Lipid Lowering Drugs (Antilipemic drugs) - Ch. 53 Flashcards
What are the 2 primary forms of lipids in blood?
Tryglycerides (TGs)
Cholesterol
-Water-insoluble fats
-Must be packaged for transport in blood
What are Lipoproteins?
Combination of lipids with proteins
What are some examples of Lipoproteins?
Chylomicrons
Very-low density lipoprotein (VLDL)
Low-density lipoprotein (LDL)
High-density lipoprotein (HDL)
Where are chylomicrons produced?
GI tract
Where are Very-low density lipoprotein (VLDL) produced?
Liver
What do Very-low density lipoprotein (VLDL) do?
Transport triglycerides to cells
What is LDL?
“Less desired”, “bad cholesterol”
-Cholesterol rich
What is LDL used for?
-Binds to receptors on cell membranes
-Cholesterol source during production of steroid hormones
What is HDL?
“highly desired” “good cholesterol”
-prevents cholesterol from building up in vessels
What does HDL do?
Absorbs cholesterol and transports it to the liver where it is recycled
What are some non-modifiable factors leading to coronary artery disease?
Age
-Male 45 years or older
-Female 55 years or older, or postmenopausal
Family history
-strong history of premature Congenital heart disease
What are some modifiable factors leading to coronary artery disease?
Current cigarette smoker
Abdominal obesity
Hypertension (BP- 140/90 or higher, or on antihypertensive drugs)
Diabetes mellitus
LDL/HDL ration
What are the 4 groups of lipid lowering drugs?
- HMG-CoA reductase inhibitors (HMGs, or statins)
- Inhibitors of Cholesterol Absorption
- Niacin (nicotinic acid)
- Fibric acid derivatives
What is HMG-CoA?
3-Hydroxy-3-methylglutaryl coenzyme A
One of age metabolites in the cholesterol synthesis pathway
What is HMG-CoA reductase?
Critical enzyme for liver cholesterol production
What do HMG-CoA reductase inhibitors do?
Reduce plasma LDL levels
Examples of HMG-CoA reductase inhibitors?
Atorvastatin (lipitor)
Rosuvastatin (Crestor) -possibly less AE
Lovastatin (Mevacor)
Simvastatin (Zocor)
What is the mechanism of action of HMG-CoA reductase inhibitors?
Inhibit HMG-CoA reductase
Lower rate of cholesterol production
Because HMG-CoA reductase inhibitors lower the rate of cholesterol production what happens?
Increased liver LDL receptors which increases plasma clearance of LDL
What are the added benefits of Statins/HMG-CoA reductase inhibitors?
Decrease VLDL (major carriers of TGs)
Raise HDL
-improves LDL/HDL ratio
What are HMG-CoA reductase inhibitors used for?
First-line drug therapy for hypercholesterolemia
Treatment of types of II and IIb hyperlipidemias
-high LDL levels
What adverse effects are associated with HMG-CoA reductase inhibitors?
Mild, transient GI disturbances
headache
Muscle pain (myalgia)
Rhabdomyolysis (rarer)
Liver injury (increased liver enzymes)
When is HMG-CoA reductase inhibitors use contraindicated?
Preganancy
Use with caution with liver dysfunction patients e.g, viral hepatitis
What racial group should have a lower dose of rosuvastatin?
Asians
What can some HMG-CoA reductase inhibitors interact with that isn’t a drug?
Grapefruit juice
-Causes CYP3A4 inhibition
What HMG-CoA reductase inhibitors interact with grapefruit juice?
Lovastatin
simvastatin
atorvastatin
What drugs do HMG-CoA reductase inhibitors interact with?
Drug inhibitors of CYP3A4
-warfarin (oral anticoagulant)
-erythromycin (macrolide antibacterial)
-ritonavir (HIV protease inhibitor)
What are some drugs that inhibit cholesterol absorption/
Bile acid-binding resins
Ezetimibe
Examples of Bile acid-binding resins (bile acid sequestrants)?
Cholestyraminde
Colestipol
What is the mechanism of action of bile acid sequestrants?
Prevent reabsorption of bile acids from small intestine
-bile acids are synthesised from cholesterol in the liver
-liver stimulated to produce more bile acids
What are bile acid sequestrants used for?
Type II hyperlipoproteinemia
relief of Pruritus associated with partial biliary obstruction (cholestyramine)
What adverse effects are associated with bile acid sequestrants?
GI disturbances : constipation, heartburn, nausea, belching, bloating
(tend to disappear over time)
Decrease absorption of fat soluble vitamins A, D, E,K
What are fibric acid derivatives (fibrates) mechanism of action?
complex
-Believed to work by activating lipoprotein lipase (which breaks down TGs in lipoproteins)
-Reduces plasma TGs
-Increase fatty acid use in tissues
What do fibric acid derivatives (fibrates) do?
Decrease plasma triglyceride levels
Increase HDL bias much as 10-25%
Examples of fibric acid derivatives (fibrates)?
gemfibrozil
bezafibrate (Bezalip)
fenofibrate (Lipidil)
What adverse effects are associated with fibric acid derivatives (fibrates)?
GI disturbances : abdominal discomfort, diarrhoea, nausea
Blurred vision
Increased risk of gallstones
Prolonged prothrombin time (fibrinogen production reduces, displacement of anticoagulants from albumin)
What is Nicotinic Acid (Niacin)?
Vitamin B3
What does Nicotinic acid (Niacin) do?
Reduce plasma TGs
What is required dosing wise when Niacin is given for its lipid lowering properties rather than just as a vitamin?
Needs a much higher dose (grams)
Why is Niacin used?
Effective and inexpensive
-often in combination with the lipid-lowering agents e.g, statins
What is the mechanisms of action of niacin?
Reduces VLDL (TGs carrier) from liver
-Inhibits lipase in adipose tissue (breaks down lipids)
-less fatty acids for TG production in liver
What adverse effects are associated with Niacin/ Nicotinic acid?
Flushing (PG release)
Pruritis (anal itchiness)
GI distress
How is flushing caused by nicotinicn acid (niacin) prevented?
take Aspirin 30 minutes before
