Side Effects Of Beta-blockers Research Articles

P-035 Catecholamine neuroreceptors are differentially located in functional regions of the human sperm

Abstract Study question How are the expression and distribution of Adrenergic and Dopamine receptors in human sperm cells? Summary answer Using ultra-high-resolution microscopy techniques, we identified that each type of catecholamine receptor is expressed in a different functional region of the human sperm. What is known already Human sperm present complex cell signalling complexes with several neuroreceptors in their membrane. The spermatozoa is a terminal differentiated cell showing specialized regions optimized for physiological processes like motility, acrosome reaction and membrane fusion during fertilization. Although indirect methods have determined the presence of catecholamine receptors in human sperm, there is no direct evidence nor description of the exact localisation of these receptors. Catecholamine receptors are the direct target of medications used to treat very frequent health problems like hypertension (beta blockers), asthma (bronchodilators) and mental health disorders (antipsychotics and antidepressants). Study design, size, duration We design the study by developing new techniques that allow us to use high-resolution microscopes (i.e. Laser Scanning Confocal Microscopy LSCM and Field Emission Scanning Electron Microscopy or FE-SEM) to identify the localisation and distribution of catecholamine receptors. We determined sperm functional regions and quantified the relative amount of the different receptors on each one of those regions to perform a statistical analysis. Participants/materials, setting, methods After informed consent and ethical approval, sperm from young, healthy donors (n = 20) were included in the study. We used the neuroblastoma cell line SH-SY5Y as a positive control. Immunolabelling techniques used specific primary antibodies for each receptor, followed by the gold-conjugated secondary antibodies for FE-SEM. Negative controls were performed by omitting the primary antibody. In FE-SEM images, we quantify the number of gold nanoparticles in the sperm cells and the background. Main results and the role of chance We confirm the differential localisation of the different receptors studied. Dopamine D2 receptors are mainly expressed on the equatorial band of the acrosome, while beta-adrenergic receptors are restricted to the terminal piece of the flagellum. In both cases, the mean number of gold particles showed statistical differences (p < 0,001) between the region of expression and the rest of the regions and the background. Limitations, reasons for caution The present study only shows the presence of the receptors on the sperm plasma membrane. The activity of those receptors should be investigated by developing bioassays based on the use of agonists and/or antagonists. A more reliable genetic overexpression or knockout approach was impossible in human sperm. Wider implications of the findings The presence of receptors on restricted regions of the sperm suggests their participation in critical physiological events, like regulation of sperm motility hyperactivation or acrosome reaction. It may also suggest a possible side effect of beta-blockers or bronchodilators with the male fertility potential that needs to be investigated. Trial registration number not applicable

Beta-blocker exposure and long-term survival in patients with transthyretin amyloid cardiomyopathy

Abstract Aims To investigate a potential association between beta-blocker exposure and long-term survival in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). Methods Real world prospective registry of 128 consecutive patients with ATTR-CM recruited in 7 hospitals. The long-term survival of patients who were receiving beta-blockers (n=65) at baseline was compared with the one of untreated controls (n=63), by means of both unweighted and inverse probability of treatment weighting (IPTW) Cox's regression analyses. Tolerance and side effects of beta-blockers were recorded. Median study follow-up was 520 days. Results Patients with ATTR-CM who were receiving beta-blockers at baseline showed statistically significant lower all-cause mortality than untreated controls (figure 1), as compared either by means of unweighted Cox's regression (hazard ratio = 0.31; 95% CI 0.12–0.19; p=0.015), or by means of Cox's regression with IPTW (hazard-ratio = 0.18; 95% CI 0.08–0.41; p<0.001). The protective effect of beta-blockers was stronger in the subgroups of ATTR-CM patients with previous atrial fibrillation/flutter, previous heart failure hospitalization, left ventricular ejection fraction <50%, NTproBNP>1000 pg/ml, and NYHA class III or IV (figure 2). The overall rate of beta-blocker suspension due to side effects in the study population was 25% (95% CI 15.5%–34.5%). Bradycardia and hypotension were the most frequent side effects leading to drug withdrawal. Conclusions In this real world, prospective, multi-institutional registry, patients with ATTR-CM who received beta-blockers presented lower all-cause mortality than untreated controls. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): PFIZERSOCIEDAD GALLEGA DE CARDIOLOGIA Figure 1. SurvivalFigure 2. Subgroup analysis

Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders.

