Dyslipidemia Therapeutics Flashcards
(124 cards)
1
Q
dyslipidemia is a disorder of ____
A
lipoprotein metabolism
2
Q
what are the primary causes of dyslipidemia?
A
due to genetic defects and often result in heart disease in early life
3
Q
when dyslipidemia is caused by primary causes, what is the typical LDL?
A
often much higher, >5mmol/L
4
Q
what are some of the secondary causes of dyslipidemia?
A
excessive alcohol, chronic renal failure, diabetes or metabolic syndrome, obeisity, hypothyroidism, nephrotic syndrome, obstructive liver disease, pregnancy, B blockers, corticosteroids, hormone replacement therapy, OCP, thiazide diuretics highly active antiretroviral therapy
5
Q
% of Canadians 18-79 with dyslipidemia
A
28%
6
Q
% of canadians 60-79 with DysLipid
A
60%
7
Q
% of Canadians 40-59 with dyslipid
A
35%
8
Q
what % of Canadians have dyslip and dont know?
A
25%
9
Q
___% of diagnosed males are controlled and ___% of diagnosed females
A
52% of males, 35% of females
10
Q
what are chylomicrons?
A
lipoprotein rich in triglycerides
11
Q
what is the function of chylomicrons?
A
delivers to muscle and adipose tissue and liver
12
Q
where is VLDL produced?
A
liver
13
Q
VLDL is delivered to ___
A
target muscle and adipose tissue
14
Q
VLDL is a precursor for ___
A
LDL
15
Q
IDL is created by ___ from what 2 other lipoproteins?
A
LPL; VLDL and chylomicrons
16
Q
LDL is converted from ____
A
VLDL
17
Q
how does LDL get taken up by cells?
A
LDL receptors
18
Q
how does LDL lead to atherosclerosis?
A
when there is a high amount of LDL in the blood, they can stick to the walls of the blood vessels, attracting WBCs and causinf inflammation and forming a plaque that leads to atherosclerosis
19
Q
what are the functions of LPL?
A
convert VLDL to IDL then LDL and breaks down chylomicrons
20
Q
what is the role of HDL?
A
take excess cholesterol back to the liver to be removed
21
Q
triglycerides are transported in the blood via ___
A
VLDL
22
Q
triglycerides are associated with low ___
A
HDL
23
Q
dietary cholesterol is absorbed through the intestines as ___ and transported to the liver
A
chylomicrons
24
Q
what organ is responsible for cholesterol homeostasis?
A
liver
25
when cells remove cholesterol from the blood, what do they use it for?
making cell membranes and steroid hormone production
26
what lifestyle changes can be implemented to lower cholesterol?
avoid smoking
healthy diet like mediterranean, DASH etc.
avoid trans fats and reduce saturated fats
get lots of fruit & veg, fibre, olive oil, legumes, nuts, whole grains
healthy weight
physical activity
moderate alcohol intake
27
list 5 complications of dyslipidemia
1. CVD (acute coronary syndrome, MI, angina, arrhythmias
2. cerebrovascular disease (stroke, transient ischemic attack)
3. pancreatitis
4. peripheral vascular disease
5. abdominal aortic aneuryssm
28
what are the many patient populations that need to be tested for dyslipid?
1. Men 40+
2. women 40+ or postmenopausal
3. south Asian and Indigenous at younger age
4. evidence of atherosclerosis
5. abnormal aortic aneurysm
6. diabetes
7. arterial hypertension
8. smokers
9. physical findings (xanthomas, arcus cornea, xanthelasmas)
10. family history of premature CVD
11. CKD
12. obesity (BMI 30+)
13. IBS
14. HIV
15. erectile dysfunction
16. COPD
17. hypertension during pregnancy
29
pregnant people with what conditions need to be screened for dyslipidemia
1. pre-eclampsia
2. HTN
3. gestational diabetes
4. gestational diabetes
5. preterm birth
6. stillbirth
7. low birth weight
8. placental abruption
30
women who have CV complications during pregnancy, how long do these risks last?
A lifetime. CVD and stroke 10-15 years after delivery
31
what values should be collected in a lipid panel?
1. total cholesterol (TC)
2. LDL
3. triglycerides (TG)
4. HDL
5. non-HDL (when TG >1.5)
6. ApoB (when TG >1.5)
7. Lipoprotein (a)
32
when should a lipid panel be done fasting?
if patient has a history of TG >4.5 mmol/L
33
when should non-HDL be included in lipid panel?
when TG >1.5
34
when should ApoB be included in a lipid panel?
when TG >1.5
35
what are 2 benefits of including Lipoprotein (a) in a lipid panel?
not affected by age, lifestyle, fasting, or inflammation. Only needs to be measured once during screening
36
t/f there is no RCTs yet that show Lp(a) improved CV outcomes
t
37
what drugs help to lower Lp(a)?
