Antihyperlipidemia Flashcards
What are the main lipids that are important for medications
Triglycerides
Cholesterol
What is the purpose of lipoproteins
Serve as carriers to transport lipids in the blood
What type of lip are responsible for carrying lipids into the artery wall
Apolipoprotein (apo)B-100
What type of lipid is apo B100
LDL
*mutations in it cause a familial hypercholesterolemia
What is VLDL and where is it found
Very low density lipoprotein
Secreted by liver and export triglycerides to peripheral tissue
What are chylomicrons
Formed in the intestine and carry triglycerides from diet, unesterfied cholesterol, and cholesteryl esters
What produces HDL
Liver and intestines
What is the only lipoprotein that DOES NOT contain apo B100
HDL
What is the purpose of HDL
Acts as scavenger to take up cholesterol from peripheral tissue and triglycerides from degradation of VLDL
What is the role of cholesterol
Responsible for proper cell membrane synthesis and formation of bile acids / steroid hormones
What is the function of triglycerides
source of energy for the body
What is primary hyperlipidemia
Genetically determined
(Increase chylomicrons)
What is secondary hyperlipidemia
Acquired
(Increase in LDL / VLDL)
What causes hypercholesterolemia
hypothyroidism
nephrotic syndrome
drugs
What causes hypertriglyceridemia
DM
Gout
Alcohol
Chronic renal failure
What are the low potency statin medications
Lovastatin
Pravastatin
What is a medium potency statin
Simvastatin
What are high potency statins
Rosuvastatin
Atorvastatin
When is Lovastatin used
Low / moderate intensity therapy to lower LDL levels
Primary & secondary prevention of coronary events
Prevention of MI/Stroke in T2 diabetes
When is Pravastatin used
Low / moderate intensity therapy to lower LDL levels
Primary & secondary prevention of coronary events
What is the MOA for statins (Low, Medium, or high potency)
Inhibits hepatic HMG-CoA reductase=
decrease in cholesterol synthesis =
Hepatocytes synthesize more LDL receptors = increase ability to remove LDL from blood
When is Simvastatin used
-Low/ mod intensity therapy to lower LDL levels
-Primary & secondary prevention of coronary events
-Approved for decr TGs, LDL, and total cholesterol
What is the use of rosuvastatin
-Most potent statin
-Mod or high intensity therapy to lower LDL levels
-Primary prevention of coronary events
-Approved for reducing risk of CV events in people w normal LDL levels
What is the use of atorvastatin
-Most potent statin
-Mod or high intensity therapy
-Primary & secondary prevention of coronary events, prevention of MI/stroke in T2 diabetes
-Approved for decr TGs, LDL, and total cholesterol
What is the indication of nicotinic acid
-Familial hyperlipidemias, severe hypercholesteremias
-Often used w other agents
-Most effective agent for incr HDL
-Lowers lip-A, LDL, and TG
What are the bile acid sequestrates
Colesevelam
Cholestyramine
Colestipol
What is the MOA for the bile acid sequestrates
-Prevent resorption of bile acid salts in intestines = incr excretion = incr synth = liver cells incr LDL receptors, incr LDL uptake and decr circulating LDL levels
What food needs to be avoided when taking HMG CoA reductase drugs and why
Grapefruit / grapefruit juice
Increased bioavailability of lovastatin and atorvastatin
What is the pharmacokinetics of pravastatin
-Oral admin
-Rapid hepatic metabolism
-Dose adjust in mod-severe renal impairment
What is the pharmacokinetics of Lovastatin
-Oral admin, take w meals
-Rapid hepatic metabolism
-Metabolized by CYP3A4
-Dose adjust in severe renal impairment
What is the pharmacokinetics of Simvastatin
Oral admin
-Rapid hepatic metabolism
-Metabolized by CYP3A4 (the 3A4 isoenzyme of cytochrome P450)
-Dose adjust in severe renal impairment
What are the adverse reactions and contraindications of low potency HMG CoA reductase inhibitors
-HA, rash, dyspepsia, cramps, flatulence, constipation, abdominal pain
-Serious adverse effects: hepatotoxicity and myopathy
-Contra in pregnancy, avoid grapefruit juice
What is the pharmacokinetics of Rosuvastatin
