Lipid lowering agents

Question 1

Name this drug:
Reduction of liver triglyceride synthesis, leading to less hepatic VLDL (thus, LDL) production; decreases lipolysis in adipose tissue, leading to lowered FFA transport to liver (thus, less triglycerides); reduced hepatic clearance of ApoAI (raising HDL)

Answer 1

Niacin (Nicotinic Acid)

Question 2

What hypolipidemic is the best agent to increase HDL?

Answer 2

Niacin (Nicotinic Acid)

Question 3

The following are side effects of which drug?

Flushing, pruritis of face and upper trunk, rashes, acanthosis nigricans (hyperpigmentation)

Answer 3

Niacin (Nicotinic Acid)

Mediated by prostaglandins…meidator of vasodilation and inflammtion…which can be reduced by NSAIDs

Question 4

Name this class of drug:
Interacts w/peroxisome proliferator-activated receptor (esp. PPARα) to stimulate LPL synthesis (enhance TG-rich lipoprotein clearance); inhibit apoC III expression (enhance VLDL clearance); stimulation of apoAI and apoAII (increase HDL)

Answer 4

Fibric Acid Derivatives (fibrates)
Clofibrate
Gemfibrozil
Fenofibrate

Question 5

Name this class of drug:
Very positively charged resins binds negative charged bile acids, inhibiting reabsorption and increasing cholesterol loss; leads to increase in LDL receptors in liver (to make more cholesterol), decreasing LDL in blood

Answer 5

Bile acid sequestrants (resins)
Cholestyramine
Colestipol
Colesevelam

Question 6

Name this class of drug:
Inhibits HMG-CoA reductase formation of mevalonate; leads to activation of SREBP, a membrane-bound transcription factor that increases LDL-R synthesis and lessens degradation; reduction in cholesterol decreases VLDL synthesis, lowering TG

Answer 6

HMG-CoA Reductase Inhibitors (Statins)

HMG-CaA Reductase fcns to synthesize cholesterol in the liver…these drugs prohibit this

Question 7

Which drugs are the most effective drugs for lowering LDLs and minimizing cardiovascular events?

Answer 7

Statins

Question 8

Which drugs are the ONLY lipid lowering drugs proven to decrease the risk of atherosclerotic heart disease?

Answer 8

statins

Question 9

T/F: Bile acid sequestrants (resins) have many side effects and are therefore not used much.

Answer 9

False
Very safe (only hypolipidemic indicated for children) because not systematically absorbed; impairs fat soluble vitamin absorption, binds other drugs (e.g., cardiac glycosides, coumarins)

Question 10

Which drug increases the LDL receptor synthesis and decreases the LDL receptor degradation as their mode of action for lowering LDLs?

Answer 10

Statins

Question 11

Name this drug:

Inhibits enterocyte absorption of cholesterol in intestine

Answer 11

Ezetimbe

Question 12

Which drug inhibits cholesterol absorption by enterocytes in jejunum, leading to less cholesterol in chylomicrons?

Answer 12

Ezetimbe

Question 13

Name this class of drug:
Inhibits an endopeptidase responsible for LDL-R degradation, resulting in higher numbers of LDL-Rs on hepatocytes

Answer 13

PCSK9 Inhibitors
Alirocumab
Evolucumab
2nd line therapy for hyper-cholesterolemia that is NOT controlled by diet and statins

Question 14

An asymptomatic 8-year-old boy is found to have an LDL-cholesterol level 25% above normal.  His HDL-cholesterol and VLDL-cholesterol levels are normal, and he has no other medical condition.  Which one of the following drugs would be prescribed to lower his LDL-cholesterol to normal levels?
	(A)	Niacin.
	(B)	Bezafibrate.
	(C)	Fluvastatin.
	(D)	Ezetimibe.
	(E)	Colestipol

Answer 14

Answer: E. Colestipol

Discussion: A bile acid sequestrant, taken as monotherapy, would be expected to lower LDL levels from 20% to 35%. This class of hypolipidemic drug is fairly safe and the only one normally prescribed for children. Colestipol is the only bile acid sequestrant among the choices.

Question 15

Which one of the following drugs lowers serum cholesterol by inhibiting a sterol transporter in
endothelial cells of the small intestine?

(A)	Bezafibrate.
(B)	Ezetimibe
(C)	Colestipol.
(D)	Colesevelam.
(E)	Atorvastatin.

Answer 15

Answer: B. Ezetimibe
Discussion: Ezetimibe is a new lipid-lowering drug that inhibits a sterol transporter that moves cholesterol into the wall of the small intestine. Colestipol and colesevelam are bile acid sequestrants that bind to cholesterol and cause its fecal excretion. Bezafibrate stimulates fatty acid oxidation and
LPL synthesis, and atorvastatin inhibits HMG CoA reductase.

Question 16

All of the following contribute to the antiatherogenicity of the high-density lipoprotein (HDL) particle except which one?
(A) HDL inhibits LDL oxidation in arteries.
(B) HDL deposits cholesterol in atheromas and xanthomas.
(C) HDL absorbs cholesterol from cell membrane turnover.
(D) HDL delivers cholesterol from peripheral tissues to the liver.
(E) Increased HDL-cholesterol levels decrease risk of coronary artery disease.

