Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharmacology > Atherosclerosis and lipoprotein metabolism > Flashcards

Atherosclerosis and lipoprotein metabolism Flashcards

1
Q

Atherosclerosis=

A

the build up of a
waxy plaque on the inside of
blood vessels.
In Greek, athere means gruel, and
skleros means hard

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Atherogensis=

A

formation of
abnormal fatty or lipid masses in
arterial walls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Atherogensis
Main risk factor is

A

high blood cholesterol

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

High Blood Cholesterol
* Estimated 28.5 million adults ≥ 20YO have TC

A

≥ 240mg/dL (High)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

New Cholesterol guidelines in 2018
* Focused on identifying…
* Statins are the primary treatment to reduce —
* Very high risk patients may need combination therapy to reach LDL ≤ –mg/dL

A

high risk and very high risk patients
cholesterol
70

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q
  • Chylomicrons
A
  • Highest proportion of triglycerides
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q
  • VLDL
A
  • Very Low Density Lipoprotein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q
  • LDL
    (2)
A
  • Low Density Lipoprotein
  • “Bad Cholesterol”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q
  • HDL
    (2)
A
  • High Density Lipoprotein
  • “Good Cholesterol”
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q
  • Total Cholesterol
    mg/dL
A
  • ≤ 200mg/dL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q
  • HDL
    mg/dL
A
  • ≥ 60mg/dL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q
  • LDL
    mg/dL
A
  • ≤ 100mg/dL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q
  • Triglycerides
    mg/dL
A
  • ≤ 150mg/dL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Friedewald Formula
Total Cholesterol=

A

LDL
“Bad Cholesterol”
+
HDL
“Good Cholesterol”
+
TG/5

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Risk Factors for ASCVD
(7)

A
  • Smoking
  • Hypertension
  • Hyperlipidemia
  • Diabetes mellitus
  • Age (men ≥45 yo, women
    ≥55yo)
  • Obesity
  • Physical Inactivity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q
  • Hyperlipidemia
    (2)
A
  • increase LDL and TC
  • decreaes HDL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Risk Assessment
ASCVD Risk Score
* Risk Factors used include:
(8)

A
  • age, gender, total and HDL cholesterol, smoking status, blood pressure, diabetes,
    and race
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Risk Assessment
ASCVD Risk Score
* Estimates…
* Used to guide…

A

10-year risk of MI or stroke
lipid therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q
  • Clinical ASCVD
    (3)
A
  • Established Coronary Artery Disease (CAD)
  • History of stroke or TIA
  • Peripheral Artery Disease (PAD)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

No need to calculate ASCVD score if patient has

A

Clinical ASCVD

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Atherogenesis
(7)

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

HDL removes
cholesterol
from

A

vessel
walls

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Atherosclerosis
Patient symptoms
(5)

A

Angina
Acute Coronary Syndrome
Unstable angina
NSTEMI
STEMI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Lipoprotein metabolism
* Exogenous pathway

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Lipoprotein metabolism
* Endogenous pathway

A
  • 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
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

HMG-CoA reductase inhibitors (Statins)
Mechanism of Action
* Inhibit…
* Rate-limiting step in…
* Also induce an increase in…

A

HMG-CoA reductase
endogenous cholesterol production
hepatic LDL receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

HMG-CoA reductase inhibitors (Statins)
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 13% to 40%
decrease 17% to 55%
decrease 2 to 28%
increase 2 to 10%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Definitions of High- and Moderate-
Intensity Statin Therapy
High
(2)

A

Daily dose lowers
LDL by ≥ 50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Definitions of High- and Moderate-
Intensity Statin Therapy
Moderate
(2)

A

Daily dose lowers
LDL by 30% -<50%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

HMG-CoA reductase inhibitors (Statins)
Clinical benefits
Primary Prevention
(4)

A
  • Target age 40-75 YO with LDL 70-189mg/dL
  • Use ASCVD risk score to guide therapy
  • Coronary Calcium Score helpful
  • Diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Use ASCVD risk score to guide therapy
* — risk = moderate intensity
statin
* — high intensity statin

A

> 7.5% to ≤ 20%
20%

32
Q

Diabetes
* All patients get at least — intensity statin

A

moderate

33
Q

HMG-CoA reductase inhibitors (Statins)
Clinical benefits
Secondary Prevention
(3)

A
  • All patients under 75 YO with
    established ASCVD
  • High intensity statin
  • Very-high risk consider combo
    therapy if LDL > 70mg/dL
34
Q

HMG-CoA reductase inhibitors (Statins)
Pleiotropic effects
* Positive:
(5)

