Brainscape's Knowledge GenomeTM

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


See full index

Cardiovascular System > Atherosclerosis Pharmacology > Flashcards

Atherosclerosis Pharmacology Flashcards

1
Q

How do cells obtain/regulate cholesterol?

A
  1. receptor-mediated uptake of LDL cholesterol
  2. de novo synthesis
  3. excess cholesterol stored as cholesterol esters (ACAT enzyme)
  4. diet
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the relationship between HDL-C and CHD, for any level of LDL-C?

A

For any level of LDL-C, HDL-C is inversely related to CHD risk

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

Therapeutic overview: Why do we administer cholesterol treatment?

A
  1. Reduce formation and rate of progression in coronary and peripheral atherosclerosis from childhood to old age
  2. Prevention of coronary events and strokes in apparently healthy persons at risk, particularly middle-aged and elderly
  3. Prevention of heart attacks, strokes, need for revascularization in persons with established atherosclerosis
  4. Prevention and treatment of pancreatitis in hypertriglyceridemia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is the dominant mechanism for controlling hepatic LDL plasma concentrations?

A

REGULATION OF HEPATIC LDL RECEPTOR PATHWAY

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

What is ASCVD?

A

Atherosclerotic cardiovascular disease

  • Heart attacks + strokes + peripheral arterial disease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the basis of treating lipid disorders that cause ASCVD?

A
  • Lowering LDL with statins lowers risk
  • Base treatment on risk
  • Secondary prevention (already has ASCVD event) is treated aggressively with high intensity statin
  • Primary prevention (no clinical disease) is assessed.
    • If 10-year risk
      • > 7.5% ⇒ treat with statins
      • 5% to 7.5% ⇒ review other risk factors
      • < 5%, ⇒ lifestyle
  • Everyone else (kids) ⇒ primordial risk ⇒ lifestyle
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

List the HMG CoA Reductase Inhibitors/Statins:

A
  1. Atorvastatin (Lipitor) (synthetic compound)
  2. Lovastatin (Mevacor) (fungal metabolite)
  3. Simvastatin (Zocor) (synthetic compound)
  4. Pravastatin (Pravachol) (fungal metabolite)
  5. Rosuvastatin (Crestor) (synthetic compound)
  6. Fluvastatin (Lescol) (synthetic compound)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

**Statins: **

Mechanism of Action

A
  • Competitive inhibitor for active site on HMG CoA reductase
    • Rate limiting step in cholesterol biosynthesis
    • statins inhibit HMGR by binding to the active site of the enzyme, thus sterically preventing substrate from binding
  • Structural analog of the HMG CoA intermediate
    • All statins share a structural component that is very similar to the HMG portion of HMG-CoA
    • more bulky and more hydrophobic than HMG-CoA
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How do statins affect the LDL receptor?

A
  • increase in LDL receptor gene
    • mechanism:
      • In response to the reduced free cholesterol content within hepatocytes, membrane-bound Sterol Regulatory Element-Binding Proteins (SREBPs) are cleaved by a protease and translocated to the nucleus
      • transcription factors then bind the sterol-responsive element of the LDL receptor gene
      • enhance transcription
      • increase the synthesis of LDL receptors
  • up-regulation of LDL receptor results in increased catabolism of LDL
    • Plasma concentration of LDL falls
    • less LDL is available to react with cellular elements in blood and blood vessel walls
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pharmacokinetics of Statins:

A

Extensive first-pass metabolism by the liver

  • Limits systemic bioavailability
  • Targets liver/site of action
    • mediated primarily by the organic anion transporter OATP1B1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q
  1. All the statins, except simvastatin and lovastatin, are administered in the what form?
  2. What form are simvastatin and lovastatin adminstered?
A
  1. **-hydroxy acid **
    • which is the form that inhibits HMG-CoA reductase
  2. lactones
    • converted to the -hydroxy acid form via the liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the major CYP reponsible for metabolizing atorvastatin, lovastatin and simvastatin?

A

CYP3A4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are the half-lives of the different statins?

