Brainscape's Knowledge GenomeTM

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


See full index

Cardio II Midterm > Drugs for Lipid Disorders - DSA > Flashcards

Drugs for Lipid Disorders - DSA Flashcards

1
Q

HMG-CoA reductase inhibitors

A

“statins” - analogs of initial precursor of cholesterol

Atorvastatin (lipitor)
Fluvastatin
Lovastatin*
Pitavastatin
Pravastatin
Rosuvastatin (crestor)
Simvastatin* (zocor)

*prodrugs hydrolyzed in GI tract to active compounds

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

Niacin

A

nicotinic acid

vit B3

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

Fibric acid derivatives (fibrates)

A

Fenofibrate

Gemfibrozil

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

Bile acid sequestrants (resins)

A

Cholestyramine
Colesevelam
Colestipol

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

Cholesterol absorption inhibitors

A

Ezetimibe (Zetia)

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

Drug combinations

A

simvastatin and ezetimibe (Vytorin)
Niacin and lovastatin extended release (Advicor)
Niacin and simvastatin extended release (Simcor)

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

New tx for homozygous familial hypercholesterolemia

A

Lomitapide

mipomersen

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

Chylomicrons

A

contains dietary TGs and cholesterol
TG:Chol is 10:1
Synthesized in intestine
Mech of catabolism: TG hydrolysis by LPL, remnant uptake by liver

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

VLDL

A

contains endogenous TGs
TG:Chol is 5:1
Synthesized in liver
Mech of catabolism: TG hydrolysis by LPL

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

IDL

A

contains endogenous cholesterol esters and TGs
TG:Chol is 1:1
Product of VLDL catabolism
Mech of catabolism: 50% to LDL mediated by hepatic lipase, 50% uptake by liver

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

LDL

A

contains cholesteryl esters
Product of VLDL catabolism
Mech of catabolism: uptake by LDL receptor (75% in liver)

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

HDL

A

contains Phospholipids, cholesteryl esters
Synthesized in liver
Mech of catabolism: uptake of cholesterol by hepatocytes

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

Statin pharmacokinetics

A

extensive first pass metabolism by liver
t 1/2 1-3 h, exceptions: atorvastatin 14 hr, rosuvastatin 19 hr
most absorbed dose excreted as bile, 5-20% in urine
Lovastatin, simvistatin, atorvastatin metabolized CYP3A4
Fluvastatin, rosuvastatin CYP2C9
Pitavastatin limited CYP450 biotransformation
Pravastatin not metabolized by CYP450s

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

Statin MOA

A

inhibit HMG-CoA reductase - rate limiting enzyme in cholesterol synthesis

Inhibits de novo cholesterol synthesis, depletes intracellular supply of cholesterol - causes cell to increase number of specific cell-surface LDL receptors that bind and internalize circulating LDLs

Increased expression of surface LDL receptors reduces circulating LDL levels

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

therapeutic benefits of statins

A

plaque stabilization
improvement of coronary endothelial function
inhibition of platelet thrombus formation
anti-inflammatory effects
Reduce LDL levels 20-55%

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

Adverse effects of statins on liver

A

elevations of serum aminotransferase activity (up to 3x) in patients with liver disease or hx of etOH abuse

Levels decrease upon suspension of drug therapy

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

Adverse effects of statins on muscle

A

creatine kinase activity levels may increase, particularly in patients who have a high level of physical activity

rhabdomyolysis (leading to myoglobinuria) occur rarely and lead to renal injury

Myopathy can occur with monotherapy, increased risk when taken with drugs such as cyclosporine, itraconazole, erythromycin, gemfibrozil, or niacin

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

Statin contraindications

A

increases warfarin levels

pregnant, lactating, likely to become pregnant

liver disease or skeletal muscle myopathy

use in children limited to homozygous familial hypercholesterolemia and heterozygous familial hypercholesterolemia

avoid with agents inhibiting or competing with CYP450 enzymes such as inducers phenytoin, griseofulvin (except for pravastatin and pitavastatin)

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

Niacin

A

Most effective agent for increasing HDL levels (30-40%)
Lowers LDL and VLDL by 10-20% and TG 35-45%
ONLY agent that reduces lipoprotein(a) levels significantly (40%)

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

Niacin pharmacokinetics

A

well absorbed, distributed to hepatic, renal, adipose tissue
extensive first pass
t1/2 60 min - BID or TID dosing
Excreted in urine unmodified and its metabolites

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

MOA of niacin

A

inhibits lipolysis of TG in adipose tissue, reducing circulating FAs which leads to less VLDL produced by liver and decreased LDL levels

Plasma TG (in VLDL) and cholesterol (in VLDL and LDL) decrease

Fibrinogen levels reduced and tissue plasminogen activator levels are increased - can reverse some endothelial cell dysfunction contributing to thrombosis associated with hypercholesterolemia and atherosclerosis