A
  • Plaque stabilization
  • Reduced inflammation
  • Improved endothelial function
  • Reduced platelet aggregability
  • Increased neovascularization of ischemic tissue
35
Q

HMG-CoA reductase inhibitors (Statins)
Pleiotropic effects
* Negative/Neutral:
(2)

A
  • Inhibition of germ cell migration during development
    (Pregnancy contraindication)
  • Immune suppression
36
Q

HMG-CoA
Adverse Drug Reaction
(2)

A

H Hepatotoxicity
M Myopathy (ranging from mild soreness to Myositis to rhabdoMyolysis

37
Q

HMG-CoA
Contraindications
(1)

A

G Girls (during pregnancy) & Growing children

38
Q

HMG-CoA reductase inhibitors (Statins)
Drug-Drug Interactions
(3)

A
  • Many DDI due to hepatic metabolism (via CYP450 3A4 or PgP)
  • Impaired statin absorption → decreased statin efficacy
  • Increased risk of myopathy (pharmacodynamics interaction)
39
Q
  • Many DDI due to hepatic metabolism (via CYP450 3A4 or PgP)
    (3)
A
  • Impaired statin metabolism→ increased risk of hepatotoxicity or myopathy
  • Impaired clearance of competing drug → increased risk of competing drug
    ADRs
  • Pravastatin and Rosuvastatin are not significantly cleared via CYP450 and
    have the least amount of DDI of this type
40
Q
  • Impaired statin absorption → decreased statin efficacy
  • Example:
A

Bile acid binding agents

41
Q
  • Increased risk of myopathy (pharmacodynamics interaction)
  • Other drugs that also have a risk of
A

myopathy (ex. Fibrates)

42
Q

HMG-CoA reductase inhibitors (Statins)
Example: Atorvastatin
* Brand name: Lipitor®
* MOA:
* Use: (2)
* ADRs:(3)
* Pregnancy category:
* Drug-Drug interactions:
(2)
* Dental implications: Myopathy may present as

A

HMG-CoA reductase inhibitor
Hyperlipidemia, Prevention of ASCVD
Elevated liver enzymes(hepatotoxicity), myopathy,
rhabdomyolysis
X (contraindicated)

  • Increased risk of myopathy with erythromycin, ketoconazole,
    itraconazole
  • Increased effects of midazolam when used in combination

weakness with
chewing or brushing teeth

43
Q

PCSK-9 Inhibitors
Mechanism of Action
* Block the action of…
* PCSK-9 promotes the
degradation of…
* Inhibition of PCSK-9 results in…

A

proprotein, subtilisin kexin type 9 (PCSK9)
LDL receptors
more active LDL receptors and lower serum LDL

44
Q

PCSK-9 Inhibitors
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease ~60%
—–
No effect

45
Q

Most potent
medication for
LDL lowering

A

PCSK-9 Inhibitors

46
Q

PCSK-9 inhibitors are given by —
Cash price was $14,500/year in 2018 price was decrease –% to ~$5,800/year

A

SQ injection
60

47
Q

Alirocumab
* Brand name: Praluent®
* MOA:
* Use:
* ADRs: (3)
* Drug-Drug interactions:
* Dental implications:

A

Binds to proprotein subtilisin kexin type 9 (PCSK9).
Preventing PCSK9 from binding LDL receptors, thereby
promoting LDL degretation within the liver

familial hyperlipidemia and high risk CV patients
Injection site reactions, diarrhea, decreasing LDL too
low

None of significance to dentistry
none

48
Q

ATP-citrate lyase (ACL) inhibitor
* Bempedoic acid (Nexletol®) only
drug in class
* Inhibit…
* Approved by the FDA in
February 2020
* Not addressed in clinical
guidelines

A

cholesterol synthesis two
-steps ahead of statins (HMG-
CoA reductase inhibitors)

49
Q

Bempedoic acid
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 15-20%
—–
—–

50
Q

Bempedoic acid
Effects on Lipid parameters
Synergistic LDL lowering when combined with

A

ezetimibe therapy

51
Q

Bempedoic acid
* Brand name: Nexletol®
* MOA:
* Use:
* ADRs: (3)
* Drug-Drug interactions:
* Dental implications:

A

Inhibit cholesterol synthesis two-steps ahead of statins
(HMG-CoA reductase inhibitors)

familial hyperlipidemia and established high risk CV
patients
Elevated uric acid, back pain, elevated liver enzymes

None of significance to dentistry
none

52
Q

Inhibitors of cholesterol absorption
(Ezetimibe and Bile acid binding agents )
Absorption inhibitor
(3)

A

Ezetimibe (Zetia®)
Also available with simvastatin
Ezetimibe/Simvastatin (Vytorin®)