-Oral admin
-Rapid hepatic metabolism
-Dose adjust in severe renal impairment and w Asian pts
What are the adverse reactions and contraindications of Rosuvastatin
HA, rash, dyspepsia, cramps, flatulence, constipation, abdominal pain
-Serious adverse effects: hepatotoxicity and myopathy
-Highest risk for rhabdomyolysis
-Contra in pregnancy, avoid grapefruit juice
What is the pharmacokinetics of atorvastatin
-Oral admin
-Rapid hepatic metabolism
-Metabolized by CYP3A4 (the 3A4 isoenzyme of cytochrome P450)
-No dose adjustment needed
What are the adverse reactions and contraindications of atorvastatin
-HA, rash, dyspepsia, cramps, flatulence, constipation, abdominal pain
-Serious adverse effects: hepatotoxicity and myopathy
-Contra in pregnancy, avoid grapefruit juice
What is the indication of nicotinic acid
-Familial hyperlipidemias, severe hypercholesteremias
-Often used w other agents
-Most effective agent for incr HDL
-Lowers lip-A, LDL, and TG
What is the MOA of nicotinic acid
-Inhibits lipolysis in adipose tissues = reduced production of free fatty acids and TGs
-Reduces VLDL secretion from liver = lowers LDL
What are the pharmacokinetics of nicotinic acid
-Oral admin
-Comes in immediate, ER, and SR preparations
*SR reduces adverse effects
What are the adverse effects and contraindications of nicotinic acid
-Flush, nausea, adb pain, gout, impaired glucose tolerance, hepatotoxicity, hypotension
-Contra in hepatic dz, peptic ulcer dz, low BP, severe gout
-Caution in diabetics, high uric acid levels, peptic ulcer dz
What is the indication of colesevelam
Bile acid sequestrate DOC
-Lowers LDL: primary hypercholesterolemia
-Can help control hyperglycemia in patients with T2 diabetes
-Chronic pruritus, digitalis toxicity
-Can be alone but usu combo w statin
What are the adverse reactions and contraindications of Colesevelam
Constipation, bloating, indigestion, nausea
Contraindicated in biliary cirrhosis, gallstones, pregnancy, hypertryglyceridemia
What are the indications for cholestyramine and colestipol
-Bile acid sequestrant
-Reduces LDL cholesterol: primary hypercholesterolemia
-Can be used alone but usu combined w a statin
What are the adverse reactions and contraindications of Cholestyramine and colestipol
-Constipation, bloating, indigestion, and nausea
-Decr uptake of fat-soluble vitamins
-Can form insoluble complexes w other drugs
What are the fibrate drugs
Gemfibrozil
Fenofibrate
What is the indication for fenofibrate
-Principal indication is hypertriglyceridemia
-Lowers VLDL and raises HDL
-More effective than gemfibrozil in lowering TGs
What are the adverse reaction and contraindications for Gemfibrozil
-Rash and GI disturbances
-Gall stones, myopathy, liver injury
-Incr risk of bleeding in pts taking warfarin, incr risk of myopathy in combo w statin
-Contra in renal, hepatic, and gallbladder dz
What are the contraindications and adverse reactions in Fenofibrate
-Rash and GI disturbances, gall stones, liver injury
-Contra in hepatic and gallbladder dz
What is the indication for Ezetimibe
-Usu used as adjunct therapy to lower LDL
-Phytosterolemia
-Mono or combo therapy w a statin
What is the MOA of Ezetimibe
-Acts on cells of the brush border of the sm intestine to inhibit dietary cholesterol absorption
-Also inhibits reabsorption of cholesterol secreted in the bile
What are the pharmacokinetics of Ezetimibe
-Absorption not affected by food
-Undergoes extensive conversion to ezetimibe glucuronide (active metabolite)
What are the adverse reactions and contraindications of ezetimibe
SE are rare
Contraindicated in patients with hepatic insufficiency and pregnancy
What is the indication of fish oil
Essential fatty acid used for dietary supplementation to lower TGs
What is the MOA of fish oil
Inhibit VLDL and triglyceride synthesis in the liver
What are the adverse effects and contraindications of fish oil
GI disturbances
Fishy aftertaste
**Contra indicated in fish allergies and patients on anticoags
What is a cholesterol absorption inhibitor drug
Ezetimibe
