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PCM Exam 2 Pharm > ANTIHYPERLIPIDEMIC DRUGS > Flashcards

ANTIHYPERLIPIDEMIC DRUGS Flashcards

1
Q

We

A
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2
Q

How is hyperlipidemia and cardiovascular mortatility linked?

A

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

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3
Q

Other risk factors for cardiovascular disease include?

A

• Cigarette smoking

  • Hypertension
  • Obesity
  • Diabetes
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4
Q

PRIMARY HYPERLIPIDEMIAS: ETIOLOGY & CLASSIFICATION?

A
  • Monogenic diseases
  • Genetic polymorphisms
  • Gene-environment interactions
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5
Q

What are the classications of Primary Hyperlipidemias?

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6
Q

What are the secondary hyperlipidemia’s?

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7
Q

What is the agents of first choice for treatment of most patients with atherosclerotic cardiovascular disease.

A

Statins are the lipid-lowering agents

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8
Q

when would you use a non-statin?

A

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

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9
Q

Why must Lipid-regulating drugs must be taken indefinitely?

A

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

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10
Q

What are the classes of ANTIHYPERLIPIDEMIC DRUGS

A

• HMG-CoA reductase inhibitors

  • Niacin
  • Bile acid-binding resins
  • Fibrates

• Cholesterol absorption inhibitors

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11
Q

Why are HMG CoA reductase inhibitors are the most important class?

A

their well-demonstrated efficacy in reducing cardiovascular morbidity and mortality.

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12
Q

HMG-CoA REDUCTASE INHIBITORS (Statins)?

A

• Atorvastatin (2nd most potent)

  • Fluvastatin ( least potent)
  • Lovastatin ( similar in potency to pravastatin)
  • Pravastatin( similar in potency to Lovastatin)
  • Rosuvastatin ( most potent)

• Simvastatin ( 3rd most potent)

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13
Q

Statins mechanism of action?

A
  • Statins are competitive inhibitors of HMG-CoA reductase, the enzyme that catalyzes the first committed step of cholesterol biosynthesis.
  • Depletion of intracellular cholesterol leads to upregulation of HMG-CoA reductase, and upregulation of the LDL receptor.
  • Upregulation of LDL receptors results in increased clearance of LDL from the blood.
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14
Q

Overall summary of STATINS effect?

A
  • Statins are more effective than other drugs in lowering LDL.
  • They also cause a decrease of plasma TG and a small increase in HDL.
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15
Q

What are the uses of Statin?

A
  • Drugs of choice for LDL reduction.
  • Reduce cardiovascular mortality.
  • Lower LDL levels in all types of hyperlipidemias.
  • Homozygotes for familial hypercholesterolemia lack functional LDL receptors and thus benefit much less from treatment with statins.
  • Contraindicated in pregnancy.
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16
Q

WHo should be recieving a statin?

A
  • Patients with ASCVD.
  • Patients with LDL 190 mg/dL or higher.
  • Patients age 40-75 years of age with diabetes and LDL 70-189 mg/dL.
  • Patients without ASCVD or diabetes with LDL 70-189 mg/dL and an estimated 10-year risk of ASCVD of 7.5% or higher.
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17
Q

What are the other effects of statin?

A
  • Improve endothelial function.
  • Decrease platelet aggregation
  • Stabilize atherosclerotic plaque.

• Reduce inflammation.

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18
Q

What are the adverse effects of Statin?

A
  • Elevation of aminotransferases. Usually not associated with other evidence of liver toxicity.
  • Myopathy and rhabdomyolysis. Rare. Rhabdomyolysis may cause myoglobinuria,leading to renal injury.
19
Q

How are statins monitored?

A
  • Aminotransferase activity should be measured at baseline, at 1–2 months, and then every 6–12 months.
  • CK should be measured at baseline. If muscle pain, or weakness appears, CK should be measured immediately and the drug discontinued if activity is significantly elevated.
20
Q

What are the common features of Niacin?

A
  • Niacin favorably affects virtually all lipid parameters.
  • Decreases VLDL, LDL and Lp(a) levels.
  • It increases HDL levels.
  • Most effective agent for increasing HDL and the only agent that may reduce Lp(a).
  • Niacin has many adverse effects which limit its use
21
Q

What is the mechanism of action of Niacin?

A
  • Niacin inhibits adenylyl cyclase in adipocytes. Leading to inhibition of hormone-sensitive lipase.
  • Transport of fatty acids to the liver is reduced. This reduces liver TG synthesis.
  • In the liver niacin inhibits synthesis and esterification of fatty acids. VLDL production is decreased.
  • Niacin increases LPL activity.
  • • The catabolic rate for HDL is decreased → HDL increases.
22
Q

Niacin Uses?

