L24 Flashcards
Receptor for HDL on liver for steroidogenic tissues
SR-B1
Scavenger receptor
What drug class is the most effective at reducing LDL
Statins
Statin mechanism of lowering cholesterol
X HMG co-reductase
- No cholesterol synthesis
More LDL-R expression b/c less LDL in circulation - sensitizes the system
Statin mechanism for CV benefits
Anti-inflam
Anti-thrombogenic
How are most statins metabolized? Exceptions?
First pass extraction in liver via CYP enzymes
Except
- Prava
- Rosuva only slightly metab by liver
Statin adverse SEs
- Hepatitis that presents as flu-like sickness
- Rhabdomyolysis - can progress to kidney failure
- New onset diabetes
- Teratogenic - don’t give to pregnant women
- Peripheral neuropathy
- cP450 drug ints
What 2 enzyme levels are you going to monitor for pts on statins
Serum liver transaminases
Creatinine
Should you give statins to diabetic pts?
Yes
Higher risk of experiencing a cardiac event or death if diabetic
But benefits»_space; risk
When should pts take their statins?
Before bed
Cholesterol levels highest at night
What are the 3 1st gen statins?
Simvastatin
Pravastatin
Lovastatin
What are the 2, 2nd gen statins?
Atorvastatin
Rosuvastatin
More potent forms
What is the mechanism of bile acid binding resins?
Bile acids contain cholesterol
- Usually recycled to preserve cholesterol stores
Instead, bind them and excrete them
Force the liver to use cholesterol to make more
Less cholesterol in circulation, reflex increase LDL-R expression
Which pts should you NOT give bile acid binders to?
High TGs
Bide acid binders also increase VLDL for unknown reasons –> increases TGs
Bind acid binder SEs
GI
Name the 2 bile acid binding resins
Cholestyramine
Colesevelam
Which cholesterol absorption inhibitor do you need to know
Ezetimibe
Ezetimibe mechanism
Blocks cholesterol and plant sterol GI absorption via X NPC1L1 Acts on dietary AND biliary cholesterol Decreases serum: - Cholesterol - LDL No change to TGs
How is ezetimibe excreted
Feces - with whatever it bound!
Evidence shows ezetimibe acts best when added to which statin specifically
Simvastatin
3 PCSK9 inhibitors you need to know
Alirocumab
Evolocumab
PCSK9 inhibitor mechanism
PCSK9 = internalization of LDL-R
Give w/ statins b/c when you ↑LDL-R, you also ↑PCSK9 levels
What is a gain of function PCSK9 mutation associated with?
FHyperlipidemia
What disease is secondarily benefited by ↓LDL
Metabolic syndrome
Fibrates mechanism
Ligand for peroxisome proliferator-activated receptor (PPAR)
= nuclear receptors
↓TG + ↑HDL
2 fibrates you need to know
Gemfibrozil
Fenofibrate
Use of fibrates
BEST method to ↓TGs
↓CV events
Which drug interaction should you keep in mind with fibrates?
Warfarin
Adjust dosing since fibrates bind plasma proteins warfarin would otherwise bind
Fibrates SEs
GI
↑risk gallstones b/c ↑biliary cholesterol
Which drug will give the largest ↑HDL
Nicotinic acid (this is the active form) Also some ↓LDL & TGs
Nicotinic acid mechansim
Activates Niacr1 on adipose tissue
X lipolysis –> no FFAs toliver for TG or VLDL synthesis
Is there a benefit to combining niacin w/ statins?
No - niacin goal is not for LDL reduction
Use alone to ↓TGs
Niacin SEs
Skin flushing
- Prostaglandin vasodilation of skin
- ↓if use time release forms
Makes diabetes worse
