Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Drug Action I > Block 2 - Dyslipidemia Pharm > Flashcards

Block 2 - Dyslipidemia Pharm Flashcards

(86 cards)

Start Studying
1
Q

What are some non-pharms of treating HLD?

A
  1. Maintain healthy diet and weight
  2. Better compliance
  3. Avoid tobacco
  4. Exercise (150-160 min/week)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are pharm options of HLD?

A
  1. HMG CoA reductase inhibitors
  2. Cholesterol synthesis inhibitors
  3. Cholesterol absorption inhibitors
  4. Fibric Acid derivatives
  5. Bile-acid binding resins
  6. Niacin (nicotinic acid)
  7. Newer drug agents – PCSK9 inhibitors, Lomitapide, and others
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the mechanism addressed using lipid lowering therapy?

A
  1. Improved endothelium-dependent vasodilation
  2. Stabilization of atherosclerotic lesions
  3. Reduction of inflammatory stimuli
  4. Prevention or slow progression of atherosclerotic lesions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the hyperclosterolemia drugs?

A
  1. Cholesterol synthesis inhibitors (Statins and Bempedoic Acid)
  2. . Cholesterol absorption inhibitors and sequestrants
  3. Niacin or Fibrates
  4. PCK9 inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the hypertriglyceridemia drugs?

A
  1. Fibrin acids
  2. Niacin
  3. Eicosapentaenoic acid (EPA) & Fish oils
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the MOA of statins?

A

Competitively inhibits the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (in nM range) – which is the rate limiting step for cholesterol biosynthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

How do statins work?

A

Decreases cholesterol synthesis producing a compensatory increase in the number of cell surface hepatic LDL receptors → Increase plasma LDL clearance

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the mechanisms of Statin activity?

A
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the purpose of lactone on statins?

A

Active center and binds to HMG binding site

Lovastatin is hydrolyzed to resemble intermediate while Atorvastatin already resembles intermediate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What falls under high intensity statin therapies?

A

Daily dose lowers LDL–C on average approximately ≥50%

  1. Atorvastatin (40-80 mg)
  2. Rosuvastatin (20 mg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is considered moderate intensity statins?

A

Daily dose lowers LDL–C on average approximately 30% to <50%

  1. Atorvastatin 10 (20) mg
  2. Rosuvastatin (5) 10 mg
  3. Simvastatin 20–40 mg‡
  4. Pravastatin 40 (80) mg
  5. Lovastatin 40 mg
  6. Fluvastatin 40 mg BID
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is considered low intensity therapy?

A

Daily dose lowers LDL–C on average approximately <30%

  1. Pravastatin 10-20 mg
  2. Lovastatin 20 mg
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What study noticed that Satins reduced hsCRP → fall in LDL?

A

CHEST study

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What study saw pravastatin reduced CRP by 17%?

A

PRINCE study

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

What is the therapeutic benefits of HMG CoA reductase inhibitors?

A
  1. Reduce major coronary events
  2. Reduce mortality
  3. Reduce coronary procedures
  4. Reduce stroke
  5. Reduces total mortality
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What are some counseling points associated with satins?

A

Pravastatin and pitastatin are metabolized with CYP3A4 (excreted in bile unwanted)

Fluvastatin and Rosuvastatin by CYP2C9

CYP3A4 is a source of DDIs

Not safe for pregnancy or breast feeding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are the side effects associated with statin?

A
  1. Muscle pain (myalgia),
  2. Myopathy and Rhabdomyolysis (Increases to 2% with niacin and 3% with fibrates)
  3. Hepatotoxicity and liver damage (rare)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What are cormordities for statin ADRs?

A
  1. Impaired hepatic (absolute) or renal (caution) function
  2. CYP3A4 drugs (Fibrates, Niacin)
  3. Unexplained increase in ALT levels
  4. > 75 YO
  5. History of stroke
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How common fatal rhabdomyolysis with statin?

A

Class effect
Increased by combo with vibrates (gemfibrozil) or niacin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is the MOA of bempedoic acid?

A
  1. An oral pro-drug, activated in the liver, that inhibits the ATP-citrate lyase (ACLY)
  2. Deceases cholesterol synthesis by inhibition of the ATP citrate lyase
  3. The decrease in cholesterol upregulates the LDL-R, leading to a increase in LDL-C clearance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the importance of ATP citrate lyase?

A

enzyme found upstream of HMG CaA reductase used for cholesterol biosynthesis

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

Brand of Bempedoic Acid?

A

Nexletol

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

Common ADRs of Nexletol?

A
  1. Muscle spasm
  2. Pain in back or limbs
  3. Gout
  4. Diarrhea (GI problems)
  5. Tendon rupture
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Common Dis of Bempedoic Acid?

