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Possible heart failure associated with pregabalin use: Case report

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Abstract

Pregabalin and gabapentin are widely used analgesic, anticonvulsant and anxiolytic agents as they are relatively reliable and easily tolerated. However, they may cause some side effects such as dizziness, somnolence, dose-dependent peripheral edema, and weight gain, which may cause patients to abandon their use. Furthermore, there are a few reports in the literature addressing elderly patients with serious chronic disease and cardiac history, who develop heart failure during pregabalin application. In this report, we present a patient with no cardiac history treated with 300 mg/kg pregabalin due to neuropathic pain, who developed peripheral and then central edema, which were determined after advanced investigations. After stopping pregabalin, the situation regressed. Then, peripheral edema developed associated with the recommended dose of gabapentin, which was used in place of pregabalin. Despite the lack of any published evidence, the New York Heart Association issued a warning about using caution when prescribing pregabalin to type III-IV heart failure patients. Though the effect mechanisms of pregabalin and gabapentin are not well known, the calcium channel relationship may lead to these side effects. In summary, we believe that pregabalin and gabapentin, which is mostly used nowadays, should be administered with care not only in patients with advanced cardiac pathology but also in all patients, due to the potential side effects.

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... Gabapentin is a common drug which was indicated for treatment of epilepcy [1] and these years it is also used as an analgesic compound. [2,3] This drug is a structural analogue of gamma-aminobutyric acid (GABA), [4] but the mechanism of action of this drug is still unknown. [2] It seems to have an inhibitory effect on α2δ subunit of Ca 2+ channels in the brain, and it might increase GABA concentration. ...
... [5] This drug is widely used as analgesic, antiepileptic, postoperative pain reducer, treatment of insomnia, Despite of these side-effects, gabapentin is used as the first option for analgesic usage due to its relative reliability, easy use, high endurance and lack of negative interaction with other drugs. [3] In this article, we present a case that has been referred to us because of multiple somatic complaints, insomnia and depressed mood. Hence, we prescribed him gabapentin, but after that, unusual side-effects that have not been seen yet such as scaling, hyperesthesia, and severe localized edema have been observed. ...
... [2,5] As usual side-effects we can mention dizziness, weight gain, asthenia, nausea, and vomiting. [3,12] In our case, neuralgia and hyperesthesia has been observed as new side effects. As a noticeable point, gabapentin consumption is for treatment of neuralgia, but here neuralgia is one of the gabapentin side-effects. ...
Article
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Gabapentin is a common drug used as analgesic and anticonvulsant and also is prescribed for insomnia, depression, obsessive - compulsive disorder and panic attack. We report a case of a 48-year-old man who is prescribed gabapentin because of insomnia, headache, and depressed mood. In the first period of using the drug no complication has been seen. However in the next period, side-effects such as hyperesthesia, scaling and severe localized edema has been observed. After several laboratory tests and imaging, no reason was found for his edema. And after discontinuing gabapentin the pain and edema was quite relieved. We found out the brand of the drug has been switched in the second stage. The point which makes our study special is the incidence of side-effects such as severe edema, scaling and hyperesthesia for the first time because of using gabapentin and changing the drug combination.
... Associations between gabapentin, pregabalin and heart failure have been reported in case reports [38,39], but not in observational studies [40,41]. These case reports and observational studies are limited to short-term follow up [38][39][40][41]. ...
... Associations between gabapentin, pregabalin and heart failure have been reported in case reports [38,39], but not in observational studies [40,41]. These case reports and observational studies are limited to short-term follow up [38][39][40][41]. To the best of our knowledge, this study is among the first to report that long-term use of gabapentin and pregabalin is associated with increased risk for adverse cardiovascular events in patients with diabetic neuropathy. ...
