WEEK 5 - Antilipemic agents:

Question 1

Antilipemic drugs

Answer 1

are used to lower abnormally high blood levels of lipids, such as cholesterol, triglycerides, and phospholipids

Question 2

Liver is where lipid metabolism takes place

Answer 2

Liver produces VLDL (very low density lipoproteins) which are necessary to transfer endogenous lipids to peripheral cells

Circulating VLDL is broken down by lipoprotein lipase (enzyme) & transferred to IDL (intermediate density lipoprotein) which is quickly transferred to LDL (low density lipoprotein

This is known as the bad cholesterol because after this process cholesterol is all that is left
HDL (high density lipoprotein) is produced in the liver and intestine where it is broken down..good cholesterol

Question 3

Two primary forms of lipids in the blood—triglycerides & cholesterol

Answer 3

Triglycerides function as energy source and are stored in the adipose tissue (fat)

Cholesterol is used to make hormones, cell membranes and bile acids

Both are water soluble fats which need to be bound to lipid carrying proteins

Question 4

LIPOPROTEINS

Answer 4

Very-low-density lipoprotein (VLDL)
Produced by the liver
Transports endogenous lipids to the cells

Low-density lipoprotein (LDL)
Known as the “bad cholesterol”

High-density lipoprotein (HDL)
Responsible for “recycling” of cholesterol
Also known as “good cholesterol”

Question 5

Coronary Heart Disease

Answer 5

The risk of coronary heart disease (CHD) in patients with cholesterol levels of 5.2 mmol/L is three to four times greater than that in patients with levels less than **4.0mmmol/L*******

Question 6

Hyperlipidemia Risk Factors

Answer 6

Generally all non-pharmaceutical means of controlling cholesterol levels should be tried for at least 6 months and if failure then drug therapy should be considered

Cholesterol levels are lowered in 6-8 weeks after the start of therapy

Question 7

Antilipemics—Drug Class

Answer 7

1. *HMG-CoA reductase inhibitors (HMGs, or statins) CAN PUT PNTS INTO LIVER FAILURE
2. Bile acid sequestrants
3. Niacin (nicotinic acid) (vitamin B3)
4. Fibric acid derivatives (Fibrates)
5. New drug Zetia (Ezetimibe) is now available as a cholesterol absorption inhibitor
   * HMG (hydroxymethylglutaryl enzyme)

Question 8

HMG-CoA Reductase Inhibitors (HMGs, or statins)

Most potent LDL reducers

Answer 8

lovastatin (Mevacor)
pravastatin (Pravachol)
simvastatin (Zocor)
atorvastatin (Lipitor)
fluvastatin (Lescol)

Question 9

HMG-CoA Reductase Inhibitors- Mechanism of action

Answer 9

WATCH FOR EFFECTS ON THE LIVER
Inhibit HMG-CoA reductase, which is used by the liver to produce cholesterol (cholesterol synthesis)

Lower the rate of cholesterol production

‘Statins’ inhibit the enzyme which decreases cholesterol production

When less cholesterol is being produced the liver increases the number of LDL receptors, therefore increasing the recycling of LDL back into the liver where it is needed to synthesize steroids, bile acid and cell membranes

Question 10

HMG-CoA Reductase Inhibitors - Indications

Answer 10

First-line drug therapy for hypercholesterolemia
Lowers cholesterol levels

Increases HDL (good)
Lowers LDL (bad)
Common drug Atrovastatin (Lipitor)

Question 11

HMG-CoA Reductase Inhibitors-Side effects

Answer 11

Mild, transient GI disturbances
Rash
Headache
Myopathy (muscle pain leading to rhabdomyolysis which is breakdown of muscle protein which leads to myoglobin and renal failure)
**Elevations in liver enzymes or liver disease

Question 12

2. Bile Acid Sequestrants

Answer 12

Cholestyramine (Questran)

Colestipol hydrochloride (Colestid)

Also called bile acid–binding resins and ion-exchange resins

2nd line agents

FOR
Type II hyperlipoproteinemia

Relief of pruritus associated with partial biliary
obstruction (cholestyramine)

