Brainscape's Knowledge GenomeTM

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


See full index

Pharm II > Drugs for the treatment of lipid disorders > Flashcards

Drugs for the treatment of lipid disorders Flashcards

1
Q

energy stored in adipose tissue derived from FFA

A

triglycerides

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

formulated into transportable particles in liver and gut in the form of

A

lipoproteins

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

composition and origin of chylomicrons

A

Exogenous/dietary triglycerides, unesterified cholesterol, cholesteryl esters

origin is the intestine

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

Very-low density lipoproteins (VLDL)

composition and origin of this lipoprotein

A

Triglycerides; some cholesteryl esters

origin is the liver

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

Intermediate-density lipoproteins (IDL)

composition and origin

A

Cholesteryl esters and triglycerides

VLDL/HDL catabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

whya re LDL the bad guys?

A

take the cholesterol out into the periphery

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

HDL

A

take cholesterol out of the cells into the liver fro making stuff

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

Large TG-rich particles formed in intestine

Carry dietary triglycerides, unesterified cholesterol, and cholesteryl esters from diet or synthesized in gut —>liver

A

Chylomicrons

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

Normally contain 15-20% of total cholesterol and most of total TG; cholesterol usually 1/5 of TG concentration

A

VLDL

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

VLDL is formed in the

A

liver

it is how we get TG to the peripheral tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

if we have high VLDL and we give them something that enhances lipatic lipase what will the result be

A

more LDL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Apo B

A

takes into account both particles >

VLDL and LDL?

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

LDL bound to (a) protein

A

Lp(a) Lipoprotein

Contribute to coronary artery disease by inhibiting thrombolysis

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

lipoproteins that contain apolipoprotein (apo) B-100

A

Lipoproteins that contain apolipoprotein (apo) B-100 convey lipids into the artery wall. These are low-density (LDL), intermediate-density (IDL), very-low-density (VLDL), and lipoprotein( a) (Lp[ a]).

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

Chylomicrons are formed in the________ and carry triglycerides of _______ unesterified cholesterol, and cholesteryl esters.

A

Chylomicrons are formed in the intestine and carry triglycerides of dietary origin, unesterified cholesterol, and cholesteryl esters. They transit the thoracic duct to the bloodstream.

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

VLDL triglycerides are hydrolyzed by LPL, yielding free fatty acids for storage in adipose tissue and for oxidation in tissues such as cardiac and skeletal muscle.

A

VLDL triglycerides are hydrolyzed by LPL, yielding free fatty acids for storage in adipose tissue and for oxidation in tissues such as cardiac and skeletal muscle.

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

if someone has a TC 220

HDL of 30 and TG of 185 what is there total TG LDL

A

(TC)- (1/5th of TG + HDL )

220-67=153

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

calculate non HDL

TC 220
HDL 30
TG 185

A

220-20

TC-HDL

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

what measurement is most predictive of ASCVD risk

A

non-HDL

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

desirable LDL

A

<100

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

optimal TG

A

<150

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

why do you treat high TG

A

more than 500 b/c of acute pancreatitis

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

boderline TG

A

150-199

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

what is the tx for someone with TG at 180

A

emphasis weight reduction and increased physical activity as well as minimize

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

drugs that elevate LDL

A 
some progestins 
anabolic steroids
danazol
isotetinoin 
immunosuppressive 
amiodarone
thiazide diuretics
glucocorticoids
TZDS
fibric acids
long chain omega fatty acids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

drugs that elevate TG

A 
oral estrogens
tamoxifen
raloxifen
retinoids
immunosuppresives
interferon
Beta-blockers
atypical antipsychotics 
protease inhibitors 
thiazide diuretics
glucocorticoids
rsoiglitazone
bile acide sequestrants
L-asparaginase
cyclophosphamide
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

diet characteristics and dz that are associated with elevated LDL or TG

A 
Anorexia nervosa
ckd
Nephrotic syndrome
DM
HIV
autoimmune
pregnancy
PCOS
menopause
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

drugs used for the tx of dyslipidemia

A 
HMG CoA reductase inhibitors (statins
Fibric Acid derivatives
Niacin
Bile Acid Binding Resins
Intestinal Sterol Absorption Inhibitors
Omega-3 Fatty Acids
CETP Inhibitors
PCSK-9 Inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

