Drugs Used In Hyperlipidemia Flashcards
The longer and lower the reduction in circulating LDL-C, the lower the incidence of
CHD
Cholesterol esters and triglycerides are insoluble in water and circulate in blood as
Lipoprotein particles
Low density lipoprotein ApoB is recognized by the
LDL receptor
The LDL receptor internalizes circulating
LDL
A transcription factor that serves as the master regulator of cholesterol levels in the cell
SREBP (Sterol Regulatory Element Binding Protein)
In a low cholesterol diet, SREBP is
Activated
Results in increase in cholesterol biosynthesis and increase in receptor-mediated LDL endocytosis from the plasma
SREBP activation
In a high-cholesterol diet, SREBP is not activated and thus we see a decrease in
Cholesterol biosynthesis and LDL receptors
The most effective and best tolerated agents for treating dyslipidemia
Statins
Statins function as
HMG-CoA reductase inhibitors
Competitive inhibitors of HMG-CoA reductase
- Inhibits cholesterolgenesis
- Increase expression of LDL receptor
Statins
Inactive lactose pro drugs hydrolysis to active drugs
Statins
Statin absorption varies from 40% to 75% except for
Fluvastatin (almost completely absorbed)
Statins have half-lives of 1-3 hours except for
- ) Atorvastatin?
- ) Rosuvastatin?
- ) 14 hours
2. ) 19 hours
Hepatic cholesterol biosynthesis is maximal from midnight-2 AM, so we want to take them in the
Evening (except for the ones w/ the long half-lives)
Contraindicated in women who are pregnant, lactating, or likely to become pregnant
Statins
Most efficacious agents for severe hypercholesterolemia
-More TG lowering activity compared to other statins
Atorvastatin and Rosuvastatin
Two toxic/adverse effects of Statins are
- ) Hepatotoxicity
2. ) Diabetes Mellitus
While statin therapy can reduce occlusive vascular events by 40-50%, many patients discontinue statins due to
Myopathies
Monoclonal antibodies (mAbs) against PCSK9 protein
PCSK9 inhibitors
Diverts LDLR from recycling pathway towards lysosome for degradation
PCSK9
A cholesterol absorption inhibitor
Ezetimibe
Ezetimibe’s site of action is at the
NPC1L1 cholesterol transporter
Selectively inhibits intestinal cholesterol absorption and also plant sterols
Ezetimibe
Increases expression of hepatic LDL receptors, decreases intestinal delivery of cholesterol to the liver, and decreases cholesterol content of atherogenic particles
Ezetimibe
The average reduction in LDL-C with drug alone is
18%
Ezetimibe is synergistic with
-Additional 25% decrease compared to statin alone
Statins
Highly positively charged and bind negatively charged bile acids
-The bound bile acids are then excreted in stool
Bile acid sequestrants
Decline hepatic cholesterol content, increase LDL receptors, increase clearance of LDL from plasma, and lower LDL-C
Bile acid sequestrants
However, bile acid sequestrants do upregulate
HMG-CoA reductase
Use with extreme caution or avoid completely in patients with severe hypertriglyceridemia
Bile Acid Sequestrants
You must take with meals or there is no effect
Bile acid sequestrants
Used to treat heterozygous FH
Bile acid sequestrants
Can cause constipation, bloating, heart burn, and diarrhea
Bile acid sequestrants
These side effects can be relieved by increasing fiber or by mixing bile acid sequestrant with
Psyllium Seed
Can interfere with the absorption of many other drugs
-Should wait 3-4 hours after taking to take another drug
Bile acid sequestrants
What’re soluble vitamin B3
Niacin (nicotinic acid)
Has favorable effects on all lipid profiles, but there are a lot of adverse effects
Niacin
Has the primary effect of inhibiting VLDL secretion, thereby decreasing production of LDL
Niacin
Inhibits lipolysis of TG by hormone-sensitive lipase
Niacin
Increased CHD risk associated with TG levels greater than 150 mg/dL
Hypertriglyceridemia
Elevated triglycerides (greater than 500 mg/dL) can lead to
Pancreatitis
Activated the peroxisome proliferator-activated receptor-alpha
Vibrates
A transcription factor regulating genes that control lipid metabolism
Vibrates
Primary effect is to reduce plasma TG
-Only a modest decrease in LDL
Fibrates