Article
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Background Gabapentin and pregabalin are commonly prescribed medications to treat pain in patients with diabetic neuropathy. Gabapentin and pregabalin can cause fluid retention, which is hypothesized to be associated with cardiovascular diseases. However, whether long-term use of gabapentin and pregabalin is associated with adverse cardiovascular diseases remains unknown. This study aims to examine the association between gabapentin use, pregabalin use and several adverse cardiovascular events. Methods This retrospective cohort study used propensity score matching within patient electronic health records (EHRs) from a multicenter database with 106 million patients from 69 health care organizations in the US. The study population comprised 210,064 patients who had a diagnosis of diabetic neuropathy and were prescribed diabetic neuropathy medications in their EHRs. The exposure cohort comprised patients who were prescribed gabapentin or pregabalin to treat diabetic neuropathy. The comparison cohort comprised patients who were not prescribed either gabapentin or pregabalin but were prescribed other drugs to treat diabetic neuropathy. The outcomes of interest were myocardial infarcts, strokes, heart failure, peripheral vascular disease, and venous thromboembolic events. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for 3-month and 5-year risk for adverse cardiovascular events between the propensity score-matched cohorts. Results Both gabapentin and pregabalin were associated with increased risk of 5-year adverse cardiovascular events compared with the comparison group. In patients prescribed gabapentin, the highest risk was observed for deep venous thrombosis (HR: 1.58, 95% CI 1.37–1.82), followed by pulmonary embolism (HR: 1.5, 95% CI 1.27–1.76), peripheral vascular disease (HR: 1.37, 95% CI 1.27–1.47), stroke (HR: 1.31, 95% CI 1.2–1.43), myocardial infarction (HR: 1.25, 95% CI 1.14–1.38) and heart failure (HR: 1.14, 95% CI 1.07–1.21). In patients prescribed pregabalin, the highest risk was observed for deep venous thrombosis (HR: 1.57, 95% CI 1.31–1.88), followed by peripheral vascular disease (HR: 1.35, 95% CI 1.22–1.49), myocardial infarction (HR: 1.29, 95% CI 1.13–1.47), pulmonary embolism (HR: 1.28, 95% CI 1.04–1.59), stroke (HR: 1.26, 95% CI 1.12–1.42), and heart failure (HR: 1.2, 95% CI 1.11–1.3). There were significant associations between short-term (3 month) gabapentin use and heart failure, myocardial infarction, peripheral vascular disease, deep venous thrombosis, and pulmonary embolism. Short-term (3 month) pregabalin use was associated with deep venous thrombosis, peripheral vascular disease. Conclusion In patients with diabetic neuropathy who were prescribed gabapentin and pregabalin, there is an increased risk for heart failure, myocardial infarction, peripheral vascular disease, stroke, deep venous thrombosis, and pulmonary embolism with long-term use. Our findings suggest that increased risk for adverse cardiovascular events, along with other side effects, the efficacy of pain control and the degree of tolerance of the patient, should be considered when prescribing gabapentin and pregabalin long-term in patients with diabetic neuropathy.
... [4][5][6] An increase in the incidence of hyponatremia and systolic dysfunction has been reported in elderly and mainly heart failure patients. [7,8] There are also publications in the literature that report pregabalin-induced hepatotoxicity, [9] visual hallucinations in a patient with Charles Bonnet syndrome, [10] and heart failure in a patient without a cardiac problem. [8] Dizziness and somnolence are frequent and important factors to terminate the use of pregabalin. ...
... [7,8] There are also publications in the literature that report pregabalin-induced hepatotoxicity, [9] visual hallucinations in a patient with Charles Bonnet syndrome, [10] and heart failure in a patient without a cardiac problem. [8] Dizziness and somnolence are frequent and important factors to terminate the use of pregabalin. [2] Pierce et al. [11] reported a case of gabapentine-induced hearing loss in a patient with diabetes mellitus and acute renal failure, Top et al. [12] have reported to detect sensorineural hearing loss due to gabapentin following gabapentin use in the presence of coronary artery disease, diabetes mellitus, and hypertension. ...
Article
Full-text available
Pregabalin and gabapentin are similar compounds with analgesic, anticonvulsant, and anxiolytic characteristics. Due to these pharmacological features, they are commonly used throughout the world in neuropathic pain treatment and anxiety disorders. Mild to moderate side effects of the central nervous system, such as dizziness and somnolence, are important factors in deciding to terminate the use of pregabalin. Studies have also reported that the use of dose-dependent pregabalin resulted in peripheral edema and weight gain. Described in this case report is hearing loss occurring after an increase in the drug dose of a patient using pregabalin.In this case, we wanted to present the occuring hearing-loss after an increase in the drug dose of the patient already using pregabalin.
... After discontinuing pregabalin, the edema resolved. 11 Gabapentin was substituted for pregabalin and the edema returned. The second one describes a 44-year old woman with spinal stenosis prescribed gabapentin for pain. ...
Article
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Background: Through actions of calcium channel trafficking inhibition and sodium/water retention, pregabalin may increase the risk of acute heart failure (AHF). Objective: The objective of this study was to determine the prevalence of heart failure (HF) acute exacerbations, measured by a composite of emergency department (ED) visits, per-patient per-year (PPPY) hospitalizations, time-to first ED admission, and time-to hospitalizations in pre-existing HF patients taking pregabalin compared with those who were pregabalin-naive. Methods: A retrospective cohort study of pregabalin users with HF were propensity score-matched to pregabalin-naïve patients with HF to evaluate the composite of ED admissions or PPPY hospitalizations, time-to first ED admission, and time-to hospitalizations during the 365 days post-index. Doubly robust generalized linear regression and Cox-proportional hazard regression modeling were undertaken for analysis of differences between groups. Results: The matched cohort of 385 pregabalin users and 3460 pregabalin nonusers were principally middle-aged, equally gender distributed, and primary Caucasian. Most patients were on guideline-directed HF medical therapy. The estimated cumulative incidence of the primary outcome was a hazard ratio of 1.099 (95% CI: 0.789-1.530; P = 0.58). Conclusion and relevance: This large, single-center, cohort study shows pregabalin is not associated with an increased risk of AHF events in patients with pre-existing HF.
... 6 7 While pregabalin has been linked to peripheral oedema and case reports do describe a possible association with HF, this is rare. 8 Our patient's pregabalin was continued and his EF improved, making pregabalin a less likely cause. In a case report, duloxetine therapy has been noted to worsen pre-existing HF but is not causative. ...
