The role of statin drugs in combating cardiovascular diseases



Suresh Pichandi et al. / Int J Cur Sci Res. 2011; 1(2): 47 - 56.

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Increasing LDL uptake

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.

3.Atorvastatin

Atorvastatin is a cholesterol-lowering medication that blocks
the production of cholesterol (a type of fat) in the
body.Atorvastatin reduces low-density lipoprotein (LDL)
cholesterol and total cholesterol in the blood. Lowering your
cholesterol can help prevent heart disease and hardening of the
arteries, conditions that can lead to heart attack, stroke,and
vascular disease.Atorvastatin is used to treat high
cholesterol.Atorvastatin is also used to lower the risk of stroke,
heart attack, or other heart complications in people with coronary
heart disease or type 2 diabetes.

In rare cases, atorvastatin can cause a condition that results in
the breakdown of skeletal muscle tissue. This condition can lead to
kidney failure. Call your doctor at once if you have unexplained
muscle pain or tenderness, muscle weakness, fever or flu
symptoms, and dark colored urine.This medication can cause birth
defects in an unborn baby. Do not use if you are pregnant. Use an
effective form of birth control, and tell your doctor if you become
pregnant during treatment.Do not take atorvastatin if you are
pregnant or breast-feeding, or if you have liver disease.

Atorvastatin is used to treat dyslipidemias,which are disorders
characterized by abnormal levels of lipids in the blood. Specifically,
atorvastatin is used along with dietary therapy to decrease
elevated serum total cholesterol and low-density lipoprotein
cholesterol (LDL-C; so-called “bad” cholesterol), apolipoprotein B
(apo B), and triglyceride concentrations. It is also used to increase
concentrations of high-density lipoprotein cholesterol (HDL-C; the
so-called “good” cholesterol).

Familial hypercholesterolemia is an inherited condition
characterized by high cholesterol levels. Atorvastatin is used to
lower cholesterol in individuals as young as ten years who have
familial hypercholesterolemia (LDL-C levels >than 190 mg/dl (or
>than 160 mg/dl) and who have a family history of coronary heart
disease (CHD).

The lipid-lowering effect of atorvastatin reduces the risk of CHD.
Therefore, atorvastatin is used as primary prevention of heart
attack,stroke, or angina in people who have multiple risk factors
for CHD: age, smoking,high blood pressure,low HDL-C, or a family
history of early CHD. Primary prevention refers to interventions
that prevent the first occurrence of a disease or condition. Primary
prevention of CHD is done for people who have no clinical evidence
of cardiovascular disease but who at risk. Atorvastatin is also used in
primary prevention of cardiovascular events (e.g., heart attack,
stroke)in people with type 2 diabetes.

Atorvastatin is also used as secondary prevention. Secondary
prevention refers to interventions that protect against recurrence of
a disease or condition. Secondary prevention with atorvastatin is
done in people who have CHD. In these people, atorvastatin is used
to reduce the risk of heart attack, stroke, or hospitalization for
congestive hear failure (CHF). Atorvastatin has also been shown to
slow the progression of coronary atherosclerosis in patients with
CHD [7].

Atorvastatin is taken as tablets by mouth once a day, with or
without food. Tablets containing 10 mg, 20 mg, 40 mg, or 80 mg are
available. Low doses may be given initially, with gradual escalation
depending on changes in blood lipid concentrations and the
presence or absence of side effects.

4.Fluvastatin

Fluvastatin (trade names Lescol, Canef, Vastin) is a member of the
drug class of statins, used to treat hypercholesterolemia and to
prevent cardiovascular disease. Fluvastatin is an enzyme blocker
(HMG-CoA reductase inhibitor), also known as a "statin". It is used
along with a proper diet to help lower cholesterol and fats
(triglycerides) in the blood. In general, this drug is prescribed after
non-drug treatment options have not been fully successful at
lowering cholesterol (e.g., diet change, increase in exercise, weight
loss if overweight). Reducing cholesterol and triglycerides help
prevent strokes and heart attacks.

High blood LDL cholesterol is first treated with exercise, weight
loss, and a diet low in cholesterol and saturated fats. When these
measures fail, cholesterol-lowering medications such as fluvastatin
can be added. The National Cholesterol Education Program (NCEP)
has published treatment guidelines for use of these medications.
These treatment guidelines take into account the level of LDL
cholesterol as well as the presence of other risk factors such as
diabetes, hypertension, cigarette smoking, low HDL cholesterol
level, and family history of early coronary heart disease. Blood
cholesterol determinations are performed in regular intervals
during treatment so that dosage adjustments can be made.

Fluvastatin is generally well- tolerated by most patients. The
medication should be used with caution in patients with alcohol or
liver diseases. Persistently abnormal liver blood tests are rare, but
may lead the doctor to discontinue the medication. Rare cases of
muscle inflammation (myositis) and breakdown have been
reported with other medications in the same class. Muscle
breakdown causes the release of muscle protein (myoglobin) into
the blood and kidney tubules, and may result in kidney failure [8].

Side effects are rare. Minor side effects include constipation,
diarrhea, fatigue, gas, heartburn, headache, insomnia, and joint
pains. Major side effects include abdominal pain or cramps, blurred
vision, dizziness, easy bruising or bleeding, itching, muscle pain or
cramps, rash, and yellowing of the skin or eyes.



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