Lesson C2 - Drugs used for the Treatment & Prevention of Atherosclerosis Flashcards
One of the functions of the coronary arteries in the heart is to supply oxygen-carrying blood to
the heart. In atherosclerosis, a fatty sludge infiltrates the inner coronary artery walls so that the
narrowed coronary artery will carry less blood
the narrowed coronary arteries cannot supply sufficient oxygen-carrying blood and the individual
experiences pain in the chest known as
angina pectoris
With increased blockage of the coronary artery,
a portion of the heart muscle may be deprived of oxygen-carrying blood leading to irreversible
damage to a portion of the heart muscle, a condition referred to as
myocardial infarction
commonly referred to as a heart attack
The three major types of lipids are
cholesterol (C), cholesterol esters (CE), and
triglycerides (TG).
Cholesterol is a
waxy, fat-like, ring-structured chemical present in all cells in the body. It is a
component of cell membranes and it is used for the synthesis of sex hormones, bile salts and
vitamin D.
Cholesterol only endangers health if the concentration in the blood is
elevated and if it infiltrates arterial walls, narrowing the lumen, decreasing blood flow, and hence
decreasing the amount of
oxygen available
Fats (C, CE and TG) are insoluble in water and they are therefore packaged for transport as
lipoproteins
Chylomicrons: These are the largest of the lipoproteins. They are formed in the intestine and
carry
triglycerides of dietary origin.
Very low density lipoproteins (VLDL): These lipoproteins are secreted by the liver and carry
triglycerides to body tissues.
Low density lipoproteins (LDL): LDL is sometimes referred to as the “bad” lipoprotein
because it is taken up by macrophages (large white blood cells) and play a role in increasing fatty
deposits inside the arteries and
thickening the inside of blood vessels.
High density lipoproteins (HDL): HDL is referred to as the “good” lipoprotein because it
transports cholesterol away from the arteries to the liver where cholesterol is biotransformed into
bile acids and excreted. In this way, HDL helps to protect against heart disease.
Secondary Hyperlipoproteinemias- These arise as complications of more generalized metabolic disturbances such as diabetes
mellitus, hypothyroidism, or
chronic ingestion of large amounts of alcohol.
Primary Hyperlipoproteinemias
-This type of hyperlipoproteinemia arises from an inherited single-gene defect inherited in a
predictable Mendelian fashion.
- Hyperlipoproteinemias may be caused by a combination of subtle genetic factors acting together with environmental insults.
Desirable levels of total cholesterol in adults is considered to be less than
200 mg/dL
5.5 mmol/L
Borderline to high levels in adults are considered to be
200-239 mg/dL
High levels in adults are considered to be greater than or equal to
240 mg/dL
An accurate heart-risk
assessment requires a detailed blood lipid (fat) analysis and a calculation of the
HDL/LDL ratio.
The following needs to be done in conjunction with lowering of lipids:
(a) Cessation of smoking.
(b) Therapy of hypertension.
(c) Institution of physical fitness program.
(d) Control of blood glucose in diabetics.
(e) Therapy of hypothyroidism.
(f) Therapy of alcohol dependence
The diet should be low in
cholesterol and saturated fats
There are four major drugs used in the treatment of the hyperlipoproteinemias
cholestyramine,
gemfibrozil, niacin (nicotinic acid) and lovastatin (and several related compounds, e.g. simvastatin).
Cholestyramine is a large, insoluble, positively-charged resin that binds bile acids in the intestine
and prevents their
reabsorption
Cholesterol is metabolized in the liver to bile acids which are then excreted into the
intestine
. Cholestyramine is therefore useful in hyperlipoproteinemias
in which
LDL levels are elevated
The major therapeutic use of gemfibrozil is in the treatment of
f hypertriglyceridemia
VLDL is
elevated. Gemfibrozil decreases levels of VLDL in plasma due to causing enhanced breakdown
of triglycerides and
decreased secretion of VLDL by the liver.
Niacin inhibits secretion of VLDL from the liver, and since LDL is a product of VLDL, it also
decreases production of
LDL.
Niacin (Nicotinic Acid, Vitamin B3)
is the most effective agent in increasing levels of HDL.
Lovastatin and related compounds – simvastatin, fluvastatin, atorvastatin and pravastatin (this class has been referred to as
statins
Lovastatin and related compounds inhibit the enzyme which catalyzes the rate-limiting step in
cholesterol biosynthesis. This enzyme is known as HMG-CoA reductase
Lovastatin and related compounds
is the most effective in lowering LDL and total cholesterol.
It is known that lowering cholesterol levels in
patients with high cholesterol levels decreases the risk of
coronary heart disease.
statins – have certainly resulted in major improvements in the treatment of the
hyperlipoproteinemias
