Lipid-lowering

Question 1

Statins

Answer 1

• Atorvastatin

* Pravastatin

Question 2

Absorption blockers

Answer 2

ADJUCT TO STATIN

*Ezetimibe

Question 3

Bile Acid Sequestrants/Resins

Answer 3

*Cholestyramine

Question 4

Nicotinamide derivatives

Answer 4

*Gemfibrozil

Question 5

PCSK9 inhibitors

Answer 5

Evolocumab

Question 6

How to replenish hepatic cholesterol “pool”

Answer 6

• UP biosynthesis of cholesterol (UP HMG-CoA reductase)

* UP LDL receptor expression –> UP LDL blood clearance (transcriptional up-regulation, response to statin therapy)

Question 7

Insoluble fiber

Answer 7

*not digested
*lignins/cellulose/apple skin
COLON FUNCTION

Question 8

Soluble Fiber

Answer 8

• Oats, psyllium, pectin, metamucil) - gel-like

* resides in intestine

Question 9

Fiber

Mech

Answer 9

• absorbs cholesterol

* GI motility changes (up speed of passage, slow absorption of cholesterol

Question 10

Omega-3 Polyunsaturated Fatty Acids (PUFAs)

Answer 10

LOVAZA = if HIGH TG level

*UP clearance TGs

NEED in MIs, Stroke deaths, Cardiac, sudden death

Fish 2x week = DOWN CHF, cardiac related death

Question 11

Statins. molecule

Answer 11

• stuctural analog = HMG-CoA (3-hydroxy-3-methylglutaryl

* Atrovastatin = Lipitor

Question 12

Statin

Mech

Answer 12

*Inhibition of HMG CoA Reductase

• DOWN chol synth
• UP synthesis hepatic LDL receptors
• UP LDL clearance = DOWN LDL cholesterol
• small = Down TG, up HDL

Question 13

Statins

Metab

Answer 13

• most given at night , NOT ATORVASTATIN
• ATORVASTATIN = CYP 3A4
• PRAVASTATIN = metab sulfation, NOT P450, NOT protein bound (others are)
• urine

Question 14

Statin

Absorption

Answer 14

Atorvastatin, Pravastain = decreased w/ food

Question 15

Intensity statin

Answer 15

LIPID LOWERING ABILITY

• Atorvastatin = high intensity
• Pravastatin = lower intensity

Question 16

Statin

half lives

Answer 16

Atorvostatin - 14 hr (take any time of day)

Pravastatin = short, only take at night

Question 17

Statin

Lipophilic/ hydrophilic

Answer 17

Atrovastatin = Lipophilic

Pravastatin = Hydrophilic

Question 18

Statin

S.E.

Answer 18

• Hepatic toxicity
• Serum aminotransferase = activity elevation (liver dz/alcohol abuse)
• ***Myopathy/Myalgia (not in trials)

Question 19

Statin

S.E. w/ other drugs

Answer 19

• w/ Gemfribrozil = inhibits update + myopathy
• Rx affectign CYP3A4/2C9
• NONE w/ PRAVASTATIN

Question 20

Statins

Gemfibrozil blocks

Answer 20

• OAT P1B1
• OAT P1B3
• OAT P2B1

Block statins transport of chol from blood to bile canaliculus

Question 21

Statins

Less common S.E.

Answer 21

• Up DM

* CNS= cognitive dysfunction (not sure)

Question 22

Cholestrol Absorption blockers

Mech

Answer 22

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

Question 23

Ezetimibe

AMDE

Answer 23

(Chol absoprtion blocker)

• NO P450 metab
• both Rx + metabolite inhibit chol absorption
• enterohepatic circulation (repeated) = long duration

Question 24

Cholestyramine

Mech

Answer 24

(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

Question 25

Cholestyramine S.E.

Answer 25

(Bile acid sequestrant) * GI * Absorption other Rx impaired

Question 26

Niacin Mech

Answer 26

* ****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

Question 27

Niacin Metab

Answer 27

*big 1st pass

Question 28

Niacin S.E.

Answer 28

* NO pregger * cutaneous Flushing = declines 1-2 weeks * Hepatotoxicity * GI = dyspepsia

Question 29

Fibrates

Answer 29

*DOWN TG (50%) varies

Question 30

Gemfibrozil Mech

Answer 30

(Fibrate) * Agonist = PPAR-alpha receptor * DOWN TG = Up TG-rich lipoproteins * UP TG, UP VLDL clearance

Question 31

Gemfibrozil T1/2? Pregnancy?

Answer 31

* half-life = short (1 hr) | * crosses placenta

Question 32

Gemfibrozil Use

Answer 32

High TG | Drug of choice

Question 33

Gemfibrozil S.E.

Answer 33

* NO w/ renal/hepatic function * NO kids, preg * GI discomfort * Myopathy (w/ statin) *Warfarin/Oral contraceptives = UP effect

Question 34

PCSK9 does?

Answer 34

Endocytoses LDL receptor, breaks it down (not recycled) If inhibit = recycle LDL

Question 35

Evolocumab S.E.

Answer 35

(PSK9 inhibitor) *nasopharyngitis

Question 36

Evolocumab Use

Answer 36

* familial HTN | * combined with statin (max dose)

Question 37

PCSK9 Inhibitor Results study

Answer 37

*DOWN composite CV death, MI, stroke ONLY WITH STATIN (+ all combined)