A 57-year-old man is seen in the office after an episode of acute pancreatitis. Hospital evaluation found no evidence of gallstones. The patient does not consume alcohol, but he does have a history of severe hypertriglyceridemia. He was treated with a fibrate medication in the past but could not tolerate it due to liver toxicity. He has no history of diabetes mellitus or hypertension. On examination, the patient has no abdominal tenderness. Laboratory studies show normal hepatic and pancreatic enzyme levels, but the patient again has a severely elevated triglyceride level. The physician prescribes the appropriate medications and explains that the patient is likely to experience skin flushing and warmth after taking the pills. Which of the following is the primary agent mediating these side effects?

Question

A 57-year-old man is seen in the office after an episode of acute pancreatitis.  Hospital evaluation found no evidence of gallstones.  The patient does not consume alcohol, but he does have a history of severe hypertriglyceridemia.  He was treated with a fibrate medication in the past but could not tolerate it due to liver toxicity.  He has no history of diabetes mellitus or hypertension.  On examination, the patient has no abdominal tenderness.  Laboratory studies show normal hepatic and pancreatic enzyme levels, but the patient again has a severely elevated triglyceride level.  The physician prescribes the appropriate medications and explains that the patient is likely to experience skin flushing and warmth after taking the pills.  Which of the following is the primary agent mediating these side effects?

Quizplus · Accepted Answer

Nicotinic acid, or niacin, has been used in the treatment of hyperlipidemia for almost 4 decades. It is effective in raising HDL cholesterol levels, as well as lowering triglycerides and LDL levels. Niacin's main side effects are cutaneous flushing, warmth, and itching; these are primarily mediated by release of prostaglandins (particularly PGD₂ and PGE₂). Aspirin, which inhibits prostaglandin synthesis, can significantly reduce these side effects if given 30-60 minutes before niacin administration. The side effects are also reduced with slow-release preparations or if niacin is taken with meals. They are worst when niacin is first initiated and tend to fade over time due to tachyphylaxis. (Choice A) Vancomycin-induced "red man syndrome" is mediated by histamine release due to non-IgE- mediated mast cell degranulation. (Choice B) Platelet-activating factor is a powerful phospholipid activator produced by a number of cells, including neutrophils, basophils, platelets, and endothelial cells. It is a mediator of platelet aggregation. (Choice D) Serotonin syndrome is a potential side effect of selective serotonin reuptake inhibitors. It is characterized by abnormal mental status, autonomic hyperactivity, and muscular rigidity with hyperreflexia. (Choice E) Substance P is a polypeptide neurotransmitter involved in mediating pain signals in the peripheral and central nervous systems. Topical capsaicin causes release of substance P, resulting in burning pain in the area of application. Prolonged use causes depletion of substance P, and the pain diminishes with time. Educational objective: Niacin is used in the treatment of hyperlipidemia. It increases HDL levels and decreases LDL levels and triglycerides. Niacin causes cutaneous flushing, which is mediated by prostaglandins and can be diminished by pretreatment with aspirin. __________ References: Aspirin reduces cutaneous flushing after administration of an optimized extended-release niacin formulation. (http://www.ncbi.nlm.nih.gov/pubmed/17323787) Niacin use and cutaneous flushing: mechanisms and strategies for prevention. (http://www.ncbi.nlm.nih.gov/pubmed/18375236)

A 57-Year-Old Man Is Seen in the Office After an Episode