Dyslipidemia

Question 1

HMG-CoA Reductase inhibitors MOA

Answer 1

completely inhibits HMG-CoA reductase

upregulates LDL receptors in the liver allowing for more LDL to be delivered reducing plasma cholesterol

within the ER, SREBP is present

contains a REG domain and bHLH domain and SCAP

SCAP keeps the SREBP with the ER when sterols are present

when sterols are depleted by statins, this complex translates to the golgi apparatus

S1P cleaves between REG and bHLH domain

S2P cleaves the bHLH domain from the golgi allowing it to be translocated to the nucleus

Increases LDL-R
Increases hepatic LDL uptake

Question 2

Statin indication

Answer 2

Hypercholesterolemia

20-60% reduction in LDL
10-33% reduction in TG
5-10% increase in HDL

Initiated right after MI without regards to lipid levels

Question 3

Metabolism of statins

Answer 3

CYP3A4: Lovastatin, Simvastatin and Atorvastatin
-Inhibits can increase levels: macrolide antibiotic, cyclosporine, ketoconazole, grapefruit juice

CYP2C9: Fluvastatin and Rosuvastatin
-Inhibits can increase levels: cimetidine, metronidazole, amiodarone

Sulfation: Pravastatin

Enterohepatic Recirculation and CYP2C8/9: Pitavastatin

Question 4

Side effects of statins

Answer 4

Rhabdomyolysis (myopathy)
-dose related
-monitor CPK
- increase incidence when combined with gemfibrozil and other CYP inhibitors

Treatment:
d/c statin and evaluate CPK
evaluate for exacerbating conditions like exercise
start the same or lower dose once symptoms resolve
if CPK > 10x UNL then d/c statin
OTC products: CoQ 150-200 mg prior to statin rechallenge and during course of statin therapy to reduce muscle SE

Question 5

Hepatotoxicity

Answer 5

monitor serum transaminase activity
-related to underlying liver disease or alcohol abuse

obtain LFT at baseline
repeat LFT when indicated
if LFT is 3x UNL d/c

increase incidence of type 2 diabetes
-reducing cholesterol in membranes of pancreatic b cells

Question 6

Contraindications with statins

Answer 6

acute liver disease

unexplained, persistent evaluations of transaminases

pregnancy, breastfeeding

MONITOR IN PT WITH RENAL OR HEPATIC IMPAIRMENT

CAUTION IN PT > 75

Check FLP at baseline–> 4 -12 weeks–> 3-12 months

Question 7

Bempedoic Acid

Answer 7

t1/2: 21 hours
used in adjunct to statins

Question 8

Warnings of Bempoidic acid

Answer 8

gout
risk of tendon rupture
avoid in concomitant therapy with simvastatin > 20 and pravastatin >40 (myopathy)

Question 9

PCSK9 inhibitors mechanism

Answer 9

Binds to PCSK9 and prevents it from binding to LDL receptor
Without PCSK9 attached, the LDL receptor is recycles to cell surface and can continue clearing LDL particles

Question 10

PSCK9 Side effects

Answer 10

injection site rxn
myalgia
gi upset
flu symptoms
increased LFT’s

Question 11

mRNA PCSK9 inhibitor

Answer 11

Inclisiran

siRNA hybridizes PCSK9 mRNA and directs degradation of mRNA in hepatocytes

HeFH and ASCVD

Question 12

Inclisiran Side Effects

Answer 12

injection site rxn
arthralgia
UTI
diarrhea
bronchitis
pain in extremities
dyspnea

Question 13

Omega 3- fatty acids

Answer 13

Lovaza (EPA + DHA)
Omtryg (EPA + DHA)
Vascepa (EPA only)

Question 14

Omega-3 fatty acid mechanism

Answer 14

omega-3 fatty acids are poor substrates for enzymes responsible for TG synthesis

inhibits esterification of other fatty acids

Question 15

Indications of omega 3 fatty acids

Answer 15

severe hypertriglyceridemia > 500

lipid lowering agent is given before lovaza

Question 16

Omega 3 fatty acid side effects

Answer 16

can increase LDL-C levels

exempting vascepa

combined with statins to counteract LDL increase

Question 17

Statin Intensity

Answer 17

Low:
Simvastatin 10 mg
Pravastatin 10-20 mg
Lovastatin 20 mg
Fluvastatin 20-40 mg

High:
Atorvastatin 40-80 mg
Rosuvastatin 20-40 mg

Question 18

Secondary factors for moderate hypertriglyceridemia

Answer 18

medications:

Oral estrogens, tamoxifen, raloxifene, retinoids, glucocorticoids

cyclosporine, tacrolimus, sirolimus, cyclophosphamide, interferon

Beta blockers, thiazides, antipsychotics, rosiglitazone, bile acid sequestrants, L-asparginase

Question 19

Drug interactions with Bile acid-binding resins

Answer 19

acetaminophen, thiazides, warfarin, digoxin, fibrates, ezetimibe, OC, corticosteroids, TzDs

Question 20

Non statin recommendations

Answer 20

1st line: Ezetimibe
- If LDL is not at goal after maximal statin
-Pt has DM and ASCVD risk > 20%

2nd line: PCSK9 Inhibitors
-If LDL is not at goal after max statin + zetia
-cannot tolerate

3rd line: Bile acid binding resins
-If < 50% reduction of LDL after max statin + zetia and TG > 300