Mod 1 lecture 3: antihyperlipidemia agents Flashcards
what are lipids
hydrophobic molecules made from mostly hydrocarbon chains
what his hyperlipidemia
excess lipids in the blood
what are types of lipids
fats - triglycerides
sterols - cholesterol
phospholipids - emulsifiers, lipid bilayer
what are lipoproteins
serve as carriers to transport lipids (cholesterol, triglycerides) in the blood
what type of proteins carry lipids into the atery wall
Apolipoprotein (apo) B- 100
what is LDL
low density lipoprotein. - contains (apo) b100
what is VLDL
very-low density lipoprotein
secreted by liver and export triglycerides to peripheral tissues
contain (apo) b100
what is chylmicrons
formed in the intestine and carry triglycerides of dietary origin, unesterified cholesterol and cholesteryl esters
contain (apo) B100
what is HDL
produced by liver and intestine
cholesterol is primary component in core
act as scavengers to take up cholesterol from peripheral tissues and triglyceride from degradation of VLDL
DO NOT contain (apo) B-100
what is the decreasing order of atherogenicity
LCL
VLDH
Chylomicrons
HDL
what is cholesterol
lipid
responsible for proper cell membrane synthesis and formation of bile acids and steroid hormones
primarily produced in the liver
INSOLUBLE in water so must be bound to lipoproteins for transport
what are tyriglycerides
main lipid component of dietary fat and fat deposits of animals
excess stored primarily in fat cells (adipocytes)
source of energy for body
INSOLUBLE in water so must be bound to lipoproteins for transportation
what are the classification of hyperlipidemia
primary (familial;hereditary) hyperlipidemia: genetically determined - type 1, 2a,2b, 3,4,5
secondary (acquired) hyperlipidemia:
- hypercholesterolemia: hyperthyroidism, nephrotic syndrome and drugs
- hypertriglyceridemia: DM, alcohol, gout, chronic renal failure
what is optimal total cholesterol level
less than or equal to 200 mg/dL
what is the optimal LDL-C level
less than or equal to 100 mg/dL
what is the optimal triclyceride level
less than or equal to 150 mg/dL
what is the optimal HDL level
greater than or equal to 60 mg/dL
what is TLC diet
Therapeutic lifestyle change diet for hyperlipoporteinemia
vegetables, fruits, whole grains
legumes and nuts
low-fat dairy produces
low-fat poultry (without skin)
fish and seafoods
non-tropical vegetable oils
what are the main classes of drugs used to treat hyperlipidemia
HMG CoA Reductase Inhibitors
Bile Acide Sequestrates
Nicotinic Acid
Cholesterol Absoprtion Inhibitor
Fibric Acids
Omega-3 Fatty Acids
what are the different HMG CoA reductase inhibitors
Statins
Atorvastatin (lipitor)
Lovastatin (mevacor)
Pravastatin (pravachol)
Rosuvastatin (crestor)
Simvastatin (Zocor)
what is the MOA for HMG CoA Reductase Inhibitors
Inhibits hepatic HMG-CaA reductase -> decrease in cholesterol synthesis -> hepatocytes synthesis more LDL receptors, increase ability to remove LDL from blood
what is HMG CoA reductase
a rate of controlling enzyme of the metabolic pathway that produces cholesterol
when are HMG CoA reductase inhibitors usually taken
taken at night usually
rosuvastatin and atorvastatin CAN be taken in the morning
what are low intensity therapies used to lower LDL levels
Lovastatin
Pravastain
Simvastatin
when are HMG CoA reductase inhibitors usually taken
taken at night usually
rosuvastatin and atorvastatin CAN be taken in the morning
what are the high potent statin medications
Rosuvastatin
Atorvastatin
what are the indications for HMG CoA reductase inhibitors
used to lower the risk of atherosclerotic cardiovascular disease events
helps lower plasma cholesterol levels in all types of hyperlipidemias
what should be avoided when using HMG CoA reductase inhibitors
avoid grapefruit or grapefruit juice (increased bioavailability of lovastatin and atorvastatin)
when is HMG CoA reductase inhibitors contraindicated?