Article
A man in his 60s with penetrating ileocolonic Crohn's disease (CD), recently started on ustekinumab therapy, presented with new onset dyspnoea, paroxysmal nocturnal dyspnoea and dependent oedema. He was diagnosed with heart failure (HF) 10 months after starting ustekinumab therapy. His symptoms resolved with discontinuation of ustekinumab and he had recovery of his cardiac function. Though initial studies that led to the U.S Food and Drug Administration (FDA)approval for ustekinumab did not detect a signal for HF, postmarketing surveillance has detected rare cases of HF after initiation of the medication. This is one of the few reported cases of HF associated with ustekinumab therapy for CD.
... La prise de prégabaline peut favoriser une décompensation cardiaque globale chez les insuffisants cardiaques [131,132]. Sa prise chronique peut entrainer une cardiomégalie avec un épanchement péricardique et une insuffisance cardiaque gauche [133] ou une cardiomyopathie avec hypertrophie ventriculaire gauche et dysfonction bi-ventriculaire pouvant être partiellement résolutives à l'arrêt du traitement [134]. ...
Article
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Résumé L’objectif de cette revue de la littérature est de réaliser une synthèse de l’état des connaissances concernant l’épidémiologie, la pharmacologie, la toxicologie clinique et analytique des abapentinoïdes. La classe pharmacologique des gabapentinoïdes est principalement représentée par la gabapentine et la prégabaline, qui ont été commercialisées autour des années 2000. Rapidement après leur commercialisation, des cas de mésusage ont été documentés dans des contextes d’abus et de dépendance. Ce sont des médicaments bien tolérés et les intoxications aiguës sont le plus souvent bénignes, sauf en cas de poly-intoxication en particulier avec des opiacés. La prégabaline augmente le risque de décès par overdose aux opiacés. En l’absence d’antidote spécifique, la prise en charge repose sur un traitement symptomatique. De nombreuses méthodes analytiques permettant la détection et le dosage de la prégabaline et de la gabapentine dans le sang, les urines et les cheveux ont été publiées, aujourd’hui les analyses sont le plus souvent effectuées en chromatographie liquide couplée à la spectrométrie de masse en tandem. La recherche des gabapentinoïdes devrait être effectuée systématiquement dans les cas de décès liés à l’usage de substances. ---- DOI https://doi.org/10.1016/j.toxac.2020.10.019 ----
... Unlike central side effects, gastrointestinal and metabolic dysfunction related to gabapentinoid use are less common and do not share a clear dose-response relationship or well-defined pathogenesis [135,150]. In this regard, the increased evidence of the association of pregabalin with peripheral edema and worsening of heart failure symptoms is noteworthy [151,152]. The mechanisms underlying these effects are not totally clear, but the peripheral edema may be the result of antagonism of the L-type calcium channel in the vasculature causing vasodilation, similar to the mechanism of action of calcium channel blockers used to treat hypertension [153]. ...
... We observe strong coherence across the three modalities for each topic. Such coherence can be reflected on many different aspects including, but not limited to i) medications treating diseases, such as Donepezil/Memantine and dementia (in T3); ii) medications treating disease comorbidities, for example, in T11 (Kidney), major depressive disorder affects one in five patients with CKD, and Sertraline is a potential antidepressant treating for CKD patients with depression (31); iii) medications causing disease conditions as side-effects, for example, in T6 (Heart), Gabapentin is a widely used analgesic, anticonvulsant and anxiolytic agent, but authors in (32) reported that taking Gabapentin will increase the risk of having heart failure for elderly patients; iv) procedures associated with diseases, such as evaluating blood pressure and body mass index for patients with cardiovascular diseases (T1). Moreover, with the multimodal topics, given one clinical event, we constructed its interactions with other events by calculating their similarities (see Methods), and the detailed results are provided in Supplemental Figure 7. ...
Preprint
Identification of clinically meaningful subphenotypes of disease progression can facilitate better understanding of disease heterogeneity and underlying pathophysiology. We propose a machine learning algorithm, termed dynaPhenoM, to achieve this goal based on longitudinal patient records such as electronic health records (EHR) or insurance claims. Specifically, dynaPhenoM first learns a set of coherent clinical topics from the events across different patient visits within the records along with the topic transition probability matrix, and then employs the time-aware latent class analysis (T-LCA) procedure to characterize each subphenotype as the evolution of these learned topics over time. The patients in the same subphenotype have similar such topic evolution patterns. We demonstrate the effectiveness and robustness of dynaPhenoM on the case of mild cognitive impairment (MCI) to Alzheimer's disease (AD) progression on three patient cohorts, and five informative subphenotypes were identified which suggest the different clinical trajectories for disease progression from MCI to AD.
... Appropriate differentiation between the two pathologies is essential, so that unnecessary medications or procedures may be avoided 6,7 . Moreover, anticonvulsant medications have been reported to have cardiotoxicity. ...