These compounds are structural analogs of HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme

A

statins

Lovastatin, atorvastatin, fluvastatin, pravastatin,
simvastatin, rosuvastatin, and pitavastatin

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

primary prevention

A

high risk (angina) without an MI or a stroke It has become standard practice to initiate reductase inhibitor therapy immediately after acute coronary syndromes, regardless of lipid levels.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

when to treat

A

moderate to high dose with greater than 7.5% estimated 10 year risk age 40-75

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

transport dietary/synth fats to cells and to liver (to be made into VLDL and sent out again)

A

Chylomicrons

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

when do we see the elevation of chlomicrons

A

). Elevated for 10-12h after a meal.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

a key enzyme used by cells to “pick” fats off the various “fat trucks” (chylomicrons, LDL, VLDL, etc) as they float by.

A

o LPL (lipoprotein lipase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

. Effectively, the______ and ________ are important for getting LDL out of commission and back to liver.

A

. Effectively, the ApoB proteins and LDL receptors are important for getting LDL out of commission and back to liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

fat-filled macrophages

A

foam cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what would you need when considering statin in an individual with clinical ASCVD

A

fasting lipid panel
ALT
CK (if indicated)
consider evaluation for other secondary casues

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

MOA of bile acid sequesterants

A

Resin binds bile in intestine = insoluble complex → excreted in feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

LDL lowering we see with BAS

A

Resin binds bile in intestine = insoluble complex → excreted in feces

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

adverse effects of BAS

A

GI: constip, abd discomfort, bloating, flatulence, activation of diverticulitis. (high d/c rates)

Metabolic: INCREASE in TG by 10% in pts (esp if has high TG’s already)

not for pt with high TG

May reduce absoprtion of fat sol vitamins & folate → hypothrombinemia in chronic use

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

CI of BAS

A

if TG >400

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

what is the dosing issue with BAS

A

Binds other anionic agents (amiodarone, oral anticoag, digoxin, gemfibrozil, glipizide, phosphate supplements, piroxicam, propranolol, diuretics, thyroid hormone

therefore → wait 4-6h b4 taking other drugs

VERY hard to do since dosed 3x/d

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

BAS seen with LESS DDI

A

Colesevelam (Welchol®)

Tablets (3x/d)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Niacin MOA

A

Inhibits FA mobilization from peripheral tissue

reduces LDL 15-20% (at higher doses) and TG as well as increasing HDL (at lower doses) 20-35%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

biggest ADE with Niacin

A

Flushing: more common w/ IR → vasodilate in 20 min; lasting 20-60 min

can take ibuprofen 30 mins before or titrate to avoid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

other than flushing what are the ADE seen with Niacin

A

Eyes: conjunctivitis, blurred vision, dry eyes

Metabolic: ↑A1c (worst if fat, high A1c, hyperuricemia)

Hepatotoxic: reported mainly w/ SR preps, reversible w/ d/c

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

CI of Niacin

relative and absolute

A

Absolute: liver dz, PUD

Relative: DM, gout, renal dz

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Therapeutic range of Niacin

A

Most effect w/ 1.5-2gm/d IR

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Four major statin benefit groups:

A
  1. Clinical ASCVD
  2. Primary LDL-C >190
  3. DM aged 40-75 & LDL 70-189 & no clinical ASCVD
  4. No clinical ASCVD or DM but has LDL between 70-189 & ASCVD risk >7.5%.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What is clinical ASCD?

A

Acute coronary syndrome

Hx of MI or angina

Coronary or other arterial procedures to “revascularize”

Stroke or TIA

Peripheral artery disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

place in Tx for niacin

A

pt that can’t tolerate a stating (myopathy)

but cardiovascular benefit is not well studied

52
Q

MOA of HMG CoA reductase inhibitors

A

competitive inhibition of HMG-CoA ( an early step in cholesterol synthesis)

Leads to upregulation of the LDL receptor and increased catabolism of LDL (LDL-C) and precursor particles ( TG).

