Lipid Lowering Agents

Question 1

What is “bad chlosterol” and why ?

Answer 1

LDL-C, low density lipoprotein - cholesterol
When LDL-C presents in excessive number, LDLs deposite cholesterol in and around smooth muscle fibre in arteries, forming fatty plaques and increasing the risk of coronary artery disease

Question 2

Examples of HMG-CoA reductase inhibitor?

Answer 2

Atorvastatin
Pravastatin
Simvastatin

Question 3

The rate limiting enzyme for cholesterol synthesis?

Answer 3

HMG-CoA Reductase

Question 4

MOA of statins:

Answer 4

1. Inhibit the HMG-CoA reductase

2. Upregulate LDL receptor on cell surfface

Question 5

When pt taking atorvstatin 40mg, c/o muscle aching and dark tea color urine , what happen, what shoul u advice the pt to do ?

Answer 5

1. Myopathy and rhabdomyolysis due to ADR from atorvastatin
2. Ask the pt to stop taking atorvstatin, adequate, plenty of hydration, and check CK, and monitor for urine output and color

Question 6

Pt with severe hypercholesterolaemia, tried all kinds of oral lipid lowering agent, the cholecterol level, still suboptional, what shoud u consider to prescribe ?

Answer 6

PCSK9 inhibitor

Such as evolocumab alirocumab

Question 7

Pt fasting blood, show TG 5.6. What should u prescibe ?

Will it lower LDL -c?

Answer 7

Fibrates ( fibric acid derivatives).
E.g. fenofibrates,
Gemfibrozil
Clofibrate

Fibrates increase activity of lipoprotein lipase, which break the TG, decreasing TG in plasma. It lower TG level, does not lower LDL-C

Question 8

The lipid lowering agent inhibits the TG synthesis

Answer 8

Omega-3-acid ethyl esters , inhibit the diglyceride
Acyltransferase, which is responsible for TG biosenthesis.
Such as Omacor (EPA & DHA ethyl esters)

Question 9

MOA of Niacin

Answer 9

1. Niacin strongly inhibits lipolysis in adipose tissue , thus both TG and cholesterol are lowered
2. It increases HDL -C (unsure mechanism)
3. Decreasing fibronogen and increase plasminogen activator, can help to reverse the thrombosis a/w hypercholesterolemia and atherosclerosis

Question 10

What are the lipid lowering agents work on the exogenous pathway?

Answer 10

1. Bile acid binding resins ( e.g. cholestyramine)
2. Inhibitors of intestinal sterol absorption
   E.g. ezetimide

Question 11

The lipid lower agents may leads to diarrhoea, nausea, flarulence?

Answer 11

1. Bile salt binding resins

2. Omega 3 acid ethyl esters

Question 12

The lipid lowering agents might cause impaired hepatic function?

Answer 12

1. Statins
2. Ezetimide
3. Fibrates

Question 13

Impaired absorption of lipid soluable vitamins (A,,D, E and K)?

Answer 13

Cholestyramine

Bile salt binding resins

Question 14

Ezetimibe

Answer 14

Is an inhibitor of intertinal sterol absorption by selectively inhibiting the cholesterol transporter protein NPC1L1. NPC1L1 expressed on both instestine and liver. Thus ezetimibe inhibit the reabsorption of both endogenious (billiary) and exogeneous cholesterol.

Leadint to reduction of LDL, monotherapy, would decrease 18% in LDL

It readily absorbed, and conjugated in the instestinal wall to an active glucoromide
May cause side effect of impaired liver function amd diarrrhoea.

Question 15

Vytorin

Answer 15

Combination of ezetimibe and simvastatin.

Question 16

Lipid lower agents for type IIa familial hypercholesterolemia, due to decrease in LDL receptor=>high LDL?

Answer 16

1. Statins
2. PCSK9 inhibitors( evolocumab, alirocumab)
3. bile acid binding resins(cholestyramine)
4. Intertinal sterol absorption inhibitor ( ezetimibe)

Question 17

Lipid lowering agents for type III: familial dysbetapoproteinemia, due to over production or underutilization of IDL , leading to elevation on beta VLVL?

Answer 17

1. Fibrates (e.g. gemfibrozil, fenofibrates, clofibrates)

2. Statins

Question 18

Lipid lowering agents for type IIb: mixed hyperlupidemia, due to over production of VLDL by liver, leading to high LDL and VLDL?

Answer 18

1. Statins
2. Omega 3 acid ethyle esters (in combination with statins)
3. Niacin (nicotinic acid, vit B3) (widely used.)
4. Bile acid binding resins ( cholestyramine) (in combination with niacin)
5. Ezetimide

Question 19

Lipid lowering agents used for type IV: familial hypertriglyceridemia, caused by overproduction +/- decreasing in removal of VLDL TG , leading to increased VLDL?

Answer 19

1. fibrates (gemfibrozil, fenofibrate, clofibrate)
2. Niacin ( nitotinic acid, Vit B3)
3. Omega 3 acid ethyl ester ( with diet measures)

Question 20

Eztimide is a prodrug for

Answer 20

Need to be conjugated in the intestine or liver to an active glucuronide

Question 20

Eztimide is a prodrug for

Answer 20

Need to be conjugated in the intestine or liver to an active glucuronide