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Review
. 2023;30(2):216-221.
doi: 10.15388/Amed.2023.30.2.14. Epub 2023 Jul 31.

Narrative Literature Review of Potential Atrial Fibrillation Mechanism of Action Induced by Discontinuation of Benzodiazepines

Agnė Okulevičiūtė  1 , Gabija Laubner Sakalauskienė  2
Affiliations
Review

Narrative Literature Review of Potential Atrial Fibrillation Mechanism of Action Induced by Discontinuation of Benzodiazepines

Agnė Okulevičiūtė et al. Acta Med Litu. 2023.

Abstract
in English, Italian

Introduction: Benzodiazepines are commonly prescribed but often misused, leading to dependence and withdrawal symptoms. Increased worldwide prescriptions raise adverse effects and overdose concerns, especially for the elderly. Caution is needed in prescribing and considering alternative treatments to minimize risks.

Aim: Narrative literature review of potential atrial fibrillation mechanism of action induced by discontinuation of benzodiazepines.

Materials and methods: Database PubMed was searched using the combinations of keywords - "Benzodiazepine AND atrial fibrillation OR peripheral benzodiazepine receptors", "history of benzodiazepines", "benzodiazepines mechanism of action", "benzodiazepines indications", "benzodiazepines adverse effects" and "benzodiazepines withdrawal effects". Non-full-text and non-English scientific publications were removed. A total of 31 publication was included.

Discussion: Benzodiazepines (BZDs) were synthesized in 1955 and initially considered less toxic than barbiturates. They interact with GABA-A receptors, causing hyperpolarization and inhibitory effects in the central nervous system. BZDs are used to treat various clinical disorders, but long-term use can lead to adverse effects and withdrawal symptoms. There is evidence that genetic diversity can influence the response to BZDs through GABA receptors. The interaction between benzodiazepines and peripheral benzodiazepine receptors may influence calcium ion channels, affecting cardiac action potential and contractility, and discontinuation of these medications can potentially contribute to atrial fibrillation. Additionally, benzodiazepines may directly affect calcium channels, causing antiarrhythmic effects and vasodilation.

Conclusion: In summary, benzodiazepines, once considered safer sedatives, now raise concerns about misuse, dependence, and withdrawal symptoms. While there is a potential link between discontinuing benzodiazepines and atrial fibrillation through mechanisms involving peripheral benzodiazepine receptors and cardiac calcium channels, causality remains uncertain and multifaceted. Further research is needed to clarify these mechanisms, and healthcare providers should exercise caution in long-term benzodiazepine prescriptions while exploring alternative treatment strategies to mitigate risks.

Įvadas: Benzodiazepinai yra vieni iš dažniausiai skiriamᶙ vaistᶙ, tačiau dažnai netinkamai vartojami, dėl ko išsivysto priklausomybė, o nutraukus vartoti šiuos vaistus – atsiranda nutraukimo sindromo simptomai. Vis dažnesnis šiᶙ vaistᶙ skyrimas kelia susirūpinimą dėl perdozavimo, ypač skiriant jᶙ vyresniems pacientams. Siekiant sumažinti nepageidaujamᶙ reiškiniᶙ atsiradimą vartojant šiuos vaistus, dėmesingiau turėtᶙ būti išrašomi šie vaistai, kartu apsvarstoma alternatyvaus gydymo galimybė.

Tikslas: Mūsᶙ tikslas buvo pateikti literatūros apžvalgą benzodiazepinᶙ nutraukimo sukelto prieširdžiᶙ virpėjimo mechanizmo tema.

Medžiaga ir metodai: PubMed duomenᶙ bazėje naudojant raktažodžiᶙ derinius „Benzodiazepine AND atrial fibrillation OR peripheral benzodiazepine receptors“, „history of benzodiazepines“, „benzodiazepines mechanism of action“, „benzodiazepines indications“, „benzodiazepines adverse effects“ ir „benzodiazepines withdrawal effects“ buvo atlikta moksliniᶙ šaltiniᶙ paieška. Nepilno teksto ir ne anglᶙ kalba publikacijos į apžvalgą nebuvo įtrauktos. Šia tema apžvelgta 31 publikacija.

Diskusija: Pirmą kartą benzodiazepinai buvo susintetinti 1955 m., tuo metu jie laikyti saugesniais preparatais nei barbitūratai. Šie vaistai centrinėje nervᶙ sistemoje sąveikauja su GABA-A receptoriais, sukelia hiperpoliarizaciją ir slopinamąjį efektą. Benzodiazepinai yra vartojami įvairiems klinikiniams sutrikimams gydyti, tačiau ilgalaikis jᶙ vartojimas gali sukelti nepageidaujamᶙ reiškiniᶙ ir nutraukimo sindromą. Yra tyrimᶙ, rodančiᶙ, kad benzodiazepinᶙ veikimą per GABA receptorius gali lemti genetinė įvairovė. Sąveika tarp benzodiazepinᶙ ir periferiniᶙ benzodiazepinᶙ receptoriᶙ gali paveikti kalcio jonᶙ kanalus, širdies veikimo potencialą ir susitraukimo dažnį, o šiᶙ vaistᶙ nutraukimas gali prisidėti prie prieširdžiᶙ virpėjimo atsiradimo. Be to, benzodiazepinai gali tiesiogiai paveikti kalcio kanalus, sukeldami antiaritminį poveikį ir vazodilataciją.

Išvada: Apibendrinant galima teigti, kad anksčiau saugesniais raminamaisiais vaistais laikyti benzodiazepinai dabar kelia susirūpinimą dėl netinkamo vartojimo, priklausomybės ir vartojimo nutraukimo simptomᶙ. Nors yra galimas benzodiazepinᶙ vartojimo nutraukimo ir prieširdžiᶙ virpėjimo atsiradimo mechanizmo ryšys, veikiant periferinius benzodiazepinᶙ receptorius ir širdies kalcio kanalus, tačiau priežastinis ryšys lieka neaiškus ir daugialypis. Siekiant patvirtinti šiuos mechanizmus yra būtini tolesni tyrimai, o gydytojai, skirdami benzodiazepinus ilgalaikiam vartojimui, turi būti atsargūs, kartu apsvarstyti alternatyvius gydymo metodus, kad būtᶙ mažiau benzodiazepinᶙ vartojimo ir nutraukimo sukeliamᶙ reiškiniᶙ.

Keywords: atrial fibrillation; benzodiazepines; peripheral benzodiazepine receptors.

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Conflict of interest statement

The authors have stated that there are no conflicts of interest.

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