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The Cochrane Database of Systematic... Sep 2013Beta (β) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been... (Review)
Review
BACKGROUND
Beta (β) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial because of the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication. This is an update of a review first published in 2008.
OBJECTIVES
To quantify the potential harmful effects of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance and skin temperature when used in patients with peripheral arterial disease (PAD).
SEARCH METHODS
For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2013, Issue 2).
SELECTION CRITERIA
Randomised controlled trials (RCTs) evaluating the role of both selective (β1) and non-selective (β1 and β2) beta blockers compared with placebo. We excluded trials that compared different types of beta blockers.
DATA COLLECTION AND ANALYSIS
Primary outcome measures were claudication distance in metres, time to claudication in minutes and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures included calf blood flow (mL/100 mL/min), calf vascular resistance and skin temperature (ºC).
MAIN RESULTS
We included six RCTs that fulfilled the above criteria, with a total of 119 participants. The beta blockers studied were atenolol, propranolol, pindolol and metoprolol. All trials were of poor quality with the drugs administered over a short time (10 days to two months). None of the primary outcomes were reported by more than one study. Similarly, secondary outcome measures, with the exception of vascular resistance (as reported by three studies), were reported, each by only one study. Pooling of such results was deemed inappropriate. None of the trials showed a statistically significant worsening effect of beta blockers on time to claudication, claudication distance and maximal walking distance as measured on a treadmill, nor on calf blood flow, calf vascular resistance and skin temperature, when compared with placebo. No reports described adverse events associated with the beta blockers studied.
AUTHORS' CONCLUSIONS
Currently, no evidence suggests that beta blockers adversely affect walking distance, calf blood flow, calf vascular resistance and skin temperature in people with intermittent claudication. However, because of the lack of large published trials, beta blockers should be used with caution, if clinically indicated.
Topics: Adrenergic beta-Antagonists; Atenolol; Humans; Intermittent Claudication; Metoprolol; Peripheral Vascular Diseases; Pindolol; Propranolol; Randomized Controlled Trials as Topic; Regional Blood Flow; Walking
PubMed: 24027118
DOI: 10.1002/14651858.CD005508.pub3 -
American Family Physician Dec 1998Patients receiving antidepressant monotherapy may be partially or totally resistant to treatment in 10 to 30 percent of cases. In patients who have experienced only... (Review)
Review
Patients receiving antidepressant monotherapy may be partially or totally resistant to treatment in 10 to 30 percent of cases. In patients who have experienced only partial treatment results, the clinician should first consider optimizing antidepressant dosage or lengthening therapy. Antidepressant drug substitution should generally be reserved for use in patients who haven't responded at all (nonresponders). Combining two or more antidepressants is generally not recommended, as this approach may obscure adequate monotherapy evaluation and lead to significant adverse effects or drug-drug interactions. Use of electroconvulsive therapy is recommended in patients with psychotic and severe refractory depression. Augmentation therapy is often efficacious in patients who exhibit a partial antidepressant response. Lithium and thyroid hormone have been the most extensively studied augmentative agents but, more recently, pindolol and buspirone have also been used for this purpose.
Topics: Antidepressive Agents; Buspirone; Depression; Drug Resistance; Drug Therapy, Combination; Humans; Lithium; Pindolol; Serotonin Agents; Serotonin Antagonists; Serotonin Receptor Agonists; Triiodothyronine
PubMed: 9861879
DOI: No ID Found -
British Journal of Clinical Pharmacology Oct 19811 This study aimed (1) to measure the whole blood to plasma (WB:P) and red blood cell to plasma (RBC:P) concentration ratios of propranolol in healthy volunteers and two...
1 This study aimed (1) to measure the whole blood to plasma (WB:P) and red blood cell to plasma (RBC:P) concentration ratios of propranolol in healthy volunteers and two types of patients, and (2) to compare the concentration ratios of the lipophilic drug propranolol with moderately lipophilic pindolol and hydrophilic atenolol. 2 There was no significant difference between the WB:P and RBC:P ratios of propranolol concentration in healthy volunteers and neurological patients compared with hypertensive patients. The mean +/- s.d. WB:P ratios of propranolol concentration in the three groups were 0.74 +/- 0.03, 0.71 +/- 0.05, and 0.76 +/- 0.08 respectively. The mean RBC:P ratios were 0.39 +/- 0.08, 0.36 +/- 0.11, and 0.47 +/- 0.15 respectively. WB:P and RBC:P concentration ratios of propranolol were linearly correlated with the free fraction of drug in plasma. Propranolol was 90% bound in plasma. 3 The mean WB:P and RBC:P ratios of pindolol in seven volunteers were 0.69 +/- 0.08 and 0.37 +/- 0.14 respectively. Pindolol was 71.4 +/- 8.6% bound to plasma proteins. The concentration of pindolol in the RBC was linearly correlated with that unbound in plasma. 4 In four healthy volunteers, the mean WB:P concentration ratio of atenolol was 1.07 +/- 0.25 and the mean RBC:P ratio was 1.15 +/- 0.55. 5 The similarity of the RBC:free plasma drug concentration ratios for all three drugs suggests that the use of organic solvent partition coefficients for the prediction of in vivo distribution may be unreliable.
