Metoprolol-Associated Central Nervous System Complications

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Abstract

Metoprolol is a common medication used by the elderly because it is affordable and has proven to decrease mortality in cardiovascular disease. Multiple studies have reported central nervous system (CNS) side effects associated with use of beta-blockers. The risk of beta-blocker CNS side effects is directly associated with the lipophilic property of the drug.

We present the case of an 84-year-old male presented to the clinic complaining of increased confusion, fatigue, lightheadedness, nightmares, sleep disturbance, and gait problems for four weeks. The patient was evaluated for neurogenic and cardiogenic causes of his symptoms and both were ruled out. We believe that further review of his medical chart and medication reconciliation will lead us to the underlying cause of his symptoms.

Despite being an effective treatment option, there are risks associated with beta-blocker therapy. The most common symptoms are psychiatric conditions, bizarre and vivid dreams, sleep disturbances, delirium, psychosis, and visual hallucinations. Elderly patients who are started on beta-blockers require close monitoring for any adverse neurological symptoms.

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Paracetamol serum concentrations in preterm infants treated with paracetamol intravenously: a case series

Christ-jan van Ganzewinkel, Thilo Mohns, Richard van Lingen … (2012)

Introduction Until now, studies on paracetamol given intravenously have mainly been performed with the pro-drug propacetamol or with paracetamol in preterm babies above 32 weeks of gestation. Studies in these babies indicate that intravenous paracetamol is tolerated well, however studies on the efficacy of intravenous paracetamol are lacking. There are no pharmacokinetic data on the administration of multiple doses of paracetamol in preterm babies with a gestational age below 32 weeks. Case presentation We present a case series of nine Caucasian preterm babies, six boys and three girls, with a mean gestational age of 28.6 weeks (range 25.9 to 31.6 weeks). Case one, a girl with a gestational age of 25 weeks and six days, presented with necrotizing enterocolitis. In the second case, a female baby with a gestational age of 26 weeks and two days presented with hematoma. In case three, a female baby with a gestation of 26 weeks and one day developed intraventricular hemorrhage. In case four, a male baby with a gestational age of 31 weeks and four days presented with pain after vacuum delivery. Case five, a female baby born after a gestation of 29 weeks and six days presented with hematoma. In case six, a male baby with a gestation of 30 weeks and six days presented with hematoma. In case seven, a male baby, born with a gestational age of 30 weeks and six days, presented with caput succedaneum and hematoma. In case eight, a male baby, born after a gestation of 28 weeks and four days, developed abdominal distention. Case nine, a female baby, born with a gestational age of 27 weeks and three days presented with hematoma. These babies were treated with intravenous paracetamol 15 mg/kg every six hours. Serum concentrations and aspartate transaminase were determined after prolonged administration. Pain scores were assessed using the Premature Infant Pain Profile. Conclusion Paracetamol serum concentrations ranged from 8 to 64 mg/L after eight to 12 doses of intravenous paracetamol. Adequate analgesia was obtained in seven babies. During paracetamol therapy the median serum level of aspartate transaminase was 20 U/L (range 12 to 186 U/L). This case series indicates that prolonged intravenous administration of paracetamol in preterm babies with a gestational age of less than 32 weeks is tolerated well in the first days after birth. However, in the absence of proper pharmacokinetic data in this age group we cannot advocate the use of paracetamol intravenously.

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Beta-blockers and central nervous system side effects.

J Mcainsh, J. Kennedy Cruickshank (1989)

Beta-adrenergic blocking drugs are a widely used, well tolerated and effective treatment for a variety of cardiovascular and noncardiovascular disorders. Over the years, beta-blockers have been associated with an incidence, albeit low, of CNS side effects. The question of interest, however, is whether the incidence is the same for all members of the class or whether other properties, such as hydrophilicity, have a bearing on the incidence of this type of side effect? This article addresses this question. In pharmacokinetic terms the lipophilic beta-blockers have been shown, both in animals and man, to readily cross the blood-brain barrier in contrast to hydrophilic beta-blockers. This is thought to have possible clinical relevance with respect to the relative incidence of CNS side-effects. To clarify the situation every published clinical paper, in which the beta-blockers propranolol (highly lipophilic, nonselective, no intrinsic sympathomimetic activity (ISA)), pindolol (moderately lipophilic, nonselective, moderate ISA), metoprolol (moderately lipophilic, beta 1-selective, no ISA) and atenolol (hydrophilic beta 1-selective, no ISA) were compared, was assessed for information pertaining to CNS side effects. This comprehensive review of the literature has shown, with few exceptions, that the incidence of CNS side effects such as sleep disturbances, dreaming, nightmares and hallucinations following clinically accepted doses of the four beta-blockers under scrutiny is generally low and that effects on short-term memory are minimal or absent. However, within this group of four drugs the incidence of these side effects is lowest with hydrophilic atenolol and generally highest with pindolol and propranolol. Metoprolol occupies an intermediate position. This order is in agreement with the pharmacokinetic observation that the more hydrophilic the molecule, the less is found in the brain tissue of both animals and man, although in the case of pindolol other factors may be important. The clinical relevance of studies involving psychometric testing is not clear.

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The influence of beta-blockers on delayed memory function in people with cognitive impairment.

Gediminas Gliebus, Carol Lippa (2015)

Adrenergic signaling is important for the retrieval of intermediate-term contextual and spatial memories. The role of norepinephrine in retrieval requires signaling through beta1-adrenergic receptors in the hippocampus. Environmental cues activate the locus ceruleus, the main adrenergic nucleus of the brain, when an environmental stimulus is memorable. This leads to norepinephrine activation in the hippocampus, which is important for retrieving memories. Although beta-blockers do not impair cognition in normal subjects, this article explores the possibility that central nervous system (CNS)-active beta-blockers could affect delayed memory in patients with cognitive impairment. The authors investigated the influence of beta-blockers on delayed memory function in cognitively impaired patients. There was a trend for worse delayed memory retrieval in patients who were on CNS-active beta-blockers. These data support the notion that common medications used in cognitively impaired elderly patients can worsen cognition and that careful selection of medications may help to maximize retrieval of newly formed memories.

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Author and article information

Journal

Journal ID (nlm-ta): Cureus

Journal ID (iso-abbrev): Cureus

Journal ID (issn): 2168-8184

Title: Cureus

Publisher: Cureus (Palo Alto (CA) )

ISSN (Electronic): 2168-8184

Publication date (Electronic, pub): 22 May 2020

Publication date (Electronic, collection): May 2020

Volume: 12

Issue: 5

Electronic Location Identifier: e8236

Affiliations

[1 ] Internal Medicine, HCA Citrus Memorial Hospital, Inverness, USA

[2 ] Internal Medicine, Citrus Memorial Hospital, Inverness, USA

Author notes

Rony Shah rony.shah@ 123456hcahealthcare.com

Article

DOI: 10.7759/cureus.8236

PMC ID: 7306637

SO-VID: 85f7dcfd-b510-4bf6-b1dd-29c8d21e51a2

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This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Metoprolol-Associated Central Nervous System Complications

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The Dynamic Brain

Most cited references 10

Paracetamol serum concentrations in preterm infants treated with paracetamol intravenously: a case series

Beta-blockers and central nervous system side effects.

The influence of beta-blockers on delayed memory function in people with cognitive impairment.

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