A
  1. lovastatin (1 - 4 hours)
  2. simvastatin (1 - 2 hours)
  3. atorvastatin ( 20 hours )
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What do statins have a high affinity for?

A

highly bound to plasma proteins

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

**Statins: **

Major Adverse Effect

A

all statins have been associated with myopathy and rhabdomyolysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Definitions:

  1. Myopathy
  2. Rhabdomyolysis
A
  1. Myopathy
    • muscle pain without creatinine kinase (CK) elevation or less frequently with mild CK elevation
    • Muscle disease/weakness
  2. Rhabdomyolysis
    • muscle symptoms with marked CK elevation and with creatinine elevation
    • breakdown of muscle fibers that leads to the release of myoglobin into the bloodstream
    • Myoglobin is harmful to the kidney and often causes kidney damage
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What are minor adverse effects caused by statins?

A
  • GI side effects
  • Increase in liver enzymes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Myopathy risk increases in ______ relationship to statin dose and plasma concentration

A

Myopathy risk increases in direct relationship to statin dose and plasma concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

How do genetics play a role in statin intolerance?

A
  • A single nucleotide polymorphism in SLCO1B1
    • ​which encodes an organic anion transporter that regulates the hepatic uptake of statins
  • Genetic variants of SLCO1B1 lead to reduced hepatic uptake and increased levels of statins in the blood,
    • provide the mechanism for increased risk of myopathy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What other drugs can increase the risk of myopathy when taken in combination with statins?

A
  • Drugs are those metabolized primarily by CYP3A4
    1. certain macrolide antibiotics (e.g., erythromycin )
    2. azole antifungals (e.g., itraconazole )
    3. cyclosporine
    4. HIV protease inhibitors
    5. gemfibrozil
      • inhibits OAT1B1
      • interferes with transformation of most statins by glucuronidases
  • Associated with increased plasma concentrations of statins and their active metabolites
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is contraindicated in statin therapy?

A
  • Hypersensitivity
  • Active liver disease
  • Women who are pregnant, lactating, or likely to become pregnant should not be given statins
    • May down-regulate biosynthesis of cholesterol as well as many important metabolic intermediates
    • May have secondary effects on sterol-dependent signaling molecules (Sonic Hedgehog)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Statin Lipoprotein Profile:

  1. TG
  2. LDL
  3. HDL
A
  1. TG
    • > 250 mg/dl: decrease by 20-55%
    • < 250 mg/dl: decrease by 25%
    • the higher the baseline TG level, the greater the TG-lowering effect​
  2. LDL
    • ​decrease by 20-55%
  3. HDL
    • ​increase by 5-10%​
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Statins:

Clinical Use

A

First line therapy in hypercholesterolemia when at risk for myocardial infarction

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

Statins are effective in almost all patients with high LDL-C levels. What is the exception?

A

patients with homozygous familial hypercholesterolemia

  • have very attenuated responses to the usual doses of statins because both alleles of the LDL receptor gene code for dysfunctional LDL receptors
  • the partial response in these patients is due to a reduction in hepatic VLDL synthesis associated with the inhibition of HMG-CoA reductase–mediated cholesterol synthesis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Statins:

Potential Cardioprotective Effects Other Than LDL Lowering

A
  1. Increased endothelium-dependent relaxation
  2. Stabilize plaques/prevent plaque rupture
  3. Decrease LDL oxidation
  4. Decrease platelet aggregation
  5. Decrease C-reactive protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Bile Synthesis and Function

A
  • Cholesterol converted to bile acid by enzyme 7alpha-hydroxylase
    • Conjugated bile acids secreted from the liver and stored in the gall bladder
    • passed through the bile duct into the intestine
  • Function is to emulsify lipids in food to enable fat digestion and absorption through the intestinal wall.
    • Most bile acids are reabsorbed, returned to the liver via the portal vein, and re-secreted
  • Conversion to bile salts is the only mechanism by which cholesterol is excreted (~0.8 g/day)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Name a bile acid-binding agent:

A

cholestyramine

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

**Cholestyramine: **

Mechanism of Action

A
  • anion-exchange resins
    • highly positively charged and binds negatively charged bile acids
  • Large size ⇒ resins are not absorbed, and the bound bile acids are excreted in the stool
    • more than 95% of bile acids are normally reabsorbed.
  • interruption of this process depletes the pool of bile acids ⇒ hepatic bile-acid synthesis increases
  • As a result, hepatic cholesterol content declines, stimulating the production of LDL receptors
    • an effect similar to that of statins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

How is cholestyramine similar to statins?

