Cardio Exam 1 (Anderson, Jacobsen and Cantrell)

Atherosclerosis

Accumulation of white blood cells, calcium, fatty material, and scar tissue into a plaque on the artery wall

Put these events in order

LDL cholesterol oxidation → foam cell formation → thrombus formation

Saturated fatty acids

Have no C=C bonds

Palmitic acid and steric acid are common types of…

Saturated fatty acids

Unsaturated fatty acids

Have at least one C=C bond

Oleic acid, arachadonic, and linoleic acid are common types of…

Unsaturated fatty acids

Omega carbon

Opposite end as alpha carbon

Omega-3 carbon means

that the double bond is present at that carbon

Why are omega 6 vs omega 3 fatty acids act different?

The double bond is the location of oxidation and could lead to harmful by products

What is the starting material in cholesterol biosynthesis?

Acetyl CoA

T/F: bile acids are products of cholesterol and are amphiphathic

True

Carries cholesterol from the liver to peripheral cells

LDL

Carry cholesterol from peripheral cells to the liver

HDL

Carry triglycerides from liver to peripheral cells

VLDL

Put these in order from most to least harmful in the context of atherosclerosis

LDL, VLDL, HDL

What are the two GENERAL methods of anti-hyperlipedemic drugs

Reducing lipoprotein production and enhancing lipoprotein/cholesterol removal

List the drug classes that reduce lipoprotein production

Nicotinic acids, fibric acids, MTP inhibitors, apolipoprotein B-100 synthesis inhibitors, ezetimibe

List the drug classes that enhance circulating cholesterol removal

Anion exchange resin, HMG CoA reductase inhibitors, PCSK 9 inhibitors

Nicotinic acids MOA

Agonist of niacin receptor (GPR109A)

Nicotinic acids lead to

Reduction in LDL and triglycerides, increases in HDL

Nicotinic acid side effects

Vasodilation, hyperglycemia, increase in hypotensive agent effect, flushing

Which release form of niacin leads to the least amount of flushing?

SR, because it primarily undergoes amidation

Fibric acids MOA

PPARa (transcription factor) agonist for lipid metabolizing enzymes

Which drug class are PPARa agonists?

Fibric acids

Fibric acids lead to

Increased lipolysis, enhanced lipoprotien lipase activity, reduced VLDL synthesis due to low triglycerides

Fibrates interact with which class of drugs

Anticoagulants and statins

Fibric acid side effects

Flu-like symptoms, tumors, gall stones

Nonmicronized tablets

Micronized capsules and tablets

Hard gelatin capsules

Must be taken with food

Nanoparticle tablets

IDD-P tablets

Fenofibrate choline salt forms

Don’t require to be taken with food

Which form of fenofibrate is the most bioavailable?

Fenofibrate choline salts

What does microsomal triglyceride transfer protein (MTP) do?

Facilitates transfers of triglycerides that eventually become VLDL

MTP inhibitor (Lomitapide) MOA

Inhibits MTP which lowers VLDL levels

MTP inhibitor side effects

Triglyceride accumulation in liver with long term use

Why are MTP inhibitor suseptible to DDIs?

Due to it’s extensive CYP3A4 hepatic metabolism

Apolipoprotein B-100 Synthesis inhibitor (Mipomersen) MOA

Bind mRNA coding for AB-100 which is the main component of LDL

Why do apolipoprotein B-100 Synthesis inhibitor have an increased ½ life?

They have thiol groups which resist nuclease degradation

Which side effect/DDI is unique to apolipoprotein B-100 Synthesis inhibitor (Mipomersen) and not MTP inhibitor (Lomitapide)?

Injection site reaction

Ezetimibe MOA

Inhibits cholesterol absorption in the small intestine by inhibiting transport protein NPC1L1

Why is ezetimibe considered a “selective” agent

Because it does not interfere with the absorption of triglycerides, lipid soluble vitamins or other nutrients

What class can ezetimibe NOT be combined with? This class inhibits ezetimbe from reaching it’s site of action

Bile acid sequestrants/anion exchange resins

Bile acid sequestrants/anion exchange resins MOA

Positively charged ammonia group exchanges Cl- ion for bile acid so the bile acids can not be absorbed

How does inhibiting bile acid absorption lower cholesterol?

The liver uses cholesterol to make more free bile acids

Which class is considered “non-selective” because it binds fat soluble vitamins and drugs (warfarin, digoxin, iron etc)?

Bile acid sequestrants

Bile acid sequestrants/anion exchange resins dosage form

Powder

Which bile acid sequestrants/anion exchange resins is considered superior due to its lower number of side effects?

Colesevelam

When should bile acid sequestrants/anion exchange resins NOT be used?

When triglycerides are over 300 mg/dL

What was the first statin?

Mevastatin

Do statins have better or worse affinity than the native substrate?

10,000 fold better

Which drug class inhibits HMG CoA reductase and thus decreases cholesterol production?

Statins

What denotes a natural statin from a synthetic one?

Natural have a decaline ring and synthetics do not

Which statins are extensively metabolized through CYP3A4?

Atorvastatin, lovastatin and simvastatin

The following are risks of using which drug class?

