Lipid Lowering Drugs Flashcards
(45 cards)
What is the mechanism of the body to replenish hepatic cholesterol/make more cholesterol in the liver?
inc HMG-CoA reductase (blocked by statins)
What is the mechanism to replenish the hepatic cholesterol “pool” (that isn’t making more cholesterol in the liver)?
inc LDL receptor expression leading to inc LDL clearance from blood
How is LDL receptor expression increased?
via transcriptional up-regulation
also occurs in response to statin therapy
What dietary change can be made to lower cholesterol?
increase fiber intake
Mechanism of fiber in lowering cholesterol?
fiber absorbs cholesterol and bile acids which contain cholesterol so slows absorption of cholesterol and facilitates excretion AND causes GI motility changes that leads to increase speed of passage so slows absorption of cholesterol, glucose, and macronutrients
How does omega-3 polyunsaturated fatty acids (PUFAs) dec cholesterol?
inc clearance of triglycerides
Provide an example of a PUFA drug
Lovaza
How does Lovaza work?
20-50% dec in fasting levels of triglycerides (no impact on pancreatitis)
Is fish oil supplementation helpful?
no dec in MIs, stroke deaths, cardiac related deaths, or sudden deaths
Is diet of fish helpful?
diet including fish (2x/week) decreases cholesterol and cardiac related deaths
What two forms do statins come in?
prodrug and active form
What are the two statins we need to know?
atorvastatin (Lipitor) and pravastatin (Pravachol)
What form are atorvastatin and pravastatin in?
active
How do statins work?
structural analog of 3-hydroxy-3-methylglutaryl (HMG) Co A thus BLOCK HMG CoA REDUCTASE –> dec in cholestrol synthesis…
Also statins lower serum LDL levels indirectly by inc hepatic LDL receptor expression
What does blocking/inhibiting HMG CoA Reductase do?
decrease cholesterol synthesis which increases synthesis of hepatic LDL receptors which increases clearance of LDL and VLDL remnants from blood (so statins lower serum LDL levels indirectly by inc hepatic LDL receptor expression)
What are statin’s effects on plasma lipids?
reduction of plasma LDL cholesterol!!!! (modest reduction in triglycerides and modest increase in HDL)
Metabolism of atrovastatin
metabolized by CYP3A4
Metabolism of pravastatin
metabolized by sulfation NOT P450-dependent
Physiologic disposition of atrovastatin
half-life 14 hours
administered at any time of day
dec absorption with food
lipophilic so can cross BBB easier
protein bound
Physiologic disposition of pravastatin
half-life 2 hours
administered at night (when most cholesterol biosynthesis takes place)
dec absorption with food
hydrophilic so less smooth muscle cell effects AND more hepatoselective b/c better substrates for hepatic transporters
excreted unchanged in urine (only one)
NOT protein bound
Adverse effects of statins
1) Myopathy/Myalgia
2) Hepatic toxicity so elevation of serum aminotransferase activity so be careful with patients with liver disease and hx of alcohol abuse
3) Increased myopathy and rhabdomyolysis when used with other drugs like Gemfibrozil cuz inhibits uptake transporter and metabolism by CYPs
4) Drugs that compete/inhibit CYP3A4 or 2C9 can impact statin exposure (exception pravastatin cuz not metabolized by P450s)
5) small risk of inc DM
6) possible cognitive effects but inconsistent findings
1 adverse effect of statins
!!!Myopathy/Myalgia!!! (test question)
Statin key points: atorvastatin
lipophilic so penetrate muscle and cross BBB
source is made synthetically
undergo P450 metabolism so drug interactions
renal impairment not an issue
protein bound
dec absorption when taken with food
can take any time of day
half-life 14 hours
Statin key points: pravastatin
hydrophilic so hepatoselective and less smooth muscle cell effects
source is from fungi
no P450 metabolism (so no drug interactions with those that are)
renal impairment an issue
NOT protein bound
dec absorption when taken with food
should be taken at night (when most cholesterol biosynthesis takes place)
half-life 2 hours
excreted unchanged in urine (only one)