A

Like statins, bile acid binding resins lower intracellular cholesterol ⇒ activates the SREBP transcription factor ⇒ increases LDL receptor gene transcription

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

Cholestyramine:

Pharmacokinetics

A
  • Quaternary amine, hygroscopic powder administered as chloride salt/insoluble in water
  • Pharmacokinetics
    • not absorbed
    • reduction in plasma cholesterol concentrations usually seen within first month of therapy
    • stop drug, levels return to normal in 1 month
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Cholestyramine:

Adverse Effects

A
  • most common-constipation/bloating sensation
  • gritty consistency
  • nausea and vomiting
  • constipation
  • interferes with absorption of other drugs
  • Digitalis, thiazides, warfarin, statins, aspirin
  • modest INCREASE in TG/with time returns to baseline values
32
Q

Cholestyramine Lipoprotein Profile

  1. TG
  2. LDL
  3. HDL
A
  1. TG
    • ​​Normal levels: only transient increase
    • Levels > 250 mg/dl: further significant increase
  2. LDL
    • ​decrease by 12-25%​
  3. HDL
    • increase by 4-5%
33
Q

**Cholestyramine: **

Clincal Uses

A
  • hypercholesterolemia
    • Not recommended for individuals with hypercholesterolemia and increased TG
  • most often used as second agents if statin therapy does not lower LDL-C levels sufficiently
  • recommended for patients 11-20 years of age
34
Q

What is the main effect of nicotinic acid (niacin)?

A

MAIN EFFECT IS TO DECREASE TG

  • But it does decrease cholesterol
  • Water-soluble B-complex vitamin
    • Lipid lowering effect is unrelated to its effect as a vitamin
    • Much larger doses required
35
Q

Describe how niacin acts in adipose tissue:

A

inhibits FFA mobilization

  • role for niacin receptor 1 (GPR109A) in adipose tissue
  1. Activation of receptor causes a decrease in cAMP
  2. No activation of PKA
  3. No phosphorylation of perilipin and Hormone Sensitive Lipase (HSL)
  4. No conformational change in perilipin
  5. So no access of HSL to TG in the fat droplet
  6. TG IS NOT broken down into glycerol and FFA
  7. A DECREASE in FFA that is delivered to the liver
  8. Decrease in VLDL synthesis means overall decrease in TG
36
Q

Describe how niacin acts in the liver:

A

decreases synthesis of VLDL-TG

  • Inhibits DGAT2 (diacylglycerol acyltransferase 2),
    • enzyme that catalyzes the final reaction in TG synthesis
  1. Inhibits synthesis and reesterification of fatty acids
  2. Increases ApoB degradation
    • apoB is major protein of VLDL/LDL
37
Q

Describe how niacin affects HDL:

A
  • increases HDL-apoAI particles
    • inhibits hepatocyte surface expression of ß-chain ATP synthase
  • increases HDL biogenesis
    • increasing hepatic expression of ABCA1

This is a GOOD THING

38
Q

**Nicotinic Acid (Niacin): **

Pharmacokinetics

A
  • Oral administration
  • 3 different formulations
    • immediate release
    • Long acting release
    • extended release preparation
  • Remember that doses used for lowering cholesterol/TG much greater than those used as vitamin
    • Prescription only
39
Q

Nicotinic acid (niacin):

Major Adverse effect

A

MAJOR ADVERSE EFFECT

  • Intense cutaneous flush/pruritus
    • Occurs soon after taking the drug
      • poor compliance
    • Mediated by vasodilatory PGs
      • PGD2 from dermal macrophages
      • use of NSAIDs to block the effect
40
Q

