Week 7: Antilipidemics Flashcards
HMG CoA Reductase Inhibitors - “statins” (Atorvastatin/Rosuvastatin) MOA
- block synthesis of cholesterol in the liver by competitively inhibiting the HMG CoA reductase activity - best at lowering LDL
HMG CoA Reductase Inhibitors - drug interactions
- CYP 3A4 inhibitors - “azoles” - increase statin concentration
- CYP 3A4 inducers - “rifampin” - decrease statin concentrations
Pravastatin - not affected by grapefruit juice
HMG CoA reductase inhibitors cautions/ contraindications
- Pregnancy Category X - not safe in pregnancy
- Avoid in active liver disease
- Avoid grapefruit juice with simvastatin, lovastatin and atorvastatin - can increase toxicity
HMG CoA reductase inhibitors ADRs
- myalgias/myopathies –> increased CPK - rhabdo/metabolic acidosis
- headache
- fatigue
Statin Monitoring
- check lipid levels 4 to 6 weeks after starting therapy and then every 3 to 4 months until control is established
- LDL levels guide dose increases
- LFTs before starting therapy and then 3 to 6 months later only is suspected issues or underlying hepatic disease
Niacin MOA
- uncertain but appears to reduce VLDL synthesis - best at increasing HDL
Niacin cautions/ contraindications
- avoid w/ hx of gout
- avoid w/ hepatic dysfunction
- avoid in uncontrolled diabetes
- avoid w/ active peptic ulcers
Niacin ADRs
- pruritis, flushing, hepatotoxicity
Niacin Pt education
- take anti-inflammatory strength NSAID 30 minutes prior to dose to decrease ADRs
Fibrates (Gemfibrozil/Fenofibrate) MOA
- Increased plasma and hepatic lipoprotein lipase (LPL) activity - inhibition of cholesterol and triglyceride synthesis - inhibition of lipolysis in adipose tissue - decreased production of VLDL
- *best at decreasing triglyceride levels**
Fibrates ADRs
dyspepsia, abdominal pain - cholelithiasis
Fibrates cautions/ contraindications
- avoid in liver or renal disease
- avoid in pre-existing gallbladder disease
- avoid in pregnancy and lactation
Bile Acid Sequestrants (Cholestyramine/Questran) MOA
- indirectly blocks absorption of cholesterol by forming a nonabsorbable complex with bile acids in the intestine - increase the number of LDL receptors on the cell membrane for greater uptake in the liver and less in the bloodstream
- *can increase triglycerides**
Bile Acid sequestrants ADRs
flatulence, bloating, abdominal pain, constipation
Bile Acid sequestrants cautions/ contraindications
- avoid in pts w/ elevated triglycerides >300
- safe in pregnancy and lactation
- must take other medications and vitamins either 1 hour before or 4 hours after this medication
Cholesterol Absorption Inhibitors (Ezetimibe/Zetia) MOA
- directly blocks endogenous absorption of cholesterol - leads to a decreased delivery of cholesterol to the liver, decreased hepatic cholesterol stores, and increased clearance of cholesterol from the bloodstream
- can safely be used with -statins
Ezetimibe/Zetia ADRs
- fatigue
- diarrhea
- arthralgias/joint pain
Ezetimibe/Zetia cautions/contraindications
- avoid in liver dz
- avoid in pregnancy/lactation
PCSK9 (Evolocumab/Repatha) MOA
- subq injection - binds to circulating PCSK9 and inhibits the binding of PCSK9 to LDL receptors allowing for increased LDL receptors on the cell surface, decreasing LDL in the blood stream - 50 to 70% LDL reducation as monotherapy (can be used with statins)
Indication: genetic DO: familial homozygous hypercholesteremia
PCSK9 ADRs
- pain at injection site
- anaphyslaxis
PCSK9/Repatha cautions/ contraindications
- avoid in pregnancy/lactation
Four Major Statin Benefit Groups
- Group 1: nave clinical ASCVD - use high intensity statin if = 75y/o - use moderate intensity statin is > 75 y/o
- Group 2: No ASCVD but have LDL-C levels >/= 190 - high intensity statin unless contraindication/unable to tolerate
Group 3: No ASCVD - age 40-75 w/ diabetes and LDL levels of 70-189 - moderate intensity statin if 10yr ASCVD risk is <7.5%; high intensity statin if 10yr ASCVD risk is > 7.5%
Group 4: NO ASCVD or DM; age 40-75 w/ LDL-C 70-189 and 10yr ASCVD risk >/= 7.5%- moderate intensity statin
