Statins Flashcards
Overview of LDL, HDL, VLDL
Types of Lipids
- Cholesterol- plasma lipids-> transported by lipoproteins
- Triglycerides- plasma lipids- same
- Phospholipids
lipoproteins= cholesterol + triglycerides + 1 apolipoprotein B100 molecule (apoB)
Classification of lipoproteins
High density Lipoproteins (HDL)- why are they so good?
- Retrieve cholesterol from the artery wall and recycle
- Inhibit oxidation of atherogenic lipoproteins
- Low levels= INCREASED RISK FOR ATHEROSCLEROTIC DISEASE
Why do we treat hyperlipidemia and hypertriglyceridemia?
Causes Atherosclerosis and Acute Pancreatitis
Why treat hyperlipidemia?
Atherogenic lipoproteins inhibit the release of nitric oxide (which causes dilation)-> reduce changes in acute coronary events-> target LDL
Nonpharmacologic therapy
- Exercise and smoking cessation
- Reduce percent of calories from saturated and trans fats
- Increased intake of soluble fibers 25 g
- Fish- cold water fish
- Red Yeast Rice- OTC not regulated
Treatment of Hyperlipidemia
- HMG-CoA Reductase Inhibitors
- Cholesterol absorption inhibitors
- Bile Acid Sequestrants
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors
HMG-CoA Reductase inhibitors
MOA: competitively inhibit HMG coA reductase= rate limiting step in cholesterol biosynth
Efficacy: Most powerful drugs for lowering LDL
SE: Adverse muscle events, hepatitis dysfunction, renal dysfunction, Behavior (suicide), DM
NOT FOR PREGNANCY
Drug interactions: CYP3A4, CCB, HIV protease inhibitors, Amiodarone, Grapefruit juice, cyclosporine, HCV antivirals, Fibrates, colchicine, fusidic acid, niacin
ALSO LOWERS TRIGLYCERIDES (1ST LINE) AND LOWER CRP markers
HMG-COA reductase inhibitor choices
- strongest= Rosuvastatin and Atorvastatin
- if renal impaired= Atorvastatin or Fluvastatin
- if chronic liver disease= Pravastatin with alcohol abstinence
- Fewest drug interactions= Pravastatin, Fluvastatin, rosuvastin, and pitavastatin
- muscle related adverse effects? Pravastatin and Fluvastatin = lower risk
Statin therapy high high intensity
Lowers LDL by over 50%
Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg
Statin therapy moderate intensity
Lowers LDL from 30-50%
FLARS
Fluvastatin 40
Lovastatin
Atorvastatin 10-20
Rosuvastatin 5-10
Simvastatin 20-40
Statin therapy low intensity
Lowers by less than 30%
Pravastatin 10-20
Lovastatin 20 mg
Rule of 6
double the dose = added 6% reduction
5 mg= 40%
10 mg= 46%
HMG-COA reductase inhibitors muscle-related adverse events
Statin Associated Muscle symptoms= SAMS
relatively uncommon= 2% pts
RF: increased age, female, low body weight, kidney disease, high physical activity, hyperthyroid
Clinical features: larger muscle groups
Diagnosis? Clinical and/or Creatinine Kinase= marker for muscle degradation
Management? Discontinuation, switching statins, alternate dosing (MWF dosing- ensure compliance), Coenzyme Q (no benefit)
Rhabdomyolysis
DISCONTINUE STATIN IMMEDIATELY
Muscle necrosis
Symptoms: Myalgia, red/brown urine, elevated CK- pain, weakness, swelling
Assoc manifiestations: Fluid/electrolyte imbalance-? Cardiac dysrhythmias, AKI (myoglobin release damaging kidneys), Compartment syndrome, DIC
Management: Prompt recognition, evaluation, management, AGGRESSIVE VOLUME REPLETION
Cholesterol Absorption inhibitors
Ezetimibe (Zetia)- 2nd MC RX
MOA: impairs dietary and biliary cholesterol absoption @ brush border of intestine-> inhibit cholesterol transporter
efficacy: by 10-14% LDL
QUICK ONSET= 10 HRS
SE: arthralgia, GI, sinusitis/URI, hepatitis
alone or with another statin
Bile acid-binding resins
Cholestyramine colestipol and Colesevelam
MOA: bind to bile acids in intestine resulting in interruption of reabsorption of bile acids
MOSTLY COMBO WITH STATINS OR NICOTINIC ACIDS
AE: nausea, bloating, cramping, increase liver enzymes
Drug interactions: digoxin, warfarin, fat soluble vitamins, HCTZ, furosemide, NSAIDS, thyroxine
INCREASE TRIGLYCERIDE LEVELS BC TRICKS BODY INTO THINKING ITS LOW AND INCREASE
Proprotein convertase subtilisin/Kexin Type 9 (PCSK9) inhibitors
Evolocumab (Repatha) and Alirocumab (Praluent)
MOA: binds and inhibits PSCK9 (enzyme in liver that binds to LDL and increases it in the plasma)
REDUCTION IN RATES OF STROKE AND MI
MONO OR COMBO
AE: injection site rxn
EXPENSIVE
Indications: pts on Maximally tolerated doses of statin w/ familial hypercholesterolemia or pts with cvd needing lowering of LDL
Bempedoic acid
MOA: inhibitor of adenosine triphosphate-citrate lyase-> upstream of HMG reductase inhibit
mono or combo
AE: nasopharyngitis, myalgia, URI, elevated uric acid in gout patients-> worsen wont cause
Indications: heterozygous familial hypercholesterolemia or established atherosclerotic CVSD who require additional lowering of LDL
15-25% reduction in LDL
Combo therapies
Who requires it?
1. Familial hypercholesterolemia w/ on-tx LDL of >100 mg/dl
2. Existing CVD w/ on-tx LDL >70 mg/dlL (2ndary prevention)
3. High risk w/ TG >150 mg/dL and non HDL > 100 mg/dL
Ezetimibe + statin= no reduction in mortality but MI AND STROKE REDUCED and higher rate of LDL < 70
PCSK9- Antibodies plus statins= REDUCTION IN CARDIOVASCULAR EVENTS
Hypertriglyceridemia
Why tx? Reduce risk of pancreatitis and ASCVD
Nonpharmacologic measures:
1. Management of HTN
2. Smoking cessation
3. Sedentary lifestyle modification
4. Weight loss
5. diet and alcohol consumption
Classification:
Normal <150 mg/dL
Moderate 150-499 mg/dL
Mod-Severe 500-999 mg/dL
Severe >1000 mg/dL
Treatment of Hyperglyceridemia
- Statins
- Fibric Acid derivatives (Fibrates)
- Omega- 3 polyunsaturated fatty acids (PUFA)
- Niacin
Fibric acid derivatives (fibrates)
ex: Fenofibrate and gemfibrozil
MOA: Peroxisome proliferation-activated receptor- alpha (PPAR-alpha) agonist-> increases HDL and decreases VLDLs
AE: ASSOC MUSCLE TOXICITY, POSSIBLE RHABDOMYOLYSIS, NEPHROTOXIC, FDA BLACK BOX WARNING FOR SEVERE LIVER INJURY WITH FENOFIBRATE
Drug interactions: Warfarin
Benefits:
Reduce LDL by 10-15%
TG by 40%
increase HDL by 15-20%
