TOXICIDADE DOS BETABLOQUEADORES NA TERAPIA ANTI-HIPERTENSIVA: UM ESTUDO SOBRE EFEITOS CUMULATIVOS

Autores/as

DOI:

https://doi.org/10.61164/551g6k68

Palabras clave:

Disfunções metabólicas, Monitoramento farmacológico., Individualização terapêutica.

Resumen

A hipertensão arterial é um dos maiores desafios da saúde pública global, exigindo tratamento contínuo para reduzir a morbimortalidade cardiovascular. Os betabloqueadores destacam-se no manejo, especialmente em pacientes com cardiopatias; contudo, o uso prolongado desses fármacos pode gerar efeitos adversos cumulativos. Este estudo, baseado em uma revisão narrativa da literatura publicada entre 1990 e 2024, analisou a toxicidade crônica dessa classe de medicamentos, discutindo seus mecanismos fisiológicos, o perfil de eventos adversos e as principais estratégias de mitigação. Os achados evidenciam a ocorrência de eventos como bradicardia, fadiga, disfunções renais e alterações metabólicas, incluindo resistência à insulina e dislipidemias, fatores que comprometem a adesão e a segurança terapêutica. A toxicidade de longo prazo envolve bioacumulação, supressão simpática persistente e desregulação da homeostase glicídica e lipídica. Conclui-se que o uso crônico de betabloqueadores requer monitoramento clínico e laboratorial contínuo, titulação adequada das doses e individualização da terapia. Ademais, a incorporação de parâmetros genéticos e a consideração de alternativas farmacológicas mais seguras reforçam a necessidade de uma prática racional e personalizada no tratamento da hipertensão.

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Biografía del autor/a

  • Ludmylla Borges Gonçalves , Centro Universitário Unibras Rio Verde –Unibras, Brasil

    Orientador: Profa. Dra. Ludmylla Borges 
    Gonçalves

Referencias

ANDRADE, T. S. et al. Carbendazim exposure induces developmental,

biochemical and behavioural disturbance in zebrafish embryos. Aquatic

Toxicology, v. 170, p. 390–399, jan. 2016. DOI: https://doi.org/10.1016/j.aquatox.2015.11.017

BAKRIS, G. L. et al. Metabolic effects of carvedilol vs metoprolol in patients with

type 2 diabetes mellitus and hypertension. JAMA, v. 292, n. 18, p. 2227, 10 nov.

2004.

BANGALORE, S. et al. A meta-analysis of 94,492 patients with hypertension treated

with beta blockers to determine the risk of new-onset diabetes mellitus. The

American Journal of Cardiology, v. 100, n. 8, p. 1254–1262, out. 2007. DOI: https://doi.org/10.1016/j.amjcard.2007.05.057

BRIASOULIS, A. et al. Effects of antihypertensive treatment in patients over 65

years of age: a meta-analysis of randomised controlled studies. Heart, v. 100, n.

4, p. 317–323, 15 fev. 2014.

BURNIER, M.; EGAN, B. M. Adherence in hypertension. Circulation Research, v.

124, n. 7, p. 1124–1140, 29 mar. 2019.

CARRETERO, O. A.; OPARIL, S. Essential hypertension. Circulation, v. 101, n. 3, DOI: https://doi.org/10.1161/01.CIR.101.3.329

p. 329–335, 25 jan. 2000. DOI: https://doi.org/10.1136/rapm-00115550-200005000-00038

CHOBANIAN, A. V. et al. The seventh report of the Joint National Committee on

prevention, detection, evaluation, and treatment of high blood pressure. JAMA,

v. 289, n. 19, p. 2560–2572, 2003.