To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders. The analysis of 66 cases of adverse reactions with a clinical picture indicating, to a degree that is probable or certain, that they were the result of the combination of antidepressant with cardiovascular medication. The most common side effect (n = 25, 37.9%) was bradycardia (and other side effects of beta blockers) as a consequence of addition of metoprolol or propranolol to SSRI or bupropion. In one case combination of fluoxetine with propranolol resulted in cardiac arrest. We observed 8 cases of intensified side effects of amlodipine (swelling of lower limbs, headaches) after its combination with: fluoxetine, sertraline and paroxetine, and occurrence of myalgia, elevated aminotransferase levels, polyuria and hypotension after combination of lercanidipine with some of the SSRIs. We also found i.a. worsening of propafenone tolerance in combination with venlafaxine or bupropion, 2 cases of granulopenia associated with duloxetine-propafenone combination, 2 cases of hemorrhagic complications associated with the combination of vortioxetine-warfarin, 1 case of hyponatremia associated with the combination of vortioxetine and hydrochlorothiazide, as well as antagonizing clonidine's hypotensive effect by mirtazapine, and peripheral thrombosis following the combination of warfarin with trazodone. Because of ahigh risk of interactions and related adverse effects, especially in older patients, each decision regarding combination of a particular antidepressant with a medication used in treatment of cardiovascular disorders should be preceded by a detailed analysis of safety and risk-benefit ratio, and also be associated with the search for the safest, alternative combinations of the above-mentioned medications.

Abstract P336: Efficacy and Safety of Vasodilator Beta-Blocker in Elderly Hypertensive Patients: Result From BEFIT-KOERA Study

Purpose: Beta-blockers are efficacious in young hypertensive patients with sympathetic activation. Elderly patients have been known to be at higher risk of hypotension, bradycardia, and other side-effects of beta-blockers when compared with younger patients. This study was to evaluate efficacy and safety of vasodilator beta-blocker in elderly hypertensive patients. Methods: BENEFIT-KOREA study (BEnefits after 24 weeks of NEbivolol administration For essential hypertensIon patients wiTh various co-morbidities and treatment environments in KOREA) was a open labeled non-controlled, prospective, multicenter observational study enrolled total 3,140 subjects [1,871 male(59.6%), mean age=63.5±12.9 years old]. We evaluated efficacy and safety of vasodilator beta-blocker in elderly patients. Results: Subjects of more than 65 years old [n=1,655, 839 male (49.3%), mean age=73.6±5.8] were analyzed. Table shows that vasodilator beta-blocker is effective in reduction of blood pressure, mean arterial pressure and pulse pressure in elderly patients regardless of add-on or switched to beta-blocker. Adverse drug reaction rate was not different between age group (n=19, 1.15% vs. n=17, 1.15%). Table shows lipid profile and body mass index were not aggravated after 24-week treatment of vasodilator beta-blocker. Conclusion: Vasodilator beta-blocker is efficacious and safe without metabolic derangement in elderly patients regardless of prescription patterns. These drug effects in elderly are comparable to in younger patients.

Let’s talk about sex

Let’s talk about sex

High blood pressure, antihypertensive medication and lung function in a general adult population

BackgroundSeveral studies showed that blood pressure and lung function are associated. Additionally, a potential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed. However, side effects of beta-blockers have been investigated mainly in patients with already reduced lung function. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have an adverse effect on lung function in a general adult population.MethodsWithin the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function tests and blood pressure measurements. Additionally, information on anthropometric measurements, medical history and use of antihypertensive medication was available. Multivariable regression models were applied to study the association between blood pressure, antihypertensive medication and lung function.ResultsHigh blood pressure as well as antihypertensive medication were associated with lower forced expiratory volume in one second (p = 0.02 respectively p = 0.05; R2: 0.65) and forced vital capacity values (p = 0.01 respectively p = 0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out that only the use of beta-blockers was associated with reduced lung function, whereas other antihypertensive medication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vital capacity (p = 0.04; R2: 0.65), while the association with forced expiratory volume in one second showed a trend toward significance (p = 0.07; R2: 0.73). In the same model high blood pressure was associated with reduced forced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too.ConclusionOur analysis indicates that both high blood pressure and the use of beta-blockers, but not the use of other antihypertensive medication, are associated with reduced lung function in a general adult population.

