Therapeutics I Exam II (Dyslipidemia) Flashcards
Hyperlipidemia
What is a drug-related problem?
Any undesirable event experienced by a patient that involves (or is suspected to involve) drug therapy and interferes with achieving therapy goals and needs professional judgment to resolve.
Name the 8 drug-related problems.
- Untreated indication (need additional therapy)
- Medication use without an indication (unnecessary drug therapy)
- Dose too low
- Dose too high
- Adverse drug reactions
- Drug-Drug interactions
- Failure to receive medications
- Improper medication selection or ineffective medication
What is an untreated indication in drug-related problems?
Indication currently not treated or needs additional therapy.
What is medication use without an indication?
Indication could be treated with non-pharmacologic therapy.
What are potential causes of medication use without an indication?
- Medication used to prevent adverse drug reaction from another medication
- No indication (at this time)
What can lead to a dose being too low?
- Dosage interval not frequent enough
- Dose too low
- Duration of therapy too short
What can cause an adverse drug reaction?
- Contraindication
- Drug interaction
- Improper drug administration
What are the types of drug interactions?
- Drug-Disease interaction
- Drug-Drug interaction
- Drug-Food interaction
What are common causes of failure to receive medications?
- Ability to get to/from the pharmacy or prescriber
- Cognitive difficulty
- Cost
- Forget to take medication
- Limited understanding of medication benefit and harm or instructions
- Medication burden
- Medication not available
- Patient decides to not take medication
- Physical inability to use medication appropriately
- Suboptimal provider communication or transitions of care
What constitutes improper or ineffective drug selection?
- Inappropriate drug
- Contraindication present
- Indication not responding to medication
- More effective or evidence-based recommendation available
- Risk exceeds benefit
- Wrong route of administration or dosage form
- Therapeutic duplication
What is one challenge in identifying drug-related problems?
Access to information.
What is a key factor in patient workup?
Match patient signs/symptoms/labs/diagnostic tests/past medical history to medications the patient is prescribed.
True or False: Drug-related problems can only occur if a patient is taking multiple medications.
False.
Fill in the blank: The definition of a drug-related problem involves a patient experiencing an _______ event that interferes with achieving therapy goals.
undesirable
What should be calculated whenever sufficient information is available during patient workup?
Creatinine clearance.
What are the general categories used by the National Coordinating Council for Medication Error Reporting and Prevention?
- Category A to Category I
Category A means that no problem occurred with the medication but there is room for problems to occur. Category I means that the medication has killed the patient.
What should be monitored in addition to lab results?
Trends in lab results.
During a patient workup, the current signs, symptoms, labs, diagnostic tests, and medical history from the patient should match the ___________ the patient is currently on.
Medications
Are all medications accounted for? Are these medications optimized? Are these medications needed?
What is a challenge in identifying drug-related problems?
Access to information.
What is one common cause of drug-related problems?
Suboptimal provider communication or transition of care.
Do catalyst increase or decrease the activation energy of a reaction?
A catalyst decreases the activation energy needed for a reaction to occur therefore increasing the rate of the reaction.
T or F: Enzyme and substrate binding does not make the reaction faster.
True.
T or F: Statins are fast, loose-binding inhibitors of HMG-CoA Reducatase.
False. Statins are slow, tight-binding inhibitors of the HMG-CoA reductase enzyme because they look so similar to the transition state.
T or F: Simvastatin is not a prodrug.
False. Simvastatin is a prodrug.
Can statins induce myopathy?
Yes.
What enzyme in the liver metabolizes statins?
CYP3A4
Do statins interact with grapefruit juice?
Yes. Grapefruit juices inhibits CYP3A4 and statins are metabolized by CYP3A4. Taking these things together increases the risk of adverse effects of statins like myopathy.
Do statins interact with warfarin?
Yes. Statins inhibit several CYP3A2 enzymes and some of Warfarin is metabolized by these enzymes. Taking these medications together can potentiate the blood thinning effects of Warfarin.
T or F: Ezetimibe is a prodrug.
True. Ezetimibe inhibits the absorption of dietary cholesterol at the brush border enzymes of the small intestine.
Which statin shows the greatest increase in HDL cholesterol?
Rosuvastatin (8%)
Which statin shows the greatest decrease in LDL cholesterol?
Rosuvastatin (46%)
Which statin shows the greatest decrease in triglyceride levels?
Rosuvastatin and Atorvastatin (both 20%)
What is the definition of dyslipidemia?
Abnormal concentration of lipids in the blood. Can be too high or too low.
What is hypercholesteremia?
Increased LDL and Total Cholesterol
What is hyperlipidemia?
Increased blood concentration of LDL and triglycerides.
What is hypertriglyceridemia?
Elevated triglycerides
Cholesterol is a precursor for what two things in the body?
Bile acids and steroid hormones
T or F: Cholesterol plays no role in maintaining the cell membrane integrity.
False. Cholesterol plays a large role in maintaining the integrity of the cell membrane.
What encompasses a lipoprotein?
Lipids (cholesterol and triglycerides) and proteins
What are the 5 different types of lipoproteins?
Chylomicron
VLDL
IDL
LDL
HDL
T or F: The amount of chylomicrons in the blood is not affected after eating a meal.
False. It is heavily affected by cholesterol intake from a meal.
Very Low Density Lipoprotein (VLDL) is made by the ____________.
Liver
Very Low Density Lipoprotein (VLDL) is full of ____________ and contains apolipoprotein ____.