ČIŽMÁRIKOVÁ, R. et al. Survey of pharmacological activity and

pharmacokinetics of selected β-adrenergic blockers in regard to their

stereochemistry. Applied Sciences, v. 9, n. 4, p. 625, 13 fev. 2019. DOI: https://doi.org/10.3390/app9040625

DIPILATO, L. M. et al. The role of PDE3B phosphorylation in the inhibition of

lipolysis by insulin. Molecular and Cellular Biology, v. 35, n. 16, p. 2752–2760, 1

ago. 2015.

ETTEHAD, D. et al. Blood pressure lowering for prevention of cardiovascular

disease and death: a systematic review and meta-analysis. The Lancet, v. 387,

n. 10022, p. 957–967, mar. 2016. DOI: https://doi.org/10.2175/193864716821123468

23

FERRARIO, C. M. et al. Effect of angiotensin-converting enzyme inhibition and

angiotensin II receptor blockers on cardiac angiotensin-converting enzyme 2.

Circulation, v. 111, n. 20, p. 2605–2610, 24 maio 2005. DOI: https://doi.org/10.1161/CIRCULATIONAHA.104.510461

FRISHMAN, W. H. Beta-adrenergic blockers. Circulation, v. 107, n. 18, 13 maio DOI: https://doi.org/10.1161/01.CIR.0000070983.15903.A2

2003.

GAEDIGK, A. Complexities of CYP2D6 gene analysis and interpretation.

International Review of Psychiatry, v. 25, n. 5, p. 534–553, 23 out. 2013. DOI: https://doi.org/10.3109/09540261.2013.825581

GALLAGHER, E. J.; LEROITH, D.; KARNIELI, E. Insulin resistance in obesity as the

underlying cause for the metabolic syndrome. Mount Sinai Journal of Medicine: A

Journal of Translational and Personalized Medicine, v. 77, n. 5, p. 511–523, 14

set. 2010.

GAOHUA, L.; MIAO, X.; DOU, L. Crosstalk of physiological pH and chemical pKa

under the umbrella of physiologically based pharmacokinetic modeling of drug

absorption, distribution, metabolism, excretion, and toxicity. Expert Opinion on

Drug Metabolism & Toxicology, v. 17, n. 9, p. 1103–1124, 2 set. 2021. DOI: https://doi.org/10.1080/17425255.2021.1951223

GUTHRIE, B. et al. The rising tide of polypharmacy and drug-drug interactions:

population database analysis 1995–2010. BMC Medicine, v. 13, n. 1, p. 74, 7 dez.

2015.

ISBISTER, G. K. et al. Zero-order metoprolol pharmacokinetics after therapeutic

doses: severe toxicity and cardiogenic shock. Clinical Toxicology, v. 54, n. 9, p.

881–885, 20 out. 2016.

IZZO JR, J. L.; WEIR, M. R. Angiotensin-converting enzyme inhibitors. The

Journal of Clinical Hypertension, v. 13, n. 9, p. 667–675, set. 2011. DOI: https://doi.org/10.1111/j.1751-7176.2011.00508.x

JAMES, P. A. et al. Evidence based guideline for the management of high blood

pressure in adults: report from the panel members appointed to the Eighth

Joint National Committee (JNC 8). JAMA, v. 311, n. 5, p. 507–520, 2014. DOI: https://doi.org/10.1001/jama.2013.284427

KEARNEY, P. M. et al. Global burden of hypertension: analysis of worldwide

data. The Lancet, v. 360, n. 9349, p. 1903–1913, 2005.

KUZNIAR, T. J. et al. Coma with absent brainstem reflexes resulting from zolpidem

24

overdose. American Journal of Therapeutics, v. 17, n. 5, p. e172–e174, set. 2010. DOI: https://doi.org/10.1097/MJT.0b013e318188bdca

LESKO, L. J.; SCHMIDT, S. Individualization of drug therapy: history, present

state, and opportunities for the future. Clinical Pharmacology & Therapeutics, 5

set. 2012.