Article
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Background 6–8% of patients with acute myocardial infarction still develop ventricular arrhythmias (VA), although their incidence has lowered due to prompt antiischemic treatment. VA might determine sometimes acute symptomatic seizures. Case report A 44-year old male was admitted to our unit with acute inferior myocardial infarction. Emergency coronary angiography was performed and revealed acute occlusion of the right coronary artery. The procedure was complicated by coronary dissection, which was sealed, with good final results. After admission in the acute coronary unit, the patient developed ventricular fibrillation. He was successfully resuscitated, but developed ongoing tonic-clonic seizures, terminated after intravenous administration of several anticonvulsivant drugs. We investigated the patient for epilepsy and for other pathologies that could explain both the VA and the seizures. All investigations were within normal range. Conclusion Differential diagnosis between hypoxic and epileptic seizures is difficult and important, because it further influences patient management. Cardiac arrhythmias are a rare precipitating factor for acute symptomatic seizures, due to hypotension-induced cerebral hypoxemia. Our case illustrates the value of a multimodal approach of rare complication of a myocardial infarction.
... La prise de prégabaline peut favoriser une décompensation cardiaque globale chez les insuffisants cardiaques [131,132]. Sa prise chronique peut entrainer une cardiomégalie avec un épanchement péricardique et une insuffisance cardiaque gauche [133] ou une cardiomyopathie avec hypertrophie ventriculaire gauche et dysfonction bi-ventriculaire pouvant être partiellement résolutives à l'arrêt du traitement [134]. ...
Article
Full-text available
Résumé L’objectif de cette revue de la littérature est de réaliser une synthèse de l’état des connaissances concernant l’épidémiologie, la pharmacologie, la toxicologie clinique et analytique des gabapentinoïdes. La classe pharmacologique des gabapentinoïdes est principalement représentée par la gabapentine et la prégabaline, qui ont été commercialisées autour des années 2000. Rapidement après leur commercialisation, des cas de mésusage ont été documentés dans des contextes d’abus et de dépendance. Ce sont des médicaments bien tolérés et les intoxications aiguës sont le plus souvent bénignes, sauf en cas de poly-intoxication en particulier avec des opiacés. La prégabaline augmente le risque de décès par overdose aux opiacés. En l’absence d’antidote spécifique, la prise en charge repose sur un traitement symptomatique. De nombreuses méthodes analytiques permettant la détection et le dosage de la prégabaline et de la gabapentine dans le sang, les urines et les cheveux ont été publiées, aujourd’hui les analyses sont le plus souvent effectuées en chromatographie liquide couplée à la spectrométrie de masse en tandem. La recherche des gabapentinoïdes devrait être effectuée systématiquement dans les cas de décès liés à l’usage de substances.
... Among the most commonly encountered side-effects in treatment doses are facial rash, dizziness, drowsiness, peripheral edema and weight gain (6)(7)(8). Hyponatremia and deterioration in cardiac systolic functions were also reported especially in the elderly population with systolic heart failure (9,10). Further, hepatotoxicity induced by pregabalin use was also suggested in the literature (11). ...
Article
Full-text available
Although it was originally developed for the treatment of epilepsy, pregabalin has also been used frequently in the management of neuropathic pain and anxiety disorders recently. Owing to its widespread use in this regard, number of the cases reported with regard to both its side-effects and overdose has been escalating dramatically. More specifically, facial rash, dizziness, drowsiness, peripheral edema and weigh gain, hyponatremia and increase in systolic dysfunction especially in the elderly, hepatotoxicity and transient encephalopathy were reported with increasing incidence in the literature. We hereby reported a case of seizure and metabolic acidosis incited by pregabalin overdose, and our aim is to constitute an appeal for the fact that implementation of hemodialysis is a rapid and effective method in the treatment of seizure and metabolic acidosis in case of pregabalin intoxication.
... Similar findings were reported with different models of rat's myocardial injury [27,28]. In line with these results, clinical data demonstrated incidence of decompensated HF [7] and peripheral edema associated with PRG administration [29]. Worsening of HF has been also reported in patients with cardiac dysfunction history which was resolved within 4 days of PRG discontinuation [30]. ...
Article
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Pregabalin (PRG) possesses great therapeutic benefits in the treatment of epilepsy, neuropathic pain, and fibromyalgia. However, clinical data have reported incidence or exacerbation of heart failure following PRG administration. Experimental data exploring cardiac alterations and its underlying mechanisms are quite scarce. The aim of the present work was to investigate the effect of PRG on morphometric, echocardiographic, neurohumoral, and histopathological parameters in rats. It was hypothesized that alterations in cardiac renin angiotensin system (RAS) might be involved in PRG-induced cardiotoxicity. To further emphasize the role of RAS in the mechanism of PRG-induced cardiotoxicity, the protective potential of diminazene aceturate (DIZE), an ACE2 activator, was investigated. Results showed 44% decrease in ejection fraction and sevenfold increase in plasma N-terminal pro-brain natriuretic peptide. Histopathological examination also showed prominent vacuolar changes and edema in cardiomyocytes. In addition, PRG significantly increased angiotensin II (Ang II), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) levels, while decreased angiotensin 1–7 (Ang 1–7), angiotensin converting enzyme 2 (ACE2), and Mas receptor (MasR) cardiac levels. DIZE co-administration showed prominent protection against PRG-induced echocardiographic, neurohumoral, and histopathological alterations in rats. In addition, downregulation of ACE/Ang II/AT1R and upregulation of ACE2/Ang 1–7/MasR axes were noted in DIZE co-treated rats. These findings showed, for the first time, the detailed cardiac deleterious effects of PRG in rats. The underlying pathophysiological mechanism is probably mediated via altered balance between the RAS axes in favor to the ACE/Ang II/AT1R pathway. Accordingly, ACE2 activators might represent promising therapeutic agents for PRG-induced cardiotoxicity. Graphic Abstract Open image in new window
... None of these cases of potential pregabalin-induced worsening heart failure have reported a re-challenge of pregabalin. Similar presentations, including two cases in patients without a history of heart failure, have been reported in the literature by others (Table 1) [10][11][12][13]. Pregabalin's association with peripheral edema was not dose dependent in a systematic review and meta-analysis of 38 randomized controlled trials [6] and the case reports of worsening heart failure occurred across the dose spectrum. ...