22
Q

Therapeutic uses of niacin

A

combined with a bile acid sequestrant (resin) or reductase inhibitor in tx of heterozygous familiar hypercholesterolemia, other forms of hypercholesterolemia, and some cases of nephrosis

utilized in tx of mixed lipemia that incompletely responsive to diet

23
Q

Adverse effects of niacin

A

intense cutaneous flush (PG mediated) with uncomfortable feeling of warmth - flushing mitigated by taking aspirin before niacin or ibuprofen QD

Pruritus, rashes, dry skin or mucous membranes, acanthuses nigricans

hepatotoxicity with extended release

24
Q

Contraindications of niacin

A

hepatic disease or active peptic ulcer

DM due to niacin-induced insulin resistance which can cause hyperglycemia

25
Q

Fibrates pharmacokinetics

A 
derivatives of fibric acid
well absorbed (>90%) when taken with meal
highly bound to serum albumin
t1/2 - gemfibrozil 1.5h, fenofibrate 20h
excreted as glucuronide conjugates
26
Q

Fibrates MOA

A

agonist ligands for peroxisome proliferator-activated receptor alpha (PPARalpha)
PPARa binds to response elements in DNA, regulating expression of genes in lipoprotein structure and function
Expression levels of lipoprotein lipase increased, induces lipolysis of TG and decreases plasma concentrations
VLDL decreases, LDL modestly decreases, HDL increase moderately

27
Q

Therapeutic uses of fibrates

A

hypertriglyceridemias where VLDL predominate
Dysbetalipoproteinemia
Hypertriglyceridemia from tx with viral protease inhibitors (saquinavir, indinavir, or nelfinavir for HIV therapy

28
Q

Adverse effects of fibrates

A

mild GI disturbances, usually subside as tx continues
Lithiasis due to increased biliary cholesterol excretion - formation of gallstones

myositis - inflammation of voluntary muscle - evaluate for muscle weakness and tenderness
Myopathy and rhabdomyolysis - risk increased taking fibrates and reductase inhibitors

29
Q

Fibrate contraindications

A

drug interactions: potentiate actions of coumarin and indanedione anticoagulants

hepatic or renal dysfunction
pregnant or lactating
increased risk of gallstones, caution in biliary tract disease or those at high risk (women, obese, native americans)

30
Q

Resins

A

insoluble in water

Neither absorbed or metabolically altered by the intestine; totally excreted in the feces

31
Q

Resin MOA

A

sequestrants are positively charged bind to negatively charged bile acids (metabolites of cholesterol), increasing their excretion up to tenfold which enhance the conversion of cholesterol to bile acids in the liver via 7α-hydroxylation, (normally controlled by negative feedback by bile acids)

decline in hepatic cholesterol stimulates an increase in hepatic LDL receptor enhancing LDL clearance and lowers levels; however, this effect is partially offset by enhanced cholesterol synthesis caused by upregulation of HMG-CoA reductase (combined use of a statin substantially increases the effectiveness of resins)

32
Q

Therapeutic uses of resins

A

tx primary hypercholesterolemia - reduces LDL by 20%

Mono therapy or with niacin to treat Type IIa and IIb hyperlipidemia

relieve pruritus in those with bile salt accumulation from biliary obstruction

used for digitalis toxicity due to interaction with digitalis glycosides

33
Q

Adverse effects of resins

A

GI: constipation, N, flatulence

High doses of cholestyramine and colestipol impair absorption of fat soluble vits (ADEK)

34
Q

Contraindications of resins

A

impair absorption of tetracycline, phenobarbital, digoxin, warfarin, pravastatin, fluvastatin, aspirin, thiazide diuretics - give at least 1 hr before or 2 hrs after sequestrant to ensure absorption

Avoid or caution with diverticulitis, preexisting bowel disease, or cholestasis

35
Q

Ezetimibe pharmacokinetics

A

i) Highly water insoluble; after ingestion, it is glucuronidated in the intestinal epithelium, absorbed, and enters enterohepatic circulation as an active compound
ii) Majority is excreted in the feces (10% in the urine)
iii) 22 hour half-life

36
Q

MOA of Ezetimibe

A

selectively inhibits intestinal absorption of cholesterol and phytosterols (plant sterols); thought to inhibit the transport protein NPC1L1

ii) Effective even in the absence of dietary cholesterol because it inhibits reabsorption of cholesterol excreted in the bile
iii) Inhibited intestinal cholesterol absorption reduces the incorporation of cholesterol into chylomicrons, which reduces the delivery of cholesterol to the liver by chylomicron remnants
iv) On average, ezetimibe lowers LDL by 18% and triglycerides by 6% while raising HDL levels slightly (1.3%)

