepinephrine and dobutamine-norepinephrine groups (24 +/- 5 h) than in the norepinephrine alone group (P < 0.05). Histologic examination of lung biopsies revealed less severe lesions in the dobutamine-norepinephrine group than in the control and norepinephrine alone groups. Anatomic alterations in the lung, liver, and small intestine were less severe in the dobutamine-norepinephrine group than in the other groups.
CONCLUSIONS
In this prolonged septic shock model, association of norepinephrine with either dopamine or dobutamine resulted in the longest survival and the least severe pulmonary lesions. The combination of dobutamine with norepinephrine was associated with a better myocardial performance, greater Do(2) and [OV0312]o(2), lower blood lactate concentration and Pco(2) gap, and less anatomic injury.
Topics: Adrenergic Agents; Animals; Body Temperature; Cardiotonic Agents; Dobutamine; Dopamine; Female; Hemodynamics; Lactic Acid; Norepinephrine; Oxygen Consumption; Peritonitis; Regional Blood Flow; Respiratory Mechanics; Sheep; Shock, Septic; Survival Analysis; Sympathomimetics
PubMed: 12657850
DOI: 10.1097/00000542-200304000-00015 -
Biochemical Pharmacology Jun 2023The unsatisfactory rates of adequate blood pressure control among patients receiving antihypertensive treatment calls for new therapeutic strategies to treat...
Orally administered sodium nitrite prevents the increased α-1 adrenergic vasoconstriction induced by hypertension and promotes the S-nitrosylation of calcium/calmodulin-dependent protein kinase II.
The unsatisfactory rates of adequate blood pressure control among patients receiving antihypertensive treatment calls for new therapeutic strategies to treat hypertension. Several studies have shown that oral sodium nitrite exerts significant antihypertensive effects, but the mechanisms underlying these effects remain unclear. While these mechanisms may involve nitrite-derived S-nitrosothiols, their implication in important alterations associated with hypertension, such as aberrant α1-adrenergic vasoconstriction, has not yet been investigated. Here, we examined the effects of oral nitrite treatment on vascular responses to the α1-adrenergic agonist phenylephrine in two-kidney, one clip (2K1C) hypertensive rats and investigated the potential underlying mechanisms. Our results show that treatment with oral sodium nitrite decreases blood pressure and prevents the increased α1-adrenergic vasoconstriction in 2K1C hypertensive rats. Interestingly, we found that these effects require vascular protein S-nitrosylation, and to investigate the specific S-nitrosylated proteins we performed an unbiased nitrosoproteomic analysis of vascular smooth muscle cells (VSMCs) treated with the nitrosylating compound S-nitrosoglutathione (GSNO). This analysis revealed that GSNO markedly increases the nitrosylation of calcium/calmodulin-dependent protein kinase II γ (CaMKIIγ), a multifunctional protein that mediates the α1-adrenergic receptor signaling. This result was associated with reduced α1-adrenergic receptor-mediated CaMKIIγ activity in VSMCs. We further tested the relevance of these findings in vivo and found that treatment with oral nitrite increases CaMKIIγ S-nitrosylation and blunts the increased CaMKIIγ activity induced by phenylephrine in rat aortas. Collectively, these results are consistent with the idea that oral sodium nitrite treatment increases vascular protein S-nitrosylation, including CaMKIIγ as a target, which may ultimately prevent the increased α1-adrenergic vasoconstriction induced by hypertension. These mechanisms may help to explain the antihypertensive effects of oral nitrite and hold potential implications in the therapy of hypertension and other cardiovascular diseases associated with abnormal α1-adrenergic vasoconstriction.
Topics: Rats; Animals; Sodium Nitrite; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Antihypertensive Agents; Vasoconstriction; Calcium; Adrenergic Agents; Hypertension; Phenylephrine; Receptors, Adrenergic; Receptors, Adrenergic, alpha-1
PubMed: 37127250
DOI: 10.1016/j.bcp.2023.115571 -
Nuclear Medicine and Biology Nov 1995
Review
Topics: Adrenergic Agents; Animals; Heart; Humans; Radionuclide Imaging; Sympathetic Nervous System
PubMed: 8998461
DOI: 10.1016/0969-8051(95)02025-x -
Clinical & Experimental Metastasis Feb 2024The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an... (Review)
Review
The prevailing treatment stratagem in cancer therapy still challenges the dilemma of a probable metastatic spread following an initial diagnosis. Including an anti-metastatic agent demands a significant focus to overrule the incidence of treatment failures. Adrenergic stimulation underlying the metastatic spread paved the way for beta blockers as a breakthrough in repurposing as an anti-metastatic agent. However, the current treatment approach fails to fully harness the versatile potential of the drug in inhibiting probable metastasis. The beta blockers were seen to show a myriad of grip over the pro-metastatic and prognostic parameters of the patient. Novel interventions in immune therapy, onco-hypertension, surgery-induced stress, induction of apoptosis and angiogenesis inhibition have been used as evidence to interpret our objective of discussing the potential adjuvant role of the drug in the existing anti-cancer regimens. Adding weight to the relative incidence of onco-hypertension as an unavoidable side effect from chemotherapy, the slot for an anti-hypertensive agent is necessitated, and we try to suggest beta-blockers to fill this position. However, pointing out the paucity in the clinical study, we aim to review the current status of beta blockers under this interest to state how the drug should be included as a drug of choice in every patient undergoing cancer treatment.