Topics: Adolescent; Adult; Aged; Atenolol; Erythrocytes; Female; Humans; Hypertension; Male; Middle Aged; Pindolol; Plasma; Propanolamines; Propranolol
PubMed: 7295488
DOI: 10.1111/j.1365-2125.1981.tb01263.x -
British Journal of Clinical Pharmacology 19821 Pindolol is a non-selective beta-adrenoceptor blocking agent; its affinity to adrenoceptors in guinea pig atria (beta 1) is not significantly different from that in... (Review)
Review
1 Pindolol is a non-selective beta-adrenoceptor blocking agent; its affinity to adrenoceptors in guinea pig atria (beta 1) is not significantly different from that in guinea pig trachea (beta 1 + beta 2) and canine vascular smooth muscle (beta 2). 2 Pindolol displays a striking diversity of agonist activities in isolated tissues. Stimulant effects correspond to 40--50% of the maximum effects of isoprenaline in isolated kitten atria and guinea pig trachea and to only 10% in guinea pig atria. Effects in canine isolated mesenteric vessels are those of a full agonist, maximum responses equaling those of isoprenaline. These findings suggest that the stimulant effects of pindolol are exerted principally on beta 2-adrenoceptors. 3 Cardiac stimulation produced by pindolol in the dog is sufficient to compensate for the cardiac depression resulting from blockade of beta-adrenoceptors in the heart. Reductions in cardiac output and compensatory increases in total peripheral resistance do not occur or are much smaller than those produced by beta-adrenoceptor blocking agents lacking sympathomimetic activity. 4 Pindolol-induced relaxation of bronchial smooth muscle prevents or minimizes the bronchoconstrictor effects of injected spasmogens in the cat. 5 Pindolol has marked vasodilator activity, small doses reducing femoral and mesenteric vascular resistance by approximately 30%. Doses comparable to those used in hypertensive patients lower blood pressure by 20 mmHg in non-anaesthetized dogs.
Topics: Animals; Bronchi; Heart; Hemodynamics; Humans; In Vitro Techniques; Muscle Contraction; Muscle, Smooth, Vascular; Pindolol; Time Factors
PubMed: 7049208
DOI: 10.1111/j.1365-2125.1982.tb01904.x -
Postgraduate Medical Journal May 1980Five patients were treated with pindolol for various indications. The patients called attention to the appearance of fine tremors in their extremities 6-72 hr after...
Five patients were treated with pindolol for various indications. The patients called attention to the appearance of fine tremors in their extremities 6-72 hr after starting treatment with the drug. The tremors disappeared 24-72 hr after stopping the drug. Beta-adrenoceptor-blockers are known to suppress different types of tremor and the paradoxical appearance of tremors during pindolol treatment is attributed to its powerful partial agonist activity. To the best of the authors' knowledge this side effect has not been previously described in the literature.
Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Pindolol; Tremor
PubMed: 7443595
DOI: 10.1136/pgmj.56.655.346 -
Frontiers in Behavioral Neuroscience 2019Long-term binge alcohol consumption alters the signaling of numerous neurotransmitters in the brain including noradrenaline (NE) and serotonin (5-HT). Alterations in the...
Long-term binge alcohol consumption alters the signaling of numerous neurotransmitters in the brain including noradrenaline (NE) and serotonin (5-HT). Alterations in the signaling of these neuronal pathways result in dysfunctional emotional states like anxiety and depression which are typically seen during alcohol withdrawal. Interestingly, studies have demonstrated that the development of alcohol-induced negative affective states is linked to disrupted neurogenesis in the dentate gyrus (DG) region of the hippocampus in alcohol-dependent animals. We have previously shown that modulation of NE and 5-HT activity by pharmacological targeting of β-adrenoreceptors (β-ARs) and 5-HT1A/1B receptors with pindolol reduces consumption in long-term alcohol-consuming mice. Since these receptors are also involved in emotional homeostasis and hippocampal neurogenesis, we investigated the effects of pindolol administration on emotional and neurogenic deficits in mice consuming long-term alcohol (18 weeks). We report that acute administration of pindolol (32 mg/kg) reduces anxiety-like behavior in mice at 24 h withdrawal in the marble-burying test (MBT) and the elevated plus-maze (EPM). We also show that chronic (2 weeks) pindolol treatment (32 mg/kg/day) attenuates alcohol-induced impairments in the density of immature neurons (DCX) but not newborn cells (BrdU) in the hippocampal DG. Pindolol treatment also restores the normal proportion of newborn proliferating cells (BrdU/Ki67/DCX), newborn proliferating immature neurons (BrdU/Ki67/DCX) and newborn non-proliferating immature neurons (BrdU/Ki67/DCX) following long-term alcohol intake. These results suggest that pindolol, through its unique pharmacology may rescue some but not all deficits of long-term alcohol abuse on the brain, adding further value to its properties as a strong pharmaceutical option for alcohol use disorders (AUDs).