Beta-Blocker-Induced Psoriasis: A Rare Side Effect

Beta blockers are one of the oral agents shown to decrease cardiovascular morbidity and mortality rates in randomized, controlled trials, and hence, they are widely used for the management of many cardiovascular situations. In terms of side effects there are 3 major modes of action: (1) contraction of smooth muscles, particularly of bronchi with nonselective agents; (2) exaggerated cardiac effects; and (3) central nervous system effects. There are also some rare side effects of beta blockers, some of which are unpredictable, but the others are related to mode of action at the cellular level. Beta-blocking agents may cause psoriaform eruptions and worsen existing psoriasis. Psoriasis may be an inconvenient side effect of beta blockade. Herein, we report a case of beta-blocker-induced psoriasis.

Should beta blockers be used in the treatment of hypertension in the elderly?

The lack of benefit and the potential negative side effects of beta blockers are overstated, especially in the elderly. This emphasis has led to recommendations by some investigators that these agents not be used in the management of hypertension in this age group. There are numerous reasons why these recommendations should not be followed. The use of beta blockers in the elderly hypertensive has resulted in a reduction in strokes and congestive heart failure. In addition, it should be emphasized that elderly patients are more likely to have silent coronary artery disease or sustain myocardial infarctions. There is abundant evidence that beta blockers are effective therapy in reducing mortality once a myocardial infarction has occurred. In fact, there is a clear reduction in sudden cardiac death. Furthermore, national statistics document that elderly patients have a prevalence of congestive heart failure that varies from 6%-10%. Multiple studies have now documented that beta blockers are additive to angiotensin-converting enzyme inhibitors in reducing mortality for congestive heart failure. Thus, elderly hypertensive patients may benefit from the use of beta blockers, especially if there is evidence of ischemic heart disease, cardiac arrhythmias, or congestive heart failure.

The beta blockers: are they as protective in hypertension as in other cardiovascular conditions?

Beta blockers are frequently used to treat hypertension because of their well established safety and efficacy. Large clinical trials yield a 12%--20% decline in cardiovascular end points in hypertensive patients treated with beta blockers. However, beta blockers account for only 11% of antihypertensive prescriptions, and their use appears to be declining as newer agents with fewer side effects become available. The metabolic side effects of beta blockers have recently been examined. While they may raise triglycerides, lower high-density lipoprotein cholesterol, induce glucose intolerance, and possibly unmask diabetes, these effects have not been shown to impact their clinical effectiveness. For hypertension, beta blockers are still recommended as first-line therapy in many patients, particularly those at high risk for cardiovascular disease. They are also indicated for other cardiovascular disorders, such as congestive heart failure and postmyocardial infarction, in which mortality reductions exceed that seen with hypertension treatment in patients without cardiovascular complications. (c)2001 Le Jacq Communications, Inc.

Difficult cases in heart failure: Bridge to beta blockade in severe heart failure: the use of phosphodiesterase inhibitors.

The authors describe the use of milrinone as a bridge to beta blockade in a patient with severe heart failure. This case is clinically important because in patients with severe heart failure phosphodiesterase inhibitors, unlike beta agonists, will retain their positive inotropic and vasodilator effects in the presence of beta blockade and, in addition, these agents will attenuate the negative inotropic side effects of beta blockers. Conversely, a beta blocker associated with a phosphodiesterase inhibitor will protect against myocyte loss and arrhythmias, may prevent sudden death, and will improve long-term symptoms and exercise tolerance. This combination is being investigated in a large, multicenter, double-blind, randomized trial of intravenous milrinone vs. placebo as a therapeutic tool to allow the initiation of carvedilol orally in patients hospitalized with class III/IV heart failure. (c)2000 by CHF, Inc.

Drug Treatment—Antihypertensive Drugs—The Present Role of Beta Blockers and Alpha Blockers

There are several lines of evidence implicating increased sympathetic activity not only in the maintenance of raised blood pressure but in the pathophysiology of hypertensive complications including atherosclerosis. Beta blockers are one of the best documented classes of drugs in terms of long term safety and improvement in outcome in hypertension. They are also well established to reduce reinfarction in patients after myocardial infarction and to improve survival in patients with congestive heart failure. Side effects of beta blockers are predictable and result from excess pharmacological activity. They can often be controlled by dose adjustments.Alpha blockers reduce peripheral resistance. They are as effective as other classes at lowering blood pressure although to date there is little or no long term outcome data with this class.Reduction of sympathetic activity with beta and/or alpha blockers should remain amongst the first choices for monotherapy (or add-on therapy) in essential hypertension.