Article
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Purpose of Review The objective of this manuscript is to describe the cardiovascular effects of the gabapentinoids gabapentin and pregabalin. Recent Findings The most frequent adverse effects of gabapentin and pregabalin affect the central nervous system, such as somnolence and fatigue. Additionally, pregabalin, and a much lesser extent, gabapentin, may adversely affect the cardiovascular system. Pregabalin induces peripheral edema and may cause or exacerbate heart failure. Pregabalin use has been associated with QTc prolongation in patients taking other QTc–prolonging agents, although the relative contributions of pregabalin to QTc prolongation may be minimal. Pregabalin and gabapentin have been associated with a dose-related increased risk of atrial fibrillation. Most evidence for adverse cardiovascular effects of gabapentinoids derives from case reports and observational studies. Summary Clinicians should be aware of the potential for pregabalin and possibly gabapentin to contribute to cardiovascular dysfunction.
... A few other reports are present in literature regarding additional cardiac side effects of pregabalin [7][8][9]. However, all of them reported cases of acute decompensation in patients with advanced or early stage chronic heart failure, a disease that impact heavily on patient survival and quality of life [10][11][12]. ...
Article
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p>Pregabalin, widely used in the treatment of several pain disorders, is usually well tolerated. Uncommonly, the drug may induce cardiac side effects, rarely prolongation of the PR interval. The latter has never been described in patients with healthy heart or normal renal function. We characterize a unique case of a young man with extrapulmonary tuberculosis and no detectable or known cardiac or kidney diseases, treated with pregabalin to control the severe pain due to the involvement of the spinal cord by the tuberculosis, showing an atrioventricular (AV) block due to pregabalin administration. The reported case emphasizes the need of monitoring PR interval during treatment with pregabalin, even in patients without background of cardiac or renal diseases. </p
... Several anticonvulsant medications have been reported to have cardiotoxicity. Pregabalin has been related to heart failure [19], oxcarbazepine was reported to induce resistant V-fib [20], and carbamazepine can cause atrioventricular (AV) block [21,22], hypotension [23] or hypertension [24], and bradycardia [25]. Those side effects may further deteriorate the cardiac function. ...
Article
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It is important but difficult to distinguish convulsive syncope from epileptic seizure in many patients. We report a case of a man who presented to emergency department after several witnessed seizure-like episodes. He had a previous medical history of systolic heart failure and automated implantable converter defibrillator (AICD) in situ. The differential diagnoses raised were epileptic seizures and convulsive syncope secondary to cardiac arrhythmia. Subsequent AICD interrogation revealed ventricular tachycardia and fibrillation (v-tach/fib). Since convulsive syncope and epileptic seizure share many similar clinical features, early diagnosis is critical for choosing the appropriate management and preventing sudden cardiac death in patients with presumed epileptic seizure.
... However, serious adverse events are much less common (around 8 % or lower) and are not significantly higher than placebo [60]. Caution may be indicated regarding the use of these medications in patients with heart failure [61]. Because they are eliminated through the kidneys, the dose must be adjusted for patients with renal insufficiency. ...
Article
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Managing the pain in a patient with traumatic injuries can be a delicate and difficult task. In the acute phase the options for pain control are often limited to opioids, which must be administered cautiously as to not further disrupt the homeostasis of an already fragile patient. Careful management of sedation during this period is also crucial to patient comfort and stability. In the recovery phase, a multimodal approach to pain control is preferred, utilizing opioid and non-opioid medications, regional and neuraxial blocks if appropriate, and other treatments to help limit the patient’s discomfort. Multimodal therapy may also more effectively prevent long-term sequelae including conversion to a chronic pain syndrome and opioid dependence and abuse.
... However, a number of other factors common to SCI, including medications, inflammation, and stress [29] , should also be considered. Indeed, almost all classes of drugs commonly used to manage neuropathic pain and depression have been associated with deleterious cardiovascular effects, including anti-convulsants [30][31][32][33] (e.g., congestive heart failure), and anti-depressants [34] (e.g., heart disease). Non-traditional medications commonly used to treat pain (e.g., cannabis) may also increase the risk of CVD [35] . ...