A
  • Niacin is the most effective drug for raising HDL.
  • Particularly useful in patients with combined hyperlipidemia and low HDL levels.
  • • Effective in combination with statins.
23
Q

What are the adverse effects of Niacin?

A
  • Intense cutaneous flush after each dose of niacin when the drug is started or the dose increased.
  • Administration of aspirin prior to niacin decreases the flush, which is prostaglandin- mediated.
  • Pruritus, rashes, dry skin.
  • Acanthosis nigricans.
  • Nausea and abdominal discomfort.

Most serious adverse effects: hepatotoxicityand hyperglycemia.

  • Niacin-induced insulin resistance can cause severe hyperglycemia.
  • Niacin elevates uric acid levels and may precipitate gout.
  • Rare adverse effects: • Atrial arrhythmias • Toxic amblyopia • Toxic maculopathy
24
Q

What are the fibrates and what is their function?

A

Gemfibrozil Fenofibrate

• Fibrates lower VLDL levels and increase HDL levels.

25
Q

What is the mechanism of action of fibrates?

A
  • Fibrates activate peroxisome proliferator- activated receptor-a (PPAR-a).
  • PPAR-a receptors are expressed primarily in liver and brown adipose tissue.
  • Activation of PPAR-α by fibrates leads to adecrease in plasma TG levels and increase in plasma HDL levels.
  • The decrease in plasma TG levels is caused byincreased expression of lipoprotein lipase, decreased hepatic expression of apoC-III, and increased hepatic oxidation of fatty acids.
  • Fibrates raise HDL.
  • Fibrates may increase LDL, particularly if the TG level is greater than 400 mg/dL.
26
Q

Mechanism of action of Fibrates map?

A
27
Q

What are the uses of fibrates?

A
  • DOC in severe hypertriglyceridemia
  • Reasonable consideration in moderate hypertriglyceridemia.
  • As monotherapy, fibrates offer the highest TG reduction, followed by niacin, -3-fatty acids, statins, and ezetimibe.
28
Q

What are the adverse effects of fibrates?

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.
29
Q

What are the drug interactions of fibrates?

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.
30
Q

What are the bile-acid binding resins?

A

Cholestyramine Colestipol Colesevelam

31
Q

What are the uses of BILE ACID-BINDING RESINS?

A
  • Useful only in hyperlipidemias involving isolated increases in LDL.
  • In patients who have hypertriglyceridemia as well as elevated LDL levels, VLDL levels may increase.
  • Insoluble in water.
  • Large molecular weights (> 106): neither absorbed nor metabolized.
  • Totally excreted in the feces.
  • • 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.
32
Q

BILE ACID-BINDING RESINS: 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 adecrease in plasma LDL levels.
  • This effect is partially offset by increased cholesterol synthesis due to upregulationof HMG-CoA reductase.
  • HDL rises modestly.
33
Q

BILE ACID-BINDING RESINS: ADVERSE EFFECTS?

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.
34
Q

BILE ACID-BINDING RESINS: DRUG INTERACTIONS?

A

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

35
Q

Ezetimibe common feature?

A

CHOLESTEROL ABSORPTION INHIBITORS

  • Inhibits intestinal absorption of cholesterol and phytosterols.
  • Its primary clinical effect is to lower LDL.
36
Q

EZETIMIBE: MECHANISM OF ACTION?

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%.
37
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.
38
Q

EZETIMIBE: ADVERSE EFFECTS?

A
  • Low incidence of reversible impaired hepatic function.
  • Small increase in incidence when ezetimibe is given with a statin.
  • Myositis has been reported rarely.
39
Q

EZETIMIBE: DRUG INTERACTIONS?

A
  • Bile-acid sequestrants inhibit absorption of ezetimibe.
  • The two agents should not be administered together.
40
Q

ω-3 FATTY ACIDS and their common feaature?

A
  • Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce TG synthesis and increase fatty acid oxidation in the liver.
  • HDL levels may modestly increase.
41
Q

What are the effects of Antihyperlipidemias summary table?

A
42
Q

SUGGESTED DRUG THERAPY FOR DYSLIPIDEMIAS table?

A
43
Q

ANTIHYPERLIPIDEMIC DRUGS IN PREGNANCY?

A
  • Statins: absolutely contraindicated in pregnancy. Category X.
  • Fibrates: Category C.
  • Niacin: Category C.
  • Ezetimibe: Category C.
  • Cholestyramine & colestipol: might interfere with absorption of nutrients. Category C.
  • Colesevelam: Category B. Should be used during pregnancy only if clearly needed.
44
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A

PCM Exam 2 Pharm (14 decks)

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