4-Hyperlipidemia

vLDL is made in____
Liver
LDL is made____
from vLDL catabolism and cellular synthesis
HDL is made in _____and ______ cells
Hepatic and Intestinal cells
Exogenous Lipid metabolism
LPL converts Chylomicrons to Chylo remnants.
(from foods)
Endogenous Lipid Metabolism
-vLDL converted to IDL then LDL. SOme LDL go to subendothelial space in arteries and are oxidized & taken up by macrophages to make foam cells.
(from liver cells)
HDL reverse Transport
Excess cholesterol from peripheral tissues is removed and transportd bac to liver.
-Starts at liver/small intestine w/ APO1.
-MAcrophage takes excess cholesterol fromarteries
-too much Chol in mac signals receptors
-HDL/APO1 takes chol
CAD(Coronary artery disease)
Stable chol plaq in coronary artery
-plaq can rupture
-If muscle dies__>>>Heart attack
Cerebrovascular Disease
Chol plaq ruptures in cerebral artery casue stroke (permanant damage)
-Or TIA(temporary)
PAD (Peripheral Artery Disease)
Blocked artery in leg
-dificulty wlkng
-slows wound healing bc bad circulatn
HMG COA RED Inhibitors
-Statins
-Block convrsn of HMGCOA to mevalonic acid.
STrongest statins….longest half lifes
Crestor
Lipitor
(can be taken anytime of day)
Pt renal impaired avoid this statin
Pravastatin
Very bad cyp3a4 intrxns
Simvastatin
(Take at night )
HMG COA intrxn [STATINS]
-Azoles
-AMlodipine -Gemfibrozil
-Verapamil, Diltiazem
-MAcrolides -Grapefruit
HMG COA Adv effx [STATINS]
-HA, GI, Fatigue,myalgia (can do myopathy,rhabdo)
for HMG COA inhibs LFTs and CKs
AHA/ACC recommends agnst routine monitoring
-LFT (ALT) baseline test recommended
-CK evauated only for hi risk pt w/ muscle related side effx
HMG Contra [STATINS]
prego
hep disease (LFTs >3xULN)
rhabdo
breast feed
Cholesterol absorption INHIBITOR MOA
-ZETIA(Ezetimibe) [well tolerated/no sidefx]
-targets NPC1L1 protein. reduc absorp of cholesterol from the small intestines
CHol absorp inhib RX intrxn
BAS(bile acid seq)->tk Zetia 2 hrs before or 4 hrs aftr
-cyclosporine
-Fibrates(myopathy)
Chol abs Inhib WARNINGS
preg cat C
elderly
hep disease
myopathy
Chol ABs Inhib are considered similar to _____
Moderate dose statin
Bile Acid Seqs
and MOA
-Cholestyramine(Questran)
-Colestipol HCl(Colestid)
-Colesevelam (Welchol)
-MOA: prevents bile from small intest from going bac to liver. Depletes chol strg by forcing chol to be converted to more bile salt
Triglycerides are inc as a result of what meds?`
BAS(bile acid seq)
BAS administer________
2 hrs before or 4 hrs after any other med
(not signifcntly absrbd..excreted in feces)
Drug INTRXN BAS
-Fat solble vitamins
-B-blokcrs
-Warfrin
-Thiazide Diuretics
BAS Adverse FX
-GI constipation!!!
-bloat, nasuea,flatuence
-Inc triglyc (caution if TG>300)
-inc bleeding in Vit K def pts
Nicotinic Acids and MOA
Niacin(reg release),NIASPAN(ext release)
MOA:inhibits fat from making fatty acid to be turned into TG
Nicotinic Acids RX intrxn
Alcohol(flushing)
BAS(Niacin dec)
Warfrn(inc INR)
Nicotinic Acids SIDE FX
-Flushing/warm feeling
-GI-NVD
-Hyperglycemia (be careful w/DM pt)
-Hepatotoxic or Hyperuricemia
Dec flushing from niacin by____
giving Aspirin 1/2 to 1 hr before administration of niacin
Nicotinic Acids Contraindications
-Hep disease
-Arterial Bleeding
-Active peptic ulcer
__—DISCONTINUE(AFIB,AST/ALT>2-3ULN,Acute gout,AB pain unexplained,Perisitent Hyperglyc)
Most efective in HDL level inc (15-35%)
Nicotinic Acids
Fibric Acid Derivatives and MOA
-Fenofibrate,Gemfibrozil MOA: activates PPARs to enhace lipoprotein lipase act & inc TG rich protein breakdwn.(reduces Hepatic vLDL)
Fenofibrate ______but Gemfibrozil doesnt
Decreases LDL
Fibric Acid Derivatives require _____adj
renal adjustment (metab thru glucuronidation)
Fibric Acid Derivatives INTRXN RXs
-Statins(especlly Gemfibrozil) –>RHABDO
-BAS(dec absrp of fibrates)
-WRFRN(inc INR)
Fibric Acid Derivatives
-well tolrtd
-NVD
-Risk of Rhabdo&Myopathy
Fibric Acid Derivatives CONTRaINdication
Active Liver Disease,gall bladder dis,biliary cirhosis
-renal failure/dialysis
OMEGA 3 FATTY ACIDS and MOA
LOVAZA(EPA 465mg&DHA375mg)
VASCEPA(EPA 1000mg)
MOA: not completely defined,,,may reduce hepatic synth of TG
OMEGA 3 FATTY ACIDS may inc________
LDL up to 45% with LOVAZA due to DHA
(has not been studied w/ renal.hep impairment)
OMEGA 3 FATTY ACIDS INTRXN & Side fx
Warfarin–inc INR
SIDE FX-Nausea,burp,fish breath/taste,prolong bleeding
PCSK9 Inhibitors & MOA:

Alirocumab(q 2 weeks SQ) Evolocumab (q 2 weeks SQ) MOA:-monoclonal antibodies bind PCSK9

-inc Hepatic LDL receptors.