A

Drug increases simvastatin and pravastatin blood levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What is the MOA of Ezetimibe?
Zetia is a potent and specific inhibitor of dietary and biliary cholesterol absorption that works in the brush border of the small intestine to inhibit the absorption of cholesterol by inhibiting the intestinal Cholesterol Transporter (Niemann-Pick C1-Like 1 protein (NPC1L1))
26
How is ezetimibe metabolized?
A glucuronide (EZEG) – which has 400x greater potency
27
Fibrate MOA?
Alters gene transcription via activity at the peroxisomal proliferation activated receptor (PPAR-α) One of the drugs of choice for hypertriglyceridemia
28
What is a PPAR-a?
Nuclear receptor that modulates genes associated with fatty acid regulation
29
What are the primary effects of vibrates on liver and adipose tissue?
1. Increase LPL expression → decreased chylomicron and VLDL and plasma TG 2. Increase LDL size (less arthogenic) 3. Increase Acyl-coA synthase → fatty acid oxidation 4. Increase apoA-I and apoA-II synthesis → Increase HDL-C and reverse cholesterol transport 5. Decrease Hepatic apoC-III synthesis → Decrease plasma triglycerides 6. Increase anti-inflammatory effects on arterial wall
30
What are the lab actions of fibrin acids?
1. Lowers TGs 30–60% 2. Lowers total cholesterol ~20-40% 3. Lowers LDL-C ~5–20% (with normal TGs) 4. May raise LDL-C (with high TGs) 5. Raises HDL-C ~5–20%
31
ADRs of fibrates?
1. Increase risk of gall stones (cholecystitis) 2. Fibrates+Statin increase myopathy
32
What is nicotine acid? Is it first line?
Niacin or Niacor is a Water soluble B-complex vitamin
33
Niacin MOA?
1. Inhibits lipolysis of triglycerides, reducing FFA mobilization from the periphery 2. inhibits hormone-sensitive lipase in adipose tissue, reducing the breakdown of triglycerides to free fatty acids and the transport of free fatty acids to the liver
34
What happens in the liver when Niacin is administered?
1. Decreased TG synthesis → Decreased hepatic VLDL production 2. Niacin inhibits hepatocyte diacylglycerol acyltransferase-2 (DGAT-2), a key enzyme for triglyceride synthesis 3. Increased Hepatic and plasma VLDL → lowers LDL (which eventually comes from VLDL) 4. Decreases HDL-apoAI clearance leading to increase HDL-C levels
35
If Niacin increase HDL and decreases Lpa with is niacin not used that often for HLD?
1. Side effects, especially in combination with other lipid reducing medication's 2. Difficult to dose
36
Common ADRs of Niacin?
1. Flushing 2. Skin rashes 3. Dyspepsia 4. Hepatotoxicity 5. Muscle Pain 6. Avoid in patients with gout and peptic ulcers 7. May worsen diabetes or glucose intolerance @ higher doses 8. Avoid in pregnancy
37
What must you watch out for when someone is taking both Niacin and statins?
Myopathy may occur → reduce statin dose to 25% max
38
What study placed the role of niacin in lipid therapy into question that removed niacin/statin combos?
HPS2-THRIVE study
39
What is Slo-Niacin?
“Polygel” Controlled-release niacin formulation which may help reduce ADRs, especially flushing
40
What is Niaspan?
1. QD treatment of cholesterol and lipid disorders 2. HydroGel Programmed-Release formulation 3. Pricey, but minimizes flushing
41
What is bile acids?
Amphipathic polar derivatives of cholesterol necessary for absorption of sterols, fats, and fat soluble vitamins
42
How is bile acid eliminated?
Secreted into the intestine (~97%) returns, via the enterohepatic circulation, to the liver.
43
What are the benefits of anion-exchange resins?
"Selectively" bind the negatively charged bile acids
44
What are the bile acid sequestrant resins? Counseling point?
cholestyramine and colestipol Take other medications at least an hour prior to use so that it may not impair absorption of other drugs
45
How does colesevelam differ from the other bile acid sequestrate?
Water insoluble polymer that is not hydrolyzed by digestive enzymes, and not absorbed from the GI tract into the systemic circulation Better GI tolerability and may have less potential for drug interactions
46
What is the MOA of bile acid sequestrates?
Bind bile acids in the intestine, forming insoluble complexes which are eliminated in the feces leading to compensatory mechanisms
47
What are the compensatory mechanisms of bile acid sequestrants?
1. Reduction in the re-uptake of bile acids increases 7-hydroxylase activity (the enzyme responsible for synthesis of bile), due to the loss of feedback inhibition 2. Increases in 7-hydroxylase activity leads to increased conversion of cholesterol into bile acids 3. Increased utilization of cholesterol to increase bile acid synthesis, increases LDL receptors, which increases hepatic uptake of plasma LDL.
48
What mechanism limits BA sequestrates use in certain pateints?
increase cholesterol synthesis which may increase VLDL
49
DDIs or BA sequestrates?
Binds polar drugs such as warfarin, digoxin, thyroxine and statins… take other medications at least 1 hr before taking the resin ADEK
50
ADRs and absorption of BA sequestrants?
1. Constipation, nausea, gas 2. No absorbed systemically
