Brainscape's Knowledge GenomeTM

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


See full index

Pharmacology > Antihyperlipidemic Drugs > Flashcards

Antihyperlipidemic Drugs Flashcards

1
Q

What is Hyperlipidemia?

A

elevation of plasma cholesterol and/or TGs, or low HDL levels

** causes may be primary (genetic) or secondary

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

What is the link between plasma lipid concentrations and risk for CVD

A

as plasma cholesterol increases the risk for CVD increases as well.

Increased risk of cardiovascular mortality is most closely linked to elevated levels of LDL and decreased levels of HDL.

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

Log-Linear relationship between LDL levels and relative risk for CHD

A

For every 30-mg/dL reduction in LDL, the relative risk drops by 30%

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

Risk factors for CVD

A

Cigarette smoking
HTN
Obesity
Diabetes

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

Primary causes of hyperlipidemia include

A

Monogenic Diseases
Genetic Polymorphism
Gene-Environment interactions

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

Fredrickson class of Hyperlipidemias

  • All five types
  • Lipid profile
  • Etiology
A

Type I (Hyperchylomicronemia)

  • Lipid profile:
    • increased chylomicrons
  • Etiology:
    • Deficiency in LPL or appCII

Type IIa (familial hypercholesterolemia)- (AD inheritance)

  • Lipid profile:
    • increased LDL
  • Etiology:
    • Decreased or no functional LDL receptor

Typer IIb (Familial combined hyperlipidemia) **

  • Lipid profile:
    • increased LDL and VLDL
  • Etiology:
    • Overproduction of VLDL by the liver

Type III (Dysbetalipoproteinemia)

  • Lipid profile:
    • increased IDL
  • Etiology:
    • abnormal apoE

Type IV (Hypertriglyceridemia)**

  • Lipid profile:
    • increased VLDL
  • Etiology:
    • Overproduction and/or impaired catabolism of VLDL

Type V (Familial mixed hypertriglyceridemia)

  • Lipid profile:
    • Increased in chylomicrons and VLDL
  • Etiology:
    • Increased production or decreased clearance of VLDL and chylomicrons

**most commonly found

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

Secondary Hyperlipidemia

A

Contribute to most cases of dyslipidemia in adults

Factors:
- sedentary lifestyle, excess dietary intake of saturated fats, cholesterol, and trans fatty acids

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

Hypertriglyceridemia vs Hypercholesterolemia Factors

A

Hypertriglyceridemia

  • DM
  • Chronic renal failure
  • hypothyroidism
  • Alcohol excess
  • contraceptives
  • beta blockers
  • Glucocorticoids

Hypercholesterolemia

  • hypothyroidism
  • nephrotic syndrome
  • Obstructive Liver disease
  • glucocorticoids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Pharmacological management of hyperlipidemia

A

Statin are the lipid-lowering agent for first choice treatment for most patients with atherosclerotic CVD

In selected high-risk patients use of non-statins may be considered if statin therapy has not achieved >50% reduction in LDL.

Lipid-regulating drugs must be taken indefinitely.

When they are stopped, plasma lipoprotein levels return to pretreatment levels.

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

Antihyperlipidemic Drug (classes)

A 
HMG-Coa Reductase inhibitors
Niacin 
Bile acid binding resins
Fibrates
Cholesterol absorption inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

HMG-Coa Reductase Inhibitors

- drugs

A 
Atorvastatin 
Fluvastatin 
Lovastatin
Pravastatin
Rosuvastatin
Simvastatin

** most effective drug in lowering LDL. Also decrease plasma TG and a small increase in HDL

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

Statins MOA

A

Analog of HMG (3-OH-3-methylglutarate)

Competitive inhibitors of HMG-Coa Reductase (inhibits the first committed step of cholesterol biosynthesis)

By inhibiting cholesterol biosynthesis the intracellular cholesterol levels are depleted which leads to an up regulation of LDL receptors and will subsequently decrease plasma LDL