53
Q

Inhibitors of cholesterol absorption
(Ezetimibe and Bile acid binding agents )
Bile acid binding agents
(3)

A

Cholestyramine (Questran®, Prevalite®)
Colesevelam (Welchol®)
Colestipol (Colestid®)

54
Q

Ezetimibe
Mechanism of Action
* Blocks…
* Blocking transport protein…
* Does not affect absorption
of (3)

A

cholesterol absorption in the intestine (duodenum)
NPC1L1 in the brush border of the enterocyte
fat-soluble vitamins, triglycerides, or bile acid

55
Q

Ezetimibe
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 10-12%
decrease 18-20%
decrease 1-2%
increase 1-2%

56
Q

Ezetimibe
Effects on Lipid parameters
Synergistic LDL lowering when combined with

A

statin therapy

57
Q

Ezetimibe
* Brand name: Zetia®
* MOA:
* Use:
* ADRs:
* Drug-Drug interactions:
* Dental implications:

A

Blocks absorption of cholesterol in the intestine by
blocking the NPC1L1 transport protein

hyperlipidemia
Rare- maybe back pain or diarrhea

None of significance to dentistry
none

58
Q

Bile Acid Binding Agents
Mechanism of Action
* Bind to…
* Prevent resorption of…
* Result in…

A

bile acid in the
intestine
bile acid
increase uptake of LDL by liver

59
Q

Bile Acid Binding Agents
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 15-21%
increase 2-16%
increase 3-9%

60
Q

Bile Acid Binding Agents
Example: Colesevelam
* Brand name: Welchol®
* MOA:
* Use:
* ADRs: (4)
* Drug-Drug interactions: (3)

A

Binds bile acid preventing resorption
hyperlipidemia
Mainly GI distress- constipation, abdominal pain, nausea,
dyspepsia

None of significance to dentistry
* Many others due to inhibition of absorption of medications
* Take 1 hour before or 2 hours after other medications

61
Q

Bile Acid Binding Agents
Example: Colesevelam-Dental Implications
(1)

A
  • Consider semisupine chair position for patient
    comfort due to GI side effects of medication
62
Q

Fibrates
Mechanism of Action
(5)

A
  • 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
63
Q

Fibrates
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 5-20%
decrease 20-50%
increase 10-20%

64
Q

Fibrates
Example: Fenofibrate
* Brand name: Tricor® and others
* MOA:
* Use:
* ADRs: (5)
* Drug-Drug interactions: (2)

A

PPARα nuclear receptor agonist increasing lipoprotein lipase levels
hyperlipidemia- specifically hypertriglyceridemia
Myopathy, dyspepsia, blurred vision/eye floaters, elevations in
liver enzymes, GI distress(abdominal pain)

None of significance to dentistry
* Increase r/o ADRs when combined with statin

65
Q

Fibrates
Example: Fenofibrate-Dental Implications
(3)

A
  • 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
66
Q

Nicotinic acid or its derivatives
Mechanism of Action
* Inhibits..
* Lowers..
* Increases..

A

hepatic VLDL secretion
serum Triglycerides and LDL
serum HDL

67
Q

Niacin
Effects on Lipid parameters
Parameter Change
Total Cholesterol:
LDL:
Triglycerides:
HDL:

A

decrease 10-20%
decrease 20-50%
increase 15-35%

68
Q

Niacin
Effects on Lipid parameters
Dose of lipid lowering effects —mg daily

A

500mg-2000

69
Q

Niacin
Adverse Drug Reactions
(5)

A
  • Flushing
  • Gastrointestinal distress
  • Liver damage/dysfunction ( liver enzymes)
  • Impaired glucose tolerance
  • Precipitate gout flare
70
Q
  • Flushing
A
  • Reduced by taking aspirin 30 minutes before dose
71
Q
  • Gastrointestinal distress
A
  • Nausea, vomiting, or diarrhea
72
Q
  • Liver damage/dysfunction ( liver enzymes)
A
  • Can occur at any time during therapy
73
Q
  • Impaired glucose tolerance
A
  • Can worsen a patient’s control of diabetes
74
Q
  • Precipitate gout flare
A
  • increase circulating uric acid level
75
Q

Niacin
* Brand name: Niaspan®
* MOA:
* Use:
* ADRs: (5)
* Drug-Drug interactions: (2)
* Dental implications:
(2)

A

Inhibits synthesis of VLDL
hyperlipidemia (particularly hypertriglyceridemia)
flushing, GI distress, Liver dysfunction, glucose intolerance, gout flare

None of significance to dentistry
* Increased risk of hepatotoxicity when combined with statin

  • Minor- may cause dizziness so be careful when standing up
  • May increase risk of bleeding

Pharmacology (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions