Dyslipidemia Flashcards
MOA of Omega 3’s
Unknown
dec. hepatic circulation vs. dec. TG synthesis
ADE Omega 3’s
FISHY BURP
indigestion
altered taste
Omega 3’s Lab effects:
Dec. TG by 60%
Cholesterol Absorption Inhibitors
drug name
Ezetimibe
Zetia, Vytorin (from the ppt)
MOA Cholesterol Absorption Inhibitors
ezetimibe, zetia, vytorin
dec. intestinal absorption of DIETARY and BILIARY cholesterol
ADE Chol. Absorption Inhibitors
Diarrhea, upset stomach, musculoskeletal, sinusitis and infections
Metabolism of Ezetimibe, Zetia, Vytorin
Glucuronidation active metabolite
NOT CYP450- advantage
Lovaza
Supplements
Fatty Fish
Drug class?
Omega 3 Fatty Acids
Fibrates Drug names
Gemfibrozil
Fenofibrate
Lofibra, Lipoforr, Trilipix, Tricor (from ppt)
MOA Fibrates
Activate PPAR-a, which modulates metabolism and catabolism of lipids
(RNA/DNA transcription)
ADE Fibrates
Abd. pain, nausea, inc SCr, inc transaminases, Myopathy
Metabolism Pathway of Fibrates
Hepatic metabolism, renal excretion (conjugated)
Fibrates place in therapy
2nd line for pts who can’t take Statins
Nicotinic Acid class
Nicotinic Acid
Niacinamide
Niacin
Niaspan (from ppt)
MOA Nicotinic Acid
? in adipose tissue, dec. TG synthesis
ADE Nicotinic Acid
FLUSHING
n/v, inc. transaminases, myopathy
How to dec. the flushing of nicotinic acid?
Take aspirin (325 mg) 30 min prior to nicotinic acid
Metabolism of Nicotinic acid
Hepatic Conjugation
renal excretion
Classes that use hepatic metabolism and renal excretion?
Fibrates and Nicotinic Acid
Bile Acid Sequestrants
drugs
Cholestyramine (powder- mix in 8 oz H20) Colestipol (p, tablet) Colesevelam (p,t) Colestid Questran
MOA Bile Acid Sequestrants
Anion exchange resins in GI tract that bind to bile acids
helps to excrete in feces
ADE Bile Acid Sequestrants
Abd Pain constipation flatulance n/v **GI Effects**
Place in therapy for bile acid sequestrants
2nd line for selected pts
Statin drugs
fluvastatin pravastatin lovastatin simvastatin atrovastatin rosuvastatin
MOA statins
inhibit HMG- CoA reductase
at rate limiting step in chol. synthesis, block step, block pathway
ADE statins
dizzy, h/a, abd pain
nausea, inc. transaminases, myopathy
Bile Acid Sequestrants DI
interfere with many drugs so take 1-2 hours AFTER other meds or other meds 4-6 hours AFTER resin
Statin effects
plaque stability angiogenesis vascular cytoprotection anti-oxidant immunomodulary anti-inflammatory anti-thrombic endothelial fxn
Order statins in low to high potency
Fluva, Prava, Lova, Simva, Atorva, Rosuva
Which statins are lipophilic?
Fluva, Lova, Simva, Atorva
so they’re good concern w/myopathy
Which statins are not lipophilic?
Prava, Rosuva
Which statin is not metabolized through the CYP450 pathway?
How it is metabolized?
Pravastatin
by sulfation
Long half life statins?
Atorva, Rousuva
Dose which statins at night?
The lower doses:
Fluva, prava, lova, simva!
Which statin has an inactive metabolite?
