5 Antihyperlipidemics

Question 1

diet strategies for atherosclerosis

Answer 1

• decrease dietary cholesterol, sat fats, trans fats that increase plasma lipoproteins
• decrease alcohol that increases VLDL levels
• limit calories from fat to 20-25% daily intake
• more omega-3

Question 2

5 drug types and 1 example each for atherosclerosis

Answer 2

• bile acid binding agent eg. resins
• cholesterol synthesis inhibitors (statins) eg. HMG-CoA reductase inhibitors
• VLDL secretion inhibitors eg. niacin
• lipoprotein lipase stimulants eg. fibric acid derivatives
• inhibitors of intestinal sterol absorption eg. ezetimibe

Question 3

describe resins and 1 example

Answer 3

• binds bile acids and prevents reabsorption (as well as drugs/fat-soluble vitamins) –> increases clearance of cholesterol
• constipation/flatulence
• eg. cholestyramine

Question 4

cholesterol synthesis inhibitors (statins) MOA, use, prodrug, active drug, toxicity

Answer 4

• they’re HMG-CoA reductase inhibitors
• prodrug - lovastatin
• active drug - atorvastatin (Lipitor)
• competitively inhibit 3-HMG CoA reductase (rate limiting in cholesterol biosynthesis)
• decrease serum LDL, increase hepatic LDL receptors –> increase LDL clearance
• but –>increases synthesis of 3-HMG CoA reductase
• for px with hypercholesterolemia at risk of MI
• to decrease LDL and decrease coronary events
• tox - altered liver function (monitor serum transminases), increase warfarin levels (monitor blood clotting time)

Question 5

VLDL secretion inhibitors MOA, use, toxicity, 1 example

Answer 5

• decreases lipolysis, decreases TAG, decreases VLDL
• decreases liver VLDL secretion
• decreases LDL
• increases HDL
• for hyperlipidemias combined with statins
• tox - cutaneous flushing/itching (prevent with aspirin), GI distress/stomach ulcers, increase in liver transaminases
• eg. niacin

Question 6

lipoprotein lipase stimulants (fibrates) MOA, use, 2 examples, toxicity

Answer 6

• ligands for PPARs that regulate lipid metabolism
• increase lipoprotein lipase –> decrease VLDL
• increase clearance of TG-rich lipoproteins
• increase apo A-I and apo A-II –> increase HDL
• gemfibrozil for familial hyperlipidemias with high VLDL
• used in combo to decrease cholesterol
• eg. gemfibrozil, fenofibrate
• tox - rare

Question 7

inhibitors of intestinal sterol absorption MOA, 1 example, toxicity

Answer 7

• inhibits intestinal absorption of phytosterols and cholesterol by targeting a transport protein NPC 1L1 –> decrease serum LDL
• synergistic with statins
• eg. ezetimibe
• tox - minimal

Question 8

4 drug combos

Answer 8

• dietary modification and drugs
• useful when increased LDL and VLDL
• useful when single agent can’t lower lipoproteins
• minimal toxicity