Answer 16

Answer: B. HDL deposits cholesterol in atheromas and xanthomas

Discussion: HDL particles have nothing to do with the formation of atheromas or xanthomas. All of the other statements are plausible explanations for why HDL particles are anti-atherogenic.

Question 17

Which one of the following is not a regulatory effect of cholesterol on the cell?
(A) Decreased activity of HMG CoA reductase.
(B) Activation of acetyl CoA:cholesterol acyltransferase (ACAT).
(C) Activation of plasma lecithin:cholesterol acyl transferase (LCAT).
(D) Inhibition of transcription of the LDL receptor gene.

Answer 17

Answer: (C) Activation of plasma lecithin:cholesterol acyl transferase (LCAT).

Discussion: Plasma LCAT esterifies free cholesterol into cholesterol esters in the HDL particle, using apoA1 as a cofactor. It is not activated by cholesterol. The other three are normal intracellular regulatory effects of free cholesterol

Question 18

Which one of the following hypolipidemic drugs produces its effect by binding to and activating the peroxisome proliferator-activated receptor α (PPARα)? 
	(A)	Niacin.
	(B)	Fenofibrate.
	(C)	Colesevelam.
	(D)	Fluvastatin.
	(E)	Ezetimibe.

Answer 18

Answer: (B) Fenofibrate.

Discussion: The fibrates are a class of hypolipidemic drugs that have several effects on lipid metabolism, all of which are initiated by the activation of PPARα, a nuclear receptor expressed in skeletal muscle, cardiac muscle, hepatocytes, and macrophages. The only fibrate in the list is fenofibrate

Question 19

Which one of the following drug combinations is rarely prescribed due to an increased risk of myositis?

	(A)	Statin + Niacin.
	(B)	Statin + fibrate.
	(C)	Statin + resin.
	(D)	Statin + ezetimibe.
	(E)	Resin + ezetimibe.

Answer 19

Answer: (B) Statin + fibrate.

Discussion: The resins are relatively free of adverse side effects, and are safely prescribed in combination with a statin or ezetimibe. The combination of a statin with a resin, ezetimibe, or niacin is safe and effective (and the first two are frequently prescribed). It is only the combination of a fibrate with a statin that is inadvisable due to a significantly increased risk of myositis.

Question 20

Which one of the following drugs produces both a significant decrease in serum LDL-cholesterol and triglyceride levels, and a pronounced increase in HDL-cholesterol levels?

(A)	Nicotinic acid
(B)	Bezafibrate
(C)	Cholestyramine
(D)	Ezetimibe
(E)	Colesevelam

Answer 20

Answer: (A) Nicotinic acid
Discussion: Nicotinic acid is the best agent available for increasing HDL-C (30 – 40%), it lowers triglycerides as effectively as statins and fibrates, and it reduces LDL-C levels by 25%. Bezafibrate produces variable effects on LDL-C and only modest increases in HDL-C. Ezetimibe has insignificant effects on triglyceride and HDL-C levels. The resins (cholestyramine and colesevelam) have no effect on HDL-C levels and can actually increase serum triglycerides.

Question 21

A combination tablet containing ezetimibe and which one of the following drugs is marketed because of their complementary mechanistic effects on the (lowering of) LDL-C levels? 
(A)	Cholestyramine
(B)	Colestipol
(C)	Colesevelam
(D)	Mevastatin
(E)	Simvastatin

Answer 21

Answer: (E) Simvastatin
Discussion: Answer: Simvastatin. A combination tablet containing 10 mg ezetimibe and various doses of simvastatin has recently been approved as Vytorin. Mevastatin was the first statin studied in
human beings, but never marketed as a drug. The first three drugs are all bile acid sequestrants (resins).

Question 22

What is the most effective lipid lowering agent for preventing future cardiovascular events?

Answer 22

Statins
It has become standard practice to initiate statins following MI or other actue coronary syndrome diseases regardless of lipid levels

Question 23

T/F: statins are safe to use in pregnancy or breastfeeding women?

Answer 23

Fase…they may be teratogenic

Question 24

What is the most important side effect for statins?

Answer 24

myopathy/rhabdomyolysis …which may show up as elevated CK levels (elevated after muscle/heart cell injury)

Question 25

Which of the lipid lowering agenst (classes) is contraindicated in hypertriglyceridemia?

Answer 25

Bile acid derivatives (resins)
Cholestyramine
Colestipol
Colesevelam

Instead use Fibrates or niacin (or statins sometimes)

Question 26

What class of lipid lowering agent is used to treat severe hypertriglyceridemia and works by causing a marked reduction in VLDL (thus, triglycerides); has only a variable and small effect on LDL; small increase in HDL (10%)

Answer 26

Fibrates
Clofibrate
Gemfibrozil
Fenofibrate

Question 27

Fibrates combined with statin therapy increases what side effect?

Answer 27

increases risk of myopathy

Question 28

Aside from flushing, what other side effects can occur with Niacin?

Answer 28

Hyperglycemia, hyperurecimia (may precipitate gout), can cause elevated Liver function tests (hepatotoxicity)