Pravastatin
High intensity statins lower LDL by
> 50%
again: atorva, rosuva
Moderate Intensity Statins lower LDL by
30-50%
Low Intensity lower LDL by
Old way of Tx
- set LDL goal
- Tx to target
- use whatever works until LDL
New way of Tx
Follow the high quality evidence from RCTs
Lifestyle Modifications:
Diet
Exercise
Always: veggie, fruit, whole grains
Sometimes: low fat dairy, poultry, fish, legumes, nontropical oil, nuts
Rarely: sweets, sweet beverage, red meat
Exercise: 3-4x/wk, 40 min, mod to vigorous intensity
Diet elevated LDL
weight gain
saturated/trans fat
anorexia
Diet elevated TG
** Excess ETOH
Wt. gain, low-fat diet, refined carbs
Drugs that elevate LDL
**steroids, diuretics, cyclosporine, amiordarone
Drugs that elevate TG
**Glucocorticoids
**Protease inhibitors
**anabolic steroids
**sirolimus
thiazide diuretics, estrogen, bile acid sequestrant, ralozifene, tamoxifen, beta blockers
Disease that elevate LDL
Nephrotic Syndrome
Biliary Obstruction
Disease that inc. TG
Nephrotic syndrome
chronic renal failure
lipodystrophies
Altered metabolism elevate LDL
hypothyroidism
obesity
pregnancy
altered metabolism to elevate TG
hypothyroidism
obesity
pregnancy
poor controlled DM- consider stabilize DM before TG
comorbidities- renal/hepatic dysfxn
hx of statin intolerance or muscle disorder
unexplained ALT elevation > 3x ULN
age over 75 years
Factors predisposing individuals to adverse events
excluding DI
Drug interactions that increase statin concentrations
aka inc risk of ADE
nicotinic acid, fibrates cyclosporine, azole antifungals macrolids, protease inhibitors verapamil, amiodarone grapefruit juice, alcohol
baseline labs to check
fasting lipid panel (for statin intensity) alanine aminotransferase (ALT) creatine kinase (CK) fasting blood glucose/ A1c for DM
drugs to check for classes other than statins
uric acid (niacin)
triglycerides (bile acid sequestrants bc they inc TG)
serum Cr/ GFR (fibrates)
ACVD 10 year risk score is specific to what 4 categories?
Male and female
White and AA populations
what factors are used in the pooled cohort other than gender and race?
Age, SBP, smoking, DM, HDL, total cholesterol, meds for BP
asses ASCVD risk factors every:
4-6 yrs in adults 20-79 yo w/o hx of ascvd
estimate 10 yr risk every 4-6 years in pts
40-79 yo w/o hx of ascvd
what are the 3 statin benefit risk groups
- LDL >= 190, age 21+
- DM + Age 40-75 yo
- ASCVD >= 7.5% and age 40-75yo
Dizziness points
less noticeable if take pill at night
lessens with time
SE not harmful if tolerable
STOP taking statins if:
There is a change in urine color to dark brown! this is rare and shows renal failure
How long on statin before benefit?
2-5 years! but it decreases LDL in 6-8 wks
if LDL is less than _____, it is reasonable to reduce the intensity.
40 mg/dl
monitor LFT’s
w/in first 3 months
if elevated usually resolves with d/c
ALT/AST elevation = normal
monitor symptoms of myopathies
CK labs
severe if CK is 10x normal- if yes it will progress to rhabdomyolitis and kidney failure
mc with DI to inc statin conc.
What is an alternative to statin for Men at risk for ASCVD?
1st Colestipol before meal
2nd Gemfibrozil
What is a statin alternative for a HIGH risk MALE?
1st Cholestyramine
Male or female with T2DM, w/ or w/out renal impairment.
Alternative to statin?
Micronized fenofibrate
Male or female with established ASCVD.
Alternative to statins?
Gemfibrozil
Colestipol
What is important to remember about the pooled cohort equation?
Only designed for naive pts.
How do you tell if your pt on lipid lowering meds can benefit from a higher intensity?
-titrate up as tolerated by pt
use opposite method if you think the intensity can be lowered and consider removing the non statin if pt is on more than one drug
TG over 1000 mg/dL
now what?
PREVENT PANCREATITIS. more than prevent ASCVD.
1st Line = FIBRATES
2nd Line= niacin and omega 3
lifestyle mod: d/c etoh, d/c meds that inc TG, tx uncontrolled DM
Pt has clinical ASCVD they need _____ intensity
HIGH intensity
A-grade recommendation
Pt has LDL >= 190 and over 21 yrs old
they need a ______ intensity statin
HIGH!!
B-grade recommendation
Pt has DM and is 40-75 yo
They need a ______ intensity
MODERATE intensity
A- grade
(if same pt ASCVD risk >7.5%– HIGH intensity)
ASCVD >= 7.5% and Age 40-75 yo
MODERATE or HIGH intensity
A-grade
assess the other risks!
What can you use if the ASCVD risk assessment is unclear?
Family history
hs-CRP >= 2 mg/ml
CAC score >= 300
ABI
What factors have uncertainty for the ASCVD risk calculation?
ApoB CKD Albuminurea Cardiorespiratory fitness Carotid intima media thickness (CIMT)