53
Q

Proprotein convertase subtilisin/kexin type 9 (PCSK9)

A

When PCSK9 binds to the LDL receptor, the receptor is broken down and can no longer remove LDL cholesterol from the blood.

blocking PCSK9 can lower blood cholesterol levels

; proprotein convertases is needed to make PCSK9 active

54
Q

Calculated LDL-C not accurate if TG is greater than

A

400

55
Q

how can you calculate LDL-C

A

Total cholesterol – (HDL + TG/5)

56
Q

normal TG

A

<150

57
Q

boderline high TG

A

150-199

58
Q

high TG

A

200-499

59
Q

If TG borderline recommended tx

A

emphasis on weight reduction, increased physical activity, alcohol intake

60
Q

NLA very high risk pt

A

ASCVD or DM with 2 or more major ASCVD risk factors for end-organ damage

61
Q

high risk NLA

A

DM with 0-1 other major ASCVD rf

  1. CKD stage 3b or 4
  2. LDL-C>190
62
Q

metabolic syndrome

A

3 or more risk facotrs

abd obesity :wais circumfrence >102 in men >88 in women

TG>150
HDL
men <40
women<50

BP >130/>85
FBS>100

63
Q

statin benefit groups

A
  1. ascvd
  2. primary LDL-c >190
  3. DM aged 40-75 with LDL-C 70-189 mg/fL and without clinical ASCVD
  4. without ASCVD or DM with LDL-C b/w 70-189 and estimated 10 year ascvd risk >7.5%
64
Q

what you should assess for with suspected lipid disease

A
  1. Assess for secondary causes of high cholesterol level
  2. Assess for familial disorders
  3. Presence of Clinical ASCVD
  4. Lipid panel values
    (3. , 4. and age determine treatment intensity)
65
Q

indications of HMG-CoA Reductase Inhibitors

A

Various dyslipidemias
Have looked at effect on cancer

Oxidative stress & vascular inflammation → Atherosclerotic lesion stability For ALL: ↑ HDL 5-10%

66
Q

what is clinical ascvd

A 
●	Acute coronary syndrome
●	Hx of MI or angina
●	Coronary or other arterial procedures to "revascularize"
●	Stroke or TIA
●	Peripheral artery disease
67
Q

Lovastatin dosage

A

20-80mg

68
Q

Pravastatin dosage

A

10-80

69
Q

Simvastatin dosage

A

5-40mg

70
Q

Rosuvastatin dosage

A

5-10mg (up to 40mg)

71
Q

atorvastatin dosage dosage

A

10-80mg

72
Q

ADE of HMG-CoA Reductase Inhibitors

A

” Myopathy/myositis = rhabdo (elevated CK, cola urine, weakness, ↓urine output, myalgia) 1:1250 pts

” Elevated A1c (NNH ranges from 300 - 500)

Elevated LFTs (<2%, toxicity?, obtain baseline LFTs)

CNS → insomnia, memory impairment, loss of

Neuropathy → paresthesia, hyperesthesia

Skin: eczematous rash (uncommon)

proteinuria with rosuvastatin doses greater

73
Q

symptoms of rnhabdomylosis

A 
dark red or cola-colored urine
decreased urine output
general weakness
muscles stiffness
muscle tenderness 
weakness of affected muscles
74
Q

how to we measure muscle breakdown associated with Hmg Coa reductase inhibitors

A

Ck (creatine kinase)

75
Q

risk factors for rhabdo

A 
Hx of statin intolerance
CYP-inhibition
>75 yO
Hx of CVA 
aSIAN
High dose statin 
hypothyroidism 
reduce renal/hepatic fxn
rheumatologic d/o
steroid myopathy 
decreased vitamin D
primary muscle disease
76
Q

what do you do if pts are at risk for rhabdo

A

check CK before starting drug

77
Q

if pt has myalgia of statin

A 
d/c until sx have been evaluated 
check CK and urine myoglobin 
r/o other causes
re challenge w/ los dose to determine cause
try another atatin
78
Q