Topics: Humans; Antihypertensive Agents; Adrenergic beta-Antagonists; Hypertension; Prognosis
PubMed: 38177715
DOI: 10.1007/s10585-023-10258-y -
The Clinical Journal of Pain Jun 2006Few randomized controlled trials of oral pharmacotherapy have been performed in patients with complex regional pain syndrome (CRPS). The prevalence of CRPS is uncertain.... (Review)
Review
Few randomized controlled trials of oral pharmacotherapy have been performed in patients with complex regional pain syndrome (CRPS). The prevalence of CRPS is uncertain. Severe and advanced cases of CRPS are easily recognized but difficult to treat and constitute a minority compared with those who meet minimum criteria for the diagnosis. Unsettled disability or liability claims limit pharmaceutical industry interest in the disorder. Many studies are small or anecdotal, or are reported on only via posters at meetings. Targeting the process of bone resorption with bisphosphonate-type compounds such as calcitonin, clodronate, and alendronate has shown efficacy in three published randomized controlled trials. Intravenous phentolamine has been studied both alone and in comparison to intravenous regional blockade or stellate ganglion block. Steroids continue to be administered by multiple routes without large-scale placebo-controlled trials. Topical medications have received little attention. There has been considerable interest in the use of thalidomide and TNF-alpha blockers for CRPS, but no published controlled trials as of yet. Numerous other oral drugs, including muscle relaxants, benzodiazepines, antidepressants, anticonvulsants, and opioids, have been reported on anecdotally. Some therapies have been the subject of early controlled studies, without subsequent follow-up (eg, ketanserin) or without an analogous well-tolerated and equally effective oral treatment (eg, intravenous ketamine). Gabapentin, tricyclic antidepressants, and opioids have been proven effective for chronic pain in disorders other than CRPS. Each has shown a broad enough spectrum of analgesic activity to be cautiously recommended for treatment of CRPS until adequate randomized controlled trials settle the issue. The relative benefit of oral medications compared with the widely used treatments of intensive physical therapy, nerve blocks, sympathectomy, intraspinally administered drugs, and neuromodulatory therapies (eg, spinal cord stimulation) remains uncertain. In summary, treatment of CRPS has received insufficient study and remains largely empirical.
Topics: Adrenergic Agents; Analgesics; Complex Regional Pain Syndromes; Diphosphonates; Humans; Steroids
PubMed: 16772796
DOI: 10.1097/01.ajp.0000194281.74379.01 -
Survey of Ophthalmology Feb 1997Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle... (Review)
Review
Latanoprost, a prostaglandin F2 alpha analogue prodrug, has been shown to be an effective ocular hypotensive agent when used alone on ocular hypertensive or open angle glaucoma patients. In various studies, the ocular hypotensive effects of latanoprost have also been evaluated when used in addition to, or in combination with, other ocular hypotensive agents. Latanoprost produces an additional reduction of intraocular pressure (IOP) when used in combination with timolol, pilocarpine, acetazolamide and dipivefrin. These represent four different classes of glaucoma drugs-beta-adrenergic antagonists, cholinergic agonists, carbonic anhydrase inhibitors, and adrenergic agonists-all of which reduce the IOP by different mechanisms (reduction of aqueous humor production, increased outflow facility, or by a mixed effect on aqueous humor dynamics). All the available evidence shows that latanoprost produces a clinically significant additive ocular hypotensive effect when used in combination with any currently available ocular hypotensive agent.
Topics: Acetazolamide; Adrenergic Agonists; Adrenergic beta-Antagonists; Animals; Carbonic Anhydrase Inhibitors; Drug Therapy, Combination; Epinephrine; Glaucoma; Humans; Intraocular Pressure; Latanoprost; Muscarinic Agonists; Ophthalmic Solutions; Pilocarpine; Prostaglandins F, Synthetic; Timolol
PubMed: 9154283
DOI: 10.1016/s0039-6257(97)80014-8