Term 1 Pharm - Lipid Drugs

Question 1

Ultimate end goal of lipid lowering drugs

Answer 1

long term survival and lessen worse cardiovascular end outcomes, NOT necessarily to lower lipid levels

Question 2

mechanisms of action lipid drugs:

Answer 2

1) Bile acid sequestrants
2) Nicotinic acid
3) Fibric acid derivatives
4) Statins
5) Inhibitors of GI absorption of cholesterol
6) New class PCSK9 inhibitors

Question 3

Lipid-containing articles in blood

Answer 3

chylomicrons, VLDL, LDL, HDL, a

Question 4

Cholesterol circulates in blood bound (mostly) to:

Answer 4

HDL, LDL, and TG particles

So to alter cholesterol in blood, we need to “go after” these particles

Question 5

What type of cholesterol should be measured?

Answer 5

We used to follow total cholesterol, but now we are much more particular to measure FASTING“bad” cholesterol (LDL-chol) and “good” cholesterol (HDL-cholesterol), since they both have important clinical implications

Question 6

List levels of Total cholesterol

Answer 6

Great: _____
Desirable: 240

Question 7

List Levels of LDL

Answer 7

Great: 160

Question 8

List Levels of HDL

Answer 8

Great: > 60
Desirable: > 50
Borderline: 40-50
Bad:

Question 9

What type of lipid drugs alter LDL receptors?

Answer 9

ALL drugs (via different pathways) UPREGULATE LDL receptors

Question 10

Old School Drugs:

Answer 10

• Cholestyramine (bile acid sequestrant)
• Nicotinic acid (vitamin)
• Gemfibrozil (fibrate)
• Ezetimibe (cholesterol absorption inhibitor)

Question 11

Newer/Better drugs

Answer 11

Statins (HMG-CoA reductase inhibitors)

• Lovastatin (Mevacor™)
• Atorvastatin (Lipitor™)
• Rosuvastatin (Crestor™)

New class, PCSK9 inhibitors (Alirocumab, Praluent™)

Question 12

Cholesterol lowering agent
Bile acid sequestrant
prevents absorption of bile salts in small bowel (gut) increasing their excretion & causing increase in bile synthesis –> increase of cholesterol synthesis –> increase of LDL receptors on surface of hepatocytes
MANY GI problems (not used often) - gas, bloating, constipation, probs with fat soluble vitamins
Lowers LDL 10-20%

Answer 12

Cholestyramine (Questran, colestipol)

Question 13

Cholesterol lowering agent
Vitamin that is also a therapeutic agent that lowers cholesterol
Lowers BOTH TG and LDL –> causes increase of LDL receptor in liver
Absorption decreased by cholestyramine

Answer 13

Nicotinic Acid = Niacin Vitamin

Niacor, etc.

Question 14

What is the effect of Statin + Niacin?

Answer 14

They do lower TG & LDL levels and increase HDL levels but they do NOT cause better clinical outcomes

But Niacin may be used in statin intolerant pts

Question 15

Lipid lowering agent
Fabric acid derivative
inhibits hepatic secretion of VLDL –> lowering LDL
But MOST useful in treating hypertriglyceridemia in types IV and V hyperlipidemia (can decrease levels by 30%) an may increase HDL a little

Answer 15

Gemfibrozil (Lopid, fenofibrate)

Question 16

Cholesterol lowering drug
primary & secondary prevention of CAD
HMG-CoA reductase inhibitor
parent drug = Lactone
causes up regulation of LDL receptors on hepatocytes causing liver to take in more cholesterol (reducing blood LDL up to 65% and increasing HDL somewhat)
Metabolized by CPT 3A4
gets transformed to an active metabolite (half life of 20-30hrs)
BE CAREFUL, watch LTFs (liver enzymes) and CPK (creatine) during first year of use –> risk of hepatitis, myopathy, etc.
Has additive effects with other lipid lowering drugs (increasing risk)
Erythromycin, cyclosporin, fluconazole, etc may inhibit CYP 3A4 metabolism causing accumulation and toxicity
AVOID in ptas with hepatitis, muscle disease and pregnant

Answer 16

Atorvastatin - Generic ($4)

Lipitor - Brand ($191)

Question 17

Most effective/powerful 2 lipid lowering drugs

Answer 17

Atorvastatin($10) (brand - Lipitor)
(80mg) - 50 to 60% reduction

Rosuvastatin = Crestor (no generic yet)
(40mg) - 50 to 60% reduction

Question 18

Cholesterol absorption inhibitor
Blocks intestinal absorption of cholesterol at bowel brush border & increases blood clearance of cholesterol
Usually combined with another drug/statin

Answer 18

Ezetimibe (Zetia)

Brand name only available $237/mo

Question 19

What advantage does Rosuvastatin have over Lipitor?

Answer 19

It lowers CRP levels BUT overall effect of decreasing total risk is NOT proven to be greater than Lipitor

Question 20

PCSK9 inhibitor
(this inhibitor usually binds to LDL receptors on hepatocytes and promotes their degradation)
This drug is a human monoclonal antibody that targets PCSK9 and increases LDL receptors in hepatocytes
Given as a SC injection every 2 weeks (half life of 12 days), cleared by proteolysis
CAN cause hypersensitivity reaction (or reaction at injection site)
Little data on long term efficacy & safety
Given to patients who don’t respond to statins

Answer 20

Praluent = Aliroc’umab

$1,120/mo!!