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Dyslipidemia Flashcards

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1
Q

statins are _____ inhibitors

A

HMG-CoA reductase

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2
Q

mechanism of statins

A

bind to HMG-CoA reductase so cholesterol cannot be formed from HMG-CoA. and up-regulation of LDL receptors

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3
Q

what are the high intensity statins?

A

Atorvastatin 40-80 mg and Rosuvastatin 20-40 mg

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4
Q

what are the classes of lipid-lowering agents

A

HMG-CoA reductase inhibitors, fibric acid derivatives, niacin, bile acid sequestrants, selective cholesterol absorption inhibitors, omega-3 fatty acids, PCSK9 inhibitors, siRNA, bempedoic acid, lomitapide, evinacumab

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5
Q

what are the lipophilic statins

A

atorvastatin, lovastatin, simvastatin

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6
Q

what are the pleiotropic effects of statins

A

reduce plaque inflammation, influence plaque stability

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7
Q

name the statins

A

atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin, pitavastatin

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8
Q

what is the rule of 7 with statins

A

doubling the dose of a statin reduces LDL by an additional 7%

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9
Q

what are the two main things that are adversely effected by statins

A

liver and muscle

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10
Q

how do statins effect the liver

A

increase AST/ALT

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11
Q

what are 3 muscle problems that can occur with statins

A

myalgias, myositis/myopathy, rhabdomyolysis

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12
Q

____ are muscle symptoms with normal creatine kinase

A

myalgias

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13
Q

______ are muscle symptoms with evidence of muscle injury (CK> normal)

A

myositis, myopathy

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14
Q

_____ is muscle symptoms with CK >10x normal and renal injury

A

rhabdomyolysis

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15
Q

which drugs have a dose cap with simvastatin and lovastatin

A

ticagrelor, amiodarone, amlodipine, conivaptan, diltiazem, ranolazine, verapamil

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16
Q

what is the role of statins in dyslipidemia

A

for types IIa, IIb, III they lower LDL up to 60%, lower triglycerides and increase HDL. they decrease total mortality, CHD mortality, major coronary events, and coronary interventions

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17
Q

what are the fibric acid derivatives

A

fenofibrate and gemfibrozil

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18
Q

what is the dosing for fenofibrate

A

145 mg qd

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19
Q

what is the dosing for gemfibrozil

A

600 mg bid ac

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20
Q

what are the adverse effects for fibric acid derivatives

A

GI, myopathy, transaminase elevations

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21
Q

what are the major interactions with statins

A

macrolide antibiotics, azole antifungals, HIV protease inhibitors, nefazodone, danazol, grapefruit juice, colchicine, cyclosporine, tacrolimus, gemfibrozil

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22
Q

what is the mechanism for fibric acid derivatives

A

PPAR alpha agonists, stimulate lipoprotein lipase, increase breakdown of VLDL, decrease VLDL synthesis from liver, increase HDL

