Hyperlipidemia Drugs Flashcards
Statin indication
High LDL, hypercholesterolemia, treatment/prevention of heart disease. Choose Pravastatin if need to use Cyclosporins!
Statin effect on LDL
↓ 20-60%
Statin effect on HDL
↑ 5-10%
Statin effect on Trigly
↓ 10-20%
Statin MOA
Inhibits HMG Co-A reductase and triggers increased LDL-R expression resulting in increased LDL clearance
Statin Adverse Effects
mild GI, mm myalgia (pain)/myopathy (weakness), RHABDOMYOLYSIS, Hepatitis
Statin Contra-indications
Pregnancy or lactation, liver disease, gemfibrozil pts (increased risk of rhabdomyolysis)
Statin Drug interactions
CYP3A4 inhibitors (erythromycin, cyclosporin and grapefruit juice increase LSA).
CYP 3A4 inducers (phenytoin, rifampin) decrease LSA.
CYP2C9 inhibitors (ketoconazole/metroconazole) increase FR.
Decreased Glucoronidation (gemfibrozil, fibrates) increases ALL statins (LSA, FR and P)
Statin Notes/Reminder
LSA=Lovastatin, Simvastatin and Atrovastatin. FR=Fluvastatin and Rosuvastatin. P=Pravastatin. Simvastatin=Zocor Myositis (inflammation) and Rhabdomyolysis are rare but occur at higher doses and in pts with polymorphism of anion transporter.
Bile Acid Binding Resins Cholestyramine Colestipol Colesevelam effect on LDL
_ 10-25%
Bile Acid Binding Resins Cholestyramine Colestipol Colesevelam effect on HDL
minimal increase
Bile Acid Binding Resins Cholestyramine Colestipol Colesevelam type and indication
High LDL, hypercholesterolemia. Drug of choice for children and women of childbearing age or who are pregnant.
Bile Acid Binding Resins (Cholestyramine Colestipol Colesevelam) effect on Trigly
minimal to slight increase
Bile Acid Binding Resins (Cholestyramine Colestipol Colesevelam) MOA
Bind to bile acids, preventing reabsorption, which diverts hepatic cholesterol to synthesis of new bile acids, stimulates LDL-R production upon drop in hepatic cholesterol pool.
Bile Acid Binding Resins (Cholestyramine Colestipol Colesevelam) Adverse Effects
mild GI, bloating. Can INCREASE trigly levels if pt has hypertriglyceridemia
Bile Acid Binding Resins (Cholestyramine Colestipol Colesevelam) Contra-indications
type III dysbetalipoproteinemia (due to risk of increased triglys)
Bile Acid Binding Resins (Cholestyramine Colestipol Colesevelam) Notes/Reminder
treat cholestasis/bile salt accumulation pt’s pruritus (itch)
Ezetimibe (Zetia) type and indication
High LDL
Ezetimibe (Zetia) effect on LDL
↓ 18%
Ezetimibe (Zetia) effect on HDL
minimal effect
Ezetimibe (Zetia) effect on Trigly
minimal effect
Ezetimibe (Zetia) MOA
Inhibits absorption of cholesterol (NPC1L1 txporter in intestine) and cholesterol excreted in bile, decrease tightly regulated hepatic pool, stimulate LDL-R production.
Ezetimibe (Zetia) Adverse Effects
mild GI symptoms, low incidence of liver problems (reversible)
Ezetimibe (Zetia) Contra-indications
pregnancy, mild to severe hepatitis, hypersensitivity to drug
Ezetimibe (Zetia) Drug interactions
Bile acid resins interfere with absorption (decrease levels). Cyclosporin increases levels of Zetia. Fibrates increase active, glucuronide form.
Ezetimibe (Zetia) Notes/Reminder
combination with HMG-CoA inhibitor makes more effective (Zetia+Zocor=Vytorin); converted in liver to active glucuronide form; NP is neimann-pick receptor
Niacin type and indication
High VLDL High LDL Low HDL. Wide applications: Can be used for hypertriglyceridemia, hypercholesterolemia, to fix low HDL levels.
Niacin effect on LDL
_ 10-20%
Niacin effect on HDL
_ 10-30% *best at increasing HDLS!
