Lipids

Question 1

Name 4 classes of drugs that can lead to acquired dyslipidemia

Answer 1

Antipsychotics
OCPs
Beta blockers
High-dose diuretics

Question 2

Inheritance & main pathophys of Familial hypercholesterolemia?

Answer 2

Dysfunction of LDL uptake (LDL receptor mutations usually) –> high blood [LDL]

Autosomal dominant inheritance

Question 3

Inherited Hyperlipoproteinemias type IIa and IIb (names & lipoprotein that are off)

Answer 3

IIa= familial hypercholesterolemia;  high LDL
IIb = familial combined hyperlipidemia;  High LDL/VLDL/TGAs

Question 4

Inherited hyperlipoproteinemia type IV: name + inheritence + defect

Answer 4

Familial hypertriglyceridemia
Autosomal dominant
High VLDL (hepatic overproduction), TGAs, total cholesterol elevated

Question 5

framingham risk score tells you what? What are the 6 components?

Answer 5

Estimates 10-year CVD risk and lipid/ApoB targets

Age, HDL, total cholesterol, systolic BP, smoking, diabetes (also diff based on gender and FMHx)

Question 6

Normal level total cholesterol

Answer 6

<5.2 mmol/L

Question 7

Normal level TGs

Answer 7

<1.7 mmol/L

Question 8

Normal level HDL

Answer 8

> 1 for men, >1.3 for women

Question 9

Normal level of LDL-C

Answer 9

<3.4 for women

Question 10

Recommended screening for dyslipidemia

Answer 10

High-risk individuals: 20-25yo for men, 30-35 for women

Low-risk: 35_ for men, 45+ for women

Question 11

Name some lab parameters of lipid metabolism, how they are determined, and which lipoproteins are included

Answer 11

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)

Question 12

All ___ -containing lipoproteins are atherogenic

Answer 12

Apo-B

Chyolomicrons, VLDL, IDL, LDL, Lp(a)

Question 13

Name 6 medications for hyperlipidemia

Answer 13

Statins
Cholesterol absorption inhibitors
Bile acid resins
Fibrates
Niacin (B3)
PCSK9 inhibitors

Question 14

Stains mechanism of action & effect

Answer 14

Inhibit HMG-CoA reductase/cholesterol production

Lower LDL in blood and TGAs, increases LDL-R and HDL

Question 15

Moderate-intensity statin therapy aims to decrease LDL-C by ____; high-intensity aims at a ___reduction

Answer 15

30-50% = moderate-intensity
50% = high-intensity

Question 16

What type of drug is ezetimibe? How does it work? How is it often used?

Answer 16

Cholesterol absorption inhibitor
Inhibit NPC1L1
Often combined w/ statins

Question 17

Metabolism of statins

Inhibitors?

Answer 17

CYP3A4, inhibited by...
Azole antifungals
Macrolides (erythromycin/clarithromycin, azith ok)
Grapefruit
Valproate
...many more

Question 18

Common ADEs of Statins

Answer 18

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

Question 19

Maintain a high index of suspicion for ____ if ____ pain occurs after administering statins.

Answer 19

Rhabdomyolysis

Muscle pain

Question 20

Complication of rhabdomyolitis

Answer 20

Can cause myoglobulinuria –> AKI (check BUN/creatinine)

Question 21

How do bile acid resins work

Answer 21

Cause BAs to be excreted rather than absorbed via enterohepatic circ –> more production, using cholesterol

Question 22

ADEs of Bile acid resins

Answer 22

GI upset
High LFTs
Myalgia

Can increase TGAs

Question 23

Bile acids decrease absorption of…

Answer 23

Warfarin, fat-soluble vitamine

Question 24

Name 2 fibrates

Answer 24

Fenofibrate, benzafibrate

Question 25

MOA of fibrates

Answer 25

Activate LPL --> TGA breakdown, increase HDL

Question 26

Fibrates usually used for what variety of hyperlibidemia?

Answer 26

Hypertriglyceridemia

Question 27

ADEs of fibrates

Answer 27

Dyspepsia Myopathy (rhabdo risk) Cholelithiasis (decreases cholesterol --> BA conversion in liver, bile supersat w/ chol) High LFTs

Question 28

Contraindication for using fibrates

Answer 28

Renal insufficiency Gallbladder disease Liver failure

Question 29

PCSK9 inhibitors are used in whom? MOA?

Answer 29

High-risk patients who fail statins | Monoclonal Ab inhibits PCSK9 which usually degrades LDL-r --> more LDL-R recycling and LDL uptake

Question 30

Are fibrates and/or PCSK9 inhibitors usually combined with statins?

Answer 30

Fibrates - in exceptional cases (mixed dyslipidemia) | PCSK9 commonly combined w/ statins and/ or cholesterol absorption inhibitors

Question 31

Niacin MOA

Answer 31

Inhibits lipolysis & FA release in adipose (blocks HSL) --> lower TGs/LDL, higher HDL

Question 32

Name 3 substrates of CYP 2C9

Answer 32

Sulfonylureas Warfarin Fluvastatin (so they can competitively inhibit each other's metabolism!)

Question 33

2 statins metabolized by CYP 34A

Answer 33

Simvastatin | Lovastatin

Question 34

Common CYP 3A4 inducers

Answer 34

Anticonvulsants Dexamethasone Rifampin St John's Wort