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

Statins (potency levels for LDL and TG)

- they are the very similar

A 
Rosuvastatin is the most potent
Atorvastatin is the second most 
followed by simvastatin 
Lovastatin and pravastatin have similar potency 
Fluvastatin is the least potent
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Statins Uses

A

DOC for LDL reduction
reduces Cardiovascular mortality
Lowers LDL in all types of hyperlipidemias
Hyperlipidemia Type IIa (homozygous) do not benefit much because of the lack functional LDL receptors
** contraindicated in pregnancy

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

Who should be treated with a statin? (4 groups)

A
  • ASCVD
  • LDL 190mg/dL or higher
  • Patients age 40-75 with diabetes and LDL 70-189 mg/dL
  • Patients w/o ASCVD or diabetes with LDL 70-189 mg/dL and an estimated 10 year risk of ASCVD of 7.5% or higher
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Other effects of Statins

A

Improve endothelial function
decrease platelet aggregation
stabilizer atherosclerotic plaques
reduce inflammation

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

Statins AE and Monitoring

A

AE:
Elevation of aminotransferases
myopathy and rhabdomyolysis

Monitoring:
Aminotransferases should be measured at baseline and 1-2 months, and then every 6 months

CK should be measured at baseline and if pain or muscle weakness appears CK should be measured immediately and the drug should be D/C if activity is significantly elevated

18
Q

Niacin (Nicotinic Acid)

- general

A

Favorably affects virtually all lipid parameters

Decreases VLDL, LDL, and Lp(a) (only drug to effect Lp(a))

increases HDL (most effective agent)

Many AE which limits its use

19
Q

Niacin MOA

A

Inhibits Adenylyl cyclase in adipocytes. Leading to the inhibition of hormone sensitive lipase (prevents release of FFA)

Transport of FA to the liver is reduced and this reduces liver TG synthesis

In the liver niacin inhibits synthesis and esterification of FA. VLDL production is decreased

Increases LPL activity

the catabolism of HDL is decreased

20
Q

Niacin Uses

A

Most efficacious drug to increase HDL

Particularly useful in patients with combined hyperlipidemia and low HDL levels

Effective combo with statins

21
Q

Niacin AE

A

Intense cutaneous flushing (after each dose when drug is started or dose is increased)
- administration of aspirin prior to dose decreases flushing

Pruritus, rash, dry skin

Acanthosis nigricans

Nausea and abdominal discomfort

Hepatotoxicity and hyperglycemia

Niacin induced insulin resistance can cause severe hyperglycemia

Niacin elevates uric acid levels and precipitate as gout

Rare AE: Atrial arrhythmias, toxic amblyopia, toxic maculopathy

22
Q

Fibrates

- drugs and General function

A

Gemfibrozil
Fenofibrate

  • lower TAG and increase HDL
23
Q

Fibrates MOA

A

Activate PRAR-alpha

PRAR-alpha are primarily expressed primarily in liver and brown adipose tissue

activation of PRAR-alpha leads to decrease in plasma TG levels (increase expression of LPL, decreased hepatic expression of apocalypse-III, and increased hepatic oxidation of FA) and increase in HDL levels

** Fibrates may increase LDL particularly if the TG level is greater than 400 mg/dL

24
Q

Fibrates Uses

A

DOC in severe hypertriglyceridemia

As monotherapy, fibrates offer the highest TG reduction, followed by niacin, omega-3-fatty acids, statins, and ezetimibe.

25
Q

Fibrates AE

A

Mild GI disturbances.

Myositis. Patients with renal insufficiency may be at risk. Rhabdomyolysis has occurred rarely.

Lithiasis. Fibrates increase biliary cholesterol excretion, therefore they may cause gallstones.

26
Q

Fibrates Drug Interactions

A

Gemfibrozil inhibits hepatic uptake of statins, thus increasing plasma concentration of statins.

Gemfibrozil competes for the glucuronosyl transferases that metabolize most statins.