Triglycerides
B
Low-density lipoprotein (LDL) contains apolipoprotein ________ and lipoprotein _________.
B
little a
Low-density lipoprotein (LDL) deposits _____________ into the artery wall.
Cholesterol
VLDL is converted to VLDL remnant and _____________ which contains apolipoprotein B.
IDL (Intermediate density lipoprotein)
IDL (Intermediate density lipoprotein) contains apolipoprotein ______.
B
T or F: Estrogen decreases HDL levels.
False. Estrogen increases HDL levels.
High-density lipoprotein (HDL) is responsible for __________ cholesterol transportation.
Reverse. It brings cholesterol back to the liver.
High-density lipoprotein (HDL) contain apolipoprotein ________.
A1
T or F: Apolipoprotein B and lipoprotein little a levels can be used as a biomarker to evaluate dyslipidemia status.
True.
What is the optimal LDL level?
Below 100mg/dL (blanket statement that can be altered based on ASCVD history)
What is considered a low HDL in men?
Less than 40mg/dL
What is considered a low HDL in women?
Less than 50mg/dL
What is the optimal LDL level?
Less than 100 mg/dL
What is the normal triglyceride level?
Less than 150mg/dL
What is the desirable total cholesterol level in the body?
Less than 200mg/dL (total cholesterol include LDL, TG, and HDL)
What is a high LDL level?
160-189 mg/dL
What is a very high LDL level?
Anything greater than 190mg/dL
What is a high triglyceride level?
200-499 mg/dL
What is a very high triglyceride level?
Anything greater than 500 mg/dL
When it comes to high triglyceride levels, typically drug therapy is not started until a TG level of ________ or greater is reached.
500 mg/dL. This indicates very high triglyceride levels.
For each 1% decrease in LDL or non-HDL, there is a ________ reduction in CHD event risk over 5 years.
1%
What is the Friedewald Equation?
This equation calculates the calculated LDL.
How is non-HDL cholesterol calculated?
Subtract HDL from total cholesterol to find how much non-HDL cholesterol is present.
Non-HDL= TC-HDL
What are the two circumstances in which the Friedewald equation not be used?
- Very low levels of LDL cholesterol
- TG count above 400 mg/dL
LDL levels would need to be directly measured
What are the two different types of dyslipidemias?
Primary/Familial and Secondary/Acquired
Is heterozygous or homozygous primary/familial dyslipidemia more common?
Heterozygous dyslipidemia is more common (1 in 250) while homozygous dyslipidemia affects 1 in 250,000 people.
What is the typical LDL range from those with heterozygous primary/familial dyslipidemia?
250-450 mg/dL
What is the typical LDL range from those with homozygous primary/familial dyslipidemia?
Greater than 500 mg/dL
T or F: Someone with primary/familial dyslipidemia cannot have secondary/acquired dyslipidemia.
False. They can have both.
What are common things that lead to secondary/acquired dyslipidemia? Specifically, leads to increased LDL and triglycerides?
Weight gain, CKD, HIV, autoimmune disease, untreated hypothyroidism, pregnancy, PCOS, and menopause
Why can menopause be a cause of acquired dyslipidemia?
The lack of estrogen production leads to decreased HDL and increased LDL levels.
What are two things that just increase LDL and not triglycerides when thinking about causes for secondary/acquired dyslipidemia?
Diet and obstructive liver disease
What are two things that just increase triglycerides and not LDL when thinking about causes for secondary/acquired dyslipidemia?
Excess alcohol and diabetes mellitus
What are the 4 medications we need to know that can increase LDL levels in secondary/acquired dyslipidemia?
Thiazide diuretics, Amiodarone, Glucocorticoids, and certain long chain omega-3 FA
What are the 4 medications we need to know that can increase triglyceride levels in secondary/acquired dyslipidemia?
Thiazide diuretics, glucocorticoids, beta-blockers, and bile acid sequestrants
LDL deposits cholesterol between the media and __________ of blood vessels walls.
Intima
What triggers LDL depositing cholesterol in the walls of blood vessels?
Injury or inflammation
Inflammatory cells called ____________ engulf cholesterol deposits and turn into giant _______ cells.
Macrophages
Foam
List clinical atherosclerotic cardiovascular diseases
T or F: Patients with dyslipidemia are often very symptomatic.
False. Patients are usually asymptomatic unless ASCVD is occurring due to the dyslipidemia or they are experiencing acute pancreatitis.
Why might a patient with dyslipidemia experience acute pancreatitis?
Elevated triglycerides can build up in the pancreas, causing the release of digestive enzymes that damage the pancreatic tissue, leading to inflammation and tissue necrosis.
What are the signs of acute pancreatitis?
Abdominal tenderness and pain, fever, nausea and vomiting, and tachycardia.
T or F: Many patients presenting with dyslipidemia will have metabolic syndrome as well.
True
What is Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)?
This is what used to be called NAFLD. It is when cholesterol is being deposited in the liver and the fat eventually compromises the functioning of the liver.
What is corneal arcus?
This is cholesterol deposits in the iris of the eye.
What is xanthelasma?
This is cholesterol deposits around the eyes.
What is xanthomas?
This is cholesterol deposits in the skin.
What are the 4 labs that need to be evaluated in order to show increased risk of ASCVD from dyslipidemia?
- Apolipoprotein B levels
- Lipoprotein little a levels
- C-reactive protein levels
- Cholesterol levels (LDL, TG, and HDL)
What is excluded from the PREVENT calculator that is included in the ASCVD risk estimator?
Race
What are the 4 statin drugs we need to know?
