A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia

Jones, D. E.; Simpson, H.C.R.; Slaughter, Philenese; Lousley, S; Carter, R.D.; Cobbe, Stuart M.; Mann, J I

doi:10.1016/0021-9150(84)90099-6

Cited by 13 publications

(5 citation statements)

References 16 publications

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“…Next, we investigated the mechanisms of probucol-induced LQTS by studying the effects of probucol on I Kr Cs ϩ current in neonatal rat ventricular myocytes. Probucol is a cholesterol-lowering drug that causes LQTS in humans (Elharrar et al, 1979;McCaughan, 1982;Jones et al, 1984;Hayashi et al, 2004). We found that acute application of 100 M probucol had no effect on I Kr ( Fig.…”

Section: Probucol Reduces Erg Expression Our Results Indicate That Csmentioning

confidence: 84%

“…Whereas direct blockade of hERG channels by various compounds represents a common mechanism for drug-induced LQTS (Sanguinetti and Tristani-Firouzi, 2006), recent evidence indicates that drug-disrupted hERG trafficking represents another mechanism for drug-induced LQTS (Ficker et al, 2004;Cordes et al, 2005;Kuryshev et al, 2005;Rajamani et al, 2006). Probucol is a cholesterol-lowering drug that has been known for many years to cause LQTS and torsades de pointes arrhythmia in humans and experimental animals (Elharrar et al, 1979;McCaughan, 1982;Jones et al, 1984). In a previous report studying wild-type and M124T mutant hERG channels expressed in Xenopus oocyte, Hayashi et al (2004) showed that probucol (30 M) did not affect the hERG current amplitude during depolarization steps but decreased the tail currents as a result of a ϳ10-mV shift of activation curve to the depolarized direction.…”

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confidence: 99%

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Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Guo

Massaeli

et al. 2007

J Pharmacol Exp Ther

104

116

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The human ether-a-go-go-related gene (hERG) encodes a channel that conducts the rapidly activating delayed rectifier K ϩ current (I Kr ), which is important for cardiac repolarization. Mutations in hERG reduce I Kr and cause congenital long QT syndrome (LQTS). More frequently, common medications can reduce I Kr and cause LQTS as a side effect. Protein trafficking abnormalities are responsible for most hERG mutation-related LQTS and are recently recognized as a mechanism for druginduced LQTS. Whereas hERG trafficking has been studied in recombinant expression systems, there has been no reported study on cardiac I Kr trafficking at the protein level. In the present study, we identified that I Kr is present in cultured neonatal rat ventricular myocytes and can be robustly recorded using Cs ϩ as the charge carrier. We further discovered that 4,4Ј-(isopropylidenedithio)-bis-(2,6-di-t-butylphenol) (probucol), a cholesterol-lowering drug that induces LQTS, disrupted I Kr trafficking and prolonged the cardiac action potential duration. Probucol did not directly block I Kr . Probucol also disrupted hERG trafficking and did not block hERG channels expressed in human embryonic kidney 293 cells. We conclude that probucol induces LQTS by disrupting ether-a-go-go-related gene trafficking, and that primary culture of neonatal rat cardiomyocytes represents a useful system for studying native I Kr trafficking.

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Section: Probucol Reduces Erg Expression Our Results Indicate That Csmentioning

confidence: 84%

mentioning

confidence: 99%

Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Guo

Massaeli

et al. 2007

J Pharmacol Exp Ther

104

116

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“…Furthermore, a retrospective study in Japan, which enrolled HeFH adult patients, showed that probucol significantly reduced recurrence of cardiovascular events 36 ) . However, as probucol has the adverse effect of QT prolongation 37 ) , regular electrocardiography needs to be carried out 38 ) . In HoFH patients who have undergone lipoprotein apheresis treatment, it has been reported that ezetimibe delays new increases in LDL-C levels after treatment 39 ) .…”

Section: Treatment Of Pediatric Fhmentioning

confidence: 99%

Guidance for Pediatric Familial Hypercholesterolemia 2017

Harada‐Shiba

Ohta²,

Ohtake

et al. 2018

J Atheroscler Thromb

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This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥ 140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥ 10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be < 140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.

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“…272 Additional studies verified that the QT interval is prolonged with probucol therapy. 273 The clinical relevance, however, was questioned. 274 Yet, case reports of QT prolongation and development of torsade de pointes or syncope were published.…”

Section: Definite Associationmentioning

confidence: 99%

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

2003

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Much attention recently has focused on drugs that prolong the QT interval, potentially leading to fatal cardiac dysrhythmias (e.g., torsade de pointes). We provide a detailed review of the published evidence that supports or does not support an association between drugs and their risk of QT prolongation. The mechanism of drug-induced QT prolongation is reviewed briefly, followed by an extensive evaluation of drugs associated with QT prolongation, torsade de pointes, or both. Drugs associated with QT prolongation are identified as having definite, probable, or proposed associations. The role of the clinician in the prevention and management of QT prolongation, drug-drug interactions that may occur with agents known to affect the QT interval, and the impact of this adverse effect on the regulatory process are addressed.

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A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia

Cited by 13 publications

References 16 publications

Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Guidance for Pediatric Familial Hypercholesterolemia 2017

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

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A comparison of cholestyramine and probucol in the treatment of familial hypercholesterolaemia

Cited by 13 publications

References 16 publications

Identification of IKr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Identification of IKr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Guidance for Pediatric Familial Hypercholesterolemia 2017

Clinical Relevance and Management of Drug‐Related QT Interval Prolongation

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Product

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Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes

Identification of I_Kr and Its Trafficking Disruption Induced by Probucol in Cultured Neonatal Rat Cardiomyocytes