Ocular beta-blockers in glaucoma management. Clinical pharmacological aspects.

Topical beta-blockers reduce the intraocular pressure (IOP) by blockade of sympathetic nerve endings in the ciliary epithelium causing a fall in aqueous humour production. Two types of topical beta-blockers are available for use in glaucoma: nonselective, which block both beta 1- and beta 2-adrenoceptors; and cardioselective, which block only beta 1-receptors. Of the beta-Blockers commercially available, timolol, levobunolol, metipranolol and carteolol are nonselective, and betaxolol is cardioselective. Twice-daily timolol is probably the most effective agent in lowering IOP, although levobunolol is equally effective and can be used once daily with little difference in effect. Carteolol is used twice daily and any theoretical advantage in diminished side effects conferred by its partial beta-agonist activity compared with timolol has not been fully substantiated. Metipranolol is effective twice daily and does not have partial beta-agonist activity. Betaxolol has an effect comparable to timolol in lowering IOP, but is less effective in some patients. beta-Blockers can be used with other antiglaucoma medications, but their combined action with epinephrine (adrenaline) is suspect, particularly in the case of the nonselective beta-blockers, and the effect should be assessed in patients on an individual basis. Local stinging can be a problem in some patients with betaxolol. The most serious side effects of beta-blockers are the exacerbation of chronic obstructive airways disease with nonselective agents and the precipitation of bronchospasm in some patients. Betaxolol seems relatively free of adverse respiratory effects, although this may be dose-related and extreme caution should still be exercised in patients with any history of respiratory illness. Because of the lower risk of precipitating side effects, betaxolol is probably the beta-blocker of first choice for use in glaucoma; timolol or levobunolol are reserved for patients who do not respond satisfactorily to betaxolol and are quite free of respiratory disease.

Psoriasis as a side effect of beta blockers.

Psoriasis as a side effect of beta blockers.

Lipophilicity, hydrophilicity, and the central nervous system side effects of beta blockers.

One of the attributes of beta-adrenergic blocking agents that has distinguished these drugs from each other is degree of lipophilicity. While this feature may play a role in facilitating passage across the blood-brain barrier, it is essential to realize that crossing the barrier is not necessarily synonymous with the ability to cause central nervous system (CNS) effects. Several studies have found some degree of CNS side effects, particularly tiredness and fatigue, with atenolol, a hydrophilic beta blocker. Pindolol, a moderately lipophilic beta blocker, has been reported to cause greater disturbances on electroencephalogram (EEG) than propranolol, the most highly lipophilic beta blocker. The investigational agent bevantolol exhibits a moderate degree of lipophilicity and a low frequency of CNS side effects. Drug-induced increases in plasma catecholamine levels, the possible saturation of CNS receptor sites at relatively low drug levels, and the specific structural details of beta-blocker molecules have been suggested as possible contributory factors in determining the degree of CNS effects.

How disturbing are side effects of beta blockers.

Drug side effects are notoriously difficult to evaluate accurately. In this particular context there are further problems arising from the exclusion of many patients in some of the few published series of populations exposed to beta-blocking drugs. In some of these same series, placebo side effects appear to affect almost as many patients as the active drug. However, detailed breakdown of these side effects show significant differences in the actual complaints made by patients of each group. Apart from the well known major complications of beta-blocking drugs, the lesser but still disturbing ones to mention include generalized fatigue, muscle weakness, cold extremities, nightmares and impotence. A change of beta-blocking preparation or else lowering the dosage often ameliorates these problems.

Beta-Adrenoceptor blockade and pulmonary function in patients suffering from chronic obstructive lung disease.