Rosuvastatin (Crestor)
Atorvastatin (Lipitor)
Pravastatin (Pravachol)
Simvastatin (Zocor)
People from STATIN island RAPS
What is the brand name for atorvastatin?
Lipitor
What is the brand name for rosuvastatin?
Crestor
What is the brand name for pravastatin?
Pravachol
What is the brand name for simvastatin?
Zocor
Out of the 4 statin drugs discussed, which ones need to be adjusted for renal impairments?
All except for atorvastatin. The others need to be adjusted when CrCl is less than 30 mL/min.
Do statins need adjustments when given to those with hepatic impairments?
Yes. Atorvastatin and simvastatin are adjusted for child-pugh score of B or C while pravastatin and rosuvastatin are adjusted for child-pugh score B and not C.
What is the MOA for statins?
Statins are competitive inhibitors of HMG-CoA Reductase which is the rate-limiting step of cholesterol production.
Cholesterol and triglycerides are packaged into VLDL and leave to liver to enter the bloodstream. VLDL is broken down into _______ and then ________.
IDL
LDL
What happens to triglyceride rich VLDL if cholesterol production is decreased with statin use?
VLDL levels will also decrease.
What happens to LDL if cholesterol production is decreased?
LDL levels will decrease.
Cholesterol decreases with statins indirectly ___________ VLDL, IDL, and LDL.
Decrease
Decreased cholesterol production with statin use actually ____________ LDL receptor levels.
Increases. The body senses that there is not as much LDL and upregulates LDL receptors in order to catch as much LDL as possible.
What happens to LDL receptors when there is less cholesterol production?
LDL receptor number increases.
If LDL receptors levels increase in response to decreasing cholesterol levels, what happens to circulating LDL?
There is a decrease in circulating LDL levels as the receptors are scooping them up and out of the bloodstream.
What are the 3 pleiotropic effects of statins?
- Increase artherosclerotic lesion stability
- Decrease oxidative stress
- Decrease vascular inflammation
Statin use is contraindicated in what 4 scenarios?
-Pregnancy*
-Breastfeeding
-Active liver disease (things like cholestasis, hepatic encephalopathy, hepatitis, jaundice, acute hepatic failure, decompensated cirrhosis)
-Unexplained persistent transaminase elevations
What is unique about pregnancy being contraindicated for statin use?
In very rare cases, statin use can be continued during pregnancy at the advise of a medical care team.
Are there any caveats to statin use during breastfeeding?
No. Statins must absolutely NOT be used during breastfeeding.
T or F: It is okay to be on red yeast rice supplementation and a statin.
False. Red yeast rice resembles statin chemical structure so it would be like taking 2 statins at the same time which is advised against.
T or F: Contraceptive methods are not recommended for women of childbearing age taking statins.
False. Contraceptive methods are recommended.
If a person becomes pregnant and decides to no longer take the statin, what interventions can be done?
Non-pharmacological interventions and a possible switch the a bile acid sequestrant
Which 2 statins have the longest half life?
Atorvastatin(15-30hours) and Rosuvastatin (19 hours)
What are the two lipophilic statins?
Atorvastatin and simvastatin
What are the two hydrophilic statins?
Rosuvastatin and pravastatin
All statins are taken up into the liver via ________________/______ to be metabolized and excreted.
OAT1B1/1B3
Does cholesterol production ramp up in the morning or the evening?
The evening
Which statin has decreased absorption when eaten with food but the efficacy of the medication is not affected?
Pravastatin (the other statins do not interact with food)
Do statin need to be titrated up to the appropriate dose?
No. Statin dosing is based on the risk of ASCVD in the patient and does not need to be titrated.
What does it mean if a statin is dosed at “High Intensity”?
It will lower LDL by 50% or more
What does it mean if a statin is dosed at “Moderate Intensity”?
Lowers LDL by 30-49%
What is the high intensity dosing for atorvastatin (Lipitor)?
40-80mg
What is the high intensity dosing for rosuvastatin (Crestor)?
20-40mg
What is the moderate intensity dosing for Pravastatin (Pravachol)?
40-80mg
What is the moderate intensity dosing for Simvastatin (Zocor)?
20-40mg
What is the low intensity dosing for Pravastatin (Pravachol)?
10-20mg
What is the low intensity dosing for Simvastatin (Zocor)?
10mg
If you double the dose of a statin, LDL decreases by ______%.
6%
What are the four common adverse effects seen with statin use?
Myalgia (1 in 4 statin users)
Blood glucose changes
Arthralgia
Diarrhea (onset only typically)
Mmmmmm BAD
What is myalgia?
This is muscle symptoms with no significant increases in creatine kinase (CK)>
What is creatine kinase (CK)?
CK is released from damage muscle into the bloodstream. Elevated creatine kinase levels alert to muscle damage or injury.
What is myopathy?
This is unexplained muscle pain with a creatine kinase level greater than 10 times the upper limit.
What is rhabdomyolysis?
This is muscle pain and weakness with a creatine kinase level greater than 40 times the upper limit. There could also be kidney injury present due to myoglobinuria.
What are the signs and symptoms of rhabdo?
Unexplained muscle pain, brown/tea-colored urine, fatigue.
What are the weird and unknown side effects of statins?
Cognitive changes and LFT elevation (typically transient)
What are the rare but serious adverse effects of statins?
Hemorrhagic stroke
Hepatic failure
Rhabdomyolysis
What are the risk factors for statin-associated muscle symptoms (SAMS)?
Age, asian ancestry, comorbidities like liver and kidney disease, drug interactions, female, hypothyroidism (uncorrected), low BMI, and pre-existing muscle disease.
For someone experiencing statin-associated muscle symptoms (SAMS), it is typically located in what parts of the body?
Symmetrical/bilateral large muscle groups like both thighs and both legs.
What are the typical symptoms seen with statin-associated muscle symptoms (SAMS)?
Cramping, general fatigue, muscle aches, soreness, stiffness, tenderness, weakness
How is statin-associated muscle symptoms (SAMS) managed?
- Discontinue the statin for 2-4 weeks
A. If symptoms resolve- start at lower statin dose or switch statin or try alternative dosing
A. If symptoms do not resolve- check for other causative factors
Do statins increase or decrease blood glucose levels?
They increase blood glucose levels.
What are signs of hyperglycemia which may be seen as an adverse effect regarding statin therapy?
The 3 Polys
Polydipsia, Polyuria, and Polyphagia
T or F: Even if someone has normal glucose levels, their blood glucose levels should be monitored when on statin therapy.
False. Only test for diabetes as clinically indicated.
T or F: Statins harm those with diabetes more than they benefit them.
False. Statins benefit more than they harm those with diabetes.
What type of patients on statins are more at risk for increases in blood glucose due to the statin medication?
- Those with BMI 30 or greater
-Fasting glucose 100 or greater - metabolic syndrome
- HbA1c at or greater than 6%
T or F: Not all statins are substrates for OAT1B1.
False. All statins are taken into the liver with OAT1B1
What 3 statins are substrates for CYP3A4?
Atorvastatin
Lovastatin
Simvastin
What 2 statins are substrates for CYP2C9?
Fluvastatin and Rosuvastatin
What 4 statins are substrates for p-glycoprotein?
Pitavastatin
Atorvastatin (minor)
Lovastatin
Simvastatin
What is the good mnemonic to remember several of the drug interactions with statins?
G <3 PACMAN
Grapefruit + Gemfibrozil
Protease inhibitors
Azole antifungals
Cyclosporines + Cobicistat (Tybost)
Macrolides (not azithromycin)
Amiodarone
Non-DHP CCBs (diltiazem and verapamil)
What are the 3 medications that require a 10 mg maximum dose of simvastatin due to interactions?
Diltiazem, Verapamil, and Dronedarone
What are the 6 medications that require a 20 mg maximum dose of simvastatin due to interactions?
Amiodarone, Amlodipine, Bempedoic acid, Ezetimibe, Lomitapide, and Ranolazine
If a situation of a drug drug interaction with a statin, what should happen if a patient is prescribed a long-term interacting medication?
Change the statin
If a situation of a drug drug interaction with a statin, specifically in the acute use of a medication for stable coronary disease, what should happen with the statin?
Hold the statin and restart within 3 days of discontinuing the interacting medication.
If a situation of a drug drug interaction with a statin, specifically in the acute use of a medication for unstable coronary disease, what should happen with the statin?
Keep the statin and change the interacting acute medication.
If creatine kinase is >_______x the UL, see about possible myalgia before stating statin therapy.
10
In order to start a statin, a fasting __________ panel, liver function test, and pregnancy test (females) needs to be done in order to determine dosing and if the medication works.
Lipid.
If LFTS are 3 times greater than the upper limit or there is acute liver disease, do not start the statin
If you get any of these values for the first time doing lab work, should you redraw the labs?
Yes.
What are symptoms of hepatotoxicty?
Abdominal pain, appetite loss, dark urine, fatigue, nausea and vomiting, yellow skin and eyes.
Once statin therapy is started, when should lipid levels be rechecked?
1-3 months at first and every 3-12 months after.
If there are signs of myalgia with statin therapy, get a _______ _______ lab done.
Creatine kinase. Stop statin is CK is 10 times greater than the upper limit.
If there are any signs of hepatotoxicity with statin therapy, get a _________ lab done.
LFT (liver function test)
Statins are best used to lower LDL and not triglycerides. However, if that was your goal as well, what two statins could be used to also lower triglycerides?
Atorvastatin and Rosuvastatin due to their increased potency.
What is complete statin intolerance?
Inability to tolerate any dose or regimen of a statin.
What is partial statin intolerance?
Tolerates a lower dose than required to achieve desired outcome.
What are the guidelines for statin intolerance?
- 1 or more AE associated with statin therapy that resolves or improves after stopping statin
- Minimum of 2 statin tried with 1 at the lowest approved daily dose
What is the brand name for Ezetimibe?
Zetia
What is the MOA for Ezetimibe (Zetia)?
Inhibits cholesterol absorption from the GIT at the brush border of the small intestine. This stops cholesterol from going to the liver which increases LDL receptors and decreases production of VLDL and eventually LDL.
What are the contraindications for Ezetimibe (Zetia) use?
- moderate-severe hepatic impairment (child pugh score of B or C)
- Fibric acid derivatives due to increased risk of myopathy and cholelithiasis)
- Rare drug called leniolisib/Joenja
(PRECAUTIONED in pregnancy and breastfeeding)
Ezetimibe is a substrate for _____________ but has not effect on any CYP enzymes in the liver.
OAT1B1/1B3
For dosing ezetimibe (Zetia) in someone with renal impairment, how is the dose adjusted?
There is no renal adjustment for ezetimibe.
What is the dosing for Ezetimibe (Zetia)?
10 mg PO QD (half life is 22 hours so it is dosed once per day)
What are the common adverse effects seen with Ezetimibe (Zetia)?
Diarrhea, Hepatotoxicity, myalgia, and increased LFTs
Ezetimibe should be given more than ______ hours before and more than _____ hours after taking a bile acid sequestrant.
2
4
What are the main 3 drug interactions with Ezetimibe (Zetia)?
Fibric acid derivatives
Cyclosporine
Bile acid sequestrants
Ezetimibe (Zetia) has the greatest effect on reducing ________ levels.
LDL
What are the two fibric acid derivatives we need to know?
Fenofibrate (Tricor) and Gemfibrozil (Lopid)
T or F: Fenofibrate is a prodrug that is converted to fenofibric acid in the liver.
True
What is the brand name for Fenofibrate?
Tricor
What is the dosing for Fenofibrate (Tricor)?
48-145 mg QD
What is the MOA of fibric acid derivatives (Fibrates) like fenofibrate and Gemfibrozil?
These drugs activate the peroxisome proliferator activated receptor alpha (PPARa). This causes an increase in apolipoprotein A-1 transcription and decrease cholesteryl ester transfer protein (CETP). This works to increase HDL levels. It also activates lipoprotein lipase which converts triglycerides to free fatty acids to decrease the amount of triglycerides in the blood stream.
What is the brand name for Gemfibrozil?
Lopid
Are renal adjustments needed for fibric acid derivatives?
Yes. Fenofibrate dosing should be checked for CrCl between 30-80 mL/min and is contraindicated in those with a CrCl less than 30 mL/min.
Fibric acid derivatives have most impact on _______ and _______ levels.
HDL
Triglycerides
Which of the following statin is hydrophilic, high potency, and can be given at any time of the day?
A. Pravastatin
B. Atorvastatin
C. Rosuvastatin
D. Simvastatin
C. Rosuvastatin
What are the contraindications for fibric acid derivative use?
- Active liver disease, hepatic impairment, or unexplained persistent LFT elevations
- Severe renal impairment with CrCl less than 30 mL/im
- Pre-existing gallbladder disease
- Just Gemfibrozil- DDI with repaglinide/Prandin and simvastatin/Zocor.
Gemfibrozil is a strong inhibitor for CYP _____ and for OAT _______/_____.
CYP2C8
OAT1B1/1B3
Fenofibrate is a weak inhibitor of CYP ______.
2C9
Fenofibrate can be taken with or without food. Gemfibrozil must be taken at least _______ minutes before meals.
30 minutes
What are the 3 most common adverse effects seen with fibric acid derivatives?
Dyspepsia/ indigestion mainly seen with Gemfibrozil
Elevated LFTs, SCr, and GI issues (abdominal pain) are adverse effects of both fibric acid derivatives.
What are the 4 rare but serious adverse effects associated with fibric acid derivatives?
-Cholelithiasis (gallstones)- presents with abdominal pain, fever, N/V, pain between shoulder blades
-Pancreatitis
-PE
-Rhabdo
What are the 5 drug drug interactions with fibric acid derivatives?
Warfarin
Ursodiol
Cyclosporine
Ezetimibe
Statins
WUCES
What are the 2 Omega-3 fatty acids medications we need to know?
Lovaza and Vascepa
What is included in Lovaza?
EPA and DHA
What is included in Vascepa?
EPA
What is the dosing for Lovaza?
4 1-gram capsules QD
OR
2 1-gram capsules BID
What is the dosing for Vascepa?
2 1-gram capsules BID
OR
4 0.5-gram capsules BID
What is the generic name for Vascepa?
Icosapent ethyl
What is the generic name for Lovaza?
Omega-3 ethyl esters
Are there any contraindications for using omega-3 fatty acids?
There are none
What are the precautions for using omega-3 fatty acids?
Atrial fibrillation, bleeding, caution with fish and shellfish allergies, pregnancy, and breastfeeding
When should a healthy normal person first get a baseline lipid panel done and when should they follow up?
20 years old.
Assuming the lipid panel is within normal range, they can reassess in 4-6 YEARS
When would someone undergo a fasting lipid panel at younger age instead of a regular lipid panel?
If they have familial history of premature ASCVD
What are the 4 statin benefit groups as outlined in the 2018 ACC/AHA guidelines?
- Secondary prevention of clinical ASCVD
- LDL greater or equal to 190 mg/dL
- 40-75 years old with diabetes
- 40-75 with elevated 10 year ASCVD risk
What is categorized as VERY HIGH RISK for future ASCVD risk?
- History of more than 1 major ASCVD events
OR
- 1 major ASCVD event with more than 1 high-risk conditions
(High risk conditions include age 65 and older, prior coronary artery bypass surgery or percutaneous coronary intervention outside of ASCVD events, persistently elevated LDL above 100 despite maximally tolerated statin therapy with ezetimibe, heterozygous familial hypercholesterolemia, DM, HTN, CKD (15-59 mL/min), current smoking and congestive heart failure.
What are all the different high risk conditions associated with VERY HIGH RISK for future ASCVD events?
High risk conditions include age 65 and older, prior coronary artery bypass surgery or percutaneous coronary intervention outside of ASCVD events, persistently elevated LDL above 100 despite maximally tolerated statin therapy with ezetimibe, heterozygous familial hypercholesterolemia, DM, HTN, CKD (15-59 mL/min), current smoking and congestive heart failure.
In patients with HFeRF who have at least 3-5 more years to live and are not already on a statin, consider initiating a _____________ intensity statin to reduce the risk for ASCVD.