PCSK9 inhibitors and niacin
38
what is the recommended action if Lp(a) is greater than 50mg/dL?
control CVD risk factors and implement intensive lifestyle modifications
39
hypertriglyceridemia is defined as TG above ___
1.7 mmol/L
40
risk of pancreatitis increases when TG are above ____, but is more significant when TG above ____
5.6 mmol/L; 11.3 mmol/L
41
therapy to treat hyperttriglyceridemia generally starts if TG are above ___
10 mmol/L
42
t/f the lifestyle modifications to lower TG are similar to those for lowering cholesterol
t
43
what 5 things should be included in a patient work-up for suspected dyslipidemia?
1. patient and family hx (rule out secondary causes, premautiure CVD)
2. physical exam
3. lipid panel
4. glucose levels
5. eGFR
6. albumin creatinine ration is optional
44
what are the conditions where statins are indicated?
1. clinical atherosclerosis
2. abdominal aortic aneurysm
3. diabetes and (age 40+ or 15 year duration for peopled aged 30+, or microvascular disease)
4. CKD (age 50+, eGFR <60mL/min, or ACR >3 mg/mmol)
5. LDL 5.0+ mmol/L
45
t/f medication treatment for dyslipidemia should be considered in patient has a high FRS score (20%+)
t
46
under what conditions should a patient with an intermediate (10-19%) FRS be given mediaction management?
1. LDL 3.5 mmol/L or
2. non-HDL 4.3+ mmol/L or
3. ApoB 1.2+g/L or
4. men 50+ and women 60+ who have 1 additional risk factor for CVD (low HDL, increased weight circumference, impaired fasting glucise, smoking, HTN)
5. elevated highly sensitive C reactive protein, family Hx of premature CVD, high Lp(a) and coronary artery calcium score >0
47
what is the recommendation if patient has a <10% FRS?
dont need statin therapy
48
high dose statins are slighly more effective than moderate doses in ____ (primary or secondary) prevention for reduction of nonfatal MI and stroke
secondary
49
the benefit of statin therapy depends on patients ____ score
10 year risk score (if its highm the NNT is lower)
50
for every 1 mmol/L reduction in cholesterol, there is a __% reduction in risk for all cause mortality
10
51
for every 1 mmol/L reduction in cholesterol, there is a ____% reduction in risk for death from CVD
20
52
for every 1 mmol/L reduction in cholesterol, there is a ___% reduction in non-fatal MI
27
53
for every 1mmol/L reduction in cholesterol, there is a ___% reduction in risk for coronary revascularization
25%
54
for every 1 mmol/L reduction in cholesterol, there is a ___% reduction in ischemic stroke
21
55
what is the goal LDL?
<2.0mmol?l or a 50% reduction in LDL
56
what is the target ApoB?
<0.8 g/L
57
what is the target non-HDL?
<2.6 mmol/L
58
which drugs have the greatest impact on lowering LDL?
PCSK9 inhibitors, then statins
59
which drugs have the greatest impact on raising HDL?
fibrates & niacin
60
which drugs have the greatest impact on lowering TG?
fibrates and niacin
61
list the 6 statins mentioned in lecture
rosuvastatin, atorvastatin, simvastatin, pravastatin, lovastatin, fluvastatin
62
what are the common side effects of statins?
transient GI upset, headache, rash, muscle apin
63
statins are contraindicated in what conditions?
active liver disease, increased alcohol intake, pregnancy
64
which statins interact with CYP3A4?
atorvastatin, lovastatin, simvastatin
65
what are the statins that interact with CYP2C9 and 2C19?
fluvastatin, rosuvastatin
66
what are some common interactions with statins?
clarithromycin, erythromycin, gemfibrozil, amiodarone, digoxin, warfarin, GFJ
67
which 2 statins have fewer drug interactions compared to the others>
rosuvastatin, pravastatin
68
there is some question around whether statins elevate ____ and cause ___ issues
glucose; memory
69
what monitoring shouldd be done for statins?
1. lipids 4-12 weeks after starting, then q 3-12 months
2. baseline liver enzyme (ALT) repeat if signs of hepatotoxicity
3. baseline CK and repeat if muscl symptoms
70
define myopathy
broad term referring to muscle disease/disorder
71
define myalgia
symptoms of muscle aches
72
define myositis
symptoms along with CK elevations
73
what is rhabdoylosis?
muscle aches or weakness with CK > 20x ULN
74
what is hyperCKemia?
elevated CK withiut symptoms
75
what is done if the CK levels are <5x the upper limit of normal?
continue statin therapy with monitoring
76
what is done if the CK levels are greater >5x the upper limit of normal?
hold the statin and monitor and potentially trial other statins and or lower doses
77
if a patient is unable to tolerate a statin after trying multiple types and doses, what drugs can be used instead?
ezetimibe, PCSK9 inhibitors
78
is ezetimibe typically given as monotherapy?
usually an adjunct unless statins are not tolerated
79
t/f ezetimibe is well-tolerated
t
80
what is the general MOA of exetimibe?
decreases intestinal cholesterol absorption
81
does ezetimibe have many drug interactions?
not really
82
what is the dose of ezetimibe?