DDI for statins

A

Gemfibrozil & Nelfinavir (fibric acid derivative) = ↑ risk of myositis

azole antifungals

EtOH - ↑ risk of myopathy

Warfarin - ↑ prothrombin time

BAS’s - reduced absorption

79
Q

what ate the specific concerns we are worried about with rosuvastatin

A

Proteinuria when dosed >40 mg/d

Myopathy, rhabdo (esp w/ ↑ doses)

Altered metabolism in Asians: (2-fold ↑)

80
Q

which HMG coa reductase inhibitors are metbaolised by cyp3a4 and what DDI are we concerned about

A

lovastatin
simvastatin and
atorvastatin

inhibited by azoles, macrolides, nefazodone, PIs, amiodarone, verapamil grapefruit juice.

81
Q

which HMG coa reductase inhibitors are metabolizes by CYP29C, major DDI

A

fluvastatin
rosuvastatin
pitavastatin
CYP29C Nelfinavir ➔ ↑ risk of myositis

82
Q

*If CrCl 30-60 how should you dose pivistatin (livalo)

A

*If CrCl 30-60 í initial 1mg

2mg max

83
Q

if you’ve never had an event and you’re being treated for lipid disorder

A

primary

84
Q

when you absorb from the gut what is the cholesterol formed

A

chylomicrons this is why we need to fast before a lipid panel

85
Q

NLA ASCVD Criteria

A

evidence of vascular disease but NOT chest pain

Myocardial infarction or other acute coronary syndrome
Coronary or other revascularization procedure

Transient ischemic attack
Ischemic stroke

Atherosclerotic peripheral arterial disease
      Included ankle/brachial 
       index < 0.90
Other documented atherosclerotic disease: 
        Coronary atherosclerosis
        Renal atherosclerosis	
       Abdominal aortic aneurysm 
      secondary to atherschlerosis

Carotid artery plaque ≥
50% stenosis

86
Q

mainstay of lipid tx

A

statins hmg-CoA

87
Q

Lipid drug of choice for HIV pt

A

pravastatin

88
Q

moderate lipid lowering

A

moderate 30-50%

89
Q

high intesity therapy should decrease lipids by

A

> 50%

atorvostatin 40-80mg
rosuvastatin 20- 40mg

90
Q

Main difference in LDL lowering is seen with initial dose

With subsequent doubling of statin dose, an additional ____ LDL lowering is seen

A

Main difference in LDL lowering is seen with initial dose

With subsequent doubling of statin dose, an additional 5-6% LDL lowering is seen

91
Q

if you have someone on a statin and they get rhabdo on low doses

A

switch the BAS

92
Q

BAS is contraindicated in

A

TG >400 mg/dl - dysbetalipoprotienemia

TG>200 (relative)

93
Q

increased HDL more than any other drug but has very little cardio protective effect

A

niacin

94
Q

how to avoid flushing with niacin

A

niaspan at night

or NSAIDS but that would have to be 3x a day

95
Q

niascin is CI in (absolute and relative)

A

Absolute: liver dz, PUD
Relative: DM, gout, renal dz

gout (changing uric acid up or down causing the white blood cells to mobilize)

if used in a pt with attacks need to be given an anti-inflammatory to avoid attack

96
Q

FIBRIC ACID DERIVATIVES MOA

A

Bind to and stimulate PPAR-a (peroxisome proliferator-activated receptor-alpha) í

↓ Apo C-III —> ↑ lipolysis of lipoprotein TG via LPL (lipoprotein lipase) —> ↓ TG

the higher the TG the more likely you are to see and increase in LDL

97
Q

why do we are about high tG

A

pancreatitis over 500

98
Q

CI of FIBRIC ACID derivatives

A

CI in pts with renal failure because of renal clearance

CrCl<30 –>Avoid
CrCl 30-60 –>Limit dose

99
Q

ADE of fibric acids

A

> 10% Dyspepsia, abd pain, cholelithiasis

1-10% fatigue, vertigo, HA, rash, N/V/D, constipation

<1% atrial fibrillation, hyperesthesia, dizziness, drowsiness, depression, blurred vision, myalgia (rhabdo!)