Article
Individuals with spinal cord injury (SCI) have a more than twofold increased risk of heart disease and stroke compared with able-bodied individuals. The increased risk appears to be in excess of the risk conferred by several well-established risk factors, including diabetes, hypertension, and sex. This raises the question whether other factors, secondary to SCI, are also contributing to the development of cardiovascular disease (CVD). Two potential factors associated with SCI and CVD are pain and depression. Both are frequently reported among individuals with SCI, develop in the acute stages of injury, and are commonly described as severe. Therefore, the primary aim of this study was to examine the relationship between pain (and types of pain) and depression with CVD among individuals with SCI. A total of 1,493 individuals (referred sample) with chronic SCI participated in a self-report cross-sectional multicenter Canada-wide survey from 2011-2012 (mean age ± standard deviation: 49.6 ± 13.9 years). After adjustment for age, sex, and injury characteristics, neuropathic pain and depression were significantly and independently associated with CVD (adjusted odds ratio and 95% confidence interval: 2.27 (1.21, 4.60) for neuropathic pain; 4.07 (2.10, 7.87) for depression). In contrast to neuropathic pain, non-neuropathic pain was not significantly associated with CVD (p = 0.13). In conclusion, these data illustrate important interrelationships between secondary complications following SCI, as well as raise the possibility of neuropathic pain (versus nociceptive pain) as a novel and emerging risk factor for CVD. © 2015 S. Karger AG, Basel.
... NDs may cause a marked reduction in physical activity, increased stress, and disturbances in autonomic dysfunction. An alternative mechanism may relate to common medications used for treatment of NDs or for related secondary complications [8] . ...
Article
Introduction There appears to be an increased risk of cardiovascular disease (CVD) among individuals with spinal cord injury [1-3] . Quantitative data concerning the risk of heart disease among individuals with other neurological disorders (NDs) are not available. Our aim was to estimate the prevalence of heart disease among individuals with NDs and to compare their risk with a control group. Methods We utilized data from the cross-sectional Canadian Community Health Survey (CCHS), as previously described [2, 4, 5] . The CCHS covers the population consisting of individuals 12 years of age and over living in the ten provinces and the three territories, and represents more than 100 health regions across Canada. Excluded from the survey's coverage are persons living on reserves, full-time members of the Canadian Forces, and institutionalized persons. Altogether, these exclusions represent less than 3% of the target population. The primary outcome variable was self-reported heart disease. The heart disease variable was selected as an overall reflection of cardiovascular health. The primary explanatory variable was a composite variable of self-reported neurological conditions (described in table 1 legend); Statistics Canada provides only grouped (composite) variables for some health conditions to protect the anonymity of individual respondents. Logistic regression models were developed, incorporating probability weighting to account for the CCHS sampling design. Multivariable models included covariates (also listed in table 1 legend) strongly associated with adverse cardiovascular profiles (e.g., Framingham risk scores) [6, 7] . Reported percentages are also probability weighed. A bootstrapping method for variance estimation for complex survey data was utilized [5] . Ethical approval for the use of the data was obtained via the publicly available data clause from the University of British Columbia. Results The final study sample included 60,343 individuals (49% male; median age category 40-44 years). There were a total of 8,368 unique individuals with an ND; this yielded a (weighted) prevalence of 13.39% for NDs. Among the total sample, the prevalence of heart disease was 4.89%. Among individuals with an ND, the prevalence of heart disease was 7.53% compared to 4.48% in individuals without an ND. Table 1 provides unadjusted and adjusted odds ratios (ORs) for heart disease. The odds of heart disease were 1.74 times greater in individuals with an ND versus individuals without an ND (95% CI 1.58, 1.90). After adjusting for sex and age, the heightened odds increased; the sex/age adjusted OR for heart disease was 2.09 (95% CI 1.89, 2.31). After adjusting for all confounders (listed in the table legend), the fully adjusted OR for heart disease was 1.97 (95% CI 1.77, 2.19). Excluding individuals who had experienced a stroke, the sex/age adjusted OR for heart disease was 1.72 (95% CI 1.52, 1.94). Discussion The present study utilized a comprehensive national survey with data collected from over 60,000 individuals to investigate the relationship between NDs and heart disease. Here, we demonstrate for the first time in a large, representative population that NDs are independently associated with significantly increased odds of heart disease. The heightened odds persist when excluding individuals with stroke. Moreover, we show for the first time that the association is independent of several known risk factors for CVD. This is important irrespective of whether NDs cause CVD, or alternatively, CVD causes neurological disorders; and indeed, the direction of causality may depend on the neurological condition under consideration, as well as the specific classification of heart disease. Indeed, several putative mechanisms may relate NDs with CVD. NDs may cause a marked reduction in physical activity, increased stress, and disturbances in autonomic dysfunction. An alternative mechanism may relate to common medications used for treatment of NDs or for related secondary complications [8] . Conclusion We report here an independent association between NDs and heart disease. Statistics Canada provides only the composite variable for these neurological conditions (with the exception of stroke and spinal cord injury), so we were not able to provide risk estimates for specific neurological disorders. Future studies should address this longitudinally, with specific NDs and classifications of heart disease to examine which conditions contribute to this observation, as well as explore potential mechanisms.
... As to the mechanism of toxicity, profound CNS depression with possible respiratory failure could cause overdose-related deaths with PRG and GBP, particularly when coadministration with opioids occurs. Cardiac complications and serotonin syndrome with opioids have also been reported [31,32]. ...