As a consequence, levels of both drugs may be increased when they are co-administered. This increases the risk of rhabdomyolysis.

Fenofibrate does not inhibit statin metabolism, and is much less likely to increase risk of rhabdomyolysis.

27
Q

Bile Acid-Binding Resin drugs

- some PK

A

Cholestyramine
Colestipol
Colesevelam

Insoluble in water
Larger molecular weight (neither metabolized nor absorbed)
Totally excreted in the feces

28
Q

Bile Acid-Binding Resin MOA

A

Bind to anionic bile acids in the intestinal lumen and prevent their reabsorption.

The resin-bile acid complex is excreted in the feces, thus preventing bile acids from returning to the liver by the enterohepatic circulation.

The reduction in bile acid concentration causes hepatocytes to increase conversion of cholesterol to bile acids

Consequently, intracellular cholesterol decreases

This leads to up-regulation of LDL receptors in the liver

Liver uptake of LDL increases, leading to a decrease in plasma LDL levels.

This effect is partially offset by increased cholesterol synthesis due to upregulationof HMG-CoA reductase.

HDL rises modestly.

29
Q

Bile Acid-Binding Resin Uses

A

Useful in hyperlipidemia involving isolated increases in LDL

Used with statins or niacin to increase LDL reduction.

Drugs of choice for pregnant women and for children.

Little effect in individuals who completely lack functional LDL receptors.

30
Q

Bile Acid-Binding Resin AE

A

GI adverse effects: bloating, nausea, cramping and constipation.

Colesevelam produces fewer GI adverse effects than cholestyramine or colestipol.

They may increase TG: contraindicated in hypertryglyceridemia.

31
Q

Bile Acid-Binding Resin Drug interactions

A

Cholestyramine and colestipol reduce absorption of several drugs and liposoluble vitamins.

32
Q

Cholesterol Absorption inhibitor

Drug and function

A

Ezetimibe

inhibits intestinal absorption of cholesterol and phytosterols

Primary clinical effect is to lower LDL

33
Q

Ezetimibe MOA

A

Ezetimibe inhibits an intestinal transport protein (NPC1L1), which takes up cholesterol from the lumen

Cholesterol absorption is reduced by 54%.

This triggers a compensatory increase in cholesterol synthesis (which can be inhibited with a statin).

Reduced delivery of intestinal cholesterol to the liver leads to upregulation of LDL receptors, which enhances LDL clearance from plasma.

The maximal efficacy of ezetimibe for lowering LDL is about 15-20%.

34
Q

Ezetimibe Uses

A

Useful in combination with a statin in patients unable to reach their LDL goal on statin monotherapy.

First non-statin drug that should be considered as an adjunct to a statin.

Ezetimibe is only used as monotherapy in patients who do not tolerate statins.

35
Q

Ezetimibe AE

A

Low incidence of reversible impaired hepatic function.

Small increase in incidence when ezetimibe is given with a statin.

Myositis has been reported rarely.

36
Q

Ezetimibe Drug Interactions

A

Bile-acid sequestrants inhibit absorption of ezetimibe.

The two agents should not be administered together.

37
Q

Omega-3 FA

General function and drugs

A

EPA and DHA reduce TG synthesis and increase fatty acid oxidation in the liver

HDL levels may modestly increase

indicated as an adjunct to to diet to reduce TG

38
Q

Suggested Drug Therapy for elevated LDL

A

Initial:
Statin

Additions:
Niacin, Resin, Ezetimibe

39
Q

Suggested Drug Therapy for elevated LDL and TG

A

Initial:
statins

Additions:
Niacin, Fibrate, omega-3 FA

40
Q

Suggested Drug Therapy isolated low HDL

A

Initial:
Statin

Addition:
Niacin

41
Q

Suggested Drug Therapy isolated sever hypertriglyceridemia

A

Initial:
Fibrate (or Niacin or omega-3 FA)

Addition:
Statin

Pharmacology (20 decks)

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