Exam3Lec4Antihyperlipidemics

Question 1

What are the 2 reasons why someone might have high cholesterol?

made a joke

Answer 1

Because of low exercise and high saturated fatty acids

Question 2

What is CHD correlated with in terms of LDL and HDL?

Answer 2

High LDL (“bad”) and low HDL (“good”)

antihyperlipidemins taken chronically

Question 3

What are the 5 ACC/AHA Guidelines on the Management of Blood Cholesterol?

Answer 3

1. Healthy lifestyle
2. Clinical ASCVD: ↓ LDL-C by > 50% with high-intensity statin with a nonstatin when LDL > 70
3. Severe hypercholesterolemia: High-intensity statin at highest tolerated dose
4. DM & LDL-C > 70 mg/dL, 40-75 y/o : Moderate-intensity statin
5. 10-year ASCVD risk > 7.5%, 40-75 y/o: Consider moderate-intensity statin

high-intensitty statin: atorvastatin/ rosuvastatin
non statin: ezetimibe or cholestyramine

Question 4

For patients who took high intensity statins Atorvastatin and Rosuvastatin daily, what happened to their LDL lvls?

Answer 4

LDL-C ↓ by > 50%

Question 5

For patients who took moderate intensity statins (a&r, S&Prav, L&F) , daily, what happened to their LDL lvls?

Answer 5

LDL-C ↓ by 30 -50%

Question 6

For patients who took moderate intensity statins (a&r, S&Prav, L&F) , daily, what happened to their LDL lvls?

Answer 6

LDL-C ↓ by 30 -50%

Question 7

For patients who took low intensity statins (P and L) , daily, what happened to their LDL lvls?

Answer 7

LDL-C ↓ by < 30%

Question 8

Which drug(s) are HMG CoA reductace inhibitors?

Answer 8

• Atorvastatin
• Lovastatin
• Pravastatin
• Rosuvastatin
• Simvastatin
• Fluvastatin
• Pitavastatin

all -statins

bolded is hy

Question 9

MOA for statins in general

Answer 9

Inhibit HMG CoA reductase which is the RLS , this inhibit de novo cholesterol synthesis therefore depleting intracellular supply of cholesterol.

Low IC cholesterol stimulates synthesis for more LDL receptors so there is more LDL uptake from blood

they are Analogs of 3-OH-3-CH3-glutaryl (a cholesterol precursor )

Question 10

Rank order potency of LDL lowering (from Greatest to Lowest)

Answer 10

Pitavastatin, Rosuvastatin, Atorvastatin > Simvastatin, Pravastatin > Lovastatin, Fluvastatin

Question 11

Atorvastatin
1. MOA
2. Therapeutic uses

Answer 11

1. MOA: Blocks HMG-COA reductase. Leads to Depletion of intracellular cholesterol by incr LDL receptors and bind & internalize circulating LDL (decr LDL, incr HDL, lower TAG))
2. Therapeutic uses: hyperlipidemia, plaque stabalization, CHD

incr in LDL receptors and block its exportation (bringing everything outside inside)

Question 12

Is atorvastatin effective for homo familial hypercholesterolemia?

Answer 12

NO, because it lacks functional LDL receptors

Question 13

Are statins risk reducers for CHD?

Answer 13

Yes, it doesnt necessarily solve the problem, it should be used in combination with diet and exercise

Question 14

Atorvastatin
1. SE
2. Drug interactions

Answer 14

1. SE: constipation, no preg, confusion/memory impairment, muscle aches, DM
2. Drug interactions: Cyclosporine, Itraconazole, Erythromycin, Gemfibrozil, Niacin

bolded hy

rhabdo=muscles

Question 15

A 43-year-old obese man with type 2 diabetes mellitus is prescribed atorvastatin for the treatment of hyperlipidemia. Which of the following is the mechanism of action of atorvastatin?
A. Triacylglycerol secretion inhibitor
B. HMG-CoA reductase inhibitor
C. Cholesterol absorption inhibitor
D. Cholesterol secretion inhibitor

Answer 15

B. HMG-CoA reductase inhibitor

Question 16

Which drug(s)s are lipolysis inhibitors?

