Page 653 - Basic _ Clinical Pharmacology ( PDFDrive )

CHAPTER 35 Agents Used in Dyslipidemia 639

HMG-CoA REDUCTASE INHIBITORS & REDUCTASE INHIBITORS &
BILE ACID-BINDING RESINS FENOFIBRATE

This synergistic combination is useful in the treatment of familial Fenofibrate appears to be complementary with most statins in
hypercholesterolemia but may not control levels of VLDL in some the treatment of familial combined hyperlipoproteinemia and
patients with familial combined hyperlipoproteinemia. other conditions involving elevations of both LDL and VLDL.
The combination of fenofibrate with rosuvastatin appears to
be especially well tolerated. Some other statins may interact
NIACIN & BILE ACID-BINDING RESINS unfavorably owing to effects on cytochrome P450 metabolism.
In any case, particular vigilance for liver and muscle toxicity is
This combination effectively controls VLDL levels during resin indicated.
therapy of familial combined hyperlipoproteinemia or other
disorders involving both increased VLDL and LDL levels. When
VLDL and LDL levels are both initially increased, doses of niacin COMBINATIONS OF RESINS, EZETIMIBE,
as low as 1–3 g/d may be sufficient in combination with a resin. NIACIN, & REDUCTASE INHIBITORS
The niacin-resin combination is effective for treating heterozygous
familial hypercholesterolemia. These agents act in a complementary fashion to normalize cho-
lesterol in patients with severe disorders involving elevated LDL.
The effects are sustained, and little compound toxicity has been
NIACIN & REDUCTASE INHIBITORS observed. Effective doses of the individual drugs may be lower
than when each is used alone; for example, as little as 1–2 g of
If the maximum tolerated statin dose fails to achieve the LDL niacin may substantially increase the effects of the other agents.
cholesterol goal in a patient with hypercholesterolemia, niacin
may be helpful. This combination may be useful in the treatment
of familial combined hyperlipoproteinemia. COMBINATIONS OF PCSK9 ANTIBODY
WITH STATIN AND EZETIMIBE
REDUCTASE INHIBITORS & EZETIMIBE
These agents can be used together to achieve maximal reduction of
LDL. Because of the need for parenteral administration of PCSK9
This combination is synergistic in treating primary hypercho-
lesterolemia and may be of use in the treatment of patients antibody and its expense, this therapy is reserved for patients with
with homozygous familial hypercholesterolemia who have some familial hypercholesterolemia or atherosclerotic vascular disease
receptor function. who do not respond adequately to other regimens.

SUMMARY Drugs Used in Dyslipidemia

Subclass, Pharmacokinetics, Toxicities,
Drug Mechanism of Action Effects Clinical Applications Interactions
STATINS
• Atorvastatin, Inhibit HMG-CoA reductase Reduce cholesterol synthesis and Atherosclerotic vascular Oral • duration 12–24 h • Toxicity: Myopathy,
simvastatin, upregulate low-density disease (primary and hepatic dysfunction • Interactions:
rosuvastatin, lipoprotein (LDL) receptors on secondary prevention) CYP-dependent metabolism (3A4, 2C9)
pitavastatin hepatocytes • modest reduction • acute coronary interacts with CYP inhibitors/competitors
in triglycerides syndromes
• Fluvastatin, pravastatin, lovastatin: Similar but somewhat less efficacious
FIBRATES
• Fenofibrate, Peroxisome proliferator- Decrease secretion of Hypertriglyceridemia, Oral • duration 3–24 h • Toxicity: Myopathy,
gemfibrozil activated receptor-alpha very-low-density lipoproteins low HDL hepatic dysfunction
(PPAR-α) agonists (VLDL) • increase lipoprotein
lipase activity • increase
high-density lipoproteins (HDL)
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