Drugs for Lipid Disorders Flashcards
(40 cards)
List of HMG-CoA reductase inhibitors (statins)
- Atorvastatin (Lipitor)
- Fluvastatin
- Lovastatin
- Pitavastatin
- Pravastatin
- Rosuvastatin (Crestor)
- Simvastatin (Zocor)
List of Niacin (nicotinic acid, vitamin B3) drugs
Niacin
List of Fibric Acid Derivatives (fibrates)
- Fenofibrate
- Gemfibrozil
List of bile acid sequestrants (resins)
- Cholestyramine
- Colesevelam
- Colestipol
List of cholesterol absorption inhibitors
Ezetimibe (Zetia)
List of New Treatments
- Lomitapide
- Mipomersen
- Evolocumab, alirocumab
Most effective agents in reducing LDL levels and best tolerated class of lipid lowering agents
HMG-CoA reductase inhibitors (statins)
What is the mechanism of action for statins?
statins are structural analogs of HMG-CoA (initial precursor of
cholesterol) and inhibit MHG-CoA reductase, the rate limiting enzyme in cholesterol synthesis; inhibiting de novo cholesterol synthesis depletes the intracellular supply of cholesterol, which causes the cell to increase the number of specific cell-surface LDL receptors that can bind and internalize circulating LDLs; increased expression of surface LDL receptors reduces circulating LDL levels
List the potency of drugs for statins
atorvastatin = rosuvastatin > simvastatin > pitavastatin = lovastatin = pravastatin > fluvastatin
What are the therapeutic benefits to statins?
- plaque stabilization
- improvement of coronary endothelial function
- inhibition of platelet thrombus formation
- anti-inflammatory effects
- Statins are also effective in lowering plasma cholesterol levels in all types of hyperlipidemias
Are statins usually take alone or in combination with something else?
Used alone or with resins, niacin, or ezetimibe
What time would you take a statin?
Primarily taken at night (cholesterol synthesis occurs predominantly at night) except the longer-acting atorvastatin, pitavastatin, rosuvastatin)
What is the function of Niacin?
Decreases TGs, LDL, Lp(a); increases HDL
What is the mechanism of action for Niacin?
inhibits the lipolysis of triglycerides in adipose tissue (the primary producer of circulating free fatty acids); by reducing circulating free fatty acids, the liver produces less VLDL and LDL levels decrease; catabolic rate for HDL is decreased; fibrinogen levels are reduced and tissue plasminogen activator levels are increased
What is the most common side effect of niacin?
- An intense cutaneous flush
accompanied by an uncomfortable feeling of warmth that occurs after each dose when drug is started or when the dose is increased (aspirin taken before niacin or once-daily ibuprofen can mitigate the flushing, which is prostaglandin-mediated); - pruritus, rashes, dry skin or mucous membranes, and ACANTHOSIS NIGRICANS
What are some contraindications for Niacin?
- Avoid in patients with hepatic disease or active peptic ulcer
- Use with caution in patients with diabetes mellitus due to niacin- induced insulin resistance, which can cause hyperglycemia (patients with insulin resistance often show signs of acanthosis nigricans due to elevated insulin levels)
- Can elevate uric acid levels
What is the mechanism of action for Fibrates?
- Agonists for peroxisome proliferator-activated receptor alpha (PPARα, a nuclear receptor); when activated, PPARα binds to DNA, regulating the expression of genes encoding proteins involved in LIPOPROTEIN structure and function (lipoprotein lipase,
apo A-I, apo A-II expression is increased and apo C-III is decreased); - Major effect is increased oxidation of fatty acids in liver and striated muscle; INCREASED LIPOLYSIS OF TG VIA LIPOPROTEIN
LIPASE WHILE INTRACELLULAR LIPOLYSIS IN ADIPOSE TISSUE IS DECREASED; VLDL levels decrease, LDL levels modestly decrease in most patients (LDL levels can increase as triglycerides are reduced), HDL levels increase moderately
Why are Fibrates useful?
Fibrates are useful in the management of hypertriglyceridemias where VLDL predominates, dysbetalipoproteinemia, and hypertriglyceridemia that results from treatment with viral protease inhibitors (e.g., saquinavir, indinavir, or nelfinavir for HIV therapy)
What is the most common adverse effect to Fibrates?
mild GI disturbances are most common adverse effects and
usually subside
What are some adverse effects of Fibrates?
- GI: increased the risk of cholelithiasis (due to an increase in the cholesterol content of bile) and should be used with caution in patients with biliary tract disease or in those at high risk (e.g., women, obese patients, Native Americans)
- Liver: increased SERUM TRANSAMINASES (up to 3X normal)
- Muscle: myositis can occur (evaluate for muscle weakness and tenderness); MYOPATHY and rhabdomyolysis have been reported (increased risk when fibrates and statins combined)
- Fibrates may potentiate the actions of anticoagulants
What are some contraindications to Fibrates?
Fibrates should be avoided in patients with hepatic or renal dysfunction; safety has not
been established in pregnant or lactating women
What is the mechanism of action for Bile Acid Sequestrants (Resins)?
- positively charged compounds bind to negatively charged bile acids (metabolites of cholesterol) and increase bile acid excretion up to tenfold
- increased excretion of bile acids enhance the conversion of cholesterol to bile acids in the liver via 7α-
hydroxylation (normally controlled by negative feedback via bile acids); - the decline in hepatic
cholesterol stimulates an increase in hepatic LDL receptor, which enhances LDL clearance and lowers levels; - however, this effect is partially offset by enhanced cholesterol synthesis caused by upregulation of HMG-CoA reductase (therefore, combined use of a statin substantially increases the effectiveness of resins)
What kind of patients receive Bile Acid Sequestrants?
- Used to treat patients with primary hypercholesterolemia (reduces LDL by approximately 20%);
- prescribed as monotherapy or in combination with niacin for
treatment of Type IIa and Type IIb hyperlipidemias; - used to relieve pruritus in patients who have bile salt accumulation (e.g., from biliary obstruction)
What are most common adverse effects to Bile Acid Sequestrants?
GI effects (e.g., constipation, nausea, and flatulence) are the most common
