Successful use of bromocriptine in the treatment of hepatic encephalopathy

Gastroenterology (Impact Factor: 16.72). 05/1980; 78(4):663-70.
Source: PubMed


Six patients with cirrhosis and severe chronic hepatic encephalopathy were treated with bromocriptine. All showed significant overall improvement clinically and in 3, the electroencephalogram became normal. The cerebral blood flow increased significantly from 32.7 +/- 2.4 (mean +/- 1 SE) to 40.5 +/- 1.5 ml/100 g brain/min (P less than 0.05). Similarly, there were significant improvements in the cerebral oxygen consumption from 2.2 +/- 0.4 to 3.3 +/- 0.4 ml/100 g brain/min (P less than 0.02) and in cerebral glucose consumption from 2.1 +/- 0.6 to 6.6 +/- 1.6 mg/100 g brain/min (P less than 0.02). Cross-over to placebo produced overall deterioration, more marked in the patients who had received the active drug for the shorter time period. No serious side effects were seen; the drug was well tolerated in doses of up to 15 mg daily and is a useful treatment for chronic hepatic encephalopathy when the response to conventional therapy has been poor.

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    • "Several studies in the brain in vivo have found this condition to be associated with a decreased oxygen consumption (Alman et al. 1956; Dam et al. 2013; Iversen et al. 2009; Morgan et al. 1980; Philips et al. 1998; Posner and Plum 1960; Strauss et al. 2003) and hence, it is likely that elevated brain concentrations of ammonia may affect energy metabolism (Ott et al. 2005; Rao and Norenberg 2001). Interestingly, it was suggested by Bessman and Bessman (1955) that ammonia-induced withdrawal of α-ketoglutarate from the tricarboxylic acid (TCA) cycle due to glutamate synthesis would decrease the efficacy of the cycle as the energy producing machinery of the mitochondria. "
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    ABSTRACT: The literature related to the effects of elevated plasma ammonia levels on brain energy metabolism is abundant, but heterogeneous in terms of the conclusions. Thus, some studies claim that ammonia has a direct, inhibitory effect on energy metabolism whereas others find no such correlation. In this review, we discuss both recent and older literature related to this controversial topic. We find that it has been consistently reported that hepatic encephalopathy and concomitant hyperammonemia lead to reduced cerebral oxygen consumption. However, this may not be directly linked to an effect of ammonia but related to the fact that hepatic encephalopathy is always associated with reduced brain activity, a condition clearly characterized by a decreased CMRO2. Whether this may be related to changes in GABAergic function remains to be elucidated.
    Full-text · Article · Mar 2014 · Metabolic Brain Disease
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    • "Reduced DAergic input in HE, would suggest that treatments which aim to increase DAergic tone may alleviate HE symptoms. In fact, improvement of 50% of HE patients with chronic portosystemic encephalopathy was reported to follow treatment of patients with either the DA precursor levodopa (Lunzer et al., 1974) or the DA D 2 receptor agonist, bromocriptine (Morgan et al., 1980). However, controlled clinical trials reported that these treatments were ineffective (Michel et al., 1980; Uribe et al., 1983) probably because the DA agonist would activate both direct and indirect DA pathways, while bromocriptine would inhibit only the indirect DA pathway. "
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    ABSTRACT: Hepatic encephalopathy (HE) is a neuropsychiatric disorder occurring as a consequence of both acute and chronic liver failure. Advanced HE is generally accompanied with extrapyramidal symptoms including rigidity and tremor, which may reflect alterations of the dopaminergic system. Recently we reported a beneficial effect of the neuroactive steroid dehydroepiandrosterone sulfate (DHEAS) in cirrhotic rats, however the mechanisms of such an effect by DHEAS were not addressed. In the present study, we describe the changes of the dopaminergic system occurring in the cirrhotic rats and concomitantly we investigated the effect of DHEAS on this system in Sprague-Dawley rats using the expression of tyrosine hydroxylase (TH) as a neuronal marker. Rats were submitted to bile duct ligation (BDL) surgery and TH immunohistochemistry was assessed in the Substantia nigra pars compacta (SNc), striatum, ventral tegmental area (VTA) and the cortex. TH immunoreactivity showed a significant diminution in both SNc and VTA concomitantly with the cortical and the striatal outputs in the BDL rats vs. controls. Three daily injections of 5mg/kg of DHEAS to BDL rats significantly normalized TH expression decrease in both SNc and VTA as well as dopaminergic projections to the striatum and the cortex of BDL rats. The present data support an involvement of the dopaminergic system in mild HE and a possible beneficial effect of the neurosteroid DHEAS as a potential pharmacological treatment of mild HE.
    Full-text · Article · Feb 2013 · Acta histochemica
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    ABSTRACT: Hepatic encephalopathy (HE) is a complication that presents in as many as 28% of patients with cirrhosis, and reported up to ten years after the diagnosis of cirrhosis. Commonly, it is observed in patients with severe hepatic failure and is characterized by neuropsychiatric manifestations that can range in severity from a mild alteration in mental state to a coma; additionally, some neuromuscular symptoms can be observed. This complication of either acute or chronic hepatic disease is the result of a diminished hepatic reservoir and inability to detoxify some toxins that originate in the bowel. Today, the role of astrocytes, specifically the Alzheimer type II cells, is known to be very important in the pathogenesis of the hepatic encephalopathy, and will be reviewed later. In conclusion, the objectives of this review are: To understand the pathogenesis of hepatic encephalopathy, To recognize the precipitating factors, as well as preventive measures for the development of the hepatic encephalopathy, To describe the new classification of hepatic encephalopathy and its clinical implications, To recognize the clinical manifestations and stages of the disease, To understand the main diagnostic tests used to detect the hepatic encephalopathy, To describe the main therapeutic treatments of hepatic encephalopathy.
    Preview · Article · Nov 2002 · Annals of hepatology: official journal of the Mexican Association of Hepatology
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