pregnancy
lactation
active or chronic liver disease (liver function checked prior to starting)
Red yeast rice
what are the adverse effects of HMG CoA reductase inhibitors
elevated liver enzymes
myopathy and rhabdomyolysis
photosensitivity
may increase affect of warfarin - check INR prior
GI upset (N/V, diarrhea, pain, dyspepsia)
what statin is labeled by the FDA for decreasing triglycerides as well as LDL and total cholesterol
Atorvastatin (Lipitor)
what is lovastatin (mevacor)
low potency HMG CoA reductase inhibitor
take with meals
immediate release
avoid grapefruit or grapefruit juice
what are atorvastatin (lipitor) and Rosuvastatin (crestor)
HMG CoA reductase inhibitor
MOST potent LDL-C lowering statin
avoid grapefruit/gf juice
what is simvastatin (zocor)
Medium potency HMG CoA reductase inhibitor
metabolized by CYP450
inhibitors of CYP450 may cause increased risk of rhabdomyolosis
labeled by the FDA to treat for triglycerides, LDL and total cholesterol
what is pravastatin
low potency HMG CoA Reductase inhibitor
fully excreted in urine
what is Nicotinic acid
niacin
what is the MOA for Niacin
inhibits lipolysis in adipose tissues -> reduced production of FFA and TGs
reduces VLDL secretion from liver -> lowers LDL
what are the therapeutic uses of Niacin
familial hyperlipidemia, sever hypercholesteremias
often with used with other agents
most effective agent for increased HDL
lowers Lip-A, LDL, and TG
what are the adverse effects of Niacin
flush, N, abd pain, gout, impaired glucose toleracne, hepatotoxicity, hypotension
when is Niacin contraindicated
hepatic disease
active peptic ulcer
low BP
severe gout
be cautions when prescribing to diabetics, individuals with high uric acid levels and peptic ulcer disease
what are the effects of Niacin
increases HDL (most effective agent)
decreases lipoprotein (a)
decreases LDL
lowers triglycerides
What are Fibric Acid medications
Gemfibrozil (lopid)
Fenofibrate (tricor)
what is the MOA for fibric acid medications
activates peroxisome proliferator - activated receptors (PPAR) - > up regulate lipoprotein lipase, induce HDL synthesis and decrease liver production of apolipoprotein C
what are the therapeutic uses of fibric acids
hypertriglyceridemia
treatment in type III hyperlipidemia (dysbetalipoproteinemia)
low HDL
when are Fibric Acids contraindicated
co-administration with statin therapy increases risk for myopathy and rhabdomyolysis
avoid in renal and hepatic dysfunction
avoid in preexisting gallbladder disease or biliary chirrhosis
what are the AE of fibric acid toxicity
Gi disturbances (most common)
gallstones
myopathy
hepatic dysfunction
increase effects on warfarin - INR check prior to starting
what are the effects of fibric acids
decreases secretion of VLDL
increases lipoprotein lipase activity
increase HDL
what are bile acid sequestrate medications
Cholestyramine (Questran, prevalite)
Colesevelam (Welchol)
Colestipol (colestid)
what is the MOA for bile avid sequestrates
prevents resorption of bile acid salts in intestines -> increases excretion - > increase synthesis -> liver cells increase LDL receptors, increase LDL uptake and decrease circulating LDL levels
what are the indications for bile acid sequestrates
type IIa and type IIb hyperlipidemias
elevated LDL
digitalis toxicity
chronic pruritis
when are bile acid sequestrates contraindicated
Biliary cirrhosis, biliary obstruction
gallstones (cholelitheiasis)
hypertriglyceridemia
GI obstruction
preexisting coagulopathy (hemophilia)
caution in hypothyroid pateints
pregnangy, lactation
prolonged used caution in renal disases
what are the AE of bile acid sequestrates
constipation
bloating
nausea
flatulence
interferes with absorption of some drugs/fat-soluble vitamin A,
d, E and K
reported to increase serum triglyceride concentration
what are the effects of bile acid sequestrants
decrease LDL (significant but less than seen in statins)
What is cholestyramine
(questran, prevalite)
bile acid sequestrate
anonion-exhange resin that binds negatively changed bile acids and salts in small intestines
resin/bile acid complex excreted in feces
can relieve prurutis caused by accumulation of bile aids in patients with biliary stasis
What is cholesterol absorption inhibitor
Ezetimbie (zetia)
What is the MOA of ezetimbie (zetia)
acts on cells of the brush border of the small intestine to inhibit dietary cholesterol absorption
also inhibits reabsorption of cholesterol secreted in the bile
What is the inidcations for ezetimbe (zetia)
used as adjunct therapy to lower LDL
phytosterolemia
mono or combo therapy with statin
what are the contraindications of zetia
severe hepatic insufficiency
pregnancy/lactation
what are the AE of zetia
SE rare: hepatic dysfunction (low)
myositis
what are the effects of zetia
inhibits reabsorption of cholesterol excreted in bile
decreased LDL and phytosterols
what are the omega-3 fatty acids
alpha-linolenic acid (ALA)
eicosapentaenoic avid (EPA)
Docosahexaenoic acid (DHA)
what is the MOA for omega 3 fatty acid
inhibit VLDL and triglycerides synthesis in liver
what are the indications for omega 3 fatty acid
lowering triglycerides
(used as an adjunct to diet and exercise
when is fish oil contraindicated
avoided if pt has a hx of fish hypersensitivity
pts on anticoagulant, thrombolytic or anti-platelet therapy as bleeding may be increased
what are the AE of fish oil
GI upset - abd pain, N and diarrhea
fishy aftertaste
increased bleeding risk with those already on anticoags
need to monitor
what is Vytorin
combination of Ezetimibe (zetia) and simvastatin (zocor)
what is Advicor
combination of lovastatin and Niacin
what is Caduet
combination of amlopdipine/atorvastatin
what are the injectable medications (monoclonal antibodies)
alirocumab (praluent)
Evolocumab (repathya)
