Dyslipidemia meds Flashcards
What synthesizes cholesterol?
The liver
Where do we get additional cholesterol?
From our diets
Give two features about cholesterol
It has a membrane structure
It is a precursor to steroid hormones
What is the formula for total cholesterol (endogenous and dietary)?
Total-C = (LDL + HDL + VLDL)
What is your bad cholesterol? What is the shorthand for this?
Low density lipoproteins
LDL
What is your good cholesterol? What is the shorthand for this?
High density lipoproteins
HDL
What is the shorthand for triglycerides?
VLDL
What is the optimal LDL measurement?
< 100 mg/dL
What LDL measure is classified as high?
160-180 mg/dL
What are the 2018 ACC/AHA adult recommendations
See slide 10
What are some causes of secondary dyslipidemia?
Diabetes Hypothyroidism Obstructive liver disease Chronic renal failure Drugs
List some lifestyle changes that can lower LDL
TLC diet (reduced intake of cholesterol-raising nutrients and LDL lowering therapeutic options)
Weight reduction
Increased physical activity
Choice of lipid lowering drugs
See slide 17
What are the most commonly prescribed drugs for increased cholesterol?
HMG CoA Reductase Inhibitors
AKA statins
By what % do statins tend to reduce LDL and TG by?
18-55% (LDL)
7-30% (TG)
By what % do statins increase HDL?
5-15%
What are some major side effects of statins?
Myopathy (increased CK)
Increased liver enzymes (increased AST/ALT)
What are some contraindications for statins?
Absolute: liver disease
Relative: use with certain drugs
Give some examples of things that statins have demonstrated therapeutic benefits for.
Reduced major coronary events
Reduce CHD mortality
Reduce stroke
What is the MOA of statins?
Block rate -> limiting step in cholesterol synthesis
When do we see statin induced myopathy?
Serum CK >10x ULN with unexplained muscle pain
When do we see statin induced rhabdomyalysis?
Serum CK > 40x ULN with unexplained muscle pain or weakness
When do pts at risk of statin induced myopathy tend to present?
In the first 12 months
Which statin poses the highest risk for induced myopathy?
High dose simvastatin
What internal element causes simvastatin to pose the risk for induced cardiomyopathy?
CYP3A4
What should you do if pts experiences SEs on a statin?
Try a different one
Give two examples of statins?
Atorvastatin
Rosuvastatin
What is an issue with pitavastatin?
Its very expensive and not generically available as of 2/11/19
By what percent does rosuvastatin lower LDL??
63%
By what percent does atorvastatin lower LDL?
57%
By what percent does simvastatin lower LDL?
46%
How many high dose pts developed myopathy while on simvastatin?
52
How many low dose pts developed myopathy while on simvastatin?
22
How many high dose pts developed rhabdo while on simvastatin?
22
How many low dose pts developed rhabdo while on simvastatin?
0
What is the FDA simvastatin black-box warning?
Restricting dosing of 80 mg of simvastain
When can pts be put on 80 mg of simvastatin?
When they have been taking it for >12 months
What should pts on an 80 mg dose w/o adverse effects do when they need to take a contraindicated drug?
They should switch to another statin
What should pts who’s LDL goal cannot be reached on the 40 mg dose of simvastatin?
They should be switched to a statin w/ less risk of cardiomyopathy
List some drugs that are contraindicated with simvastatin
Itraconazole Eythromycin HIV protease inhbitors Nefazodone Gemfibrozil Cyclosporin Danazol
With what drugs should we not exceed 10 mg simvastatin with?
Amiodarone
Verapamil
Diltiazem
With what drugs should we not exceed 20 mg simvastatin daily?
Amlodipine
Ranolazine
What is an odd contradiction with simvastatin?
Not ingesting > 1 quart of grapefruit juice daily
Are elevated transaminases on statins a reason to dc?
No
Are statin side effects agent specific or class specific?
Agent specific
What should you do with unexplained myalgias w/o CK elevation?
Try a different statin
How many pts receive new scripts for simvastatin?
Very few
What is the MOA of bile acid sequestrants?
Bind dietary cholesterol
What are the major actions of bile acid sequestrants (BAS)?
Reduce LDL 20-25%
Raise HDL 3-5%
May increase TG
What are some SEs of BAS?
GI distress/constipation, diarrhea, bloating
Decreased absorption of other drugs
When are BAS agents contraindicated?
Severe hepatic impairment Raise TG (esp > 400 mg/dL)
Give some examples of BAS
Cholestyramine
Colestipol
Colesevelam
What is an issue with colesevelam?
Its very exepnsive ($561)
When do we usually give BAS?
As add on therapy to max dose statins
What are the major actions if Niacin?
Lowers LDL by 5-25%
Raises HDL by 15-35%
Lowers TG by 10-50%
What is a major SE of niacin?
Flushing
How do we minimize flushing with Niacin?
Pretreatment with NSAIDS 30-60 minutes prior to ingestion
When is niacin usually used?
As add on therapy
Not monotherapy
Not often used
What was needed to prove the efficacy of niacin?
A new large trial
What did the niacin trial show?
Niacin did not reduce incidence of primary composite endpoint (??)
What happened with the niacin trial?
Trial was stopped early
What was an unexpected increase in the niacin trial?
Strokes increased
What was the basic conclusion of the niacin trial?
Niacin doesnt reduce CVA risk but does increase risk CVA risk so its little used
How much do fibric acids decrease TG and VDL by?
25-50%
How much do fibric acids lower LDL?
5-20%
Might fibric acids raise LDL?
Yes, with high TG
How much might fibric acids raise HDL by?
10-20%
What are two fibric acids?
Gemfibrozil
Fenofibrate
What class is ezetimibe a part of?
A drug of a new class that inhibits intestinal absorption of cholesterol
How much does ezetimibe lower LDL?
2-25%
What is the effect of ezetimibe with statins?
Increases effects of statin by 10-15% w/o side effects
When is ezetimibe well tolerated?
At 10 mg/d
What is vytorin?
Exetimibe + simvastatin
What are PCSK9 inhibitors?
New class of monoclonal antibodies
What do PCSK9 inhibitors do when they are added to statins?
Reduce LDL by 50-60%
How do you administer PCSK9 inhibitors?
SC injection q2-4 weeks
What place do PCSK9 inhbitors have in therapy?
Add on to max dose statins
What is a new class of drug not yet FDA approved?
Bempedoic acid
FDA labeling requested in Feb 2019
How often do you give bempedoic acid?
Daily
What is the MOA of bempedoic acid?
Inhibits ATP citrate lyase (key enzyme in chol synthesis)
What is the PO dose of bempedoic acid?
180 mg once daily
Did bempedoic acid show a decrease in LDL?
Yes
Did bempedoic acid decrease non-HDL?
Yes
Did TC decrease on bempedoic acid?
Yes
What are two other things that bempedoic acid decrease?
Apolipoprotein B
High-sensitivity CRP
Fixed dose statin therapies
See slide 46