LEWINGTON, S. et al. Age specific relevance of usual blood pressure to

vascular mortality: a meta analysis of individual data for one million adults in

61 prospective studies. The Lancet, v. 360, n. 9349, p. 1903–1913, 2002. DOI: https://doi.org/10.1016/S0140-6736(02)11911-8

LIU, X.; TESTA, B.; FAHR, A. Lipophilicity and its relationship with passive drug

permeation. Pharmaceutical Research, v. 28, n. 5, p. 962–977, 30 maio 2011. DOI: https://doi.org/10.1007/s11095-010-0303-7

MANCIА, G. et al. 2013 ESH/ESC guidelines for the management of arterial

hypertension. European Heart Journal, v. 34, n. 28, p. 2159–2219, 2013. DOI: https://doi.org/10.1093/eurheartj/eht151

MANINI, A. F. et al. Validation of the prognostic utility of the electrocardiogram for

acute drug overdose. Journal of the American Heart Association, v. 6, n. 2, 2 fev.

2017.

MESSERLI, F. H.; GROSSMAN, E.; GOLDBOURT, U. Are beta blockers

efficacious as first line therapy for hypertension in the elderly? A systematic

review. JAMA, v. 279, n. 24, p. 1903–1907, 1998. DOI: https://doi.org/10.1001/jama.279.23.1903

MESSERLI, F. β-blockers in hypertension—the emperor has no clothes: an open

letter to present and prospective drafters of new guidelines for the treatment of

hypertension. American Journal of Hypertension, v. 16, n. 10, p. 870–873, out.

2003.

MIDDLEKAUFF, H. R.; COOPER, Z. D.; STRAUSS, S. B. Drugs of misuse: focus on

vascular dysfunction. Canadian Journal of Cardiology, v. 38, n. 9, p. 1364–1377,

set. 2022.

MOHER, D. et al. Preferred reporting items for systematic reviews and meta

analyses: the PRISMA statement. PLoS Medicine, v. 6, n. 7, 2009.

MORTLOCK, R. et al. A comparative evaluation of propranolol

pharmacokinetics in obese versus ideal weight individuals. Chemico-Biological

Interactions, v. 371, p. 110351, fev. 2023. DOI: https://doi.org/10.1016/j.cbi.2023.110351

25

RAHIMI, K.; EMDIN, C. A.; MACMAHON, S. The epidemiology of blood pressure

and its worldwide management. Circulation Research, v. 116, n. 6, p. 925–936,

2015.

RAU, T. et al. Impact of the β1-adrenoceptor Arg389Gly polymorphism on heart

rate responses to bisoprolol and carvedilol in heart-failure patients. Clinical

Pharmacology & Therapeutics, v. 92, n. 1, p. 21–28, 23 jul. 2012.

RAUF, M. A. et al. Frequency of cardiac events in patients admitted with dengue

fever at Kuwait Teaching Hospital Peshawar. International Journal of Health

Sciences, v. 7, n. S1, p. 85–92, 13 abr. 2023.

RICKLI, H. et al. Betablockers in heart failure: Carvedilol Safety Assessment (CASA

2-trial). European Journal of Heart Failure, v. 6, n. 6, p. 761–768, 12 out. 2004. DOI: https://doi.org/10.1016/j.ejheart.2003.11.025

RIZOS, C. V. Antihypertensive drugs and glucose metabolism. World Journal of

Cardiology, v. 6, n. 7, p. 517, 2014. DOI: https://doi.org/10.4330/wjc.v6.i7.517

SCHIFFRIN, E. L. Vascular remodeling in hypertension. Hypertension, v. 59, n. 2, DOI: https://doi.org/10.1161/HYPERTENSIONAHA.111.187021

p. 367–374, fev. 2012.

SHRESTHA, S. et al. Angiotensin converting enzyme inhibitors and angiotensin

II receptor antagonist attenuate tumor growth via polarization of neutrophils

toward an antitumor phenotype. OncoImmunology, v. 5, n. 1, p. e1067744, 2 jan.

