Loch Niacin Monster Fibrates & Niacin

2.3 – “Loch Niacin Monster”: FFibrates ibrates & Niac Niacin in • Triglycerides, transported in VLDL & chylomicrons, are hydrolyzed to free fatty acids in and around extrahepatic tissues by LPL (trident passengers = triglycerides; VLDL airship; Lipo-port Lighthouse = LPL). FFAs can be converted back to triglycerides & stored in adipose tissues (adipocyte sea foam). VLDLs depleted of triglycerides go back to liver. • Total triglycerides level on lipid panel measures VLDL & chylomicrons (trident passengers). Severe hypertriglyceridemia (>1000) can cause acute pancreatitis. Less severely elevated levels are associated with atherosclerotic coronary artery disease. While cholesterol is the major driver of this, unclear if lowering triglycerides will lower risk of CVD. Clinical benefits of lowering serum triglycerides by any means have not been convincingly demonstrated. • Fibrates o Gemfibrozil (gemmed steampunk jellyfish with fibrils), fenofibrate o Several physiologic effects, which together decrease circulating triglycerides by 35-50%: ▪ Lower triglycerides by targeting VLDL. Fibrates activate PPAR-α (newspaper); PPAR-α upregulates LPL at extrahepatic sites and downregulates other inhibitors of lipolysis (using newspaper to light lighthouse). Results in facilitated clearing of VLDL & chylomicrons of triglycerides in peripheral tissues (jellyfish attacking VLDL airship → trident wielders escaping). ▪ Decreases VLDL secretion from liver. ▪ Results in ↓LDL d/t decreased baseline VLDL. However, effect is modest & inconsistent (compare with statins) (sinking LDL ship) ▪ ↑HDL (HDL submarine lifted out of water). Directly activate ApoAI & ApoAII production by hepatocytes, allowing increased production of HDL; effect is mild. o Adverse effects ▪ Muscle toxicity, especially in pts also on statins (statin pirate eating drumstick) ▪ Modest increase in risk of cholesterol gallstones d/t increased bile cholesterol (seagulls on piles of stones). Should be used cautiously in patients with existing biliary tract disease. • Niacin = Vitamin B3 (steampunk sea monster “Nessie”) o At pharmacological doses, ↓VLDL secretion (sea monster eating VLDL ship over by liver base). Mechanism poorly understood. Can also decrease triglyceride release from adipose tissues. o ↓LDL d/t ↓VLDL (breaking LDL ship) o ↑HDL as much as 30%; most effective medication for increasing HDL currently available (lifting HDL sub). Mechanism poorly understood. Decreases HDL cholesterol transfer & delays HDL clearance o Adverse effects ▪ Poorly tolerated overall ▪ Cutaneous flushing and warmth mediated by prostaglandins on administration (sea monster is red & furnace driven; soldiers using a pro-slugger bat). Uncomfortable, but harmless. • NSAIDs can be used to prevent flushing from niacin. Aspirin ½ hour before niacin can help mediate this effect. ▪ ↑glucose, with hyperglycemia in already susceptible patients (rider with candy jar) ▪ ↑LFTs (white LFT flag). May cause severe hepatotoxicity, jaundice, fulminant hepatitis (burning liver base). Unpredictable. Regular monitoring of LFTs is mandatory. ▪ ↑urea. Occasionally precipitate gout (yellow needles – recurring symbol; yellow yarn for gout tophus) • Omega-3 fatty acids o Most often from fish oil (steampunk fish with omega-shaped tails). o Can decrease production of VLDL & ApoB; reduce serum triglycerides by as much as 30% (anchors & tridents in the water) o Has been shown to improve several CV risk factors, including mortality from CV disease, with little to no associated risk.