Answer 16

Niacin: nicotinic acid, Vitamin B3

hy

Question 17

Niacin
MOA

Answer 17

1. Inhibits TAG lipolysis in adipose tissue.
2. decr tag syntheis, decr LDL, incr HDL
3. incr tissue plasminogen activator, decr fibrinogen
4. Reverse some endothelial cell dyfxn, contributing to clots w/ hypercholesterolemia & atherosclerosis

TAG lipolysis-> fatty acid (adiose to liver)-> TAG->VLDL-> LDL

Question 18

Niacin
1. Therapeutic uses
2. Side effects
3. Pharmacokinetics
4. Drug interactions

Answer 18

1. Therapeutic uses: hyperlipidemia, lower LDL, INCR HDL THE MOST
2. Side effects: flushing, Hyperuricemia (gout), DM, hepatitis
3. Pharmacokinetics: Converted into nicotinamide which has no activity
4. Drug interactions: Statins: ↑ muscle & liver toxicity risk

you can decr flushing with ASA and IBU
you need a higher dose to decr LDL
HALLMARK IS THAT IT INCR HDL THE MOST

Question 19

Which drug(s) are fibrates?

Answer 19

Fenofibrate, Gemfibrozil

bolded is hy

Question 20

Gemfibrozil
MOA

Answer 20

1. Peroxisome proliferator-activated receptor-α (PPAR-α) agonists
2. decr TAG by incr lipoprotein lipase), incr HDL, decr LDL

PPAR-α regulates lipid metabolism
HALLMARK=DECR TAG THE MOST

Question 21

Gemfibrozil
1. Therapeutic use
2. SE
3. Drug interactions

Answer 21

1. Therapeutic use: hyperlipidemia
2. SE:Hepatitis, Myositis (weakness, stiffness), Gallstones (incr biliary cholesterol excretion)
3. Drug interactions: warfarin, statins

Statins: ↑ muscle & liver toxicity risk

Question 22

Which drug(s) are Bile acid sequestrants?

Answer 22

1. Cholestyramine
2. Colestipol
3. Colesevelam

bolded is hy

Question 23

Cholestyramine
MOA

Answer 23

1. Anion exchange resins which bind (-) charged bile acids & salts in small intestines
2. Resin/bile acid complex excreted in feces-> inhibiting entereohepatic recycling
3. More chol is converted to bile acids, incr LDL uptake via incr in receptors, lower splasma LDL, incr HDL

bile acids (-), seqestrants (+)

Bile acid sequestrants only stay in GI tract. It binds to bile acid and it prevents it from being recycled from SI to its excreted. The body converts more choel to bile salts in the liver and you see incr in LDL receptor formation.

Question 24

What is sodium torocholate?

Answer 24

Bile acid

Question 25

**Cholestyramine** 1. Therapeutic use 2. SE 3. Drug interactions

Answer 25

1. Therapeutic use: hyperlipidemia 2. SE: Constipation, N/V, Flatulence 3. Drug interactions: Interfere w/ absorption of **acidic drugs: Warfarin, Niacin, Digoxin & Vitamins A, D, E, K** ## Footnote Vitamins A, D, E, K are lipid/fat soluble it can be taken up w/ bile acid

Question 26

Which drug is Considered the safest class of lipid-modifying drugs during pregnancy? | hy

Answer 26

Cholestyramine | hy ## Footnote on exam

Question 27

Which drug(s) are cholesterol absorption inhibitors?

Answer 27

Ezetimibe

Question 28

**Ezetimibe** MOA

Answer 28

* **Inhibits cholesterol absorption at the brush border of the intestines & liver via NPC1L1, incr LDL-R expression** * decr LDL, decr TAG, inr HDL

Question 29

**Ezetimibe** 1. Therapeutic use 2. SE 3. Pharmacokinetcs

Answer 29

1. Therapeutic use: hyperlipidemia 2. SE: GI upset 3. Pharmacokinetcs: UGT

Question 30

Can you use **Ezetimibe** with statins?

Answer 30

YES, its weaker to decr LDL so its safe to use with statins if you need to decr LDL more

Question 31

List the effect for each drug

Answer 31

1. Statins have the **greatest effect on decr LDL** compared to other drugs 2. Fibrates have the **greatest effect on decr TAG** compared to other drugs 3. Niacin has the **greatest effect on Incr HDL** compared to other drugs 4. Bile acid sequestrants **can reduce LDL but not as great as statins**, so it can be used with statins to reduce LDL more. 5. Bile acid sequestrants **can actually incr TAG** in some pts and can lead to pancreatis 6. Cholesterol absorption inhibitors are **the worst at reducing LDL**, so it can be used with statins to reduce LDL more ## Footnote know 1-3

Question 32

Which drug(s) are Microsomal triglyceride transfer protein inhibitors? | ly

Answer 32

Lomitapide | ly

Question 33

**Lomitapide** MOA | ly

Answer 33

1. **Microsomal triglyceride transfer protein inhibitor** 2. **Prevents assembly of apo-B containing lipoproteins** (chylomicrons & VLDL in liver & GIT) -> decr plasma LDL concentrations | ly