**Nicotinic acid (niacin): **

Other Adverse Effects

A
  • GI effects
    • nausea/vomiting, abdominal pain, diarrhea
    • Avoid in patients with peptic ulcer
  • elevated liver enzymes/usually no hepatic toxicity
    • BUT MAJOR concern if combined with statins
  • Hyperurecemia
    • Contraindicated in patients with gout
  • Increases fasting glucose levels/niacin-induced insulin resistance
    • Questionable use in patients with diabetes
41
Q

What are the contraindications for niacin?

A
  1. Peptic Ulcer
  2. Gout
  3. Hepatic Disease
  4. Diabetes
42
Q

What can happen if niacin is combined with statins?

A

Combined use with statin increases risk of myopathy

43
Q

Niacin Lipoprotein Profile

  1. TG
  2. LDL
  3. HDL
  4. Lp(a)
A
  1. TG decreased by 35-50%
    • Within 4-7 days
  2. LDL decreased by 25%
    • 3-6 weeks for maximal effect
  3. HDL increased by 15-30%
    • added benefit is increased HDL
  4. Lp(a) reduced by 40%
    • May be risk factor
44
Q

**Nicotinic acid (niacin): **

Clincal Uses

A
  • Hypercholesterolemia & hypertriglyceridemia
    • High LDL and low HDL
  • Typically not first line therapy for hypercholesterolemia
    • Severe cases that do not respond to resins
    • Not first choice because of side effects
  • Only lipid-lowering drug that reduces Lp(a)
45
Q

What inhibits cholesterol absorption?

A

Ezetimibe

46
Q

**Ezetimibe: **

Mechanism of Action

  • What is the net result?
A

inhibits cholesterol transfer from intestinal lumen into intestinal cell

  • binds to a protein transporter called Niemann Pick Cl-like 1 protein (NPCL1)
    • on or within brush border membranes of intestinal cells.
  • net result:
    • decreased rate of cholesteryl ester incorporation into chylomicrons
    • reduced flux of cholesterol from intestine to liver
    • reduced flux of cholesterol to VLDL
  • lowers plasma LDL-C because increased expression of LDL receptors
47
Q

Ezetimibe:

Pharmacokinetics

A
  • Oral administration
  • Metabolized (glucuronidation) to active metabolite
  • Half-life: 22 hours
48
Q

**Ezetimibe: **

Adverse Effects

A
  • Well tolerated
  • Side effects increase if combined with other drugs, like statins
49
Q

Ezetimibe Lipoprotein Profile

  1. TG
  2. LDL
  3. HDL
A
  1. TG
    • decrease by 5%
  2. LDL
    • decrease by 15-20%
  3. HDL
    • increase by 1-2%
50
Q

Ezetimibe:

Clinical Uses

A
  • Primary hypercholesterolemia
  • Combined with statins
    • Simvastatin + ezetimibe
    • Further decrease in LDL-cholesterol
    • Two differing pharmacological approaches
51
Q

What is a potential downside to combination therapy of ezetimibe + statins?

A

may increase risk of myopathy

52
Q

What are the Fibric Acids/Fibrates/PPAR activators?

What is the general function of these drugs?

A
  1. Gemfibrozil
  2. Fenofibrate (2nd generation drug)
  • Primarily lower the levels of TG-rich lipoproteins
53
Q

Fibric Acids/Fibrates/PPAR activators:

Mechanism of Action

A
  • effects mediated by interaction with peroxisome proliferator activated receptors (PPARs) that regulate gene transcription
  • bind to PPAR-alpha (expressed 1˚ in liver and brown adipose tissue)
  • PPAR bind as heterodimers with retinoid X receptor to specific response elements and alter the transcription rate of target genes
54
Q

What are the net effects of fibric Acids/fibrates/PPAR activators?