• diabetes elevation

• transaminase elevation

• cataract development

Statins

List these in order from most to least potent

Rosuvastatin, atorvastatin, simvastatin, pravastatin

Lovastatin IR and ER formations have different administration instructions, choose the correct pairing

IR = with food, ER = without food

Other cardioprotective effects of statins

Anti-inflammatory, reduced lipoprotein oxidation

Do statins undego extensive first pass metabolism?

Yes

The following enzymes should be monitored when using what drug class?

• Hepatic transaminases (liver injury)

• Creatine phosphokinase (muscle injury)

Statins

PCSK9 inhibitor MOA

Inhibiting PCSK9 enhances LDL receptor localization to the cell membrane, so more LDL can be taken into the cell and degraded

PCSK9 Inhibitor DDI’s

None

PCSK9 inhibitor formulation

Injection and oral

If a patient has NO evidence of current atherosclerotic cardiovascular disease (ASCVD) and we want to prevent the development of ASCVD, what type of prevention should be used?

Primary prevention

If a patient has evidence of current atherosclerotic cardiovascular disease (ASCVD) and we want to prevent the progression of the disease, what type of prevention should be used?

Secondary prevention

The following are risk factors for what disease state?

• Smoking

• Diabetes mellitus

• Dyslipidemia

• Hypertension (or use of antihypertensive drugs)

Atherosclerotic cardiovascular disease

What age is considered a “major risk factor” for ASCVD

Men 45 or older, women 55 or older

Are lifestyle factors such as obesity and inactivity considered “major risk factors” for ASCVD?

Yes

<3% estimated 10-year risk

Low

3-5% estimated 10-year risk

Borderline

5-10% estimated 10-year risk

Intermediate

>10% estimated 10-year risk

High

The following are used in which type of prevention strategy?

• Lifestyle interventions

• Medication interventions

Primary and secondary prevention

Aspirin is used for which type of prevention?

Secondary only

List the ABCD’S of ASCVD prevention

Aspirin

Blood pressure goal

Cholesterol (in patients likely to benefit)

Diabetes management

Smoking cessation (all patients)

How is the recommendation of aspirin use for the primary prevention of ASCVD ranked?

IIb (might be helpful)

Finish the statement below:

As ASCVD absolute risk increases…

so does the BENEFIT of using aspirin as a primary prevention measure

Which class of drugs are also known as isobutyryl carboxylic acids?

Fibric acids

Non-HDL cholesterol

Gives the total amount of all atherogenic components of cholesterol

When should treatment be considered in young people?

When there is history of familial hypercholesterolemia, family history of CVD, or LDL >160

What drugs can elevate LDL/triglycerides?

Retinoic acid derivatives, anabolic steroids and protease inhibitors

What disease can significantly elevated triglycerides lead to? This disease risk is higher than the risk of ASCVD if triglycerides are the only elevated lipid.

Pancreatitis

Treatment for isolated high triglycerides

Fibric acids, omega-3 fatty acids or olezarsen if severe

Are supplements like plant sterols, red yeast rice, or fish oil (OTC dose) recommended as treatment for hyperlipidemia?

No, they are not recommended as a replacement for pharmacotherapy

What kind of effect do lifestyle changes have on LDL levels?

They can have a large (20-30%) reduction cumulatively

Baseline lipid profile, LFT’s, creatine kinase and A1c should be gathered for patients starting on which class of medication?

Statins

When should LFT’s be monitored in patients receiving statin therapy?

Only if they experience symptoms of liver disease

When should creatinine kinase levels be monitored in patients receiving statin therapy?

Only if they experience myalgia

Is coenzyme Q10 an appropriate treatment for statin induced myalgia?

It may be considered if it is likely to improve the patient’s adherence to the statin

Which statin does not use a P450 pathway and instead is metabolized via sulfation?

Pravastatin

Which fibric acid can NOT be used with statins due to its inhibition of statin clearance?

Gemfibrozil

Which two statins can lower LDL by 50% or more?

Atorvastatin and rosuvastatin

T/F: patients need to be titrated up to a high intensity statin dose

False, they can immediately be started on a high intensity dose

T/F: very high risk ASCVD is defined as having had 2 or more ASCVD events OR 1 event and 2 or more high risk conditions

True

What is the goal LDL for very high risk patients? (secondary prevention)

Less than 55 mg/dL

What is the LDL goal for the primary prevention in LOW risk patients?

Less than 100 mg/dL

What is the LDL goal for the primary prevention in INTERMEDIATE risk patients?

Less than 100 mg/dL

What is the LDL goal for the primary prevention in BORDERLINE risk patients?

Less than 100 mg/dL

What is the LDL goal for the primary prevention in HIGH risk patients?

Less than 70 mg/dL

What is lipoprotein A?

Atherogenic particle similar to LDL that can deposit cholesterol on artery walls

In primary prevention, which three disease states is it recommended for lipid lowering therapy to be initiated REGARDLESS of the risk calculator?

Diabetes, chronic kidney disease, or HIV

What is the LDL goal for primary prevention patients with diabetes, chronic kidney disease or HIV?

<100 mg/dL

Apolipoprotein B is the main component of which types of lipids?

All atherogenic lipoproteins (LDL, VLDL, chylomicrons)