Drugs for Lipid Disorders Flashcards
Lovastatin, atorvastatin, fluvastatin, pitavastatin, pravastin, siimvastatin and rosuvastatin are all inhibitors of _
HMG-CoA
Fenofibrate and gemfibrozil are _
Fibric acid derivatives (fibrates)
Cholestyramine, colesevelam and colestipol are _
Bile acid sequestrants (resins)
name a cholesterol absorption inhibitor
Ezetimibe (Zetia)
What are three drug combination to treat hyperlipidemia?
- Ezetimibe and Simbastain
- Niacin and lovastatin
- Niacin and simvatatin
New treatment for homozygous familial hypercholesterolemia include
Lomitpide and mipomersen
Cholesterol and saturated and transfat are the main factors that increase serum _
LDL
Total fat, alcohol, and exess calories increase serum _
triglycerides
Dietary management of hyperlipoproteinemia is always the first option unless a patient has _ in which case drug therapy is the first option.
Familial hypercholesterolemia
What class of lipid lower drugs are the most effective in reducing LDL levels and best tolerated class of lipid lowering agents.
HMG-CoA reductase inhibitors (Statins)
Statin drugs are analogs of _
HMG-CoA which is an initial precursor of cholesterol.
Which statins are prodrugs and thus must be hydrolyzed in the GI to active compounds?
Lovastatin and simvastatin
Which statins have the longest half life?
atorvastatin (14hrs) and rosuvastatin (19hrs)
Which statin is almost completely absorbed when given orally, while most others varies 40-75%
Fluvastatin
Which statins are metabolized by
A. CYP3A4
B. CYP2C9
A. Lova, simva, and atorvastatin
B. Fluva, rosuvastatin
Explain the MOA for statins
Inhibits HMG-CoA and thus inhibits de novo synthesis of cholesterol. this in turn causes cell to increase cell surface LDL receptors and internalize LDL and thus reduce circulating LDL’s
Which statin has the highest potency?
Atorvastain and rosuvastain
What therapeutic benefits does statins have beside lowering LDL
stabilize plaques, improve coronary endothelial function, inhibition of platelet thrombus formation, and anti-inflammatory effects.
Why should statins be taken in the evening/night?
Cholesterol synthesis occurs primarily at night
What are some contraindications for statins?
- pregnancy/lactating
- liver disease/skeletal muscle myopathy
- avoid use with other agents that inhibit or compete CYP450 enzyme except pravastatin and pitavastatin) such as phenytoin, griseofulvin
what are some adverse effects of statins?
Liver: elevates aminotransferase activity
Muscle: elevates creatinine kinase activity; rhabdomyolysis –> renal injury; myopathy esp in combo with cyclosporine, intraconzaole, erythromycin, gemfibrozoil or nicin
- Increases warfarin levels
WHat drug class is know to be most effective in increasing HDL levels while lower LDL and VLDL and triglyerides?
Niacin (nicotinic acid, vit B3)
What lipid-lowering agent is best known to reduce lipoprotein levels significnatly (up to 40%)
Niacin
What is the MOA of niacin drugs?
inhibits lipolysis of triglycerides in adipose tissue and thus reduce circulating free fatty acids, and thus liver produces less VLDL and thus decreases LDL
2. Fibrinogen levels are also reduced and tPA levels are increased which can reverse endothelial dysfunction
Niacin is often used in combo with 1 and is utilized in the treatment of mixed lipemia that is incompletely response to diet
bile acid sequestrant (resin)
What adverse effects are associated with Niacin?
Intense cutaneous flush (uncomfortable feeling of warmth - can be helped if aspirin or ibuprofen before niacin dose)
- pruritis, rashes, dry skin/mucous membranes, acnthosis nigricans
What are some contraindications for niacin?
- liver disease –> hepatoxicity
- peptic ulcer
- caution in pts with DM (niacin-induced insulin resistance –> hyperglycemia)
What is the MOA for gemfibrozil and fenofibrate?
(these are fibric acid derivatives)
- Agonists for PPAR-alpha which binds to preroxisome proliferator-response elements (encodes lipoprotein structure and function–>incrase lipoprotein lipase) –> induce lipolysis of triglycerides and ultimately decrease plasma concentration of triglycerides
what is the indication for gemfibrozil and fenofibrate?
- management of hypertriglyceridemias where VLDL predominates
- dysbetalipoproteinemia
- adjunct to HIV therapy
what adverse effects are associated with gemfibrozil and fenofibrate?
- GI disturbances (most common)
- llithiasis (cuz of increased biliary cholesterol excretion) –> gall stones
- myositis (muscle weakness); myopathy
fibrates are known to potentiate the actions of _
coumarin and indanedione anticoagulents
Fibrates are contraindicated in pts with _
- hepatic or renal dysfunction
- pts with increased risk of gallstones
Colestipol, choestryamine and colesevelam are all 1 which binds to 2 and increase their excretion, and thus enhances the conversion of cholesterol to bile acids in the liver via 3 which is normally controlled by negative feedback by bile acids. The decline in hepatic cholesterol stimulates an increase in 4 receptors which enhances 5 clearance. But becuase this enhances cholesterol synthesis, these drugs are usually used in combo with 6
- bile acid sequestrants (resins)
- bile acids
- 7a-hyroxylatation
- LDL
- LDL
- HMG-CoA inhibitors (statins)
What are the therapeutic uses of bile acid sequestrants?
- primary hypercholesterolemia
- in combo with niacin for tx of Type IIa and Type IIb hyperlipidemias
- pruritis
- digitalis toxicity
What adverse effects are associated with bile acid sequestrant?
- GI issues most common
- at high dose impairs (ADEK vitamins absorption)
- Cholestryramien andcolestipol impairs absorption of drugs such tetracycline, phenobarbital, digoxin, warfarin, pravastain, fluvastatin, aspirin, thiazide diuretics (
Ezetimibe is a _ 1_ that which enters enterohepatic circulation as an active compound and inhibits intestinal absorption of cholesterol and phytosterols and inhibits transport protein NPC1L1
cholesterol absorption inhibitor
What is ezetimibe used for?
- various forms of elevated cholesterol diseases such as primary hypercholesterolemia (w/wo statins), homozygous familial hypercholesterolemia (in combi with ator or simvastain), mixed hyperlipidemia (in combo with fenofibrate)
what adverse effects/contraindications are associated with ezetimibe?
no significant drug interaction but should be avoid with bile acid sequestrant cuz it inhibits ezetimibe absorption
what combination of drugs would have the greatest effect in lowering LDL and TG’s?
Statins and Fibrates
What combination of drugs would have the greatest effect in lowering LDL and increasing HDL?
Statins and Niacin
What combination of drugs would have the greatest effect in lower TG’s and increasing HDL?
Nacian and Fibrates
What is the MOA for lomitapride?
directly binds to and inhibits microsomal triglyceride transfer protien which is located in the lumen of the ER. MTP inhibition prevenst the assembly of apo-B lipoproteins in enterocytes and hepatocytes –> reduced production of chylomicrons and VLDL and –> reduce LDL-C concentration
What is lomitapride FDA approved for?
homozygous familial hypercholesterolemia
what is the common adverse effect of lomitap? ride
GI symptoms, increased liver aminotransferase levels, and hepatic fat accumulation
What is mipomersen approved for?
homozygous familial hypercholesterolemia
what is the MOA of mipomersen?
antisense oligonucleotide that targets apoliporotein B-100 mRNA and disrupts its function which is needed for transport and removal of atherogenic lipids.
what adverse effects are associated with mipomersen?
- injection site RXN
- flu like symptoms
- Headaches
- elevated liver enzymes
