CHAPTER

Farmakoterapi
Hyperlipidemic

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Learning Outcomes

1 Explain the importance of triglycerides

and cholesterol and their role in
atherosclerosis.
2 Discuss the treatment of
hyperlipidemia.
3 Explain the mechanism of action of five
different hypolipidemic drugs.

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Learning Outcomes
4 Explain why the HMG-CoA inhibitors
are more effective than other
hypolipidemic drugs.
5 Discuss the main adverse effects of
each hypolipidemic drug class and how
liver function tests are affected.
6 Explain the essential terminology
associated with atherosclerosis and
hypolipidemic drugs.

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Atherosclerosis
• Atherosclerosis is a
progressive condition
that leads to CAD and
PAD.

• Fat buildup inside the

arteries—plaque • CAD—coronary artery
disease
• PAD—peripheral
artery disease
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Statistics (American Heat Assoc.)

• 2005 stats:
– 2400 deaths each day
– 1 death every 37 seconds
– 1 out of every 5 deaths in the US

• http://sociedades.cardiol.br/socerj/area-
cientifica/CIRCULATIONAHA.108.191261
v1.pdf

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Atherosclerosis
• There are two • Plaque buildup can
types of plaque block arteries,
buildup: causing:
– Stable – Angina
– Unstable – TIA
– Stroke
– Intermittent
claudication

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Cholesterol
• Critical substrate for the body:
– Fundamental building block of steroid
hormones

– Essential for building cell membranes, the

myelin sheath, and the brain

– Core component of bile salts, which help

digest dietary fats

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Lipoproteins
• There are several
different
lipoproteins:
– Low-density lipoprotein (LDL)
– Very-low-density lipoprotein (VLDL)
– High-density lipoprotein (HDL)

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Triglycerides

• Main form of fat from diet

• Provide body with energy

• Chylomicrons:
– Very large lipoproteins that deliver
triglycerides to muscle and fat tissue

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Monitoring the Disease

• Risk factors for
atherosclerosis
– Age
– History of smoking
– Hypertension
– Premature menopause
– Obesity
– Diabetes mellitus
– Hyperthyroidism

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Monitoring the Disease

• The goals of treatment are:

– Lowering LDL cholesterol

– Reducing total serum cholesterol and
triglycerides

– Increasing HDL cholesterol

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Hypolipidemic Drugs

• There are five

groups of drugs
– HMG-CoA reductase
used in the inhibitors
management of – Cholesterol absorption
hyperlipidemia: inhibitors
– Bile acid sequestrants
– Fibric acid derivatives
– Nicotinic acid
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HMG-CoA Reductase Inhibitors

• Also referred to as statins
• MOA—inhibit enzyme that causes
cholesterol synthesis
• IND—adjunct to dietary treatment to
decrease total serum and LDL
cholesterol:
– Reduce LDL level up to 30%
– Raise HDL level up to 20%

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HMG-CoA Reductase Inhibitors

• An early, very important step in this
process is the conversion of acetyl-CoA
molecules into HMG-CoA, which is then
converted to mevalonic acid by HMG-CoA
reductase. Mevalonic acid is a rate-limiting
pivotal step in steroid and cholesterol
synthesis
• The liver makes two-thirds of the daily
cholesterol requirement.

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HMG-CoA Reductase Inhibitor

• All of the statins reduce LDL up to 30 percent.
When a greater reduction of LDL is required,
simvastatin (Zocor), atorvastatin (Lipitor), and
rosuvastatin (Crestor) reduce more than 45
percent; in fact, rosuvastatin and atorvastatin
have been demonstrated to reduce up to 60
percent.
• All of the statins raise the HDL level up to 20
percent. Again, simvastatin (Zocor), atorvastatin
(Lipitor), and rosuvastatin (Crestor) increase
HDL more than 30 percent.

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HMG-CoA Reductase Inhibitors

• Adverse effects:
– Headache, dizziness, alteration of taste,
insomnia, abdominal cramping and
photosensitivity
• May cause myalgias, leg ache, and
muscle weakness
• Contraindicated during pregancy

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Cholesterol Absorption Inhibitors

• Ezetimibe:
– MOA—blocks absorption of cholesterol
in the intestines
• Decreases VLDL
• Decreases circulating LDL cholesterol
– IND—treatment of hyperlipidemia in
conjunction with diet alteration

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Cholesterol Absorption Inhibitors

• Ezetimibe:
– Modestly reduces total cholesterol, LDL,
and triglyceride blood levels
– Ideal to combine with other
hypolipidemic drugs
– Adverse effects—abdominal pain,
fatigue, coughing, diarrhea, back pain,
and arthralgia

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Bile Acid Sequestrants

• MOA—bind bile salts and cholesterol
in the GI tract, preventing absorption
of both
• IND—hyperlipidemia:
– Increased elimination of bile salts, cholesterol,
and other fats in the feces.
– Adverse effects include GI disturbances,
severe constipation, and fecal impaction.
– Most serious adverse effect is intestinal
obstruction.
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Nicotinic Acid
• MOA—affects cholesterol synthesis
through a G proteinScoupled receptor:
– Inhibits triglyceride lipase
– Stimulates lipoprotein lipase
– Decreases free fatty acid release and
removes triglycerides
• IND—hyperlipidemia
• Adverse effects—flushing, nausea,
vomiting, and diarrhea
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Fibric Acid Derivatives

• Gemfibrozil:
– MOA—inhibits breakdown of fat into
triglycerides, and limits liver production
of triglycerides
– IND—to decrease triglycerides
– Adverse effects—nausea, vomiting,
diarrhea, and flatulence

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Hypolipidemic Drugs

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Preferred Therapy

• All hypolipidemic drugs are indicated as

adjunctive therapy to reduce elevated
cholesterol levels.
• HMG-CoA reductase inhibitors are the
most prescribed.
• Cholestyramine can also be used in the
treatment of partial biliary obstruction.

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Contraindications
• Systemic hypolipidemic drugs should not
be used in patients with liver dysfunction.

• Bile acid sequestrants should not be used

in patients with biliary obstruction.

• Statins should not be used in pregnant

women.

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Drug Interactions

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