Lipids Flashcards
Name 4 classes of drugs that can lead to acquired dyslipidemia
Antipsychotics
OCPs
Beta blockers
High-dose diuretics
Inheritance & main pathophys of Familial hypercholesterolemia?
Dysfunction of LDL uptake (LDL receptor mutations usually) –> high blood [LDL]
Autosomal dominant inheritance
Inherited Hyperlipoproteinemias type IIa and IIb (names & lipoprotein that are off)
IIa= familial hypercholesterolemia; high LDL IIb = familial combined hyperlipidemia; High LDL/VLDL/TGAs
Inherited hyperlipoproteinemia type IV: name + inheritence + defect
Familial hypertriglyceridemia Autosomal dominant High VLDL (hepatic overproduction), TGAs, total cholesterol elevated
framingham risk score tells you what? What are the 6 components?
Estimates 10-year CVD risk and lipid/ApoB targets
Age, HDL, total cholesterol, systolic BP, smoking, diabetes (also diff based on gender and FMHx)
Normal level total cholesterol
<5.2 mmol/L
Normal level TGs
<1.7 mmol/L
Normal level HDL
> 1 for men, >1.3 for women
Normal level of LDL-C
<3.4 for women
Recommended screening for dyslipidemia
High-risk individuals: 20-25yo for men, 30-35 for women
Low-risk: 35_ for men, 45+ for women
Name some lab parameters of lipid metabolism, how they are determined, and which lipoproteins are included
TGs (chylomicrons, VLDL, IDL) - measured directly
Non-HDL cholesterol (chylos, VLDL, IDL, LDL, Lp(a)) - indirectly (ApoB) calculated from total - HDL
LDL cholesterol: calculated using Friedwald formula (total C - HDL - TG/5) or directly ($$)
HDL cholesterol: directly
Total cholesterol: all of the above
Lp(a) - directly (genetic, RF)
All ___ -containing lipoproteins are atherogenic
Apo-B
Chyolomicrons, VLDL, IDL, LDL, Lp(a)
Name 6 medications for hyperlipidemia
Statins Cholesterol absorption inhibitors Bile acid resins Fibrates Niacin (B3) PCSK9 inhibitors
Stains mechanism of action & effect
Inhibit HMG-CoA reductase/cholesterol production
Lower LDL in blood and TGAs, increases LDL-R and HDL
Moderate-intensity statin therapy aims to decrease LDL-C by ____; high-intensity aims at a ___reduction
30-50% = moderate-intensity 50% = high-intensity
What type of drug is ezetimibe? How does it work? How is it often used?
Cholesterol absorption inhibitor
Inhibit NPC1L1
Often combined w/ statins
Metabolism of statins
Inhibitors?
CYP3A4, inhibited by... Azole antifungals Macrolides (erythromycin/clarithromycin, azith ok) Grapefruit Valproate ...many more
Common ADEs of Statins
Headache GI Upset Liver (LFT increase) Myalgia (ok if CK normal) Statin-assoc myopathy (muscle pain/weakness); myositis if high CK, may progress to rhabdomyolysis
Maintain a high index of suspicion for ____ if ____ pain occurs after administering statins.
Rhabdomyolysis
Muscle pain
Complication of rhabdomyolitis
Can cause myoglobulinuria –> AKI (check BUN/creatinine)
How do bile acid resins work
Cause BAs to be excreted rather than absorbed via enterohepatic circ –> more production, using cholesterol
ADEs of Bile acid resins
GI upset
High LFTs
Myalgia
Can increase TGAs
Bile acids decrease absorption of…
Warfarin, fat-soluble vitamine
Name 2 fibrates
Fenofibrate, benzafibrate
MOA of fibrates
Activate LPL –> TGA breakdown, increase HDL
Fibrates usually used for what variety of hyperlibidemia?
Hypertriglyceridemia
ADEs of fibrates
Dyspepsia
Myopathy (rhabdo risk)
Cholelithiasis (decreases cholesterol –> BA conversion in liver, bile supersat w/ chol)
High LFTs
Contraindication for using fibrates
Renal insufficiency
Gallbladder disease
Liver failure
PCSK9 inhibitors are used in whom? MOA?
High-risk patients who fail statins
Monoclonal Ab inhibits PCSK9 which usually degrades LDL-r –> more LDL-R recycling and LDL uptake
Are fibrates and/or PCSK9 inhibitors usually combined with statins?
Fibrates - in exceptional cases (mixed dyslipidemia)
PCSK9 commonly combined w/ statins and/ or cholesterol absorption inhibitors
Niacin MOA
Inhibits lipolysis & FA release in adipose (blocks HSL) –> lower TGs/LDL, higher HDL
Name 3 substrates of CYP 2C9
Sulfonylureas
Warfarin
Fluvastatin
(so they can competitively inhibit each other’s metabolism!)
2 statins metabolized by CYP 34A
Simvastatin
Lovastatin
Common CYP 3A4 inducers
Anticonvulsants
Dexamethasone
Rifampin
St John’s Wort