Moderate
In patients 75 years or younger with clinical ASCVD and are not at very high risk, initiate a ______________ intensity statin to reduce LDL by over 50% hopefully.
High
In patients with clinical ASCVD who are not at very high risk and are intolerant to high-statin therapy, consider switching to a _________ intensity statin to reduce LDL by 30-49%.
Moderate
In patients who are at very high risk for ASCVD, what medication should they start on?
High intensity statin
In patients who are at very high risk for ASCVD and are already maxed out for their high intensity statin but their LDL is still greater than 70, initiate ______________ therapy.
Ezetimibe (10mg PO QD)
In patients who are at very high risk for ASCVD and are already maxed out for their high intensity statin and Ezetimibe (Zetia) but there LDL is still greater than 70 or their non-HDL is greater than 100, what therapy should be initiated next?
PCSK9 inhibitor like Evoloeumb or Alirocumab
A patient presents with an LDL greater than 190 mg/dL, what medication should they be start on?
High intensity statin
A patient presents with an LDL greater than 190 mg/dL and high intensity statin dosing is initiated. When they are reassessed, their LDL has not gone down by at least 50%, what medication should be intiated?
Ezetimibe
A patient presents with an LDL greater than 190 mg/dL and high intensity statin dosing is initiated. When they are reassessed, there LDL is greater than 100mg/dL, what medication should be initiated?
Ezetimibe
A patient that initially presented with an LDL greater than 190 mg/dL has been started on a high intensity statin and Ezetimibe. When they came back to the clinic, their LDL had still not reached a 50% reduction from baseline and their triglycerides were less than 300 mg/dL. What medication should be initiated at this point?
Bile acid sequestrant like Cholestyramine (Questran)
A 45 year old white female presents to the clinic with T2D and LDL of 153 mg/dL. Should she be started on a medication to reduce her risk for ASCVD?
Yes. Based on the primary prevention statin group she should be started on a moderate-intensity statin. However, if her calculated ASCVD risk was greater than 20%, we would start her on a high-intensity statin and Ezetimbie.
If someone between the ages of 20-39 has T2D and an LDL between 70 and 189, what is the protocol for starting medication to reduce their ASCVD risk?
It may be reasonable to start a statin therapy in this group if they are risk enhancers.
What are diabetes-specific risk enhancers that can help decide initiation of medication therapy in 20-39 year old with diabetes and an LDL between 70 and 189?
-Diabetes duration: T2D for more than 10 years or T1D for more than 20 years
- Albuminuria 30 mcg or greater
- GFR less than 60 mL/min
- Retinopathy or neuropathy or ankle brachial index less than 0.9 (no idea what that means lol)
Should omega-3 fatty acids like Vascepa and Lovaza be taken with or without food?
Take with food
Do omega-3 fatty acids interact with CYPs?
Nope! They do interaction with drugs that increase bleeding risks.
What is unique about the omega-3 fatty acid Lovaza?
Lovaza can actually increase LDL
What are the main adverse effects associated with omega-3 fatty acids?`
Bleeding, GI upset (constipation, diarrhea, nausea), LFT elevation, A. Fib, and LDL increase seen with Lovaza.
Omega-3 fatty acid medications exert their effect mainly by decreasing _____________.
Triglycerides (Remember that Lovaza can increase LDL).
What are PCSK9-Inhibitors?
These are proprotein convertase subtilisin/Kexin type 9 modulators.
T or F: Using PCSK9-Inhibitors allows patients to better tolerate statins.
True.
What are the 2 PCSK9-Inhibitors we need to know?
Evolocumab (Repatha) and Alirocumab (Praluent)
As a last resort, we typically add PCSK9-inhibitors to a high-intensity statin and Ezetimibe. What is the actual indication for these PCSK9-inhibitor drugs?
Heterozygous Familial Hypercholesterolemia
What is the dosing for Evolocumab (Repatha)?
140mg SubQ every 2 weeks or 420mg SubQ monthly
What is the dosing for Alirocumab (Praluent)?
75 mg SubQ every 2 weeks or 300 mg SubQ monthly
What is the MOA of PCSK9-inhibitors?
They inhibit PCSK9 from targeting LDL receptors for internalization and degradation. This allows for more LDL receptors to eat up all the LDL floating in the blood.
T or F: The safety and efficacy of PCSK9 inhibitors has not be established for pregnancy and breastfeeding.
True
What are the contraindications for PCSK9-inhibitor use?
The only contraindication if for Evolocumab (Repatha) and that is a latex allergy due to the prefilled syringe that the medication comes in.
Are there any renal or hepatic dosing adjustments for PCSK9-inhibitors?
There is no dosing adjustment for either as there is no data in that subgroup.
What are the 6 commonish adverse effects associated with PSCK9-inhibitors?
Glucose changes, LFT elevation (transient), injection site rxns, myalgia, neurocognitive events, and ophthalmologic events.
When thinking about drug-drug interactions with PCSK9-inhibitors, what should we be looking out for?
Look out for the weird drug names.
They medications interact with Efgartigimod alfa and rozanolixizumab.
What is the brand name for the PCSK9-inhibitor Evolocumab?
Repatha
What is the brand name for the PCSK9-inhibitor Alirocumab?
Praluent
What is the brand name for the drug Inclisiran?
Leqvio
What is the MOA for Inclisiran (Leqvio)?
This medication is a small interfering ribonucleic acid (siRNA) that prevent PCSK9 translation in the liver. This allows for more LDL receptors to take more LDL out of the bloodstream.
What is the dosing for Inclisiran (Leqvio)?