10mg PO UID
83
there has been a trial hich showed that patient whith CKD when taking a combo of simvastatin & ezetimibe, what was the result?
reduced incidence of CV events (SHARP)
84
a trial showed that after ACS, the combination of ezetimibe and simvastatin showed what results?
positive CV and cerebrovascular outcomes and can be considered if a potent statin is not tolerated
85
give 3 examples of fibrates
bezafibrate, fenofibrate, gemfibrozil
86
what are some of the ADRs of fibrates?
GI upset, rash, abdominal pain
87
what are some of teh C\I for fibrates?
severe hepatic impairment, gallbladder dx and renal dx
88
fibrates are most effective for lowering ___, but can also lower ___ and raise ___
TG; LDL; HDL
89
dosing for bezafibrate
400mg SR daily (max 600mg/day)
90
feno-micro dosing
200mg UID
91
feno-supra dosing
160mg UID
92
gemfibrozil dosing
300mg BID (1500mg/day) not really used anymore
93
gemfibrozil is contraindicated if patient is already taking what class of drug?
statin
94
what monitoring needs to be done for fibrates?
liver function tests, TG, CBC, renal function, lipid parameters
95
give 3 examples of bile acid sequestrants (resins) given in lecture
1. cholestyramine granules
2. colestipol granules or tablets
3. colesvelam granules or tablets
96
what is a special administration instruction for the resin granules?
mix with juice, milk, water, applesauce before ingesting
97
how do the doses start when starting a resin?
start low and titrate up for tolerability
98
what are some of the ADRs of resins?
constipation, nausea, bloating
99
what are some of the C/I for resins?
biliary obstruction, TG>4.6 and use caution if they are >2.3
100
what are some drug interactions with resins?
lots of things, especially fat-soluble vitamins. Should space out all medications by 2-4hrs from resins
101
resins have been shown to have positive CV outcomes as monotherapy, but what limits their use?
drug interactions and tolerability
102
are resins safe in pregnancy and in children?
yes
103
at high doses, Niacin may lower ___ and ____ and raise ____
LDL & TG; HDL
104
how does the dosing start with niacin?
start low and titrate up
105
which form of Niacin may cause less fluching?
Niaspan (rx version of Niacin)
106
what are some of the ADRs of Niacin?
GI upset, flushing, increased LFTs with doses >2g or the SR formulation
107
Niacin is c/i in what conditions?
severe PUD, chronic liver dx, sevre gout, caution in diabetes
108
is there research evidence to back up the use of Niacin?
not really. No CV benefit found when combined with statins and one study was stopped due to increase in stroke
109
what needs to be monitored if Niacin is being used?
liver function tests, blood glucose if diabetic, lipid panels
110
give 2 examples of PCSK9 inhibitors
1. evolocumab
| 2. alirocumab
111
dosing of evolucumab
140mg q 2 weeks or 420mg q 4 weeks
112
dosing of alirocumab
75-150mg q 2 weeks, or 300mg q 4 weeks
113
what is an important factor to consider when thinking about using a PCSK9 inhibitor?
they are injections and they are very expensive
114
in which patients are PCSK9 inhibitors used?
high risk patients who have not reached targets with the max tolerated doses of other agenst like statins or statins and ezetimibe. Also may be useful in patients with familial hypercholesterolemia or in secondary prevention
115
what are some of the side effects of PCSK9 inhibitors?
pharyngitis, injection site rxns, allergic rxns
116
PCSK9 inhibitors have shown positive CV outcomes in patients with ____
ASCVD
117
what is the 1st line for secondary prevention?
high dose statin or max toleated dose
118
in secondary prevention, if LDL is greater or equal to ___, or non-HDL is greater or equal to ____ or ApoB is greater or equal to ____, adding a PCSK9 inhibitor or ezetimibe is recommended
1.8mmol/L; 2.4mmol/L, 0.7g/L
119
which secondary prevention patients get the most benefit from the addition of a PCSK9 inhibitor?
1. recent acute coronary event (ACS) w/i last year
2. clinical evidence of ASCVD and any of the following: diabetes or metabolic syndrome, polyvascular disease, symptomatic PAD, recurrent MI, MI in past 2 years, previous CABG surgery, LDL 2.6+ or heterozygous FH, lipoprotein a 60mg/dl+ or 120mmol/L+
120
what is the current evidence around omega 3 fatty acids?
no CV outcome data, but useful in decreasing TG, which can reduce risk of pancreatitis (2-4g per day)
121
omega 3 should be used with caution in patients with increased risk of ____
bleeding
122
what is Icosapent ethyl and what is the evidence for its use in dyslipidemia?
an Rx grade EPA ethyl (Vascepa). Showed benefit in secondary prevention and in patients with diabetes and 1 or more CV risk factors with elevated TG (1.5-5.6) who were already on a statin (REDUCE IT trial)
123
what is the dosing of Vascepa?
2000mg daily
124
how much physical activity is recommended to reduce lipids>
150 min of moderate to vigorous aerobic exercise (weekly?)