A
  1. increased lipolysis and plasma clearance of TG-rich lipoproteins
    • activation of lipoprotein lipase
    • reduce production of lipoprotein lipase inhibitor, apoCIII
  2. reduced availability of FFA for TG synthesis
    • increase B-oxidation pathway
  3. c. inhibition of de novo fatty acid synthesis
    • decrease acetyl-CoA carboxylase
    • decrease fatty acid synthase
  4. increases in HDL – cholesterol
    • increases synthesis of 2 proteins in HDL: apoA1 and apoAII
55
Q

**Fibric Acids/Fibrates/PPAR activators: **

Pharmacokinetics

  • What is the difference of metabolism between fenofibrate and gemfibrozil?
A
  • Oral administration
  • Plasma protein binding
  • Half-life varies (1 hr for gemfibrozil/20 hrs for fenofibrate (increased with renal impairment)
  1. Fenofibrate is metabolized to active metabolite
    • excreted predominantly as glucuronide conjugates
    • 60-90% of an oral dose is excreted in the urine
  2. Gemfibrozil metabolized into inactive metabolites
56
Q

Fibric acids/Fibrates/PPAR actvators:

Adverse effects

A

Generally well-tolerated

  • GI symptoms-most common
  • Increased risk of gall stones
  • Less common are hematological/hepatic function abnormalities
  • increased creatine kinase if also being treated with a statin….lead to renal failure
  • Use is contraindicated in patients with renal impairment
  • Gemfibrozil can increase systemic statin concentrations by blocking transporter in liver
57
Q

What drugs does gemfibrozil interact with?

A

Statins

  • Gemfibrozil inhibits uptake of active hydroxy acid forms of statins by transporter
    • first-pass hepatic uptake of these statins by transporter OATP1B1 after their oral administration
    • If not taken up into liver, increased plasma concentration
58
Q

Fibric acid Lipoprotein Profile

  1. TG
  2. LDL
  3. HDL
A
  1. TG
    • decrease 30-50%
  2. LDL
    • decrease 15-20%
      • HIGHLY VARIABLE
      • 2nd generation drugs (fenofibrate) more likely to decrease LDL 15-20% in patients with TG < 400 mg/dL
  3. HDL
    • increase 5-15%
59
Q

Fibric acids/Fibrates/PPAR activators:

Clinical Uses

A

patients with high TGs and low HDL associated with metabolic syndrome or type 2 diabetes

  • treatment of hypertriglyceridemia
  • reduces the risk of CHD development in Fredrickson type IIb
60
Q

Drugs of choice for hypercholesterolemia:

What are some things to consider when choosing such drugs?

A
  1. HMG CoA reductase inhibitors-first choice agents
    • Which one?
    • Safety?
    • Lifetime treatment
  2. Bile acid resins
    • Long-term safety
    • Younger patient age range
    • Add on to statins
  3. Ezetimibe
    • Safety as monotherapy vs MAYBE…add-on to statins
  4. Niacin
    1. Patient compliance side effects
    2. Both elevated TG and cholesterol
    3. Low HDL
    4. Care when combined with statins
61
Q

Drugs of choice for hypertriglyceridemia:

A
  1. gemfibrozil/fenofibrate
    • drug of choice in patients with type III hyperlipoproteinemia and severe hypertriglyceridemia (TG > 1000 mg/dl)
  2. niacin
    • second line choice
  3. omega-3 fatty acid
62
Q

What are the omega-3-fatty acids that have therapeutic effects?

A
  • Eicosapentaenoic acid
    • (EPA 20:5 n−3)
  • Docosahexaenoic acid
    • (DHA 22:6 n−3)
63
Q

What is the therapeutic mechanism of omega-3-fatty acids?

A
  • inhibit (−) lipogenesis
    • inhibit diacylglycerol acyl transferase (DGAT), phosphatidic acid phosphohydrolase (PA), and hormone-sensitive lipase
  • stimulate (+):
    • β-oxidation
    • phospholipid synthesis
    • apolipoprotein (apo) B degradation
  • end result is a reduced rate of secretion of very-low-density lipoprotein (VLDL) TG
64
Q

Omega-3-fatty acids:

Pharmacokinetics

A
  • Oral:
    • 4 g/day as a single daily dose or in 2 divided doses
  • Onset of action is slow
65
Q

Omega-3-fatty acids:

Adverse Effects

A
  • Fish allergy
  • May increase LDL levels
  • May increase liver enzymes
  • Prolongation of bleeding time has been observed in some clinical studies
66
Q

What are omega-3-fatty acids clinically used for?

