Hepatotoxicity associated with sustained-release niacin

Dalton, Thomas A.; Berry, Robert S.

doi:10.1016/0002-9343(92)90689-9

Cited by 88 publications

(31 citation statements)

References 12 publications

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“…Side effects include flushing, nausea, vomiting, decreased appetite, abdominal discomfort, diaphoresis, hypotension, hyperglycemia, and hepatic dysfunction. [1][2][3] Some patients prefer the sustained-release preparations, which cause less flushing. However, hepatitis may develop after only a short course with low doses of the sustained-release preparations.…”

Section: Discussionmentioning

confidence: 99%

“…However, hepatitis may develop after only a short course with low doses of the sustained-release preparations. [1][2][3] Pathologically, niacin hepatotoxicity causes centrolobular cholestasis and parenchymal necrosis. Hepatotoxicity is dose related and not a hypersensitivity response.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5][6] The sonographic alterations detected within the liver resulting from viral and other forms of acute hepatitis have been described since 1980, although the alterations were not attributed to niacin toxicity. 7 We report the sonographic appearance of a "starry sky liver" in a single patient with niacininduced hepatitis.…”

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confidence: 99%

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Ultrasonographic findings in niacin-induced hepatitis.

Scheer

Perlmutter²,

Ross³

et al. 1999

Journal of Ultrasound in Medicine

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Niacin-induced hepatitis is a rare complication in patients treated with sustained-release niacin preparations to control hyperlipidemia and hypercholesterolemia. [1][2][3][4][5][6] The sonographic alterations detected within the liver resulting from viral and other forms of acute hepatitis have been described since 1980, although the alterations were not attributed to niacin toxicity. 7 We report the sonographic appearance of a "starry sky liver" in a single patient with niacininduced hepatitis. CASE REPORTA 50 year old man was admitted with a 4 week history of recurring sharp lower abdominal pain with nausea. On the day of admission these symptoms became more acute. He was seen by his private medical doctor and found to have a blood pressure of 80/40 mm Hg and was sent to the emergency department for further evaluation.Eight weeks prior to admission the patient had begun a regimen of 500 mg of sustained-release niacin for hypercholesterolemia. The daily dosage of niacin was gradually increased over several weeks to a total dose of 2000 mg/day. The patient did not drink alcohol, and he was taking no other medications. Physical examination revealed a low grade fever, tachycardia, and hypotension. The sclerae were anicteric. The right upper quadrant was tender; however, no hepatosplenomegaly was present.On admission, an abdominal ultrasonographic examination was obtained to determine if cholecystitis, bile duct obstruction, or an abdominal aortic aneurysm was present. The sonogram demonstrated a markedly hypoechoic liver (Fig. 1). The liver echogenicity was decreased compared to that of the normal kidneys (Fig. 2). Relatively echogenic portal triads were conspicuous against the hypoechoic hepatic background. The size and contour of the liver, spleen, and aortic aorta were normal. The common duct had a normal diameter of 2 mm, and no dilated intrahepatic biliary radicles were present. No hepatic masses were demonstrated. The gallbladder contained three small polyps but otherwise had a normal ultrasonographic appearance. No ascites was present.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Ultrasonographic findings in niacin-induced hepatitis.

Scheer

Perlmutter²,

Ross³

et al. 1999

Journal of Ultrasound in Medicine

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“…В отдельных случаях гипотензия или гипоперфузия могут быть лекарственно обусловле-ны воздействием ниацина [9], кокаина, метамфета-мина [26]. Физикальные изменения при этом у па-циентов могут отсутствовать или выявляться толь-ко на ЭКГ.…”

Section: этиология острой печеночной недостаточностиunclassified

Acute Liver Failure in Adults: Etiology, Clinical Manifestations, Methods of Correction

Лукашик¹,

Karpov²

2017

Arhivʺ vnutr. med.

