WEEK 5 - Antilipemic agents: Flashcards
Antilipemic drugs
are used to lower abnormally high blood levels of lipids, such as cholesterol, triglycerides, and phospholipids
Liver is where lipid metabolism takes place
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
Two primary forms of lipids in the blood—triglycerides & cholesterol
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
LIPOPROTEINS
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”
Coronary Heart Disease
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*******
Hyperlipidemia Risk Factors
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
Antilipemics—Drug Class
- *HMG-CoA reductase inhibitors (HMGs, or statins) CAN PUT PNTS INTO LIVER FAILURE
- Bile acid sequestrants
- Niacin (nicotinic acid) (vitamin B3)
- Fibric acid derivatives (Fibrates)
- New drug Zetia (Ezetimibe) is now available as a cholesterol absorption inhibitor
* HMG (hydroxymethylglutaryl enzyme)
HMG-CoA Reductase Inhibitors (HMGs, or statins)
Most potent LDL reducers
lovastatin (Mevacor) pravastatin (Pravachol) simvastatin (Zocor) atorvastatin (Lipitor) fluvastatin (Lescol)
HMG-CoA Reductase Inhibitors- Mechanism of action
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
HMG-CoA Reductase Inhibitors - Indications
First-line drug therapy for hypercholesterolemia
Lowers cholesterol levels
Increases HDL (good) Lowers LDL (bad) Common drug Atrovastatin (Lipitor)
HMG-CoA Reductase Inhibitors-Side effects
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
2. Bile Acid Sequestrants
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)
Bile Acid Sequestrants-MECH OF ACTION
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
Bile Acid Sequestrant- SIDE EFFECTS
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
3. Niacin (Nicotinic Acid)
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
Niacin (Nicotinic Acid)- Mechanism of action
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
NIACIN- Indications
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
NIACIN SIDE EFFECTS
Flushing (due to histamine release)
Pruritus
GI distress
ASA or NSAID should be taken 30mins before to decrease cutaneous flushing
4. Fibric Acid Derivatives
Clofibrate
Gemfibrozil (Lopid)
Fenofibrate (Tricor)
Fibric Acid Derivatives- MECH OF ACTION
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)
Fibric Acid Derivatives- INDICATIONS
Treatment of hyperlipemia
Decrease the triglyceride levels
Increase HDL by as much as 25%
Fibric Acid Derivatives-SIDE EFFECTS
Abdominal discomfort Diarrhea Nausea Increased risk of gallstones Prolonged prothrombin time (PT) Liver studies may show increased function
*Obtain baseline liver function studies
Very high incidence of elevated liver functions
Powder forms must be taken with a liquid, mixed thoroughly
but not stirred vigorously and NEVER taken dry (Cholestryamine)
Other medications should be taken 1 hour
before or 4 to 6 hours after meals to avoid interference with absorption
Clofibrate often causes constipation;
instruct patients to increase fiber and fluid intake to offset this effect
Decrease the triglyceride levels
Fibric Acid Derivatives
flushing is a very common side effect
NIACIN
Effective, inexpensive, often used in
combination with other lipid-lowering agents
Vitamin B3
cholesterol absorption inhibitor
. Zetia (Ezetimibe)
Potent LDL reducer
Simvastatin (Zocor)
Triglycerides
function as energy source and are stored in the adipose
