Hyperlipidemia Drugs Flashcards
Structure and Function of Lipoproteins
Structures that transport lipids (cholesterol and triglycerides in the blood)
Consist of a hydrophobic core; a hydrophilic shell; and at least one apolipoprotein, which serves as a recognition site for receptors on cells.
Lipoproteins that contain apolipoprotein B-100 transport cholesterol and TGs from the liver to peripheral tissues.
Lipoproteins that contain apolipoproteins A-I or A-II transport cholesterol from peripheral tissues back to the liver.
Classes of Lipoproteins
Very low-density lipoprotein (VLDL), LDL and high-density lipoproetin (HDL).
VLDL
Very low-density lipoproteins
VLDLs transport triglycerides to peripheral tissues.
The contribution of VLDLs to ASCVD is unclear.
LDL
LDLs transport cholesterol to peripheral tissues.
Elevation of LDL cholesterol greatly increases the risk of ASCVD.
By reducing LDL cholesterol levels, atherosclerosis can be arrested or reversed, which reduces morbidity and mortality from ASCVD.
HDL
HDLs transport cholesterol back to the liver.
HDLs protect against ASCVD.
Role of Low-Density Lipoprotein cholesterol in Atherosclerosis
Atherogenesis is a chronic inflammatory process that begins with accumulation of LDLs beneath the arterial endothelium, followed by oxidation of LDLs.
Guidelines for Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk
All adults older than 20 years should be screened every 5 years.
Dietary modification along with exercise is the primary method of reducing LDL cholesterol to the target level.
Therapy with cholesterol-lowering drugs must continue lifelong. If these drugs are withdrawn, cholesterol levels return to pretreatment values.
HMG-CoA Reductase Inhibitors (Statins)
Most effective for lowering LDL cholesterol. Few AE.
Slow progression of ASCVD, reduce the number of adverse cardiac events and reduce mortality.
Statins reduce LDL cholesterol levels by increasing the number of LDL receptors on hepatocytes, thereby enabling hepatocytes to remove more LDLs from the blood. The process by which the number of LDL receptors is increased begins with the inhibition of HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis.
Four statins- atorvastatin, fluvastatin, lovastatin and simvastatin are metabolized by CYP3A4; therefore, their levels can be increased by CYP3A4 inhibitors (e.g., cyclosporin, erythromycin, ketoconazole, ritonavir).
Can cause liver damage. Tests of liver fucntion should be done at baseline, 6-8 weeks after, and every 6-12 months there after.
Should not be used during pregnancy.
Statin AE
Myopathy (Rhabdomylosis)- unusual muscle pain, soreness, tenderness, or weakness should inform the provider. A marker for muscle injury- CK- should be measured at baseline, before starting the drug; periodically thereafter; and whenever signs or symptoms that could be caused by myopathy or myositis develop.
Bile-Acid Sequestrants
(colesevelam) reduce LDL cholesterol levels by increasng the number of LDL receptors on hepatoctes. The mechanism is complex and begins with prevention of the reabsorption of bile acids in the intestine.
Older bile acid sequestrants are not absorbed from the GI tract, and therefore do not cause systemic adverse effects. However, they can cause constipation and other GI effects. (GI effects with one newer sequestrant, colesevelam, are minimal).
Form complexes with other drugs, thereby preventing their absorption. Accordingly, oral medications should be administered within 1 hour before the sequestrant or 4 hours after.
Ezetimibe
Lowers LDL cholesterol by reducing cholesterol absorption in the small intestine.
Can cause muscle injury.
Gemfibrozil and other Fibrates
most effective drugs for lowering TG levels.
Can cause muscle injury.
Niacin
Reduces LDL and TG levels and raises HDL levels. Drug also causes adverse effects in nearly all patients.
In patients with a history of CVD who are taking a statin (simvastatin) adding niacin can reduce CV risk factors (it can elevate HDL cholesterol and lower TGs) but it does not reduce the risk of CV events.
Immediate release formulation cause intense flushing of the face, neck and ears in most patients. Flushing can be reduced by taking aspirin or ibuprofen 30 minutes before dosing, by dividing the total daily dose into smaller doses taken more often, or by using an extended release product (Niaspan)
Can cause liver injury. Risk is highest with older sustained-release formulations and lowest with extended-release niacin.
PCSK9 Inhibitors
Praluent, Repatha
New type of drug class used for patients with high LDL levels, specifically in patients with heterozygous familial hypercholesterolemia or atherosclerotic heart problems who need additional lowering of LDL cholesterol. The