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РезюмеВ статье проведена систематизация информации об этиологии, эпидемиологии и клинических проявлениях острой печеночной недостаточ-ности. Приведены статистические данные о частоте ее встречаемости при разных нозологических формах, описаны наиболее часто разви-вающиеся осложнения, изложены основные подходы к терапии. Цель обзора -улучшить осведомленность врачей об острой печеночной недостаточности. AASLD -Американская ассоциация по изучению заболеваний печени, АН -аналоги нуклеоз(т)идов, ВГА -вирус гепатита А, ВГВ -вирус гепатита В, ВГЕ -вирус гепатита Е, ВГС -вирус гепатита С, ВЧД -внутричерепное давление, ОПН -острая печеночная недостаточность, ОЦК -объем циркулирующей крови, ПН -печеночная недостаточность, ПЭ -печеночная энцефалопатия, СВР -системная воспалительная реакция, ЦП -цирроз печени Ключевые слова: ВведениеОстрая печеночная недостаточность (ОПН) ха-рактеризуется острым, быстро прогрессирующим поражением печени с высоким процентом леталь-ных исходов. Прогноз заболевания во многом за-висит от своевременной диагностики и уточнения повреждающего фактора, ранней правильно на-значенной этиотропной и патогенетической те-рапии. Литературные данные по ОПН постоянно обновляются. Представленный обзор основан на результатах анализа опубликованных исследований в оте чественной и зарубежной литературе, включая современные международные подходы к ведению пациентов с острой печеночной недостаточностью, рекомендациях, базирующихся на мнении отдель-*Контакты/Contacts.

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“…12,13 Other issues include gastrointestinal (GI) side effects 14 and hepatotoxicity. [15][16][17] Additionally, patients need to take large quantities of the drug (grams per day) due to its short half-life, which also leads to compliance issues. To alleviate this associated flushing side effect, an extended release formulation of nicotinic acid (NIASPAN) is available by prescription.…”

mentioning

confidence: 99%

Discovery of a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia

Qin¹,

Rao²,

Chen³

et al. 2010

ACS Med. Chem. Lett.

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Nicotinic acid has been used clinically for decades to control serum lipoproteins. Nicotinic acid lowers very low-density lipoprotein (VLDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa), and it is also effective in raising high-density lipoprotein (HDL)-cholesterol. However, nicotinic acid has several side effects in clinical use. The most notable is intense cutaneous vasodilation "flushing" on the upper body and face. We discovered a pyranopyrimidinedione series to be nicotinic acid receptor agonists. A potent nicotinic acid receptor agonist from this series {5-(3-cyclopropylpropyl)-2-(difluoromethyl)-3H-pyrano[2,3-d]pyrimidine-4,7-dione}with reduced flushing side effect in dogs was identified.KEYWORDS Nicotinic acid, agonist, flushing, dyslipidemia, VLDL, HDL N icotinic acid (NA) has been used as a drug to lower very low-density lipoprotein (VLDL)-cholesterol, lowdensity lipoprotein (LDL)-cholesterol, and lipoprotein-a (LPa), and it is also effective in raising high-density lipoprotein (HDL)-cholesterol in plasma. [1][2][3][4][5][6][7] Studies have demonstrated that nicotinic acid is able to reduce the rate of nonfatal myocardial infarction (MI) and decrease total mortality of patients with a previous history of heart disease. 8,9 In combination with statins, nicotinic acid provided better therapeutic benefit than taking statins alone. 10,11 Despite all of these encouraging clinical benefits, nicotinic acid is known to have side effects that limit its clinical use. The most notable is a severe cutaneous flushing sensation on the upper body and face. 12,13 Other issues include gastrointestinal (GI) side effects 14 and hepatotoxicity. [15][16][17] Additionally, patients need to take large quantities of the drug (grams per day) due to its short half-life, which also leads to compliance issues. To alleviate this associated flushing side effect, an extended release formulation of nicotinic acid (NIASPAN) is available by prescription. 18 More recently, a combination of extended release nicotinic acid and an antagonist of the prostaglandin D2 receptor (DP) (Tredaptive) has been introduced in Europe. Studies have shown that patients taking this combination of drugs experienced reduced flushing symptoms in comparison with taking nicotinic acid alone. 19 Nicotinic acid binds with high affinity to a G-proteincoupled receptor, GPR109a, expressed in human adipose tissue. A highly related G-protein-coupled receptor, GPR109b, that shares 95% identity and is only expressed in human and chimpanzee, was also identified. [20][21][22][23] GPR109b is a low affinity receptor for nicotinic acid. It has been hypothesized that activation of GPR109a by nicotinic acid decreases intracellular cAMP levels in adipocytes. As a downstream effect, protein kinase A activity is reduced, leading to a decrease in hormone sensitive lipase activity, eventually causing the reduction of intracellular triglyceride (TG) hydrolysis and free fatty acid (FFA) secretion. This decrease of FFA production from adipo...

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Hepatotoxicity associated with sustained-release niacin

Cited by 88 publications

References 12 publications

Ultrasonographic findings in niacin-induced hepatitis.

Ultrasonographic findings in niacin-induced hepatitis.

Acute Liver Failure in Adults: Etiology, Clinical Manifestations, Methods of Correction

Discovery of a Potent Nicotinic Acid Receptor Agonist for the Treatment of Dyslipidemia

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