Niacin effect on Trigly
_ 30-80%
Niacin MOA
THREE MOA situations: 1-block of HSTL causes decreased lipolysis in adipocytes which decreases FFA (decrease triglys) which decreases VLDL and then LDL.
2-increased apo A-1 needed to build HDL (increase HDL),
3-decreased thrombosis due to decreased lipoprotein (a)
Niacin Adverse Effects
skin flushing, hepatitis (elevation of liver enzymes and severe hepatotoxicity), GOUT (hyperuricemia), hyperglycemia, peptic ulcers
Niacin Contra-indications
diabetics (due to possible CHO intolerance), hx of Gout, impaired liver function, pregnancy (risk of gestational diabetes)
Niacin Drug interactions
**use of Niacin is really limited by poor tolerability, many side effects**
Niacin Notes/Reminder
pre-treatment with NSAIDS can reduce skin flushing (suggests a PG mechanism for the flushing). Elevated triglys are a risk factor for pancreatitis!
Fibrates (Gemfibrozil Fenofibrate) type and indication
High VLDL, Low HDL. Good for pts. w/ very high triglys that may be at risk for pancreatitis. Drug of choice for Familial dysbetalipoproteinemia
Fibrates (Gemfibrozil Fenofibrate) effect on LDL
may increase LDL in genetic pts.
Fibrates (Gemfibrozil Fenofibrate) effect on HDL
↑ 10-20%
Fibrates (Gemfibrozil Fenofibrate) effect on Trigly
↓ 40-80%
Fibrates (Gemfibrozil Fenofibrate) MOA
drug is ligand for perioxisome proliferator activated receptor alpha (PPAR-alpha) protein, which regulates transcription of genes in lipid metabolism. Increases lipoprotein lipase (LPL) which metabolizes CyM, and increases FA oxidation in liver, decreasing VLDLs. Increases ApoA1 which increases HDLs. Decreases apoCIII synthesis (building block of LDL)
Fibrates (Gemfibrozil Fenofibrate) Adverse Effects
nausea, skin rashes, increased cholesterol gallstones (block of bile acid production enzyme leads to more free cholesterol), hepatitis, myopathy, rhabdomyolysis (rare, more with Gemfib)
Fibrates (Gemfibrozil Fenofibrate) Contra-indications
pt hx of cholelithiasis (gall stones). Gemfibrozil affects liver uptake of statins and metab/excretion. Fenofibrate is drug of choice for combo therapy b/c doesn’t interfere w/statins.
Fibrates (Gemfibrozil Fenofibrate) Drug interactions
STRONG PROTEIN BINDERS, lots of interactions!! No statins (increased risk of rhabdomyolysis, must choose Feno if have to), Cyclosporin (risk of renal tox), Sulfonylureas (inc hypoglycemia) or Warfarin (inc risk of bleeding)
Fibrates (Gemfibrozil Fenofibrate) Notes/Reminder
VLDL is very triglyceride rich and is precursor to LDL. CyM are expogenous form of triglys, metabolized by LPL in capillary. Elevated triglys are a risk factor for pancreatitis!
Familial Hypercholesterolemia
Hyperlipoproteinemia Type IIa
0.2% frequency
LDL receptor defect
↑ LDL
Atherosclerosis +++
Familial apoB100 defect
Hyperlipoproteinemia Type IIa
0.1% frequency
↓ Binding of LDL to LDLR
↑ LDL
Atherosclerosis +++
Polygenic Hypercholesterolemia
Hyperlipoproteinemia Type IIa
Relatively common
Unknown defects result in impaired clearance of LDLs
↑ LDL
Atherosclerosis +++
Familial Combined Hyperlipidemia
Type IIb
0.5% frequency
Unknown (polygenic): Overproduction of B100 & triglycerides (VLDL) and decreased clearance of LDL
↑ VLDL and ↑ LDL
Atherosclerosis +++ (insulin resistance w/obesity often)
Familial Dysbetalipoproteinemia
Hyperlipoproteinemia Type III
0.02% frequency
Mutant ApoE: Increased production/decreased clearance of VLDL remnants
↑ IDL
Atherosclerosis +++