PubMed: 31849624
DOI: 10.3389/fnbeh.2019.00264 -
Biological Psychiatry Oct 2000Preclinical studies suggest that augmentation of selective serotonin (5-HT) reuptake inhibitors by the 5-HT(1A) receptor agent pindolol might reduce the delay between... (Review)
Review
Preclinical studies suggest that augmentation of selective serotonin (5-HT) reuptake inhibitors by the 5-HT(1A) receptor agent pindolol might reduce the delay between initiation of treatment and antidepressant response, an effect largely mediated by blockade of 5-HT(1A) autoreceptors in the dorsal raphe nuclei. Although some controlled clinical trials suggest that pindolol might reduce latency to selective serotonin reuptake inhibitor response in acute depressive episodes, the effect is moderate and highly variable. Recent positron emission tomography studies investigating the occupancy of 5-HT(1A) receptors in humans by pindolol have shown that at the dose used most often in clinical trials the occupancy is low and variable, which might explain the inconsistent clinical results. Positron emission tomography studies also suggest that pindolol might be more potent at blocking 5-HT(1A) autoreceptors than at blocking postsynaptic receptors, a property that may be useful in this pharmacologic strategy. Thus, the positron emission tomography data support the potential of pindolol to augment the antidepressant response of selective serotonin reuptake inhibitors, but also imply that this potential has not been fully evaluated. Here we review the clinical trials, the positron emission tomography studies, and the possible mechanisms of pindolol augmentation. It is also suggested that positron emission tomography may be used to define therapeutic dosing early on in the process of clinical evaluation of new treatment strategies.
Topics: Animals; Brain; Cerebrovascular Circulation; Clinical Trials as Topic; Depressive Disorder, Major; Drug Synergism; Fluoxetine; Humans; Paroxetine; Pindolol; Rats; Selective Serotonin Reuptake Inhibitors; Tomography, Emission-Computed
PubMed: 11063979
DOI: 10.1016/s0006-3223(00)00993-8 -
The Cochrane Database of Systematic... Oct 2008Beta (ss) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Beta (ss) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial due to the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication.
OBJECTIVES
To quantify the potential harm of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance, and skin temperature when used in patients with peripheral arterial disease (PAD).
SEARCH STRATEGY
The Cochrane Peripheral Vascular Diseases (PVD) Group searched for publications describing randomised controlled trials (RCTs) of beta blockers in PAD in their Trials Register (last searched 6 May 2008) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, Issue 2). We handsearched relevant journals and conference proceedings.
SELECTION CRITERIA
Randomised controlled trials evaluating the role of both selective (beta1) and non-selective (beta1 and beta2) beta blockers compared with placebo. We excluded trials comparing different types of beta blockers.
DATA COLLECTION AND ANALYSIS
Primary outcome measures were claudication distance in metres, and the time to claudication in minutes, and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures were calf blood flow (ml/100 ml/min), calf vascular resistance, and skin temperature (degrees C).
MAIN RESULTS
We included six RCTs fulfilling the above criteria, with a total of 119 patients. The beta blockers studied were atenolol, propranolol, pindolol, and metoprolol. None of the trials showed a statistically significant worsening effect of beta blockers on either the primary or secondary outcomes. There were no reports of any adverse events with the beta blockers studied.
AUTHORS' CONCLUSIONS
There is currently no evidence that beta blockers adversely affect walking distance in people with intermittent claudication. However, due to the lack of large published trials beta blockers should be used with caution if clinically indicated.
Topics: Adrenergic beta-Antagonists; Atenolol; Humans; Intermittent Claudication; Metoprolol; Peripheral Vascular Diseases; Pindolol; Propranolol; Randomized Controlled Trials as Topic
PubMed: 18843692
DOI: 10.1002/14651858.CD005508.pub2