284 mg SubQ initially, then at 3 months, then every 6 months.
What are the contraindications for use for Inclisiran (Leqvio)?
Pregnancy and breastfeeding
What are the 2 adverse effects associated with Inclisiran (Leqvio)?
Arthralgia and injection site rxn
PSCK9-inhibitors and Inclisiran (Leqvio) have the greatest impact on _________ and _________.
LDL and Triglycerides (only TG due to the statin that these medications are likely paired with)
What are the 3 bile acid sequestrants we need to know?
Cholestyramine (Questran)
Colesevelam (Welchol)
Colestipol (Colestid)
What is the brand name for the bile acid sequestrant Cholestyramine?
Questran
What is the brand name for the bile acid sequestrant Colesevelam?
Welchol
What is the brand name for the bile acid sequestrant Colestipol?
Colestid
What is the dosing for the bile acid sequestrant Cholestyramine (Questran)?
4 grams daily or BID.
(max 24 grams/day)
What is the dosing for the bile acid sequestrant Colesevelam (Welchol)?
3 tablets BID or 6 tablets daily
Also comes in powder for a suspesion
What is the dosing for the bile acid sequestrant Colestipol (Colestid)?
2 grams daily or BID
(max 16 grams/day)
What is unique about bile acid sequestrants?
They are not systemically absorbed so there is no need for renal or hepatic dosing adjustments.
What is the MOA for bile acid sequestrants?
Bile acids are + charged and bind to - charged bile acids. The bile acids are secreted so less goes back to the liver. The liver then needs more cholesterol to make more bile acids and so on and so forth. It eventually runs low on cholesterol which decreases VLDL, IDL, and LDL while the LDL receptors increase and eat up more LDL.
Bile acid sequestrants have the greatest impact on ____________ levels.
LDL
What are the contraindications for use for bile acid sequestrants?
Biliary obstruction, GI obstruction, hyperTG induced pancreatitis
T or F: Colesevelam (Welchol) can be intiated if a patient has TGs higher than 500 mg/dL.
False. Do not initiate this medication if their TGs are that high.
What are some precautions that need to be taken when initiating bile acid sequestrants?
Phenylketonuria and decreased absorption of fat-soluble vitamins as bile acid sequestrants are binders.
What is the one big main adverse effect seen with bile acid sequestrants?
Constipation
Do bile acid sequestrants interact with other medications?
Avoid using deferasirox (Exjade) and mycophenolate (Cellcept), check all narrow TI drugs (Levo, oral contraceptives), and do not forgot that they bind fat-soluble vitamins as well.
To be safe though, give medications 1 hour before and 4-6 hours after the bile acid sequestrant.
T or F: It is okay to break or crush bile acid sequestrant tablets.
False. The tablets are big and need to be swallowed whole in order to work.
Do bile acid sequestrants bind the drug leflunomide (Arava), a medication for rheumatoid arthritis?
Yes
T or F: Bile acid sequestrants can be used in pregnancy but it avoided based on provider due to the medication binding fat-soluble vitamins in prenatal vitamins.
True.
What are the two citrate lyase inhibitors we need to know?
Bempedoic acid (Nexletol) and Bempedoic acid-Ezetimibe (Nexlizet)
T or F: Bempedoic acid (Nexletol) is a prodrug.
True. It is a prodrug that is converted the active metabolite bempedoyl-CoA
What is the MOA of citrate lyase inhibitors like bempedoic acid?
They inhibit adenosine triphosphate citrate lyase which is upstream of HMG-CoA Reductase. This inhibits cholesterol synthesis before the rate limiting step.
What is the dosing for bempedoic acid (Nexletol)?
180 mg PO QD with or without food in addition to a maximally tolerated statin
Bempedoic acid (Nexletol) is a weak inhibitor of OAT _______/_____.
1B1/1B3
T or F: When combining pravastatin or simvastatin with bempedoic acid, there is no dose restrictions.
False. As Bempedoic acid is a weak inhibitor of OAT1B1/1B3 in which statins are substrates for, there is a dosing restriction. For pravastatin it is 40mg/day and for simvastatin it is 20mg/day.
Pravastatin can not exceed _________ per day in the patient is also taking bempedoic acid.
40 mg
Simvastatin can not exceed _________ per day in the patient is also taking bempedoic acid.
20 mg
Is there any renal or hepatic adjustments that need to be made from bempedoic acid dosing?
No.
What are the 2 common adverse effects associated with bempedoic acid?
Hyperuricemia (increase in uric acid, be careful in those with gout) and thrombocytosis (elevated platelet count)
What are the 2 weird and newly reported adverse effects seen with bempedoic acid (Nexletol)?
A.fib and tendon rupture
What are the two contraindications for bempedoic acid use?
Pregnancy and breast feeding
What is the main precaution for bempedoic acid use?
Gout!
Bempedoic acid has the greatest effect on ___________. However, it is likely the Ezetimibe is a better option.
LDL
What is the brand name for bempedoic acid?
Nexletol
What is niacin/ nicotinic acid?
This is vitamin B3 and it can be used for dyslipiedmia.
Why is niacin typically avoided?
It has no outcome data for its use with statins.
T or F: If the niacin product does not cause flushing, like niacinamide, the medication does not work for dyslipiedmia.
True. The product needs to induce flushing for it to work.
What is the main adverse event regarding niacin use?
Flushing (dizziness, hypotension, warmth). This can be prevented by taking aspirin or Tylenol 30 minutes prior to dose.
