Lipid-lowering Flashcards
Statins
- Atorvastatin
* Pravastatin
Absorption blockers
ADJUCT TO STATIN
*Ezetimibe
Bile Acid Sequestrants/Resins
*Cholestyramine
Nicotinamide derivatives
*Gemfibrozil
PCSK9 inhibitors
Evolocumab
How to replenish hepatic cholesterol “pool”
- UP biosynthesis of cholesterol (UP HMG-CoA reductase)
* UP LDL receptor expression –> UP LDL blood clearance (transcriptional up-regulation, response to statin therapy)
Insoluble fiber
*not digested
*lignins/cellulose/apple skin
COLON FUNCTION
Soluble Fiber
- Oats, psyllium, pectin, metamucil) - gel-like
* resides in intestine
Fiber
Mech
- absorbs cholesterol
* GI motility changes (up speed of passage, slow absorption of cholesterol
Omega-3 Polyunsaturated Fatty Acids (PUFAs)
LOVAZA = if HIGH TG level
*UP clearance TGs
NEED in MIs, Stroke deaths, Cardiac, sudden death
Fish 2x week = DOWN CHF, cardiac related death
Statins. molecule
- stuctural analog = HMG-CoA (3-hydroxy-3-methylglutaryl
* Atrovastatin = Lipitor
Statin
Mech
*Inhibition of HMG CoA Reductase
- DOWN chol synth
- UP synthesis hepatic LDL receptors
- UP LDL clearance = DOWN LDL cholesterol
- small = Down TG, up HDL
Statins
Metab
- most given at night , NOT ATORVASTATIN
- ATORVASTATIN = CYP 3A4
- PRAVASTATIN = metab sulfation, NOT P450, NOT protein bound (others are)
- urine
Statin
Absorption
Atorvastatin, Pravastain = decreased w/ food
Intensity statin
LIPID LOWERING ABILITY
- Atorvastatin = high intensity
- Pravastatin = lower intensity
Statin
half lives
Atorvostatin - 14 hr (take any time of day)
Pravastatin = short, only take at night
Statin
Lipophilic/ hydrophilic
Atrovastatin = Lipophilic
Pravastatin = Hydrophilic
Statin
S.E.
- Hepatic toxicity
- Serum aminotransferase = activity elevation (liver dz/alcohol abuse)
- ***Myopathy/Myalgia (not in trials)
Statin
S.E. w/ other drugs
- w/ Gemfribrozil = inhibits update + myopathy
- Rx affectign CYP3A4/2C9
- NONE w/ PRAVASTATIN
Statins
Gemfibrozil blocks
- OAT P1B1
- OAT P1B3
- OAT P2B1
Block statins transport of chol from blood to bile canaliculus
Statins
Less common S.E.
- Up DM
* CNS= cognitive dysfunction (not sure)
Cholestrol Absorption blockers
Mech
ADJUNCT
*block chol absorption from intestine
*inhibits NPC1L1 (Niemann-Pick C1 like 1) (brush border)
- DOWN intestinal chol delivery to liver => DOWN Cholesterol in chylomicrons/ remnants (atherogenics)
- UPs LDL receptors = LDL clearance
Ezetimibe
AMDE
(Chol absoprtion blocker)
- NO P450 metab
- both Rx + metabolite inhibit chol absorption
- enterohepatic circulation (repeated) = long duration
Cholestyramine
Mech
(Bile acid sequestrant)
- binds bile acids, chol metabolites
- stop reabsorption, more excretion, DEPLETES BILE ACIDS
- more chol to bile
- Up regulation LDL receptors = more clearance
- UP regulation HMG-CoA reductase
Cholestyramine
S.E.
(Bile acid sequestrant)
- GI
- Absorption other Rx impaired
Niacin
Mech
- **UP HDL ,
- huge dose = DOWN TG + LDL (S.E.), also result of HDL raise
- STOP lipolysis (lipase) in adipose tissue
- DOWN free fatty acid transport to liver (DOWN VLDL synthesis)
- DOWN TG synth in liver
Niacin
Metab
*big 1st pass
Niacin
S.E.
- NO pregger
- cutaneous Flushing = declines 1-2 weeks
- Hepatotoxicity
- GI = dyspepsia
Fibrates
*DOWN TG (50%) varies
Gemfibrozil
Mech
(Fibrate)
- Agonist = PPAR-alpha receptor
- DOWN TG = Up TG-rich lipoproteins
- UP TG, UP VLDL clearance
Gemfibrozil
T1/2?
Pregnancy?
- half-life = short (1 hr)
* crosses placenta
Gemfibrozil
Use
High TG
Drug of choice
Gemfibrozil
S.E.
- NO w/ renal/hepatic function
- NO kids, preg
- GI discomfort
- Myopathy (w/ statin)
*Warfarin/Oral contraceptives = UP effect
PCSK9 does?
Endocytoses LDL receptor, breaks it down (not recycled)
If inhibit = recycle LDL
Evolocumab
S.E.
(PSK9 inhibitor)
*nasopharyngitis
Evolocumab
Use
- familial HTN
* combined with statin (max dose)
PCSK9 Inhibitor
Results study
*DOWN composite CV death, MI, stroke ONLY WITH STATIN (+ all combined)
