Lipid Lowering Agents Flashcards
Most effective drugs for lowering LDL
HMG-CoA Reductase
Inhibitors (Statins)
• Nonlipid beneficial cardiovascular actions of statins
– Promote plaque stability
– Reduce the risk for cardiovascular (CV)
events
Statins can show
- Reduction of LDL cholesterol
- Elevation of HDL cholesterol
- Reduction of triglyceride levels
Statin MOA
Mechanism of action: -Competitive inhibitors of hydroxymethylgluta ryl (HMG) CoA reductase, the ratelimiting step in cholesterol biosynthesis.
***Increase the # of
LDL receptors on
hepatocytes.
Statins should be adminstered in the
evening – cholesterol synthesis
normally increases during the night
Statins have a significant
first pass effect
Lovastatin absorption is increased
food
statin ADR
Common – headache, rash,
GI disturbances
• Rare AE: myopathy/rhabdomyolysis,
hepatotoxicity.
Stain interactions
Drug interactions
– With other lipid-lower drugs, drugs that inhibit CYP3A4.
Statin routine monitoring of
f serum creatine
kinase (CK) levels is not recommended.
Check baseline aminotransferase levels
prior to initiating
statin therapy; do not
routinely monitor when on statins
Recheck lipid panel
6 to 8 weeks after
initiation or change of treatment
Hepatic Dysfunction
in statin therapy - Clinical studies -
0.5 to 3.0 percent occurrence of
persistent elevations in aminotransferases,
primary in the first 3 months, dose dependent.
• Rare – severe liver injury (typically 3 to 4 months
after initiation).
statin previous ____
LFT prior to initiation (routine monitoring
of LFT now not necessary).
ALT level more than 3x the upper level of
normal, confirmed on two occasions.
– Use different
statin, dose reduction, alternative day
therapy
Statin can cause
muscle adverse events
mild muscle injury
muscle aches, tenderness, or
weakness can localize to certain muscle
groups or be diffuse.
myositis
– muscle inflammation, moderate
elevation of CK
rhabdomyoloysis
– muscle disintegration
or dissolution.
• If patient reports muscle symptoms,
btain
a CK blood level
• CK value is > 10x increase
ULN: stop
therapy
CK value is < 10x increase ULN
can
continue, follow symptoms and CK level
weekly, OR stop and re-evaluate
• Routine monitoring of CK in asymptomatic
patients is
not necessary.
Niacin uncommonly
Uncommonly used – lower LDL
Niacin increases
• Increases HDL levels
– Does little to improve outcomes – AIM-HIGH trial
2011
Niacin combo with __ no longer used
Combo of niacin with statin – no longer used
Niacin concerns about
Concerns about niacin monotherapy (AIMHigh trial)
Niacin can rais
Can raise HDL – but generally no recommendation to use for this
Niacin use is alos
limited as it is not well-tolerated
niacin ADR
– Skin (flushing, itching)
• Intense flushing initially; can pretreat with aspirin
325mg 30 minutes before each dose.
***Decreased with sustained-release (SR) version of
niacin
– Gastrointestinal (gastric upset, n/v, diarrhea)
– Hepatotoxicity (severe liver damage has
occurred) – baseline LFTs, and monitor
– Hyperglycemia
– Gouty arthritis
Niacin baseline ___ should be obtained and monitored
LFT
Bile Acid Sequestrants MOA
MOA: bind bile acids in the intestine, resulting in
interruption of the reabsorption of bile acids
Bile Acid Sequestrants reduction in
Reduction in cholesterol pool lowers intrahepatic
cholesterol, promotes synthesis of LDL receptors.
Receptors bind LDL from the plasma, causing
further reduction in blood cholesterol.
Bile Acid Sequestrants reduce
Reduce LDL cholesterol levels
Bile Acid Sequestrants used primarliy as adjucts to
Used primarily as adjuncts to statins.
Bile Acid Sequestrants use often limited as
side effects – GI (nausea,
bloating, cramping, increase in liver enzymes)
Cholesterol Absorption Inhibitor - Ezetimibe
– Impairs dietary and biliary cholesterol
absorption at he brush border of the intestines
– Most commonly prescribed to lower LDL-C after statins
Cholesterol Absorption Inhibitor theraputic use
– Reduces total cholesterol, LDL cholesterol,
and apolipoprotein B
– Approved for monotherapy and combined use
with statins
Fibric Acid Derivates (Fibrates) most effective
• Most effective drugs available for lowering TG levels (as
much as 50%
Fibric Acid Derivates (Fibrates) can raise
Can raise HDL cholesterol
Fibric Acid Derivates (Fibrates) little or no effect
• Little or no effect on LDL cholesterol
Fibric Acid Derivates (Fibrates) can increase the risk for
Can increase the risk for bleeding in patients taking
warfarin
Fibric Acid Derivates (Fibrates) can increase the risk for
• Can increase the risk for rhabdomyolysis in patients
taking statins
Fibric Acid Derivates (Fibrates) three durgs in US
– Gemfibrozil [Lopid]
– Fenofibrate [Tricor, others]
– Fenofibric acid [TriLipix
Fibric Acid Derivates ADR
Adverse effects: have been associated
with muscle toxicity and is more profound
with those patients also treated with a
statin.
Fibric Acid Derivates ADR effect can be medicated by
Effect can be mediated by a competitive
inhibition of CYP3A4.
Fibric Acid Derivates safer options
Pravastatin and Fluvastatin are NOT
extensively metabolized by the CYP3A4
• Maybe safer when combination therapy is required
with a fibrate, but this is not certain
Fibric Acid Derivates interactions
Interactions – interfere with the
metabolism of warfarin (warfarin should be
reduced by 30% in these patients).
