Hyperlipidemia/Hypertriglyceridemia

Question 1

“-Statin” drug route/MoA

Answer 1

• PO
• MoA: inhibits HMG CoA reductase –> less cholesterol in liver –> increased removal of LDL from blood into liver

Question 2

“-Statin” drug indications

Answer 2

• homo/heterozygous high cholesterol
• PRIMARY prevention of cardiovascular events
• ex. atorvaSTATIN, simvaSTATIN, rosuvaSTATIN
  1ST LINE

Question 3

“-Statin” AEs

Answer 3

• Common: arthralgia/myopathy/myositis
• Less: hepatitis/jaundice
• Significant: rhabdomyolysis, hepatic failure (rare)

Question 4

Ezetimibe route/MoA

Answer 4

• PO
• MOA: blocks transport of cholesterol from intestine to liver –> increase of LDL receptors on liver –>more LDL removed from circulation

Question 5

Ezetimibe indications

Answer 5

• homozygous high chol.
• PRIMARY high cholesterol
• off label: secondary prevention of cardiovascular events
  ADJUNCTIVE to -statins or can also be used alone

Question 6

Ezetimibe D-D interactions

Answer 6

• Fibrates –> avoid combination
• Bile acid sequestrants –> impaired absorption
• cyclosporine
• Warfarin –> possible increase of INR

Question 7

Ezetimibe AEs

Answer 7

• Common: Diarrhea, Myalgia, resp infection
• Less: elevated AST/ALT
• Sig: rhabdomyolysis, pancreatitis, cholecystitis, anaphylaxis

Question 8

PCSK9 Inhibitor drug types (2)

Answer 8

• monoclonal antibodies: AlirocuMAB
  EvolocuMAB
  &
• RNA type
  Inclisiran

Question 9

PCSK9 Inhibitors route/MoA (-MABs)

Answer 9

• SubQ
• blocks PCSK9 from degrading LDL receptors –> more LDL receptors to clear LDL from bloodstream

Question 10

PCSK9 Inhibitors route/MoA (inclisiran)

Answer 10

-SQ
- blocks mRNA that encodes for PCSK9 production –> less PCSK9 = more LDL receptors –> more LDL removed from circulation

Question 11

PCSK9 Inhibitors Indications

Answer 11

• Homozygous familial high chol.(-MABs)
• heterzygous (RNA)
• primary hyperchol. (-MABs)
• secondary prevention of cardiovascular events
• ADJUNCTIVE after statins/ezetimibe stop working

Question 12

PCSK9 Inhibitor AEs

Answer 12

• common: injection site reaction
• Less: liver disorder
• Sig: hypersensitivity, angioedema

Question 13

ATP Citrate Lyase (ACL) inhibitor drug/route/MoA

Answer 13

• Drug: Bempedoic Acid
• route: PO
• MoA: activated in liver; inhibits cholesterol synthesis in liver –> increase in LDL receptor –> increase clearance of LDL from circulation

Question 14

ACL inhibitor indication

Answer 14

• heterozygous familial chol
• atherosclerotic CVD
  -ADJUNCTIVE when -statins/ezetimibe stops working

Question 15

ACL inhibitor AEs

Answer 15

do not use if pregnant
- Common: gout, hyperuricemia
- Less: liver disorder, BPH in men
- Sig: tendon rupture, A-fib, anemia/thrombocytopenia

Question 16

Bile Acid Sequestrants route/MoA

Answer 16

• PO
• MoA: promotes bile excretion in feces–> decreased bile acid availability–> increased uptake of LDL to liver, less in circulation

Question 17

Bile Acid Sequestrants Drug & indication

Answer 17

• Colesevelam
• Heterozygous familial high chol.
• atherosclerotic CVD
• ADJUNCTIVE when -statins and ezetimibe stop working

Question 18

Bile Acid Sequestrants AEs

Answer 18

• Common: “belly effects” abd pain; constipation, N/V
• Less: vitamin A, D, E, K deficiency
• Sig: hyper-triglyceridemia, pancreatitis, gallbladder calculi

Question 19

Contraindications of Bile Acid Sequestrants (colesevelam)

Answer 19

• when TG > 500
• if hx of pancreatitis caused by high TG
• bowel obstruction

Question 20

Fibric Acid derivatives Inidications

Answer 20

• hypertriglyceridemia
• prevention of CVD
• ADJUNCTIVE/alternate to omega 3; also if TGs>500

Question 21

Fibric Acid derivatives (drugs/route/MoA)

Answer 21

• Gemfibrozil/fenofibrate
• PO
• MoA: activates PPAR-alpha –> more LPL (lipoprotein lipase) –> less fatty acids available in liver to release triglycerides

Question 22

Contraindications of Fibric acid derivative

Answer 22

• severe renal impairment
• active liver dx
• gallstones
• breast feeding

Question 23

Fibric Acid derivative SEs

Answer 23

• Common: abdominal pain; N/V/D; dyspepsia; rash/itching; mylagia; increased liver enzymes
• Less: photosensitivity
• Sig: rhabdomyolysis; delayed hypersensitivity

Question 24

VLDL Synthesis Inhibitors indications

Answer 24

• CV risk reduction with hypertriglyceridemia
• ADJUNCTIVE if statins stop working; also for CVD/DM

Question 25

VLDL synthesis inhibitors (drugs/route/MoA)

Answer 25

- omega 3/fish oil & icosapent ethyl - PO - MoA: inhibition of acyl-CoA --> decreased triglyceride synthesis --> decreased VLDL --> decreased LDL mediated plaque formation

Question 26

Omega 3 AEs

Answer 26

- common: eructation/dypepsia - Less: skin rash, increase liver enzymes - Sig: bleeding tendency disorder; A-fib/A-flutter

Question 27

Microsomal TG transfer protein (MTP) inhibitor indication

Answer 27

- homozygous familial high chol. - ADJUNCTIVE to other cholesterol lowering meds, when statins stop working - only if high chol. is their only condition

Question 28

MTP inhibitor drug/route/MoA

Answer 28

- Lomitapide - PO - MoA: binds MTP in liver & intestine --> blocks transport/formation of VLDL/chylomicron particles --> decrease level of both in blood stream --> decreased LDL formation

Question 29

MTP inhibitor (lopitamide) AEs

Answer 29

- major GI issues (abd distension, constipation, D/N/V) - Increased liver enzymes --> additional hepatic lab monitoring required

Question 30

Angiopoietin-Like Protein 3 (ANGPTL3) inhibitor indication

Answer 30

- Homozygous familial high cholesterol - ADJUNCTIVE to other LDL lowering meds

Question 31

(ANGPTL3) inhibitor drug/route/MoA

Answer 31

- Evinacumab - route: IV - MoA: inhibits ANGPTL3 --> promotes clearance of VLDL remnants before they are metabolized to LDL

Question 32

(ANGPTL3) inhibitor AEs

Answer 32

- infusion related rxns - hypersensitivity/anaphylaxis - also respiratory infections, GI issues, dizziness, limb pain - avoid pregnancy during use and for 5 months after last admin