Atherosclerosis and Lipoprotein Metabolism Flashcards by Michael McMahan

_______= the build up of a
waxy plaque on the inside of
blood vessels.

Atherosclerosis

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________= formation of
abnormal fatty or lipid masses in
arterial walls

Atherogensis

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What is the main risk factor for atherosclerosis/atherogenesis?

High blood cholesterol

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What lipoprotien has the highest percentage of triglycerides?

Chylomicrons

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What lipoprotein has the least number of triglycerides?

HDl

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What lipoprotein is the bad cholesterol?

LDL

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What lipoprotein is good cholesterol?

HDL

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What is the optimal cholesterol level (mg/dL) for total cholesterol?

< or equal to 200 mg/dL

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What is the optimal cholesterol level (mg/dL) for HDL?

> or equal to 60 mg/dL

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What is the optimal cholesterol level (mg/dL) for LDL?

< or equal to 100 mg/dL

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What is the optimal cholesterol level (mg/dL) for triglycerides?

< or equal to 150 mg/dL

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Risk Factors for \_\_\_\_\_\_
• Smoking
• Hypertension
• Hyperlipidemia
•  LDL and TC
•  HDL
• Diabetes mellitus 
• Age (men ≥45 yo, women 
≥55yo)
• Obesity 
• Physical Inactivity

ASCVD

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Do men or women have a higher risk for ASCVD?

Men

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What are the 7 steps of artherogenesis?

Endothelial dysfunction
Endothelial injury
LDL deposits into vessel wall
Formation of foam cells (macrophages filled with LDL)
Fatty streak
Inflammation (smooth muscle growth)
Fibrous cap over lipid core

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he process of HDL mobilizing cholesterol and transporting back
to the liver is called ______

‘reverse cholesterol transport’

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\_\_\_\_\_\_\_ pathway of lipoprotein
• Cholesterol and TG absorbed from diet 
transported as chylomicrons to muscle 
and adipose tissue
• Chylomicrons metabolized by 
lipoprotein lipase to release TG
• Chylomicron remnants (mostly 
cholesteryl esters) return to the liver
• Cholesterol in liver may be 1) stored,  
2) turned into bile, or 3) enter 
endogenous pathway

Exogenous

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Chylomicrons metabolized by

______ to release TG

lipoprotein lipase

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_______ pathway of lipoprotein metabolism
• Cholesterol and TG made in liver leave as VLDL
• VLDL metabolized by lipoprotein lipase to
release TG- VLDL becomes LDL
• LDL provides cholesterol source for cells to
make cell membranes- also atherogenesis
• Cell use an LDL-receptor to take up LDL
• Liver releases HDL to collect cholesterol and
return to liver (reverse cholesterol transport)
• Cholesteryl ester transfer protein (CETP)
facilitates the transfer of cholesterol to HDL

Endogenous

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_________

facilitates the transfer of cholesterol to HDL

Cholesteryl ester transfer protein (CETP)

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____ provides cholesterol source for cells to

make cell membranes- also atherogenesis

LDL

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VLDL metabolized by ________ to

release TG- VLDL becomes LDL

lipoprotein lipase

MOA of \_\_\_\_\_:
• Inhibit HMG-CoA reductase
• Rate-limiting step in 
endogenous cholesterol 
production
• Also induce an increase in 
hepatic LDL receptors

Statins

How do statins affect lipid parameters?
TOC
LDL
Triglycerides
HDL

Decrease TOC
Decrease LDL
Decrease TG
Increase HDL

____ intensity statins
Daily dose lowers
LDL by ≥ 50%

High

_____ intensity statins Daily dose lowers LDL by 30% -<50%

Moderate

``` Pleiotropic effects of ______: • Positive: • Plaque stabilization • Reduced inflammation • Improved endothelial function • Reduced platelet aggregability • Increased neovascularization of ischemic tissue • Negative/Neutral: • Inhibition of germ cell migration during development (Pregnancy contraindication) • Immune suppression ```

Statins

What are the 3 adverse reactions to statins? | HMG

Hepatotoxicity Myopathy Girls (preggo) and Growing children

______ and ______ are not significantly cleared via CYP450 and have the least amount of DDI of this type

Pravastatin and Rosuvastatin

* MOA: HMG-CoA reductase inhibitor * Use: Hyperlipidemia, Prevention of ASCVD * ADRs: Elevated liver enzymes(hepatotoxicity), myopathy, rhabdomyolysis * Pregnancy category: X (contraindicated) * Drug-Drug interactions:• Increased risk of myopathy with erythromycin, ketoconazole, itraconazole * Increased effects of midazolam when used in combination * Dental implications: Myopathy may present as weakness with chewing or brushing teeth

Atorvastatin | • Brand name: Lipitor®

``` ______ Mechanism of Action • Block the action of proprotein subtilisin kexin type 9 (PCSK9) • PCSK-9 promotes the degradation of LDL receptors • Inhibition of PCSK-9 results in more active LDL receptors and lower serum LDL ```

PCSK-9 Inhibitors

What are the PCSK-9 inhibitors?

