Lipid Lowering Drugs Class PDF

Lipid Lowering Drugs (Antilipemic Drugs) Chapter 53 Objectives Review the role of lipoproteins on plasma lipid transport Identify the drugs that alter plasma lipopropteins and triglycerides Understand how statins reduce plasma low-density lipoproteins Describe the adverse effects, cau...

Lipid Lowering Drugs (Antilipemic Drugs) Chapter 53 Objectives Review the role of lipoproteins on plasma lipid transport Identify the drugs that alter plasma lipopropteins and triglycerides Understand how statins reduce plasma low-density lipoproteins Describe the adverse effects, cautions and contraindications in the use of statins Understand the mechanism of action of other drugs that are used to reduce plasma lipid levels Lipid Transport Triglycerides (TGs) and Cholesterol 2 primary forms of lipids in the blood Water-insoluble fats that must be packaged for transport in blood Lipoproteins are the combination of lipids with protein Lipoproteins Lipids (cholesterol, TGs, others) + Proteins (on surface of particle) Lipoproteins Chylomicrons - from GI tract Very-low-density lipoprotein (VLDL) produced by the liver transport TGs to cells Lipoproteins Low-density lipoprotein (LDL) “less desired”, “bad cholesterol” cholesterol-rich cell membranes, steroid hormones High-density lipoprotein (HDL) “highly desired” responsible for “recycling” of cholesterol also known as “good cholesterol” Coronary Artery Disease Non-modifiable factors Age Male 45 years or older Female 55 years or older, or postmenopausal Family history: strong history of premature CHD Coronary Artery Disease Modifiable Factors Current cigarette smoker Abdominal obesity Hypertension BP 140/90 or higher, or on antihypertensive medication Diabetes mellitus LOW-DENSITY LIPOPROTEIN / HIGH-DENSITY LIPOPROTEIN RATIO Lipid Lowering Drugs 4 Groups of Drugs HMG-CoA reductase inhibitors (HMGs, or statins) Inhibitors of Cholesterol Absorption Niacin (nicotinic acid) Fibric acid derivatives Lipid Lowering Drugs HMG-CoA 3-Hydroxy-3-methylglutaryl coenzyme A One of metabolites in cholesterol synthesis pathway HMG-CoA Reductase critical enzyme for liver cholesterol production Lipid Lowering Drugs: HMG-CoA Reductase Inhibitors Reduce plasma LDL levels atorvastatin (Lipitor) rosuvastatin (Crestor) newer / possibly less AE use only low dose in Asians lovastatin (Mevacor) simvastatin (Zocor) HMG-CoA reductase Inhibitors: Mechanism of action Inhibit HMG-CoA reductase important liver enzyme that produces cholesterol Lower the rate of cholesterol production causes increased liver LDL receptors increase plasma clearance of LDL HMG-CoA reductase Inhibitors Added Benefits of statins Decrease VLDL (major carriers of TGs) Raise HDL improves LDL/HDL HMG-CoA reductase Inhibitors: Indications First-line drug therapy for hypercholesterolemia Treatment of types IIa and IIb hyperlipidemias High LDL levels HMG-CoA reductase Inhibitors: Adverse Effects Mild, transient GI disturbances, headache Muscle pain (myalgia) Rarer - rhabdomyolysis (muscle breakdown) Liver injury (elevations in liver enzymes) Care with liver dysfunction patients eg viral hepatitis Not used during pregnancy Consideration with Statins Asian rosuvastatin X Grapefruit and grapefruit juice CYP3A4 inhibition some statins (lovastatin, simvastatin, atorvastatin) Interactions with Statins Grapefruit and grapefruit juice Drug Inhibitors of CYP3A4 warfarin (oral anticoagulant) erythromycin (macrolide antibacterial) ritonavir (HIV protease inhibitor) Applies to statins that are metabolized by CYP3A4 enzyme