Flashcards in Antihyperlipidemics Deck (46):
List of HMG-CoA reductase inhibitors
Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin.
What is niacin?
Nicotinic acid, VitaminB3
Fibric acid derivatives (Fibrates)
Fenofibrate (tricor), Gemfibrozil.
Bile acid sequestering drugs
Cholestyramine, colesevelam, colestipol
Cholesterol absorption inhibitors
Drugs to treat homozygous familiarl hypercholesterolemia
Lomitapide (juxtapid), mipomersen (kynamro), evolocumab (repatha).
Medications to treat heterozygous familial hypercholesterolemia.
Lipid-protein complex where lipids are transported in the blood.
Formed in intestine and found in chylomicrons and remnants.
Formed in liver, and found in VLDL, LDL, lipoprotein-a.
What are the major clinical consequences associated with dyslipidemia?
Describe characteristics of chylomicron.
1. Large, triglyceride rich. Often contain dietary fat from intestines.
2. Absent after 12-14 hours of fast.
3. Delivers dietary TG to skeletal muscle and adipose.
4. Require LPL to breakdown.
5. Remnants are taken into the liver.
Characteristics of VLDL
Lipoprotein regulated by diet, formed in liver and can be inhibited by chylomicron remnant uptake.
What is the function of VLDL
Carry TG from liver to peripheral tissue. Often hydrolyzed by LPL, to release FFA into the adipose tissue.
What is LDL
Major cholesterol transport lipoprotein. Carries cholesterol to extrahepatic tissues.
What is HDL
The good cholesterol as if carries cholesterol back to the liver. Formed from liver and gut.
What is the role of LPL?
Digest TG contained withing chylomicrons and VLDL to produce FFA and glycerol.
Where can LPL be found?
On the inner surface of the capillary endothelial cells of muscle and adipose tissue.
Types of primary hypertriglyceridemias.
1. Primary chylomicronemia.
2. Familial hypertriglyceridemia.
3. Familiar combined hyperlipoproteinemia.
4. Familial dysbetalipoproteinemia.
Types of primary hypercholesterolemias.
1. Familial hypercholesterolemia (FH).
2. Familial ligand-defective apolipoprotein B.
3. Familial combined hyperlipoproteinemia.
4. LP(a) hyperlipoproteinemia.
1. Hypertriglyceridemia (DM, alcholism, estrogens, hypopituitarism, acromegaly).
2. Hypercholesterolemia (hypothyroid, anorexia, nephrosis, pyopituitarism, corticosteroid excess).
What history is most at risk for atherosclerotic cardiovascular disease?
3. Coronary revascularization.
5. Peripheral vascular disease.
What groups commonly benefit from statin drug intervention?
1. Clinical atherosclerotic cardiovascular disease.
2. Primary elevation of LDL >190.
3. 40-75y/o with DM.
4. No ASCVD or DM in age of 40-75.
Is there a non-pharmacologic treatment for hyperlipidemia?
Lifestyle change. Reduce serum cholesterol, total fat, alcohol, and calories. Try for 3 months and then reevaluate the need for medications.
What is the most effective in lowering LDL levels?
HMG-CoA reductase inhibitors (statins)
What is the MOA of statins?
Structurally similar to HMG-CoA, therefore inhibits HMG-CoA reductase preventing cholesterol synthesis.
What is the overall effect of blocking de novo cholesterol synthesis?
1. Upregulation of LDL receptor on the cell; lowers circulating LDL conc.
2. Provide plaque stabilization, reduced platelet thrombus formation, and anti-inflammatory
What is the primary metabolite of lovastatin, simvastatin, atorvastatin?
CYP3A4 (grapefruit juice)
What is the primary metabolizer of fluvastatin?
What are the clinical uses of statins?
1. Lower plasma cholesterol in all hyperlipidemia.
2. Will not reduce ASCVD reductions.
3. Dosage given at evening is most effective as majority of cholesterol is formed at night.
What are the high intensity statins?
Contraindications of statins?
Pregnant women, lactating women, liver disease, skeletal muscle myopathy.
What drugs interactions should you be aware of with statins?
Statins and warfarin; statin will increase warfarin levels, leading to spontaneous hemorrhage.
Most effective to reduce HDL levels, has some effect on lowering LDL/VLDL.
What is the MOA of Niacin?
1. Blocks TG lipolysis in adipose tissue. Reducing FFA, plasma TG, cholesterol, fibrinogen.
2. Increase: tissue plasminogen activator.
Helps to reduce the risk of thrombosis
What is the therapeutic use of Niacin?
Used in combination with bile acid sequestrant in Tx of heterozygous familial hypercholesterolemia and nephrosis. Used in mixed lipidemia unresponsive to dietary changes.
What is the MOA of the fibric agents (gemfibrozil, fenofibrate)?
1. Agonist ligand for nuclear transcription factor receptor peroxisome proliferative-activated receptor alpha.
*increase levels of LPL, causing TG lipolysis and decrease TG concentration*
What is the common use for Fibrates?
Managing hypertriglyceridemia with VLDL predomination. (Gemfibrozil, fenofibrate)
What is the MOA of bile acid sequestrants?
Positively charged compounds bind negatively charge bile acids helping to increase the excretion.
Excreted bile acids assist conversion of cholesterol to bile acids in liver via hydroxylation. LDL clearance is increased via reduced hepatic cholesterol, via LDL receptor upregulation.
**cholestyramine, colestipol, colesevelam**
What are the clinical applications of bile acid sequestrants (cholestyramine, colestipol, colesevelam)?
1. Primary hypercholesterolemia.
2.Type IIa/IIb hyperlipidemia
3. Relieve pruritis from biliary obstruction.
4. Tx of digitalis toxicity.
What is the MOA of cholesterol absorption inhibitors (ezetimibe)?
Selective inhibition of intestinal absorption of cholesterol and phytosterols; thought to inhibit transport of NPC1L1.
How is ezetimibe effective in lower cholesterol?
The intestinal absorption of cholesterol is inhibited by reducing the incorporation of cholesterol into chylomicrons, reducing cholesterol delivery to the liver, which would increase LDL receptors and remove LDL from plasma.
Lomitapide is used for?
Homozygous familiar hypercholesterolemia.
- binds directly to microsomal triglyceride transfer protein located in the lumen of ER. Blocking the assembly of apo-B and reducing production of chylomicrons and VLDL.
-MOA: antisense oligonucleotide for mRNA of apoB-100 preventing LDL and LDL receptor binding. Inhibiting the transport and removal of atherogenic lipids from blood.
What factors are associated with increased risk of atherosclerosis and cardiovascular disease?
Elevated levels of: alpo-B, LDL-C, VLDL.