Drugs for Lipid Disorders Flashcards
4 things known to increase VLDL
Total fat
Sucrose
Fructose
EtOH (via increased hepatic secretion of VLDL)
How long does it take to determine if dietary changes are sufficient to manage one’s lipid profile?
Approx. 1 mo.
Dietary recommendations to lower cholesterol (3)
What sort of reduction in serum cholesterol is seen?
- Limit cals from fat to 20-25% of daily intake.
- Keep saturated fats to less than 8% of daily intake.
- Limit cholesterol to less than 200 mg/day
Ranges from 10-20% adhering to these recs.
Which statins are not metabolized by CYP450s?
Pravastatin
Pitavastatin
Most of the absorbed doses of statins are excreted in what substance?
Bile
Approx. 5-20% in urine
2 most potent statins
Least potent statin
Atorvastatin = Rosuvastatin
Fluvastatin
Adverse effects of statins at the liver
Elevates serum AST, but levels decrease upon cessation of therapy.
Adverse effects of statins in muscle
CK activity increases.
Rhabdomyolysis can occur rarely ad cause renal injury.
Myopathy.
Effect of statins and Warfarin levels
Increases Warfarin levels
Who are statins contraindicated in? (3)
Women who are pregnant, lactating or want to become pregnant.
Pts. w/ liver DZ
Pts. w/ skeletal muscle myopathy
In what disease should statins be given to children?
Homozygous familial hypercholesterolemia and some w/ heterozygous familial hypercholesterolemia
PKs of Fibric acid derivatives (Fibrates):
Half-life of Gemfibrozil and Fenofibrate
Well-absorbed when taken w/ a meal, less otherwise.
Gemfibrozil: 1.5 hrs.
Fenofibrate: 20 hrs.
Fibrates are best used in the management of hypertriglyceridemias where what lipoprotein predominates?
Pts. on which type of ABX-caused hypertriglyceridemia would also benefit?
VLDL
Hypertriglyceridemia from Tx w/ viral protease inhibitors
Adverse effects (2) and contraindications (2) of Fibrates
GI effects, biliary problems (gallstones)
Increased AST
Muscular problems: myositis, myopathy, rhabdomyolysis
If pt. is taking anti-coagulation -> fibrates potentiate anti-coags.
Avoid in pts. w/ hepatic or renal dysfunction.
PKs of bile acid sequestrants
Not absorbed at all - excreted in feces.
Which 2 drug classes should not be used in tandem when treating lipid disorders?
HMG-CoA reductases (statins) and bile acid sequestrants
Which pts. would best benefit from therapy w/ bile acid sequestrants?
What can it be combined w/ to treat type IIa and type IIb hyperlipidemias?
What else can it relieve?
Pts. w/ primary hypercholesterolemia
Combined w/ Niacin.
Pruritis in pts. w/ bile salt accumulation.
Adverse effects of bile salt sequestrants
GI problems are most common.
High doses may impair fat-sol. vitamin absorption.
Pts. w/ which pre-existing conditions should not be given bile salt sequestrants?
Diverticulitis
Bowel DZ
Cholestasis
Lomitapide MOA
Inhibits MTP (microsomal transfer protein) in lumen of ER. The MTP inhibition prevents the assembly of Apo-B -> reduced chylomicrons, VLDL and LDL.
What is the problem with prescribing Lomitapide and Mipomersen?
It is over $250K/$176K and only available to people w/ Familial hypercholesterolemia
Mipomersen MOA
Inhibits Apo-B synthesis in liver -> decreased VLDL and LDL.
PCSK9 inhibitor MOA
What is it used for?
Abs bind to PCSK9 and inhibits LDL receptor metabolism.
Familial hypercholesterolemia
Complex MOA of Statins
- Inhibit HMG-CoA reductase -> decreased cholesterol.
- Low IC [cholesterol] -> increased LDL R synthesis.
- Increased LDL reuptake from blood.
- Decreased IC [cholesterol] -> decreased secretion of VLDL.
Complex MOA of Niacin
Inhibit HSL -> decrease [FFA] -> decreased VLDL synthesis.
Decrease Apo A1 clearance -> increased HDL.
Complex MOA of Fibrates
Activate PPAR-a
- Activate expression of Apo A1 and A2 -> increase HDL.
- Activate lipoprotein lipase -> increased clearance of TGs at endothelium and FFA oxidation at liver.
Major side-effects of niacin
Flushing
Hyperuricemia - gout, etc.
Ezetimibe is a…
Cholesterol absorption inhibitor
Bile salt sequestrant drugs
Colestipol
Cholestyramine
Colesevelam