51
Why shouldn't BA sequestrants be used as a monotherpay?
Should not be used as monotherapy in patients with hypertriglyceridemia since they will likely increase triglyceride synthesis
52
Brand of cholestryamine?
Questran
53
Brand of Colestipol?
Colestid
54
Brand of Colesevelam?
WelChol
55
What is the MOA of Omega-3 Fatty acid?
56
Lovaza indication? Dosage form? Effects?
Severe hyperTG 900 mg of highly purified ethyl esters of omega-3 fatty acids from fish oils. Reduce TG, TC, increases HDL 9% and LAL-C by 44.5%
57
What are the Omega-3-acid ethyl esters ADR?
1. include burping, mild flu-like symptoms, upset stomach, change in sense of taste 2. Avoid if fish or shell fish allergy
58
What is the appropriate dosing for OTC fish oil for it to have effect?
Up to 14 capsules/day for appropriate dosing
59
What is Vascepa?
Synthetic ethyl eicosapentaenoic acid (EPA) without DHA
60
What is EPA?
Reduces hepatic VLDL synthesis and secretion, and enhances TG clearance from circulating VLDL particles
61
Why is DHA not commonly used?
DHA was associated with a greater reduction in TG, but a greater increase in LDL-C compared to EPA
62
Vascepa indication? ADRs?
Hypertriglyceridema indicated as an adjunct to maximally tolerated statin therapy EPA-only Vascepa may not elevate LDL-C
63
What is familial hypercholesterolemia?
An inherited genetic disorder resulting in high levels of LDL-C and increased risk of atherosclerosis
64
What are the risks of heterozygous FH?
risk of premature cardiovascular disease and death affecting 1:2500 people
65
What is the the difference between heterozygous and homozygous FH?
Heterozygous FH is characterized by high LDL cholesterol and a family history of high cholesterol, atherosclerosis, early heart disease or stroke Homozygous FH is rare (~1 in a million) and characterized by extremely high levels of LDL cholesterol and symptoms seen in childhood
66
What is used to treat FH?
Lomitapide (Juxtapid)
67
What is the MOA of Lomitapide?
Inhibits the microsomal triglyceride transfer protein (MTP or MTTP) which is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.
68
What is MTP?
(microsomal triglyceride transfer protein) is responsible for lipidation (or transfer of triglycerides) onto apoB48 containing chylomicrons in the gut and onto apoB100 containing VLDL particles in the liver.
69
What does the inhibitor of MTP look like?
Blocking MTP reduces hepatic VLDL, LDL and Lp(a) production and intestinal chylomicron formation
70
What are the metabolic effects of lomitapide?
Decreases LDL-C, TC, apo B, TG, and non HDL
71
What are the main considerations of Lomitapide?
Hepatoxicity risk → only available through REMS program
72
What is the role of PCSK9?
a protein secreted by hepatocytes which “chaperones” the LDL receptor (LDL-R) inhibits LDL receptor recycling and earmarks LDL-Rs for lysosomal degradation
73
What is the role of LDL receptors?
Responsible for the removal of LDL particles from blood and into hepatocytes
74
What are MOA of PCSK9 inhibitors?
Monoclonal antibodies that bind to PCSK9 protein, thereby inhibiting its binding to and effects on the LDL receptor → reducing LDL levels and degradation of LDL recepotrs
75
What are the PCSK9 meds?
Repatha (evolocumab) and Praluent (alirocumab)
76
ADRs of Repatha (evolocumab) and Praluent (alirocumab)?
1. Sore throat 2. ISR 3. Flu-like symptoms 4. Elevated LFT 5. Elevated plasma glucose and HbA1C
77
What happens if you have a rare serious reaction to Repatha (evolocumab) and Praluent (alirocumab)?
Discontinue medication if showing signs of anaphylasis
78
Why is Miomersen not used today?
Kynamro's hepatoxcity risk was too high
79
What was the MOA of Miomersen?
antisense oligonucleotide which binds to messenger RNA coding for apolipoprotein B-100 (apoB-100), the main component of low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL
80
What is Inclisiran?
small interfering RNA (siRNA) which inhibits hepatic synthesis of PCSK9 in adults with heterozygous familial hypercholesterolemia familial heterozygous hypercholesterolemia
81
Dosing of Inclisiran? ADRs?
SQ injection Q3M then 6 month 1. Pain 2. Diarrhea 3. Cough, SOB
82
What is Angiopoietin-like protein 3 (ANGPTL3)?
An inhibitor of lipoprotein lipase (LPL) and endothelial lipase (EL), retarding clearance of triglyceride-rich lipoproteins upstream of low-density lipoprotein production, thereby increasing plasma triglycerides, LDL cholesterol, and HDL cholesterol.
83
MOA of Evinacumab (Evkeeza)
binds to and inhibits the ANGPTL3, which promotes VLDL clearance and decreases hepatic VLDL secretion, thereby reducing the conversion of VLDL to LDL, resulting in decreased LDL-C levels.
84
Loss-of-function mutations in ANGPTL3 results in ___ and _____
Hypolipidemia and reduction in CV risk
85
Indication for Evinacumab?
homozygous familial hypercholesterolemia (HoFH).
86
ADR of Evinacumab?
1. nasopharyngitis (runny nose, rhinorrhea, nasal congestion) 2. influenza-like illness 3. sore throat 4. dizziness 5. nausea

Drug Action I (32 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions