Hyperlipidemia: Prelecture

Question 1

MOA: HMG-CoA reductase inhibitors

Answer 1

Inhibit Cholesterol Synthesis

Induce LDL receptor increase on Cell membrane

Question 2

Low Intensity Statins

Answer 2

Lowers LDL by about <30%

Fluvastatin 20-40mg
Lovastatin 20mg
Pitavastatin 1mg
Pravastatin 10-20mg
Simvastatin 10mg

Question 3

Moderate Intensity Statins

Answer 3

Lowers LDL by about 30-<50%

Anything that isn’t Low or High intensity

Question 4

High Intensity Statins

Answer 4

Lowers LDL by about >50%

Atorvastatin 40-80mg
Rosuvastatin 20-40mg

Question 5

Time course of Statin Efficacy

Answer 5

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

Question 6

Why is HPS important

Answer 6

Large trial 25K

Showed all had equal CHD benefit from LDL dec regardless of baseline

Question 7

Why is PROVE-IT important

Answer 7

LDL <70 better than <100 in ACS pt

Question 8

Why TNT important

Answer 8

LDL <70 better than <100 hyperlipidemic CHD pts

Question 9

Why REVERSAL important

Answer 9

Statins reduce Atherosclerotic plaque size and prevent progression

Question 10

Statin Adverse effects

Answer 10

GI
Headache
SAMS
** Rhabdomyolysis **

Question 11

Statin Drug interactions

Answer 11

All but pravastatin metabolism via CYP450

Rosuva/Fluvastatin = few DI

Question 12

Which drugs do you want to avoid with Statin?

Answer 12

Fibrate, risk of rhabdomyolysis risk

Question 13

Which statin can be dosed at any time of day

Answer 13

Rosuvastatin and Atorvastatin

Question 14

When to start low dose of statin

Answer 14

if patient on 3A4 inhib
Renal insufficiency (Clcr <30-60, minus atorvastatin)

Question 15

Simvastatin 80 has….

Answer 15

increased risk of Myopathy
Increased SAM

no one should start dose, but can continue if already taking

Question 16

Drugs contraindicated with Simvastatin

Answer 16

Itra,Keto,Posaconazole
Ery,Clari,Telithromycin
Gemfibrozil

Question 17

Drugs that shouldn’t exceed 10mg simvastatin with

Answer 17

Amiodarone
Verapamil
Diltiazem

Question 18

Drugs that shouldn’t exceed 20mg simvastatin with

Answer 18

Amlodipine

Question 19

Fruit that should be avoided with Simvastatin

Answer 19

Grapefruit juice >1 quart daily

Question 20

Statin Safety

Answer 20

Caution higher intensity statins in asians/ history of hemorrhagic stroke

Question 21

Characteristics predisposing patients to side effects of statins

Answer 21

75yrs+
unexplained ALT elev X 3
previous statin intolerance
taking drugs affecting statin metabolism
serious comorbidities

Question 22

Rhambdomyolysis

Answer 22

Muscle pain, weakness,tenderness, dark urine

can be fatal

muscle cell breakdown and release into bloodstream

Question 23

What should you measure prior to statin that is hallmark of Rhambdomyolysis

Answer 23

CK

Question 24

How to manage myopathy

Answer 24

decrease dose of original statin and or low dose differential statin and gradually increase as tolerated

Question 25

Statins may raise....

Answer 25

Blood glucose and A1C

Question 26

Contraindications of Statins

Answer 26

Pregnancy Category X Acute Liver disease Lactation and breastfeeding

Question 27

Toxic monitoring parameters of statins?

Answer 27

CK level | AST/ALT

Question 28

PCSK9 Inhibitors MOA

Answer 28

inhibition of PCSK9 = increase LDL receptors, decreasing LDL in blood

Question 29

How are PCSK9 inhibitors different than statins?

Answer 29

Promote modulation of receptor that clears cholesterol, not blocking synthesis injectable, every 2-4 weeks

Question 30

PCSK9 inhibitor Indications and agents

Answer 30

adjust to diet and max tolerated statin doses Evolocumab (Repatha) Alirocumab (Praluent) Bococizumab Inclisiran

Question 31

Assessing PCSK9 inhibitors

Answer 31

relatively safe effective, lower LDL 43-64% Cost is high, keeping from use

Question 32

Niacin MOA

Answer 32

decrease hepatic synthesis/secretions of VLDL Alters metabolism and production of HDL **Most potent agent to increase HDL, decrease TGs

Question 33

Niacin Efficacy and Safety

Answer 33

Flushing** major SE | way less effective in reducing LDL, not really recommended

Question 34

Niacin Flushing

Answer 34

Occurs in most patients inc dose may inc flushing most develop tolerance

Question 35

Niacin Strategies to minimize flushing

Answer 35

30-60min before dose take ASA,Ibupr 200 or other NSAID Take at end of meals Avoid hot liquids ER = less flushing and hepatotoxicity

Question 36

Niacin Ease of Use

Answer 36

dose titration can be confusing for IR OTC doesn't equal RX

Question 37

Niacin Toxic monitoring

Answer 37

Glucose, Uric Acid, LFTs

Question 38

Fibric Acid Derivatives

Answer 38

Gemfibrozil (Lopid) Fenofibrate (Tricor) Clofibrate (Atromid) Fenofibric Acid (Trilipix)

Question 39

Fibric Acid Derivatives MOA

Answer 39

PPARa agonists increase HDL, decrease TG levels, increase LDL particle size

Question 40

Fibric Acid Derivatives Efficacy

Answer 40

small effects on LDL Reserved for increased TGs lvls clinical evidence decrease CHD events(less than statins)

Question 41

Fibrate side effects

Answer 41

Gi side effects Fenofibrate better tolerated than Gemfibrozil Never use together with Statins

Question 42

Fibrate Toxic monitoring

Answer 42

LFTs baseline and then every 6 month, signs/symptoms of myopathy or rhabdomyolysis

Question 43

Ezetimibe MOA

Answer 43

Inhibits cholesterol absorption in small intestine works at brush border of small intestine gets continuously recycled

Question 44

Ezetimibe efficacy

Answer 44

lowers LDL by like 10-20%, usually used as an add on. Doesn't do much for HDL/TG

Question 45

Ezetimibe safety

Answer 45

Well tolerated, few side effects and no clinical DI Easy to use, once daily Cost isn't crazy

Question 46

Bile Acid Sequestrants

Answer 46

Cholestyramine (Question) Colestipol (Colestid) Colesevelam (WelChol)

Question 47

Bile Acid MOA

Answer 47

Exchange CL ion for bile acid, preventing body from reabsorbing Bile acids which help cholesterol absorption.

Question 48

Bile Acid Efficacy

Answer 48

15-30% LDL reduction, primarily used for LDL and maybe as add on Ezetimibe usually preferred add on tho

Question 49

Bile Acid Side effects

Answer 49

Not used much due to Side effects/ DI Abdominal pain, bloating, constipation, bind to bunch of drugs

Question 50

Lomitapide (Juxtapid)

Answer 50

MTP inhibitor prevents chylomicron formation used only in patients with familiar hyperlipidemia. probs won't be used often + not in current guidelines.