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23
Q

fibric acid derivatives are preferred to lower ____

A

triglycerides

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24
Q

role of fibric acid derivatives in dyslipidemia

A

lower triglycerides, lower LDL a bit, increase HDL, reduce major coronary events

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25
drug interactions with fibric acid derivatives
anticoagulants, cyclosporine, HMG-CoA reductase inhibitors, sulfonylureas
26
how do fibric acid derivatives interfere with anticoagulants
increase INR
27
how do fibric acid derivatives interfere with cyclosporine
increase or decrease effects
28
how do fibric acid derivates interfere with HMG-CoA reductase inhibitors
increase myopathy risk (GEMFIBROZIL)
29
how do fibric acid derivatives interfere with sulfonylureas
increase hypoglycemia (GEMFIBROZIL)
30
what are the forms of niacin
nicotinic acid, vitamin B3
31
how does niacin work
decrease production of VLDL in hepatocytes, increase HDL in circulation
32
adverse effects with niacin that make it unfavorable
GI exacerbation of peptic ulcer, skin flushing and itching, hepatotoxicity, myopathy, hyperglycemia, hyperuricemia
33
role of niacin in dyslipidemia
lower LDL and triglycerides, increase HDL, reduction in major coronary events
34
what are the PCSK9 inhibitors
alirocumab, evolocumab
35
what is the brand name of alirocumab
praluent
36
what is the brand name of evolocumab
repatha
37
what is PCSK9
it is an enzyme that takes LDL receptors out of commission and degrades them which is bad
38
what is the mechanism of PCSK9 inhibitors
they bind to and inhibit PCSK9 so it can't degrade the LDL receptors, now the LDL receptors can take LDL out of the blood like gang busters!
39
what are the adverse effects of PCSK9 inhibitors
injection site reactions, hypersensitivity, neurocognitive events (not really tho)
40
role of PCSK9 inhibitors in dyslipidemia
types IIa, IIb lowers LDL by 40-70% which makes it good for statin intolerant patients or adjunct to maximally tolerated statins, lowers CHD mortality/events
41
what is the alirocumab dose for primary dyslipidemia
75 or 150 mg SC q 2 weeks; or 300 mg SC q 4 weeks
42
what is the alirocumab dose for HoFH
150 mg SC q 2 weeks
43
what is the evolocumab dose for primary dyslipidemia
140 mg SC q 2 weeks or 420 mg q monthly
44
what is the evolocumab dose for HoFH
420 mg SC q monthly, may increase to q 2 weeks if needed
45
what is the siRNA drug for dyslipidemia
Inclisiran
46
what is the brand name for inclisiran
leqvio
47
what is a downfall of inclisiran
requires administration by a clinician
48
what is inclisiran indicated for
HeFH, clinical ASCVD
49
adverse events of inclisiran
injection-site reactions, arthralgia, antibody development
50
what is arthralgia
joint pain/aches
51
what is the role of inclisiran in dyslipidemia
types IIa, IIb, ASCVD and FH, lowers LDL 50%, adjunct to maximally tolerated statins
52
inclisiran is attached to a molecule called _____ that allows rapid and targeted uptake of inclisiran by the liver through interactions with ASGPRs expressed exclusively on hepatocytes
GalNAc
53
inclisiran binds to ____
RISC
54
what happens after inclisiran binds to risc
the sense and antisense strands separate, the antisense strand directs RISC to find complementary RNA which it cleaves, inhibiting PCSK9 protein synthesis
55
what are the bile acid sequestrants
cholestyramine, colesevelam, colestipol
56
how do the bile acid sequestrants work
they cause the liver to produce more bile acids, lowering LDL secondary to LDL receptor upregulation
57
what are the adverse effects of bile acid sequestrants
GI nausea, bloating, constipation, decrease absorption of other drugs, hypertriglyceridemia
58
role of bile acid sequestrants in dyslipidemia
lower LDL, increase HDL, increase triglycerides (BAD), reduction in major coronary events, reduction in CHD mortality
59
what is the selective cholesterol absorption inhibitor
ezetimibe
60
how does ezetimibe work
it inhibits cholesterol absorption by the intestinal mucosal wall (niemann-pick C1-like 1, NPC1L1 protein). decreases cholesterol delivery to the liver and increases blood clearance of cholesterol
61
ezetimibe works on which fat pathway
exogenous
62
what does ezetimibe upregulate
LDL receptors
63
ezetimibe drug interactions
bile acid sequestrants, cyclosporine, amiodarone, verapamil
64
ezetimibe adverse effects
GI
65
ezetimibe by itself lowers LDL by __%
20
66
ezetimibe with a statin adds an additional __% reduction in LDL
25
67
ezetimibe dosing
10 mg qd
68
role of ezetimibe in dyslipidemia
type IIa, lowers LDL, synergistic with statins
69
what are the omega 3 fatty acids
omega-3 ethyl esters, icosapent ethyl, non-prescription fish oil (no effect)
70
mechanism of omega 3 fatty acids
inhibit acyltransferase, increase peroxisomal beta-oxidation in liver, decrease triglyceride synthesis from liver
71
what is the brand name of omega 3 acid ethyl esters
lovaza
72
what is the brand name of icosapent ethyl
vascepa
73
what is the indication for lovaza
adjunct to diet in patients with TRG >500
74
what are the indications for vascepa
adjunct to diet in patients with triglycerides > 500. reduce the risk of MI/stroke//revascularization/unstable angina requiring hospitalization in patients on maximally tolerated statins w/ TRG > 150 and ASCVD or DM and 2 risk factors
75
role of omega 3 fatty acids in dyslipidemia
lower triglycerides, no change or slight increase in LDL and HDL, reduction in CV events (vascepa)
76
dosing of omega 3 fatty acids
4 g po qd
77
adverse effects for omega 3 fatty acids
GI: belching, dyspepsia, altered taste; rash; arthralgia
78
drug interactions with omega 3 fatty acids
anticoagulants- potential for increased bleeding
79
what drug class is bempedoic acid
ACL inhibitor (adenosine triphosphate-citrate lyase)
80
what is the mechanism for bempedoic acid
prevents pyruvate---> acetyl CoA (a step ahead of statins)
81
what is the role of bempedoic acid in dyslipidemia
lower LDL, adjunct to maximally tolerated statins, ASCVD and FH
82
what are the adverse effects for bempedoic acid
hyperuricemia, tendon rupture/injury
83
what are the drug interactions for bempedoic acid
simvastatin dose cap 20 mg, pravastatin dose cap 40 mg
84
what is lomitapide indicated for
HoFH only
85
why is lomitapide in the REMS program
hepatotoxicity
86
role of lomitapide in dyslipidemia
lowers ldl around 40%
87
drug interactions with lomitapide
moderate to strong inhibitors of CYP3A4
88
adverse reactions for lomitapide
GI (nausea, diarrhea, vomiting, hepatic steatosis, transaminitis), change in liver fat content (fat soluble nutrient deficiency)
89
what is evinacumab
a recombinant human monoclonal antibody that inhibits angiopoietin-like protein 3
90
what is the mechanism of evinacumab
inhibits lipoprotein lipase and endothelial lipase, leading to decreased LDL, HDL, and TRG
91
what is evinacumab for
HoFH ONLY
92
adverse reactions with evinacumab
nasopharyngitis, dizziness, flu-like symptoms, infusion-related reactions, teratogenicity

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