100
Q

Gemfibrozil (Lopid®)
Fenofibrate (Tricor®)

are both

A

fibric acids

101
Q

Ezetimibe
(Zetia®)

10mg QD

A

” Inhibits absorption of cholesterol in small intestine

102
Q

ADE Ezetimibe

Zetia®

A

” GI sx: abd pain, D
“ Fatigue
“ Arthralgia
“ Back pain

103
Q

orphan drug used for

homozygous familial hypercholesterolemia (HoFH) w/ LDL-C > 500mg/dL

A

Lomitapide
(Juxtapid®)

and

Mipomersen
(Kynamro®)

104
Q

” Manmade antibodies that target proteins in the body that prevent the elimination of LDL cholesterol

A

PCSK9 Inhibitors

105
Q

Injectable drugs that can be used w/ statins

A

PCSK9 Inhibitors

106
Q

PCSK9 Inhibitors

A

increase LDL receptor

Reduce LDL 59-66% in combo w/ moderate intensity statin
“ Proof of efficacy TBD

107
Q

Ezetimibe
(Zetia®)
MOA

A

” Inhibits absorption of cholesterol in small intestine

108
Q

Lomitapide

Juxtapid®

A

Microsomal triglyceride transfer protein (MTP) inhibitor - resides in lumen of the endoplasmic reticulum í thus prevents apo B-containing lipoprotein assembly

109
Q

Mipomersen
(Kynamro®) . moa

SC injection q wk

A

” Inhibits apolipoprotein B-100 synthesis

110
Q

non pharm tx for lowering lipids

A 
omega 3 (lovaza)
soluble fiber
sitosanol (margarine)
red yeast 600mg
garlic
111
Q

these lipoproteins are responsible for taking the lipids to the liver

A

chylomicrons

when food is absorbed in the liver it is absorbed into this

112
Q

liver transforms chylomicrons and makes

A

VLDL

113
Q

chylomicrons originate in the

A

intestine

114
Q

as your going down in density you have _____ fat and more _______

A

you have less fat and more cholesterol as you are going down in density

115
Q

APOE

A

protein on the VLDL that binds to the receptors on the liver and makes this lipoprotein into LDL

116
Q

lipid lowering drugs that are CI in pts with high TG

A

BAS >400

Gemfibrozi l>500

117
Q

Therapeutic range of nIacin

A

less than 2mg

doesn’t have cardio protective evidence that statins does

118
Q

what drugs are we worried about pt getting DM

A

Niacin can increase A1C

high intensity statins has been shown to increase dm

119
Q

Increase in gout attack seen with what lipid med

A

niacin

changing uric acid level in either direction causes wbc to mobilize

120
Q

main reason we treat hyperlipidemia and what drug would be best for this

A

fibric acids
gemfibrozil
fenofibrate

121
Q

fibric acid derivates are metabolized how?

A

hepatically metabolized
metabolites
excreted in the urine
avoid in CrCl<30 or CKD

122
Q

cholilethiasis is a complication of what medication

A

fibric acid derivatives (10%)

123
Q

MOA of PCSK9

A

man made antibodies that target proteins in the body that prevent the elimination of LDL increasing LDL receptor and inhibiting protein that destroys the receptor

124
Q

indications of PCSK9

A

very high risk of another event

seen with LDL cholesterol fomr 59-66%

125
Q

PSCK9 drug names

A

evolucumab

alirocumab

126
Q

other non drug tx for lowering cholesterol

A 
fiber
omega 3 fatty acids
garlic
sitosanol (margarine)
red yeast 600mg  (statin)
127
Q

lovaza

A

fish source that lowers TG

for someone that doesn’t tolerate fibric acid

can elevate liver enzymes

maybe some benefit in heart failure

Pharm II (16 decks)

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