Alirocumab | Evolocumab

What is the most potent LDL lowering med?

PCSK-9 inhibitors

• MOA: Binds to proprotein subtilisin kexin type 9 (PCSK9). Preventing PCSK9 from binding LDL receptors, thereby promoting LDL degretation within the liver • Use: familial hyperlipidemia and high risk CV patients • ADRs: Injection site reactions, diarrhea, decreasing LDL too low • Drug-Drug interactions: None of significance to dentistry • Dental implications: none

Alirocumab | • Brand name: Praluent®

``` • Bempedoic acid (Nexletol®) only drug in class • Inhibit cholesterol synthesis two -steps ahead of statins (HMG- CoA reductase inhibitors) • Approved by the FDA in February 2020 • Not addressed in clinical guidelines ```

ATP-citrate lyase (ACL) inhibitor

How does ACL inhibitors affect lipid parameters?

Lowers LDL

• MOA: Inhibit cholesterol synthesis two-steps ahead of statins (HMG-CoA reductase inhibitors) • Use: familial hyperlipidemia and established high risk CV patients • ADRs: Elevated uric acid, back pain, elevated liver enzymes • Drug-Drug interactions: None of significance to dentistry • Dental implications: none

Bempedoic acid | • Brand name: Nexletol®

``` ______ Mechanism of Action • Blocks cholesterol absorption in the intestine (duodenum) • Blocking transport protein NPC1L1 in the brush border of the enterocyte • Does not affect absorption of fat-soluble vitamins, triglycerides, or bile acid ```

Ezetimibe

What is Ezetimibe's effect on lipid parameters?

Decrease TOC, LDL, and TG Increases HDL Not as effective as statins

` • MOA: Blocks absorption of cholesterol in the intestine by blocking the NPC1L1 transport protein • Use: hyperlipidemia • ADRs: Rare- maybe back pain or diarrhea • Drug-Drug interactions: None of significance to dentistry • Dental implications: none

Ezetimibe | • Brand name: Zetia®

``` _________ Mechanism of Action • Bind to bile acid in the intestine • Prevent resorption of bile acid • Result in increase uptake of LDL by liver ```

Bile Acid Binding Agents

What are the effects of lipid parameters of bile acid binding agents?

Increased HDL and TG* | Decreased LDL

• MOA: Binds bile acid preventing resorption • Use: hyperlipidemia • ADRs: Mainly GI distress- constipation, abdominal pain, nausea, dyspepsia • Drug-Drug interactions: None of significance to dentistry • Many others due to inhibition of absorption of medications • Take 1 hour before or 2 hours after other medications • Consider semisupine chair position for patient comfort due to GI side effects of medication

Colesevelam | • Brand name: Welchol®

``` _____ Mechanism of Action • Complex mechanism of action • Agonist of PPARα nuclear receptor • Increase transcription of lipoprotein lipase • Marked decrease in VLDL and triglycerides • Also increase LDL uptake and HDL synthesis ```

Fibrates

If the generic drug name has FIB in it, what type of drug in it?

Fibrates

What is the main effect on lipid parameters for fibrates?

Greatly lowers TG

• MOA: PPARα nuclear receptor agonist increasing lipoprotein lipase levels • Use: hyperlipidemia- specifically hypertriglyceridemia • ADRs: Myopathy, dyspepsia, blurred vision/eye floaters, elevations in liver enzymes, GI distress(abdominal pain) • Drug-Drug interactions: None of significance to dentistry • Increase r/o ADRs when combined with statin • Consider semisupine chair position for patient comfort due to GI side effects of medication • Avoid dental light in patient’s eyes; offer dark glasses for patient comfort due to vision side effects • May cause dry mouth

Fenofibrate | • Brand name: Tricor® and others

``` _______ Mechanism of Action • Inhibits hepatic VLDL secretion • Lowers serum Triglycerides and LDL • Increases serum HDL ```

Nicotinic acid or its derivatives

What is the main effect on lipid parameters from Niacin (nicotinic acid or its derivatives)?

Decreased TG

Adverse Drug Reactions to _____ • Flushing • Reduced by taking aspirin 30 minutes before dose • Gastrointestinal distress • Nausea, vomiting, or diarrhea • Liver damage/dysfunction ( liver enzymes) • Can occur at any time during therapy • Impaired glucose tolerance • Can worsen a patient’s control of diabetes • Precipitate gout flare •  circulating uric acid level

Niacin

* MOA: Inhibits synthesis of VLDL * Use: hyperlipidemia (particularly hypertriglyceridemia) * ADRs: flushing, GI distress, Liver dysfunction, glucose intolerance, gout flare * Drug-Drug interactions: None of significance to dentistry * Increased risk of hepatotoxicity when combined with statin * Dental implications: * Minor- may cause dizziness so be careful when standing up * May increase risk of bleeding

Niacin | • Brand name: Niaspan®