A

Adjunct to diet therapy in the treatment of hypertriglyceridemia (≥500 mg/dL)

67
Q

What are targets of future drug therapies?

A
  1. Proprotein convertase subtilisin/kexin 9 (PCSK9) Inhibitors
  2. Microsomal triglyceride transfer protein (MTP) Inhibitors
  3. Apolipoprotein B-100 (apoB-100) Inhibition
68
Q

Describe the physiological role of PCSK9 (Proprotein convertase subtilisin/kexin type 9):

Why is it a potential target for therapy?

A
  • Decreases the steady-state level of expression of the LDL receptor on the hepatocyte cell membrane
  • Autocatalytic cleavage in the ER followed by secretion into plasma where it binds the EGF-A domain of the LDLr
  • LDLr/PCSK9 complex gets internalized and targeted to the lysosomal compartment for degradation ⇒
  • Inhibition of the recycling of the LDLr back to the cell surface ⇒ increased plasma LDL levels (antibodies, siRNA)
  • No change in plasma cholesterol levels in PCSK9/LDLr KO’s ⇒ effect of PCSK9 is mediated solely via LDLr
69
Q

What does a PCSK9 antibody prevent?

  • What is the result?
A

PCSK9 antibody prevents binding of PCSK9 to the LDLR-LDL complex

  • Result:
    • increases the availability of cell-surface LDLRs
70
Q

What is microsomal triglyceride transfer protein (MTP)?

What is its role?

A
  • major cellular protein that transfers neutral lipids between membrane vesicles
  • essential chaperone for the biosynthesis of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins
    • abetalipoproteinemia patients carry mutations in the MTTP gene resulting in the loss of its lipid transfer activity.
  • Role in the regulation of cholesterol ester biosynthesis
71
Q

What is the FDA approved MTP inhibitor?

What is the mechanism of action?

A
  • Lomitapide
  • directly binds to and inhibits MTP
  • MTP inhibition prevents the assembly of apo-B containing lipoproteins in enterocytes and hepatocytes resulting in reduced production of chylomicrons and VLDL and subsequently reduces plasma LDL-C concentrations
72
Q

**MTP Inhibitors: **

Clinical Use

A

Adjunct to dietary therapy and other lipid-lowering treatments to reduce:

  • LDL-C
  • total cholesterol
  • apolipoprotein B
  • non-HDL-C in patients with homozygous familial hypercholesterolemia
73
Q

What is apolipoprotein B-100?

What is its function?

A
  • structural apolipoprotein that is an essential component of LDL-C and VLDL
  • ApoB-100 is the ligand that binds LDL to its receptor and is important for the transport and removal of atherogenic lipids
  • Elevated levels of apoB, LDL-C and VLDL are associated with increased risk of atherosclerosis and cardiovascular diseases
74
Q

What is the FDA approved Apo B-100 inhibitor?

What is the mechanism of action?

A

Mipomersen

  • 20-base sequence second-generation antisense oligonucleotide developed to inhibit synthesis of apoB-100 in the liver
  • hybridizes within the coding region of apoB-100 mRNA and activates RNase H
    • _​_RNase H degrades the mRNA strand but leaves the antisense oligonucleotide intact
75
Q

What is apo B-100 inhibition first-line therapy for?

A

first-in-class drug for treatment of homozygous familial hypercholesterolemia

76
Q

How is apo B-100 inhibtion administered?

What are adverse effects?

A
  • Pharmacokinetics:
    • subQ
  • Side Effects:
    • injection site reactions
    • flu-like symptoms
    • headache
    • elevation of liver enzymes

Cardiovascular System (35 decks)

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