2016.

SOFOWORA, G. A common β1-adrenergic receptor polymorphism (Arg389Gly)

affects blood pressure response to β-blockade. Clinical Pharmacology &

Therapeutics, v. 73, n. 4, p. 366–371, abr. 2003. DOI: https://doi.org/10.1016/S0009-9236(02)17734-4

STANEK, E. J. et al. Preferences for treatment outcomes in patients with heart

failure: symptoms versus survival. Journal of Cardiac Failure, v. 6, n. 3, p. 225

232, set. 2000.

TAGHIPOUR, M. et al. Increased sample asymmetry and memory of cardiac

time-series following endotoxin administration in cirrhotic rats. Physiological

Measurement, v. 37, n. 11, p. N96–N104, 1 nov. 2016. DOI: https://doi.org/10.1088/0967-3334/37/11/N96

TASLIDERE, B. Electrocardiography and drug intoxication. Eurasian Journal of

Toxicology, v. 4, n. 3, p. 88–92, 31 dez. 2022. DOI: https://doi.org/10.51262/ejtox.1171416

26

VIRDIS, A.; TADDEI, S. Endothelial dysfunction in resistance arteries of hypertensive

humans. Journal of Cardiovascular Pharmacology, v. 67, n. 6, p. 451–457, jun.

2016.

VOSS, T. S. et al. Effects of insulin-induced hypoglycaemia on lipolysis rate,

lipid oxidation and adipose tissue signalling in human volunteers: a

randomised clinical study. Diabetologia, v. 60, n. 1, p. 143–152, 12 jan. 2017. DOI: https://doi.org/10.1007/s00125-016-4126-x

WHELTON, P. K. Guideline for the prevention, detection, evaluation, and

management of high blood pressure in adults. Hypertension, v. 71, n. 6, p. 1269

1324, jun. 2018.

WHITE, H. L. et al. An evaluation of the β-1 adrenergic receptor Arg389Gly

polymorphism in individuals with heart failure: a MERIT-HF sub-study. European

Journal of Heart Failure, v. 5, n. 4, p. 463–468, 11 ago. 2003. DOI: https://doi.org/10.1016/S1388-9842(03)00044-8

WILLIAMS, B. et al. 2018 ESC/ESH guidelines for the management of arterial

hypertension. European Heart Journal, v. 39, n. 33, p. 3021–3104, 2018.

WILSON, T. E. Renal sympathetic nerve, blood flow, and epithelial transport

responses to thermal stress. Autonomic Neuroscience, v. 204, p. 25–34, maio

2017.

WIYSONGE, C. S. et al. Beta-blockers for hypertension. Cochrane Database of

Systematic Reviews, v. 2017, n. 1, 20 jan. 2017.

WORLD HEALTH ORGANIZATION. Global status report on noncommunicable

diseases. Geneva: WHO, 2019.

YUAN, G. et al. Voltammetric hybridization assay for the β1-adrenergic receptor

gene (ADRB1), a marker for hypertension, by using a metal organic framework

(Fe-MIL-88NH2) with immobilized copper(II) ions. Microchimica Acta, v. 184, n. 9,

p. 3121–3130, 17 set. 2017.

ZISAKI, A.; MISKOVIC, L.; HATZIMANIKATIS, V. Antihypertensive drugs

metabolism: an update to pharmacokinetic profiles and computational

approaches. Current Pharmaceutical Design, v. 21, n. 6, p. 806–822, 16 dez. 2014. DOI: https://doi.org/10.2174/1381612820666141024151119

Publicado

2025-10-20

Cómo citar

TOXICIDADE DOS BETABLOQUEADORES NA TERAPIA ANTI-HIPERTENSIVA: UM ESTUDO SOBRE EFEITOS CUMULATIVOS. (2025). Revista Multidisciplinar Do Nordeste Mineiro, 19(02), 1-26. https://doi.org/10.61164/551g6k68