Flashcards in Drugs used in Dyslipidemia Deck (66)
What are some drugs used to reduce cholesterol?
-HMG-CoA reductuase inhibitors (STATINS)
-Bile acid resins
all share a common mechanism of increasing LDL receptors on the liver
What do Statins do?
inhibit the rate-limiting step of cholesterol biosynthesis lowering LDL by 25-60%
What happens when Statins inhibit cholesterol synthesis?
a transcription factor called Sterol Regulatory Element Binding Protein 2 that normally signals HMG CoA reductase to make more cholesterol when it is low, instead binds to a sterol response element (SRE) to signal the production of more LDL receptors causing LDL to go down
How do bile acid resins work?
traps bile acids so that they cant recirculate from the ileum and cant go back to the liver to make cholesterol and then the same process occurs as with statins leading to reduced LDL
What does Ezetimibe do?
binds to the demon pick (sp?) receptor in the gut which is responsible for the dietary uptake of free cholesterol and lowers LDL
How does Niacin work?
reduces synthesis of VLDL
(lowers LDL by up to 20%)
How do Statins work?
part of the molecule (open acid ring) mimics the structure of the substrate for HMG CoA reductase, mevalonate
What are some types of Statins?
Lovastatin and Simvastatin (both naturally occurring)
What are Lovastatin and Simvastatin metabolized by?
CYP3A4 (the others are active)
What is one benefit of Pravastatin?
muscle side effects are low
Which statins are the most effective?
Atorvastatin and rosuvastatin
then Lovastatin and Simvastatin
How is SREBP maintained with cholesterol levels are high in the body?
it remains quiescent by binding to sterol cleavage activating protein (SCAP)
What are the high intensity statins (reduce LDL by 50+%)?
atorvastatin (40-80mg) and rosuvastatin (20-40 mg)
anyone at high risk for heart disease should be on these
What are the moderate intensity statins (reduce LDL by 30-50%)?
Atorvastatin, (10-20mg) rosuvastatin (5-10 mg)
Pitavastatin, (2-4 mg)
What are the low intensity statins (reduce LDL by less than 30%)?
Pitavastatin, (1 mg)
Which statins are most susceptible to drug-drug interactions?
Lovastatin and Simvastatin (CYP3A4 substrates)
What is the least statin susceptible to drug-drug interactions?
How are Rosuvastatin and Fluvastatin metabolized?
How are most statins excreted?
Fecal (pravastatin is 20% renal- others are lower)
What would be the preferred statin for a patient with renal failure?
Fluvastatin (very minimal renal excretion)
What are some drugs that inhibit CYP3A4?
What are some drugs that p-glycoprotein (responsible for pumping foreign toxins back into the lumen if they make it out somehow) mediated intestinal reabsorption?
cyclosporine, grapefruit juice
P-gP is responsible for pumping a lot statin back into the lumen and is responsible for its low bioavailability in part
What is a side effect of statins that can be particularly bad?
All statins depend on what for uptake into the liver for first as?
OTB1- a defect in the transporter would lead to very high levels of statin and then some of it would make its way to muscle causing myocytis
What are some adverse effects of STATINS?
-generally well tolerated
-increased Liver enzymes
-sleep disturbance, memory loss
What is the difference between myalgia and myositis?
In myalgia you have muscle pain/weakness without CPK rise and in myositis you see increased CPK
Are STATINS teratogenic?
STATINS are not effective against what?
hemorrhagic stroke- good for MI, stroke, CHD, etc.
Are bile acid resins systemic?
Nope, they just pass through the gut and bind bile acids so they cannot be recovered via enterohepatic circulation
secondary to STATINS