Rifampicin and the relief of pruritus of hepatic cholestatic origin

Airede, A. K. I.; Weerasinghe, H. D.

doi:10.1111/j.1651-2227.1996.tb14176.x

Cited by 3 publications

(2 citation statements)

References 6 publications

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“…Numerous candidate pruritogens are present in bile and up-regulated in cholestatic patients, including opioids, lysophosphatidic acid, bilirubin, and bile acids (BAs). Therapies targeting these mechanisms, such as opioid antagonists, rifampicin, and BA-binding resins like cholestyramine, are frontline therapy for cholestatic itch (6)(7)(8)(9).…”

mentioning

confidence: 99%

MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus

Meixiong

Vasavda

Snyder

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

113

119

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Patients suffering from cholestasis, the slowing or stoppage of bile flow, commonly report experiencing an intense, chronic itch. Numerous pruritogens are up-regulated in cholestatic patient sera, including bile acids (BAs). Acute injection of BAs results in itch in both mice and humans, and BA-modulating therapy is effective in controlling patient itch. Here, we present evidence that human sensory neuron-expressed Mas-related G protein-coupled receptor X4 (MRGPRX4), an orphan member of the Mrgpr family of GPCRs, is a BA receptor. Using Ca2+ imaging, we determined that pathophysiologically relevant levels of numerous BAs activated MRGPRX4. No mouse Mrgpr orthologs were activated by BAs. To assess the in vivo relevance of BA activation of MRGPRX4, we generated a humanized mouse with targeted expression of MRGPRX4 in itch-encoding sensory neurons. BAs activated MRGPRX4+ sensory neurons at higher levels compared with WT neurons. Compared with control animals, MRGPRX4+ mice scratched more upon acute injection of BAs and in a model of cholestatic itch. Overall, these data suggest that targeting MRGPRX4 is a promising strategy for alleviating cholestatic itch.

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mentioning

confidence: 99%

MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus

Meixiong

Vasavda

Snyder

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

113

119

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“…Second-line agents include rifampin and phenobarbital. Both modify bile acid metabolism through microsomal enzyme induction, and in addition, phenobarbital exerts an antipruritic effect through its sedative action [1, [4][5][6]. Third-line agents include opioid antagonists (Naloxone, Nalmefene, Naltrexone), the serotonin antagonist ondansetron, s-adenosyl methionine (SAMe), and hypnotic agents such as propofol.…”

Section: Introductionmentioning

confidence: 99%

Pruritus

Franco

1999

Curr Treat Options Gastro

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The treatment of patients with pruritus of liver disease poses a challenge to the clinician. Resins (cholestyramine or colestipol) in quantities of 4 to 16 grams a day should be the initial agents used. In those who remain refractory, diphenhydramine should be added, although sedation may limit the use of higher doses. If symptoms still persist, rifampin up to 600 mg/day can be added to the above regimen with close monitoring of hepatic function. If, despite this combination, pruritus persists and quality of life remains poor, experimental therapies in the form of oral opioid antagonists, and orthotopic liver transplantation should be considered.

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Itch complicating malignant diseases

Żylicz¹,

Krajnik²

2011

Supportive Oncology

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Rifampicin and the relief of pruritus of hepatic cholestatic origin

Cited by 3 publications

References 6 publications

MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus

MRGPRX4 is a G protein-coupled receptor activated by bile acids that may contribute to cholestatic pruritus

Pruritus

Itch complicating malignant diseases

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