Question 34

**Lomitapide** 1. Therapeutic use 2. SE 3. Pharmacokinetcs

Answer 34

1. Therapeutic use: **homozygous familial hypercholesterolemia** 2. SE: liver damage, no pregnancy 3. Pharmacokinetcs: CYP3A4 substrate: DI, Hepatic dysfxn | know bolded

Question 35

Which drug(s) are PCK9 inhibitors? | hy

Answer 35

**Evolocumab** | hy

Question 36

**Evolocumab** MOA

Answer 36

1. **Selectively binds to PCSK9 & prevents PCSK9 from degrading LDL receptors in hepatocyte lysosomes which ↑ # of recycled LDL receptors** 2. incr # of LDL receptors therefore decr LDL plasma concentrations ## Footnote its a monoclonal antibody pcsk9 degrades ldl receptors

Question 37

**Evolocumab** 1. Therapeutic use 2. SE

Answer 37

1. Therapeutic use: *homo or hetero hypercholesterolemia*, CVD, *statin therapy* 2. SE: Nasopharyngitis, UPRI, Flu, Back pain, Injection site rxns , *Allergic reactions*

Question 38

What are fish oils? | ly

Answer 38

Omega-3-acid ethyl esters | ly

Question 39

Omega-3-acid ethyl esters 1. MOA 2. Therapeutic use 3. SE | ly

Answer 39

1. MOA: **Activation of nuclear transcription factors ( peroxisome proliferator-activated receptor-α (PPAR-α)**) this leads to liver fatty acid oxidation → ↓ TAG synthesis 2. Therapeutic use: hyperlipidemia , decr TAG, **incr HDL, incr LDL (icosapent -purest form of fish oils, incr LDL the least)** 3. SE: Thrombocytopenia, **Halitosis, Dysgeusia**, Dyspepsia, Infection, Back pain, Flu-like syndrome | ly ## Footnote found in krill oil, cold water fish, milk products for children made a joke abt halitosis and dysgeusia

Question 40

Which drug(s) are ATP Citrate Lyase Inhibitors? | hy

Answer 40

**Bempedoic acid** | hy

Question 41

**Bempedoic acid** MOA | hy

Answer 41

* **Inhibitor of ATP citrate lyase, ↑ LDL-R by ↓ cholesterol synthesis** * **Prodrug**: Active metabolite produced in liver not muscle | hy ## Footnote has less muscle toxicty/activity than statins

Question 42

**Bempedoic acid** 1. Therapeutic use 2. Side effects | hy

Answer 42

1. Therapeutic use: *heterozygous familial hypercholesterolemia*, CVD 2. Side effects: *Gout, Tendon rupture*, Anemia, ↑ Liver enzyme, Muscle spasms | hy

Question 43

Which drug(s) are siRNAs? | hy

Answer 43

**Inclisiran** | hy

Question 44

**Inclisiran** MOA

Answer 44

Small interfering RNA (siRNA) for PCSK9 mRNA, Thus inhibits PCSK9 synthesis | know this

Question 45

**Inclisiran** 1. Therapeutic use 2. SE

Answer 45

1. Therapeutic use: *Hetero hypercholesterolemia*, prevent Cardiovascular events 2. SE: antibodies, inj site rxn, arthralgia, bronchitis

Question 46

Which of the following is the most clinically important side effect of the niacin sustained release dosage form (Niaspan®)? A. Dermatitis B. Meningitis C. Nephritis D. Hepatitis

Answer 46

D. Hepatitis

Question 47

Which of the following drugs is the first line treatment for high LDL lvls? Cholestyramin Atorvastatin Niacin Evolocumab

Answer 47

Atorvastatin

Question 48

Which of teh following drugs should not be given aling side a statin due to the incr risl for muscle and liver toxicity? Gemfibrozil Niacin Both Neither

Answer 48

Both

Question 49

Which of the following drugs is a PPAR-alpha receptor agonist? Evolocumab Ezetimibe Bemoedoic acid Gemfibrozil

Answer 49

Gemfibrozil fish oil too

Question 50

A pt is taking an antihyperlipidemic and starts to experience the side effects of nausea, vomitting, constipation, and flatulance but has other systemic effect. Which of the following antihyperlipidemics is the pt likely taking? Bempoic acid Cholestyraramine Atorvastin Evolocuman

Answer 50

Cholestyraramine

Question 51

Which of the following has the gratest effect on incr HDL? Niacin Bempedoic acid Ezetimibe Atorvastatin

Answer 51

Niacin