... This fluid retention may be possibly attributed to inhibition of calcium channel which causes peripheral vasodilation and fluid leakage into the interstitial area. It may be further linked to the unexplained weight gain and may contribute to exacerbate congestive heart failure [79]. Aksakal and coworkers have recently reported that pregabalin (300 mg/day) administration for 8 months in a patient with diabetic neuropathic pain results in complete atrioventricular blockade, which is resolved within 4 days after pregabalin discontinuation. ...
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Pregabalin is an antagonist of voltage gated Ca2+ channels and specifically binds to alpha-2-delta subunit to produce antiepileptic and analgesic actions. It successfully alleviates the symptoms of various types of neuropathic pain and presents itself as a first line therapeutic agent with remarkable safety and efficacy. Preclinical studies in various animal models of neuropathic pain have shown its effectiveness in treating the symptoms like allodynia and hyperalgesia. Clinical studies in different age groups and in different types of neuropathic pain (peripheral diabetic neuropathy, fibromyalgia, post-herpetic neuralgia, cancer chemotherapy-induced neuropathic pain) have projected it as the most effective agent either as monotherapy or in combined regimens in terms of cost effectiveness, tolerability and overall improvement in neuropathic pain states. Preclinical studies employing pregabalin in different neuropathic pain models have explored various molecular targets and the signaling systems including Ca2+ channel-mediated neurotransmitter release, activation of excitatory amino acid transporters (EAATs), potassium channels and inhibition of pathways involving inflammatory mediators. The present review summarizes the important aspects of pregabalin as analgesic in preclinical and clinical studies as well as focuses on the possible mechanisms.
... [2,3,7] Yaşlı ve özellikle kalp yetmezlikli hastalarda hiponatremi ve sistolik disfonksiyonda artış bildirilmiştir. [8,9] Literatürde pregabalinin indüklediği hepatotoksisite de bildirilmiştir. [6] Pregabalin oral alınımı sonrasında hızla emilir ve %90'ın üzerindeki biyoyararlanımı ile bir saat için-de pik plazma konsantrasyonuna ulaşır. ...
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Pregabalin is an antiepileptic, analgesic and anxiolytic drug that GABA analogue with similar structure and actions to gabapentin. There are very few reports about pregabalin intoxication in the literature. A 24-year-old male presented following ingestion of 3 g of pregabalin in this report. He was managed with General Supportive Care and Symptomatic Approach (GSCSA) such as discontinuation of the drug, hydration with IV fluids, oxygenation, gastric lavage and activated charcoal administration and enhanced elimination techniques. But, it is to be noted that either the kidneys of the patients are in good functioning state or there is a hemodialysis facility in the immediate vicinity.
... 97 Case reports have described the association of pregabalin treatment with the development of peripheral edema, [98][99][100][101] peripheral edema and worsened hepatic function, 102 and with peripheral edema and pleural effusion. 103 However, other potentially causative factors were present in all patients. The exact incidence of edema in patients with GAD is uncertain, although it was significantly more frequent with pregabalin (5.9%) than with placebo (1.6%) in the fibromyalgia clinical trial database 97 and occurs in a similar proportion of patients with fibromyalgia or neuropathic pain. ...
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A PREVIOUS REVIEW SUMMARIZED WHAT WAS THEN KNOWN ABOUT THE POTENTIAL ROLE OF PREGABALIN IN THE TREATMENT OF PATIENTS WITH GENERALIZED ANXIETY DISORDER (GAD): this review provides an update on its pharmacological properties and presumed mechanism of action, the liability for abuse, and efficacy and tolerability in patients with GAD. Pregabalin has a similar molecular structure to the inhibitory neurotransmitter gamma amino butyric acid (GABA) but its mechanism of action does not appear to be mediated through effects on GABA. Instead, its anxiolytic effects may arise through high-affinity binding to the alpha-2-delta sub-unit of the P/Q type voltage-gated calcium channel in "over-excited" presynaptic neurons, thereby reducing the release of excitatory neurotransmitters such as glutamate. The findings of randomized controlled trials and meta-analyses together indicate that pregabalin is efficacious in both acute treatment and relapse prevention in GAD, with some evidence of an early onset of effect, and broad efficacy in reducing the severity of psychological and physical symptoms of anxiety. It also has efficacy as an augmenting agent after non-response to antidepressant treatment in GAD. Continuing vigilance is needed in assessing its potential abuse liability but the tolerability profile of pregabalin may confer some advantages over other pharmacological treatments in the short term for treatment in patients with GAD.
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What is known and objective Gabapentin, a γ‐aminobutyric acid derivative, is used for the treatment of partial onset seizures, postherpetic neuralgia, diabetic neuropathy and a host of other neurological disorders. Case description A 44‐year‐old woman with spinal stenosis was prescribed gabapentin for pain. Two months after initiating therapy, she was diagnosed with a new‐onset non‐ischaemic cardiomyopathy with an ejection fraction of 36% measured on a transthoracic echocardiogram. What is new and Conclusion A patient with suspected gabapentin‐induced cardiomyopathy is reported. However, to date, gabapentin therapy has not been associated with risk of the developing a cardiomyopathy.