[PCSK9promotes degradation of LDL receptors]

PCSK9 inhib indications
Familial hypercholesteremia in addition to diet and max tolerated statin therapy WARNING:sensitivity(expensive)
MTP inhibitor
-Lomitapide(juxtapid)
-Inhibits MTP,prevents formation of apoB containinglipoproteins in enterocytes & hepatocytes
-reduces chylo&vLDL formation
Indicated for familial hypercholesteremia
MTP inhibitor Adverse effx
Adverse Reactions:
NVD,ab pain
fatigue/dizzy
hepatic—steatoosis&liver transaminases inc >3xULN
Dose limit w/ Clarithromycin and Atorvastatin
Atorvastatin dose limt to 20mg/D
GRAPEFRUIT JUICE LIMIT WITH STATINS
1.2L/DAY GRAPEFRUIT WITH STATINS

CANNOT TAKE GRAPEFRUIT W/ lova or simvaSTATIN!!!!!

CANNOT TAKE GRAPEFRUIT W/
LOVA or SIMVASTATIN
CHD Prevention strategies
smoke cessat
BP reduc
Psycosocial
weight loss
nutrition
physical act(30-60mins 5-6 days/wk)
Metabolic syndrome—>>>>CV RISK CONTRIBUTIONS (3/5 OF FOLLOWING)
-HDl <50(women) <40(men)
-Trigllycerides>/= 150mg/dL
-Glucose>/= 100mg/dL
-Waist circumf>/= 35 inches(men,,,30(women)
-BP >/= 130/85mmHg
Metabolic syndrome more common in_______
Women—Afric-Amer,Hispanics
Recheck Lipid profile q 5 yrs if normal in
men>40yrs
women>50yrs
Friedewald equation for LDL-C
LDL=TC-(HDL+TG/5)
Friedewald Equation for TC
TC=LDL+(HDL+TG/5)
Friedewald for NON HDL
NON HDL=TG/5+LDL or
TC-HDL
Secondary causes of Lipid Abnormalities
Diet,Drugs,Diseases.Disordersof altred metab(preg,obese,hypothyroid)
Benefits Exceed risks for initiating STATIN in
Group 1
Pt w/ [w/o NYHA class II-IV HF or hemodialysis pt]
-ASCVD
-ACS or MI Hx
-Stable/unstable Angina
-Coronary/arterial revascularization
-Stroke,TIA, or PAD
Benefits Exceed risks for initiating STATIN in
Group 2
pt w/ LDL-C>/= 190mg/dL
Benefits Exceed risks for initiating STATIN in
Group 3
40-75yrs
w/ DIABETS and LDL-C 70-189mg/dL
w/o clinical ASCVD
Benefits Exceed risks for initiating STATIN in
Group 4
40-75yrs w/o diabetes or ASCVD
-LDL-C 70-189mg/dL
& estimated 10 yr ASVD risk of 7.5% or higher
High dose statins lower LDL by
>/= 50%
Moderate dose statins lower LDL by
30-<50%
Grp(1) STATIN initiation Tx
Hi intensity statin
(mod statin if not candidate)
Grp(1) STATIN initiation Tx
>75 yrs w/ Clinical ASCVD
Mod intensity statin
Grp(2) STATIN initiation Tx
LDL-C >/=190mg/dL
Hi intensity statin
(mod if not candidate)
Grp(3) STATIN initiation Tx
Diabetes w/ LDL-C 70-189mg/dL
Age 40-75yrs
Mod intensity statin
Grp(3) STATIN initiation Tx
Diabetes w/ LDL-C 70-189mg/dL
Age 40-75yrs
w/ estimated 10yr ASCVD risk >/=7.5%
Hi intensity statin
High Intensity Statin Therapy
atorvastatin 40-80 mg
•rosuvastatin 20-40 mg
Moderate Intensity Statin Therapy
•Atorvastatin 10 (20) mg
•Rosuvastatin(5) 10mg
•Simvastatin 20-40mg
•Pravastatin 40 (80) mg
•Lovastatin 40mg
•FluvastatinXL 80mg
•Fluvastatin40mg bid
•Pitavastatin2-4mg
Low Intensity Statin Therapy
•Simvastatin 10 mg
•Pravastatin 10-20 mg
•Lovastatin 20 mg
•Fluvastatin20-40 mg
•Pitavastatin1 mg
FibricAcids: Place in therapy
—-Caution when initiating gemfibriozilin patient on statin,WHY???
–increased risk for muscle symptoms
Consider fenofibratein combo with low or moderate intensity statin WHEN????
when TG ? 500 mg/dl
Decreasing the statin dose maybe considered when…..
2 consecutive values of LDL are < 40 mg/dl
If pt on STATIN develops DM is this a reason to stop STATIN Tx?
NO
not an indication to stop statin
PREGO WARNING w/ STATINS
should be D/C if pregnant and D/C 2-3 mobefore getting pregnant. Resume post pregnancy.
Fasting lipids panel within ______weeks after initiation or dose adjustment of statin
4-12 weeks
(Fasting lipid panel every 3-12 months after dose stable)
SIMVASTATIN dose
Patients taking diltiazem or verapamil
5-10mg
SIMVASTATIN dose
amlodipineor ranolazine–
5-20mg
Statins significantly metab by CYP3A4
-Lova
-Atorv
-Simva
Statins significantly metab by 2C9
Fluvastatin
Statins NOT significantly metab by CYP450
Prava
Rosuva
Pitava