Hyperlipidemia: Prelecture Flashcards
MOA: HMG-CoA reductase inhibitors
Inhibit Cholesterol Synthesis
Induce LDL receptor increase on Cell membrane
Low Intensity Statins
Lowers LDL by about <30%
Fluvastatin 20-40mg Lovastatin 20mg Pitavastatin 1mg Pravastatin 10-20mg Simvastatin 10mg
Moderate Intensity Statins
Lowers LDL by about 30-<50%
Anything that isn’t Low or High intensity
High Intensity Statins
Lowers LDL by about >50%
Atorvastatin 40-80mg
Rosuvastatin 20-40mg
Time course of Statin Efficacy
Usually helps when looking on scale over years
Lowers LDL-C, then endothelial function restored, inflam reduce, ischemic episode reduced, plaques stabilized = cardiac events reduced
Why is HPS important
Large trial 25K
Showed all had equal CHD benefit from LDL dec regardless of baseline
Why is PROVE-IT important
LDL <70 better than <100 in ACS pt
Why TNT important
LDL <70 better than <100 hyperlipidemic CHD pts
Why REVERSAL important
Statins reduce Atherosclerotic plaque size and prevent progression
Statin Adverse effects
GI
Headache
SAMS
** Rhabdomyolysis **
Statin Drug interactions
All but pravastatin metabolism via CYP450
Rosuva/Fluvastatin = few DI
Which drugs do you want to avoid with Statin?
Fibrate, risk of rhabdomyolysis risk
Which statin can be dosed at any time of day
Rosuvastatin and Atorvastatin
When to start low dose of statin
if patient on 3A4 inhib Renal insufficiency (Clcr <30-60, minus atorvastatin)
Simvastatin 80 has….
increased risk of Myopathy
Increased SAM
no one should start dose, but can continue if already taking
Drugs contraindicated with Simvastatin
Itra,Keto,Posaconazole
Ery,Clari,Telithromycin
Gemfibrozil
Drugs that shouldn’t exceed 10mg simvastatin with
Amiodarone
Verapamil
Diltiazem
Drugs that shouldn’t exceed 20mg simvastatin with
Amlodipine
Fruit that should be avoided with Simvastatin
Grapefruit juice >1 quart daily
Statin Safety
Caution higher intensity statins in asians/ history of hemorrhagic stroke
Characteristics predisposing patients to side effects of statins
75yrs+ unexplained ALT elev X 3 previous statin intolerance taking drugs affecting statin metabolism serious comorbidities
Rhambdomyolysis
Muscle pain, weakness,tenderness, dark urine
can be fatal
muscle cell breakdown and release into bloodstream
What should you measure prior to statin that is hallmark of Rhambdomyolysis
CK
How to manage myopathy
decrease dose of original statin and or low dose differential statin and gradually increase as tolerated
Statins may raise….
Blood glucose and A1C
Contraindications of Statins
Pregnancy Category X
Acute Liver disease
Lactation and breastfeeding
Toxic monitoring parameters of statins?
CK level
AST/ALT
PCSK9 Inhibitors MOA
inhibition of PCSK9 = increase LDL receptors, decreasing LDL in blood
How are PCSK9 inhibitors different than statins?
Promote modulation of receptor that clears cholesterol, not blocking synthesis
injectable, every 2-4 weeks
PCSK9 inhibitor Indications and agents
adjust to diet and max tolerated statin doses
Evolocumab (Repatha)
Alirocumab (Praluent)
Bococizumab
Inclisiran
Assessing PCSK9 inhibitors
relatively safe
effective, lower LDL 43-64%
Cost is high, keeping from use
Niacin MOA
decrease hepatic synthesis/secretions of VLDL
Alters metabolism and production of HDL
**Most potent agent to increase HDL, decrease TGs
Niacin Efficacy and Safety
Flushing** major SE
way less effective in reducing LDL, not really recommended
Niacin Flushing
Occurs in most patients
inc dose may inc flushing
most develop tolerance
Niacin Strategies to minimize flushing
30-60min before dose take ASA,Ibupr 200 or other NSAID
Take at end of meals
Avoid hot liquids
ER = less flushing and hepatotoxicity
Niacin Ease of Use
dose titration can be confusing for IR
OTC doesn’t equal RX
Niacin Toxic monitoring
Glucose, Uric Acid, LFTs
Fibric Acid Derivatives
Gemfibrozil (Lopid)
Fenofibrate (Tricor)
Clofibrate (Atromid)
Fenofibric Acid (Trilipix)
Fibric Acid Derivatives MOA
PPARa agonists
increase HDL, decrease TG levels, increase LDL particle size
Fibric Acid Derivatives Efficacy
small effects on LDL
Reserved for increased TGs lvls
clinical evidence decrease CHD events(less than statins)
Fibrate side effects
Gi side effects
Fenofibrate better tolerated than Gemfibrozil
Never use together with Statins
Fibrate Toxic monitoring
LFTs baseline and then every 6 month, signs/symptoms of myopathy or rhabdomyolysis
Ezetimibe MOA
Inhibits cholesterol absorption in small intestine
works at brush border of small intestine
gets continuously recycled
Ezetimibe efficacy
lowers LDL by like 10-20%, usually used as an add on. Doesn’t do much for HDL/TG
Ezetimibe safety
Well tolerated, few side effects and no clinical DI
Easy to use, once daily
Cost isn’t crazy
Bile Acid Sequestrants
Cholestyramine (Question)
Colestipol (Colestid)
Colesevelam (WelChol)
Bile Acid MOA
Exchange CL ion for bile acid, preventing body from reabsorbing Bile acids which help cholesterol absorption.
Bile Acid Efficacy
15-30% LDL reduction, primarily used for LDL and maybe as add on
Ezetimibe usually preferred add on tho
Bile Acid Side effects
Not used much due to Side effects/ DI
Abdominal pain, bloating, constipation, bind to bunch of drugs
Lomitapide (Juxtapid)
MTP inhibitor
prevents chylomicron formation
used only in patients with familiar hyperlipidemia. probs won’t be used often + not in current guidelines.