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Pregabalin is an analog of the neurotransmitter gamma-aminobutyric acid that exhibits analgesic, anticonvulsant, and anxiolytic properties. Owing to its pharmacologic properties, the drug has been used worldwide in the management of diabetic peripheral neuropathy, postherpetic neuralgia, generalized anxiety disorder, and social anxiety disorder. Although central nervous system disturbances account for the majority of pregabalin's side effects, dose-dependent peripheral edema and weight gain have also been reported. Recently, three case reports have been published documenting a possible association between pregabalin administration and chronic heart failure decompensation. We present three additional cases of possible heart failure exacerbation in patients with clinically stable heart failure who received pregabalin for neuropathic pain. Additionally, we review the literature addressing the nature and possible etiology for this adverse effect.
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Gabapentin has been shown to be well tolerated and effective in the management of the pain associated with postherpetic neuralgia (PHN). It is assumed that adverse events occurring with gabapentin are dose related, their frequency and severity increasing with increasing doses. The aim of this study was to assess the dose dependence of adverse events with gabapentin by determining the relationship between increasing doses of gabapentin and the onset and/or worsening of adverse events in patients with PHN. Data were pooled from 3 randomized, double-blind, placebo-controlled, parallel-group studies of gabapentin that focused on or included patients with PHN. Gabapentin was initiated at 300 mg/d and titrated to maintenance doses of 1800 to 3600 mg/d by day 12 to 24. The analysis of adverse events was based on 3 distinct groups: patients who received gabapentin <1800 mg/d, those who received gabapentin >or=1800 mg/d, and those who received placebo. Patients who were given higher doses of gabapentin had already received lower doses. An adverse event was recorded at the dose of its first onset and recorded again if its severity worsened at a higher dose. This study included data from 603 patients with PHN: 358 patients (196 [54.7%] women, 162 [45.3%] men; mean [SD] age, 72.3 [10.3] years) received gabapentin, and 245 (133 [54.3%] women, 112 [45.7%] men; mean [SD] age, 73.3 [10.7] years) received placebo. The 3 most common adverse events were dizziness, somnolence, and peripheral edema. Patients receiving gabapentin >or=1800 mg/d had a higher incidence of peripheral edema (7.5%) than those receiving gabapentin <1800 mg/d (1.4%) or placebo (1.6%) (P<0.002, gabapentin >or=1800 mg/d vs placebo). In contrast, the incidence of dizziness and somnolence was not higher in patients receiving gabapentin >or=1800 mg/d compared with those in the other groups. Compared with placebo recipients, patients receiving gabapentin <1800 mg/d reported a significantly greater frequency of dizziness (20.2% gabapentin <1800 mg/d vs 7.4% placebo; P<0.002) and somnolence (14.9% vs 5.8%, respectively; P=0.005). However, at >or=1800 mg/d, rates of dizziness (9.7%) and somnolence (6.9%) were comparable to those with placebo. Discontinuation rates were comparable between patients receiving gabapentin and those receiving placebo. In this pooled analysis of adverse-event data from 3 clinical trials in patients with PHN, the incidence of peripheral edema was increased when gabapentin was titrated to >or=1800 mg/d. Dizziness and somnolence, the other most commonly occurring adverse events, were transient and did not occur more frequently or worsen with titration to >or=1800 mg/d. Based on these findings, it does not appear that safety concerns should limit titration of gabapentin to achieve optimal efficacy.
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Gabapentin and pregabalin are structurally related compounds with recognized efficacy in the treatment of both epilepsy and neuropathic pain. The pharmacological mechanisms by which these agents exert their clinical effects have, until recently, remained unclear. The interaction of gabapentin and pregabalin with conventional antiepileptic and analgesic drug targets is likely to be modest, at best, and has been largely dismissed in favour of a selective inhibitory effect on voltage-gated calcium channels containing the alpha2delta-1 subunit. This mechanism is consistently observed in both rodent- and human-based experimental paradigms and may be sufficiently robust to account for much of the clinical activity of these compounds.
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Gabapentin and pregabalin bind to the alpha-2-delta calcium channel subunit and represent a novel analgesic drug class. The evidence base supporting their use for chronic neuropathic and early postsurgical pain is reviewed. Multiple, large, high-quality trials have demonstrated the safety and efficacy of gabapentin and pregabalin in neuropathic pain. Treatment-related improvement of pain and sleep positively impact upon quality of life. Sedation, dizziness and ataxia are important and relatively common adverse effects, however. Accumulating evidence indicates that gabapentin, and possibly pregabalin, also exert important effects following surgery. Multiple high-quality trials have demonstrated analgesic and opioid-sparing efficacy with gabapentin following various surgical procedures. Gabapentin and pregabalin reduce movement-evoked pain and this can lead to enhanced functional postoperative recovery. Postoperative opioid sparing is of questionable relevance since few trials have shown reduced opioid-related adverse effects. Sedation, dizziness and ataxia have been reported in only a few trials. Future larger-scale perioperative trials focused on safety assessment are needed, however. Gabapentin and pregabalin are efficacious treatments for neuropathic and postsurgical pain. Future research addressing several specific questions would serve to better delineate their optimal roles in treating these and other pain conditions.