Besides flushing, what are the two other common adverse effects seen with niacin use?
Hyperglycemia and hyperuricemia
T or F: When using niacin with a statin, it can increase the risk of ____________ and ____________________.
Rhabdo
Hepatotoxicity
What are the 3 main drug interactions with niacin?
Statins, vasodilatory agents, and alcohol
Which of the following medications should not be initiated in a patient with TG greater than 500 mg/dL?
A. Omega-3 FA
B. Fenofibrate
C. Colesevelam
D. Simvastatin
E. Bempedoic acid
C. Colesevelam
Which of the following medications should be avoided in combination with statins?
A. Cholestyramine
B. Gemfibrozil
C. Omega-3 FA
D. Bempedoic acid
E. Alirocumab
B. Gemfibrozil (this is due to its OAT 1B1/1B3 inhibition)
Which of the following drugs should be used with caution or avoided in patients with gout?
A. Omega-3 FA
B. Fenofibrate
C. Colesevelam
D. Simvastatin
E. Bempedoic acid
E. Bempedoic acid
Is being 20-39 years old with diabetes mellitus and an LDL between 70-189 considered a statin benefit group?
No. BUT, it may be reasonable to initiate statin therapy in this group if they have certain risk enhancers.
When we are thinking about primary prevention in the 2018 AHA/ACC guidelines, what range of ASCVD are we looking for?
7.5-19.9%
For a person to be considered having familial history of premature ASCVD, the father must have had it before _______ and the mother must have had it before _________. This is considered a risk enhancing factor.
55 for men
65 for women
T or F: No statin should be started during dialysis but if that patient was already on one, they can continue to stay on it.
True
What are the 8 risk enhancing factors used to determine in a person ages 20-39 without diabetes?
- Family history of premature ASCVD (m,45 +f,55)
- Primary hypercholesterolemia (LDL 160-189 and non-HDL 190-219)
- Chronic inflammatory conditions (RA, psoriasis, HIV, etc)
- Early menopause (<40)
- Pre-eclampsia
- CKD with no dialysis or transplant and GFR between 15-59 mL/min
- Metabolic syndrome
- High-risk ethnicity (east and west asian, black, native american, alaskan, hispanics)
What is the main risk enhancer that is only seen through blood work?
3 records of persistently elevated hypertriglyceridemia (TG greater than or equal to 175 mg/dL)
T or F: If someone who is on a statin that is 75 years or older and is declining or has minimal time left to life, it is okay to take them off their statin.
True. Assuming this is what the patient wants
What two medications work best in reducing triglycerides?
Omega-3 FA and Fibric acid derivatives
What is considered moderate hypertriglycermia?
175-499 mg/dL
What is considered severe hypertriglyceridemia?
Greater than 500 mg/mL
What is the TX for moderate hypertriglyceridemia?
Non-pharm (diet, exercise) and evaluating possible secondary causes
What is the TX for severe hypertriglyceridemia?
Non-pharm (VLF diet, avoid refined carbs and alcohol, eat omega-3s), evaluate possible secondary causes, and consider fibric acid therapy.
Is being 20-39 years old with DM and an LDL between 70-189 considered a statin benefit group?
No. But as this is becoming more and more common, the ACC/AHA 2018 guidelines do give us recommendations.
If someone between the ages of 20-39 yrs has diabetes and LDL between 70-189 and has diabetes specific risk factors, __________ intensity statin therapy could be initaited.
Moderate
A person between the ages of 40-75 yrs had CKD with GFR less than 60 and albuminuria greater than 30 mcg. However, their 10 yr ASCVD risk was found to be 5.2%. This patient is not on dialysis. What medication is indicated for this?
If 10 year risk is less than 7.5% in this population (40-75 with CKD), then a moderate intensity statin can be started.
A person between the ages of 40-75 yrs had CKD with GFR less than 60 and albuminuria greater than 30 mcg. However, their 10 yr ASCVD risk was found to be 12.3%. This patient is not on dialysis. What medication is indicated for this?
If 10 year risk is greater than 7.5% in this population (45-70 with CKD), a moderate intensity statin with Ezetimibe should be started.
What are the non-pharm recommendations given by the 2025 American Diabetes Association guidelines?
- Weight loss
- DASH diet
- Decrease saturated and trans fat
- Increase viscous fiber, plant sterols, omega-3 FA
- Increase PA
According to the 2025 American Diabetes Association, when should lipid panels be done for patients not yet on a statin?
- At the diagnosis of diabetes
- At initial medical evaluation
- Annually or every 5 years if younger than 40 years
Based on the 2025 American Diabetes Association, what therapy should be intiated if the patient is diabetic and has had a history of ASCVD?
Start high-intensity statin. If target LDL of below 55 is reached, continue therapy. If LDL is still above goal, add Ezetimibe or a PCSK9-inhibitor.
What is the target LDL for secondary prevention in ASCVD and Diabetes as set by the 2025 American Diabetes Association guidelines?
Less than 55 mg/dL
Based on the 2025 American Diabetes Association, what is the LDL goal when it comes to primary prevention?
Less than 70 mg/dL
Based on the 2025 American Diabetes Association, those 20-39 years old with arthersclerotic risk factors should be started on a _________ intensity statin therapy.
Based on the 2025 American Diabetes Association, those between 40 and 75 with no PMH of ASCVD should be initiated on ______________ intensity statin therapy.
Moderate
What is the #1 recommendation for reducing triglyceride levels in the body?
Weight loss! 10-20% weight loss can lead up to a 70% reduction in triglycerides.