37
Q

Therapeutic uses of Ezetimibe

A

Used to treat various causes of elevated cholesterol levels [e.g., primary
hypercholesterolemia (as monotherapy or in combination with HMG-CoA reductase inhibitors); homozygous familial hypercholesterolemia (in combination with atorvastatin or simvastatin); mixed hyperlipidemia (in combination with fenofibrate)]

38
Q

Adverse effects of ezetimibe

A

no drug interactions

avoid combining with bile acid sequestrants due to inhibition of ezetimibe absorption

39
Q

Situations when combination drug therapy useful

A

i) When VLDL levels are significantly increased during treatment of hypercholesterolemia
with a resin
ii) When LDL and VLDL levels are both elevated initially
iii) When LDL or VLDL levels are not normalized with a single agent
iv) When an elevated level of Lp(a) or an HDL deficiency coexists with other hyperlipidemias

40
Q

the ENHANCE study

A

(a) A 2-year study in patients with familial hypercholesterolemia comparing the effects of ezetimibe and simvastatin together with those of simvastatin alone
(b) Results showed a 58% reduction in LDL cholesterol with the combination compared to a reduction of 41% with simvastatin alone
(c) However, results showed no additional effect of ezetimibe on carotid intima-media thickness, a surrogate marker for coronary atherosclerosis
(d) Direct measurements of clinical endpoints such as myocardial infarction, stroke, or cardiovascular death require trials with many participants followed for years and, as a result, surrogate endpoints are often used instead for FDA approval of medication (in the ENHANCE trial, the surrogate endpoint was lower LDL cholesterol levels)

41
Q

SEAS study

A

found no reduction in major cardiovascular events with simvastatin plus ezetimibe compared to placebo, and actually found an increase in various types of cancer in patients taking the simvastatin-ezetimibe combination

42
Q

Lomitapide

A

tx of homozygous familial hypercholesterolemia

MOA: directly binds to and inhibits microsomal triglyceride transfer protein (MTP) which is
located in the lumen of the endoplasmic reticulum. 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.

substrate and inhibitor of CYP3A4

Adverse effects: GI symptoms, increased aminotransferase levels, hepatic fat accumulation

43
Q

Mipomersen

A

Tx of homozygous familial hypercholesterolemia

MOA: antisense oligonucleotide that targets apoliporotein B-100 (apoB-100) mRNA and disrupts its function
(1) ApoB-100 is the ligand that binds LDL to its receptor and is important for the transport and removal of atherogenic lipids
(2) Elevated levels of apoB, LDL-C and VLDL are associated with increased risk of
atherosclerosis and cardiovascular diseases

Adverse effects include injection site reactions (administration via subcutaneous injection once per week), flu-like symptoms, headache, and elevation of liver enzymes ≥three times the upper limit of normal (discontinue if elevations persist or are accompanied by clinical symptoms, such as hepatic steatosis

44
Q

Omega 3

A 
modify membrane function
inhibit thrombus formation
decrease inflammation
lower plasma TG
alter electrical activity of myocardium
45
Q

Type I

A 
familial hyperchylomicronemia
elevated TG
deficiency of lipoprotein lipase or normal apoliporotein CII
no increase CAD
Tx: low fat diet
46
Q

Type IIA

A

familial hypercholesterolemia
elevated LDL, normal VLDL due to block of LDL degradation - increased cholesterol but normal TG
Defects in synthesis or processing of LDL receptors

Ischemic heart disease accelerated

Tx: diet
Heterozygotes - cholestyramine and niacin or a statin

47
Q

Type IIB

A

familial combined (mixed) hyperlipidemia

increased VLDL and LDL, elevated TG and cholesterol

overproduction of VLDL by liver

tx: diet, drug therapy like IIA

48
Q

Type III

A

familial dysbetalipoproteinemia
high IDL, increased TG and cholesterol levels

overproduction or underutilization of IDL due to mutant poE

Xanthomas and accelerated vascular disease develop in patients by middle age

Tx: diet, niacin and fenofibrate, or a statin

49
Q

Type IV

A

Familial hypertriglyceridemia

VLDL increased, LDL normal or decreased –> normal or elevated cholesterol and elevated TG

Overproduction and/or decreased removal of VLDL TG in serum

accelerated ischemic heart disease

assoc with obesity, DM, hyperuricemic

Tx: diet, niacin and/or fenofibrate

50
Q

Type V

A

Familial mixed hypertriglyceridemia

serum VLDL and chylomicrons elevated, LDL normal or decreased, elevated cholesterol and greatly elevated TG

increased production or decreased clearance of VLDL and chylomicrons - genetic defect

Tx: diet, niacin and/or fenofibrate, or statin

Cardio II Midterm (16 decks)

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