Statins are competetive inhibitors of the enzyme HMG-CoA Reductase.  This enzyme is the rate-limiting step in the production of cholesterol in the liver. 

By blocking cholesterol synthesis by the liver, there is an accompanying up-regulation of LDL receptors because the tissue becomes more desperate to acquire cholesterol. (Recall: the liver needs cholesterol for the synthesis of bile!)  Because the liver cannot synthesize it anymore, it must take it up from the blood.  Furthermore, VLDL synthesis slows down because cholesterol is a required component of VLDL and is no longer being synthesized adequately.  These two effects lower blood cholesterol levels. 

The statins inhibit HMG-CoA Reductase.  

Lovastatin

Atorvastatin

overall, statins have a low incidence of adverse effects!

Nevertheless, statins (lovastatin, atorvastatin) may cause hepatotoxicity.  Therefore, check liver function when starting these drugs.  If liver aminotransferase levels reach 3x normal, discontinue drug!  They may also cause myopathy: you will see myoglobinuria due to rhabdomyolysis (rare).  It can also be tested by measuring CK-mm levels.  Remember: this unfortunate side-effect is increased if niacin or gemfibrozil are combined with the statin.

Statins are category X drugs (teratogens) that must be avoided in pregnancy!

Lovastatin is a statin drug and is therefore an HMG-CoA Reductase inhibitor.  It is used in cases of hyperlipidemia involving high LDL.  It is also used in cases of atherosclerosis and in the prevention of heart disease or stroke in at-risk patients.

NOT IN PREGNANT PATIENTS

Acute pancreatitis

(this is especially true with TGs of greater than 1000mg/dL)

In this condition there is auto-activation of pancreatic enzymes such as trypsin and pancreatic lipase.  This digests pancreatic tissue leading to fat necrosis and a great deal of pain.  Look for a patient with severe epigastric pain, hemorrhagic discoloration to the flanks and umbilicus, steatorrhea, and nausea & vomiting.

The most common cause of pancreatitis is gallstones, hypertriglyceridemia is one of the more common causes and found in the "get smashed" mnemonic.

Thiazide diuretics (hydrochlorothiazide)

Oral Contraceptives

Glucocorticoids

Ethanol (alcoholics often have hyperlipidemia)

Bile binding resins (cholestyramine) release Cl- in exchange for bile acids in the intestinal lumen and prevent their reabsorption.  Normally 95% of bile acids are reabsorbed and only 5% excreted.  The bile-binding resins promote the excretion of up to 50% of bile acids. 

This necessitates an increase in bile production by the liver.  How does the liver make bile?  from cholesterol!  So now the liver up-regulates LDL receptors and sequesters cholesterol from the blood to replenish the lost bile acids!  This lowers LDL levels. 

Resins do not decrease HDL, VLDL, or triglycerides.  However, they may promote hypertriglyceridemia in some patients!

Bile bindings have a moderate to high efficacy, though less than that of statins.  Their beneficial effects are only for LDL levels, and they may actually increase TG levels.

Cholestyramine is a bile binding resin.

Bile binding resins commonly cause constipation.  They may also cause hypertriglyceridemia and hyperchloremic acidosis.  (Recall: hyperchloremia is frequently associated with acidosis because of the body's attempts to maintain elecroneutrality).  Cholestyramine gives off Cl- in exchange for binding bile.  The Cl- is absorbed in the intestine, causing this hyperchloremia.

Resins can also bind other drugs given orally, preventing their absorption! (ex: digoxin, warfarin, thiazides, aspirin, and even vitamin K!)

Fibric acid derivatives (Gemfibrozil) are used in cases of isolated hypertriglyceridemia.

Fibrates are often combined with niacin to yield greater results.

Gemfibrozil is a fibric acid derivative.  It activates transcription factors in the nucleus that up-regulate the synthesis of Lipoprotein Lipase.  This causes an increase in VLDL removal from the plasma and a large reduction in circulating triglyceride levels.

good oral bioavailability

Ezetimibe is a inhibitor of intestinal sterol absorption.  It acts on the brush border of the intestine and inhibits the absorption of cholesterol (as well as other sterols). 

The efficacy is low to moderate, so it is never used on its own.  Most commonly it is combined with a statin, resulting in a synergistic effect that can reduce LDL levels up to 70%.

Always start with an attempt at lifestyle and diet changes unless both TGs and cholesterol are high.

If diet changes do not work, then look to the drugs.  Here, start with statins unless patient is pregnant, or a young woman (might get pregnant) or suffering from liver disease, kidney insufficiency.

Niacin! because it competes with urate for excretion

*they both utilize the acid transporter

Niacin worsens peptic ulcers by stimulating histamine release.  Remember histamine is a very potent stimulus for the release of gastric acid!

Niacin also promotes a state of insulin resistance, furthering the danger of hyperglycemia in diabetic patients.

Also recall: niacin competes with uric acid for renal excretion, so it can worsen gout.