Statin’s mnemonic

Mnemonic for Statin's drugs

Mnemonic for Statin’s drugs

Statins (or HMG-CoA reductase inhibitors) are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been associated with cardiovascular diseases, and statins are therefore used in the prevention of these diseases. Research has found that statins are most effective for treating cardiovascular disease (CVD) (secondary prevention), with questionable benefit in those without previous CVD, but with elevated cholesterol levels.

Mechanism of action

  • Inhibiting cholesterol synthesis

By inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the liver. This is significant because most circulating cholesterol comes from internal manufacture rather than the diet. When the liver can no longer produce cholesterol, levels of cholesterol in the blood will fall. Cholesterol synthesis appears to occur mostly at night, so statins with short half-lives are usually taken at night to maximize their effect. Studies have shown greater LDL and total cholesterol reductions in the short-acting simvastatin taken at night rather than the morning, but have shown no difference in the long-acting atorvastatin.

  • Increasing LDL uptake

In rabbits, hepatocytes (liver cells) sense the reduced levels of liver cholesterol and seek to compensate by synthesizing LDL receptors to draw cholesterol out of the circulation. This is accomplished via protease enzymes that cleave a protein called “membrane-bound sterol regulatory element binding protein”, which migrates to the nucleus and causes increased production of various other proteins and enzymes, including the LDL receptor. The LDL receptor then relocates to the liver cell membrane and binds to passing LDL and VLDL particles (the “bad cholesterol” linked to disease). LDL and VLDL are drawn out of circulation into the liver, where the cholesterol is reprocessed into bile salts. These are excreted, and subsequently recycled mostly by an internal bile salt circulation.

Adverse effects
Some patients on statin therapy report myalgias, muscle cramps with the potential for rhabdomyolysis (the pathological breakdown of skeletal muscle) leading to acute renal failure or, less frequently, gastrointestinal or other symptoms. Liver enzyme derangements, typically in about 0.5%, are also seen at similar rates with placebo use and repeated enzyme testing, and generally return to normal either without discontinuance over time or after briefly discontinuing the drug. Multiple other side effects occur rarely; typically also at similar rates with only placebo in the large statin safety/efficacy trials. Two randomized clinical trials found cognitive issues, while two did not; recurrence upon reintroduction suggests these are causally related to statins in some individuals. A Danish case-control study published in 2002 suggested a relationship between long-term statin use and increased risk of nerve damage or polyneuropathy, but suggested this side effect is “rare, but it does occur”; other researchers have pointed to studies of the effectiveness of statins in trials involving 50,000 people which have not shown nerve damage as a significant side effect.

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