Pulmonary function can be reduced by beta-blockers. It has been established that no beta-blocker is entirely safe in patients with chronic obstructive lung disease. An alternative medication not expected to influence pulmonary function should first be considered. This side effect of beta-blockers develops mostly in patients with reversible bronchial obstruction, and it is much less pronounced in those with irreversible bronchial obstruction. Translated into terms of clinical diagnosis, this means that problems should be expected in patients with bronchial asthma and with asthmatic bronchitis, whereas those with chronic bronchitis and emphysema are much less likely to develop relevant symptoms. It has been demonstrated that beta-blockers with intrinsic sympathomimetic activity (ISA), such as pindolol, and beta 1-selective blockers have a less marked effect on pulmonary function than nonselective beta-blockers without ISA, such as propranolol. The untoward effect can be compensated by combination with a beta-mimetic agent; this mechanism is most effective during beta 1-selective blockade.

Vascular symptoms in patients with primary Raynaud's phenomenon are not exacerbated by propranolol or labetalol.

British Journal of Clinical PharmacologyVolume 7, Issue 4 p. 401-403 Free Access Vascular symptoms in patients with primary Raynaud's phenomenon are not exacerbated by propranolol or labetalol. JA Steiner, JA SteinerSearch for more papers by this authorR Cooper, R CooperSearch for more papers by this authorJS Gear, JS GearSearch for more papers by this authorJG Ledingham, JG LedinghamSearch for more papers by this author JA Steiner, JA SteinerSearch for more papers by this authorR Cooper, R CooperSearch for more papers by this authorJS Gear, JS GearSearch for more papers by this authorJG Ledingham, JG LedinghamSearch for more papers by this author First published: April 1979 https://doi.org/10.1111/j.1365-2125.1979.tb00953.xCitations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Brick, I., Glover, W.E., Hutchison, K.J. & Roddie, I.C. (1966). Effects of propranolol on peripheral vessels in man. Am. J. Cardiol., 18, 329– 332. Farmer, J.B., Kennedy, I., Levy, G.P. & Marshall, R.J. (1972). Pharmacology of AH 5158; a drug which blocks both α- and β-adrenoceptors. Br. J. Pharmac., 45, 660– 675. Imms, F.J., Neame, R.L.B. & Powis, D.A. (1977). Responses of the cardiovascular system of the rat to noradrenaline infusions and their modification by adrenoceptor blocking agents. Br. J. Pharmac., 60, 115– 122. Johnsson, G. (1967). The effects of intra-arterially administered propranolol and H 56/28 on blood flow in the forearm—a comparative study of two β-adrenergic receptor antagonists. Acta pharmac. tox., 25, suppl. 2, 63– 74. Lund-Johansen, P. (1973). Haemodynamic changes in long-term therapy of essential hypertension: a comparative study of diuretics, α-methyldopa and clonidine. Clin. Sci. mol. Med., 45, 199S– 203S. Lundvall, V. & Järhult, J. (1976). Beta adrenergic dilator component of the sympathetic vascular response in skeletal muscle. Influence on the micro-circulation and on transcapillary exchange. Acta physiol. Scand., 96, 180– 192. Marshall, A.J., Roberts, C.J.C. & Barritt, D.W. (1976). Raynaud's phenomenon as side effect of beta-blockers in hypertension. Br. med. J., 1, 1498– 1499. McGrath, M. & Penny, R. (1974). The mechanisms of Raynaud's phenomenon: part I. Med. J. Aust., 2, 328– 333. McGrath, M.A., Peek, R. & Penny, R. (1978). Raynaud's disease: reduced hand blood flow with normal blood viscosity. Aust. N.Z. J. Med., 8, 126– 131. Peacock, J.H. (1960). The effect of changes in local temperature on the blood flows of the normal hand, primary Raynaud's disease and primary acrocyanosis. Clin. Sci., 19, 505– 512. Richards, D.A. (1976). Pharmacological effects of labetalol in man. Br. J. clin. Pharmac., 3, (4 suppl. 3), 721– 723. Zacharias, F.J., Cowen, K.J., Prestt, J., Vickers, J. & Wall, B.G. (1972). Propranolol in hypertension: a study of long-term therapy, 1964–1970. Am. Heart J., 83, 755– 761. Citing Literature Volume7, Issue4April 1979Pages 401-403 ReferencesRelatedInformation

Letter: Raynaud's phenomenon as side effect of beta-blockers.

Letter: Raynaud's phenomenon as side effect of beta-blockers.

Letter: Raynaud's phenomenon as side effect of beta-blockers.

Letter: Raynaud's phenomenon as side effect of beta-blockers.