Lipid Lowering Drugs

Statins are the mainstay of HLD treatment. Always 1st line. Dose-dependent relationship with lowering LDL. The MOA is blocking new cholesterol synthesis by inhibiting HMG CoA Reductase. Side effects include hepatotoxicity and myopathy (esp when used w/ fibrates). Statins are first and second line for Hyperlipidemia, whereas the other classes are mostly taught for historical purposes. 

PCSK9 Inhibitors are new drugs that are great at lowering LDL. It does so by making LDL receptors invincible to degradation. Side effects include some neuro-related things. Unfortunately this highly effective class is rarely used because they cost thousands of dollars. May someday replace Statins. 

Niacin is good at raising HDL. It makes your skin flush though. Niacin is the opposite of NSAIDS (it raises prostaglandins). Prostaglandins apparently make your skin flush. Pre-treatment with aspirin prevents flushing. 

Fibrates are good at lowering TG. They upregulate LPL, which sucks TG out of the blood. It also activates PPAR-a to induce HDL synthesis and drop LDL synthesis. Side effects include hepatotoxicity, myopathy and cholesterol gallstones (Fibrates block cholesterol 7a-hydroxylase). Only used for type 1 familial hypertriglyceridemia!

Bile Acid Resins are effective treatments, but their nasty GI side effects make them borderline untolerable. They work by blocking the reabsorption of bile salts, fat and cholesterol, so you poop out all of your cholesterol and intake less fat. Super potent drugs.

Ezetimibe is a less-potent Bile Acid Resin. It only prevents cholesterol absorption in the small intestine, not lipid absorption.

Fish Oil (Omega-3 FAs) are okay at improving lipid levels. Decreases LDL synthesis. Efficacy is marginal. 

Complication (Type)

Xanthoma  (1, 2, 3, 4)- pale yellow skin growths seen with severe hypertriglyceridemia. They are filled with foam cells. 

Lipemia Retinalis (1) - on fundoscopy, the vessels turn white

Milky Plasma (1) - huge layer of lipids when you centrifuge blood sample

Achilles Xanthoma (2) - xanthomas on the achilles tendon

Xanthelasma (2) - xanthomas near the face

Tuberous Xanthomas (2, 3) - big bulbous xanthomas over joints

Corneal Arcus (2)- white ring around the cornea

Palmar Xanthomas (3) - xanthomas on the palms

Abetalipoproteinemia is a rare AR lipid disease. There is a mutation in the Microsomal Transfer Protein (MTP) which manufactures B48 and B100. This means that their bodies can’t synthesize Chylomicrons or VLDL (thus no IDL or LDL either). Without Chylomicrons the gut enterocytes are unable to send dietary fat to the body! Fat accumulates inside the enterocytes, and essentially blocks the absorption of fats or fat-soluble vitamins (causes steatorrhea). These patients will present as infants with failure to thrive. Vitamin E deficiency is particularly problematic. It causes retinitis pigmentosa, spinocerebellar degeneration, acanthocytosis and ataxia. The diagnosis is made by genetic testing, but lipid panels will show very low levels of Chylomicrons, LDL and VLDL. Manage their condition by avoiding long-chain fatty acids and giving Vitamin E supplements. Recall that short and medium-chain fatty acids don’t need no stinking Chylomicrons.