Tuesday 12 July 2011

HYPERLIPOPROTEINEMIAS


Hyperlipidemiahyperlipoproteinemia, or hyperlipidaemia (British English) is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood. It is the most common form of dyslipidemia (which also includes any decreased lipid levels).
Lipids (fat-soluble molecules) are transported in a protein capsule, and the size of that capsule, or lipoprotein, determines its density. The lipoprotein density and type of apolipoproteins it contains determines the fate of the particle and its influence on metabolism.

Hyperlipidemia is a major cause of atherosclerosis and is associated with conditions such as coronary heart disease, ischemic cerebrovascular disease, and peripheral vascular disease.

Secondary causes of hyperlipidemia should be ruled out before initiation of drug therapy.

Patients who meet criteria for lipid-lowering therapy should also be given instruction about therapeutic lifestyle change.

Abbreviations used in Hyperlipoproteinemias section include:
total-C = total cholesterol
LDL-C = low-density lipoprotein cholesterol
HDL-C = high-density lipoprotein cholesterol
VLDL-C = very low density lipoprotein cholesterol
apo B = apolipoprotein B
TG = triglycerides

Blood tests for total cholesterol need not be taken in a fasting patient, but lipoprotein analyses should be taken 9–12 hours postprandially. Clinical decisions should be based on an average of 2 separate readings taken 1–8 hours apart. If the results differ by more than 30mg/dL, a third reading should be taken and the average value of the three readings used.


Step I diet: ≤30% of total calories from fat, with 8–10% as saturated fat and <300mg of cholesterol daily.
Remeasure cholesterol level in 4–6 weeks and at 3 months after start of Step I diet.


Step II diet: reduce saturated fat <7% and cholesterol to <200mg daily.
A registered dietician may be consulted for assistance with meal planning.


Coronary heart disease (CHD) includes angiographic evidence of disease as well as clinical evidence of myocardial infarction.


Positive risk factors for CHD:

a) age (male ≥45 years, female ≥55 years or premature menopause without estrogen replacement therapy)
b) smoking
c) hypertension or currently taking medication to control hypertension
d) HDL cholesterol ≤35mg/dL
e) Diabetes mellitus
f ) family history of premature CHD

Obesity and physical inactivity are not considered risk factors because they operate through other risk factors already included, although they may be considered targets for intervention.


An HDL cholesterol level ≥60mg/dL is considered a negative risk factor for CHD and its presence allows for one positive risk factor to be subtracted because high HDL cholesterol levels are associated with lower CHD risk.

DRUG THERAPY:
HMG-CoA REDUCTASE INHIBITORS (STATINS)—lovastatinpravastatinsimvastatinfluvastatin,atorvastatin

-Most effective and well-tolerated agents
-Inhibit HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis
-Increase number of LDL receptors on hepatocytes causing increased removal of LDL from the blood
-Enhance removal of LDL precursors (VLDL and IDL)
-Greater LDL reductions occur when statins administered in the PM (atorvastatin has a very long half-life and is equally effective if given in the AM)
-Serious side effects include elevated hepatic transaminases, myopathy

BILE ACID SEQUESTRANTScholestyraminecolestipolcolesevelam

-Bind bile acids in the GI tract
-Binding reduces enterohepatic circulation of bile acids, which releases feedback regulation on conversion of cholesterol to bile acids in the liver
-Enhances expression of LDL receptors which increases LDL clearance
-Safest agents because they are not intestinally absorbed
-Useful when combined with other cholesterol-lowering drugs to further lower LDL
-May raise serum triglycerides; contraindicated in persons with high triglycerides (>400mg/dL) and in familial dysbetalipoproteinemia
-GI side effects may be lessened by moderate doses of standard sequestrants or use of colesevelam
-Administer other medications 1 hour before or 4 hours after bile acid sequestrants because they may inhibit drug absorption (colesevelam does not need to be administered separately from other drugs)

NICOTINIC ACID DERIVATIVES

-Most effective for increasing HDL
-Decreases hepatic clearance of HDL
-Decreases triglycerides as well as fibrates and statins
-Decreases hepatic triglyceride synthesis resulting in decreased VLDL production which accounts for a moderate reduction in LDL
-Compliance may be limited by flushing
-Flushing may be minimized by taking doses after meals or taking aspirin (Niaspan, an extended-release formulation of nicotinic acid, is associated with less flushing)
-Other major side effects include GI upset, hepatotoxicity (greater with sustained-release preparations), hyperuricemia and gout, and hyperglycemia
-Long-term use limited by side effects; generally reserved for patients at higher short-term risk

FIBRIC ACID DERIVATIVESclofibratefenofibrategemfibrozil 

-Decrease triglycerides by stimulating fatty acid oxidation
-Produce moderate elevations of HDL
-Increase clearance of VLDL
-Produce some lowering effect on LDL although this varies among different fibrate preparations
-Drug of choice for patients with severe hypertriglyceridemia who are at risk for pancreatitis; also for patients with dysbetalipoproteinemia
-Increased risk for cholesterol gallstones with fibrate monotherapy; increased risk for myopathy if combined with a statins (avoid this combination)

CHOLESTEROL ABSORPTION INHIBITORezetimibe

-Decreases blood cholesterol by inhibiting the absorption of cholesterol by the small intestine
-May be used in combination with statins or fenofibrate
-Monotherapy is limited to statin-intolerant patients
-Absorption inhibited by bile acid sequestrants

LIPID-REGULATING AGENTomega-3 fatty acids

-Reduces hepatic triglyceride synthesis
-Used as an adjunct to diet in patients with severely elevated triglyceride levels
-Secondary causes of hypertriglyceridemia should be ruled out before initiation of therapy
-Therapy should be withdrawn in patients who do not have an adequate response after 2 months of treatment

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