Atherosclerosis and Lipoprotein Metabolism Flashcards
_______= the build up of a
waxy plaque on the inside of
blood vessels.
Atherosclerosis
________= formation of
abnormal fatty or lipid masses in
arterial walls
Atherogensis
What is the main risk factor for atherosclerosis/atherogenesis?
High blood cholesterol
What lipoprotien has the highest percentage of triglycerides?
Chylomicrons
What lipoprotein has the least number of triglycerides?
HDl
What lipoprotein is the bad cholesterol?
LDL
What lipoprotein is good cholesterol?
HDL
What is the optimal cholesterol level (mg/dL) for total cholesterol?
< or equal to 200 mg/dL
What is the optimal cholesterol level (mg/dL) for HDL?
> or equal to 60 mg/dL
What is the optimal cholesterol level (mg/dL) for LDL?
< or equal to 100 mg/dL
What is the optimal cholesterol level (mg/dL) for triglycerides?
< or equal to 150 mg/dL
Risk Factors for \_\_\_\_\_\_ • Smoking • Hypertension • Hyperlipidemia • LDL and TC • HDL • Diabetes mellitus • Age (men ≥45 yo, women ≥55yo) • Obesity • Physical Inactivity
ASCVD
Do men or women have a higher risk for ASCVD?
Men
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
he process of HDL mobilizing cholesterol and transporting back
to the liver is called ______
‘reverse cholesterol transport’
\_\_\_\_\_\_\_ 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
Chylomicrons metabolized by
______ to release TG
lipoprotein lipase
_______ 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
_________
facilitates the transfer of cholesterol to HDL
Cholesteryl ester transfer protein (CETP)
____ provides cholesterol source for cells to
make cell membranes- also atherogenesis
LDL
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®