Question 13

Bile Acid Sequestrants-MECH OF ACTION

Answer 13

Prevent reabsorption of bile acids from small intestine

Bile acids are necessary for absorption of cholesterol

Increases removal of LDL from the blood stream

Enhances the receptors to remove LDL from plasma

Resulting in bile acid excretion in the feces

Question 14

Bile Acid Sequestrant- SIDE EFFECTS

Answer 14

Constipation
Heartburn, nausea, belching, bloating

These adverse effects tend to disappear over time
Decreases absorption of fat soluble vitamins A, D, E, K
All meds should be taken 1 hour before or 4-6 hours after the administration of bile sequestrants
Powder forms must be taken with a liquid, mixed thoroughly but not vigorously stirred, and NEVER taken dry (Cholestryamine)

Take with meals to reduce GI side effects

Question 15

3. Niacin (Nicotinic Acid)

Answer 15

Vitamin B3

Lipid-lowering properties require much higher doses than when used as a vitamin

Effective, inexpensive, often used in combination with other lipid-lowering agents
SIDE EFFECTS OF RASH AND VASODILATION

Question 16

Niacin (Nicotinic Acid)- Mechanism of action

Answer 16

Thought to increase activity of lipase (enzyme), which breaks down lipids

Reduces the metabolism or production of cholesterol and triglycerides in the liver

Decreases LDL levels “bad”
Increases HDL levels “good”

Large doses cause vasodilation and cutaneous flushing
Increases release of histamine

Question 17

NIACIN- Indications

Answer 17

Effective in lowering triglyceride, total serum cholesterol, and LDL levels

Increases HDL levels

Decreases lipid levels
Effects are seen within 1 to 4 days
Maximum effects after 3 to 5 weeks

Question 18

NIACIN SIDE EFFECTS

Answer 18

Flushing (due to histamine release)
Pruritus
GI distress
ASA or NSAID should be taken 30mins before to decrease cutaneous flushing

Question 19

4. Fibric Acid Derivatives

Answer 19

Clofibrate
Gemfibrozil (Lopid)
Fenofibrate (Tricor)

Question 20

Fibric Acid Derivatives- MECH OF ACTION

Answer 20

Work by activating lipase, which breaks down cholesterol
Suppresses the release of free fatty acid from the adipose tissue

Inhibits synthesis of triglycerides in the liver
Increases the secretion of cholesterol in the bile

Reduces triglyceride levels
Decreases platelet adhesiveness (thereby induces changes in blood coagulation)

Question 21

Fibric Acid Derivatives- INDICATIONS

Answer 21

Treatment of hyperlipemia
Decrease the triglyceride levels
Increase HDL by as much as 25%

Question 22

Fibric Acid Derivatives-SIDE EFFECTS

Answer 22

Abdominal discomfort
Diarrhea
Nausea
Increased risk of gallstones
Prolonged prothrombin time (PT)
Liver studies may show increased function

Question 23

*Obtain baseline liver function studies

Answer 23

Very high incidence of elevated liver functions

Question 24

Powder forms must be taken with a liquid, mixed thoroughly

Answer 24

but not stirred vigorously and NEVER taken dry (Cholestryamine)

Question 25

Other medications should be taken 1 hour

Answer 25

before or 4 to 6 hours after meals to avoid interference with absorption

Question 26

Clofibrate often causes constipation;

Answer 26

instruct patients to increase fiber and fluid intake to offset this effect

Question 27

Decrease the triglyceride levels

Answer 27

Fibric Acid Derivatives

Question 28

flushing is a very common side effect

Answer 28

NIACIN

Question 29

Effective, inexpensive, often used in

combination with other lipid-lowering agents

Answer 29

Vitamin B3

Question 30

cholesterol absorption inhibitor

Answer 30

. Zetia (Ezetimibe)

Question 31

Potent LDL reducer

Answer 31

Simvastatin (Zocor)

Question 32

Triglycerides

Answer 32

function as energy source and are stored in the adipose