Pharmacology Dyslipidemia, Hypertension, Diuretic

Question 1

Statin MOA

Answer 1

HMG-CoA reductase inhibitors
- an enzyme that catalyzes the rate-limiting step in new cholesterol synthesis

Has a mevalonic acid-like structure that helps inhibit HMG-CoA reductase

Question 2

What are the effects of statins on lipid homeostasis (5)

Answer 2

• Decreased cholesterol synthesis (cleavage of sterol regulatory binding protein)
• Dec LDL (inc expression of LDL receptor in liver, inc removal of LDL from circulation
• Dec VLDL (precursor for LDL)
• Dec TG (due to reduced VLDL synthesis)
• Modest effect on HDL

Question 3

What are secondary MOA of statins? (4)

Answer 3

• increased production of nitric oxide by vascular endothelial cells and vasodilation
• increased atherosclerotic plaque stability
• reduced “CRP” levels
• Antiplatelet effects

Question 4

What is the MOA of drug interactions for statins?

Answer 4

Organic anion transporting polypeptide (OATP) B1 transporter
- transports statins to liver
- other drugs compete for this (rifampin, cyclosporin etc..)
- Leaves reduced efficacy of statins and inc circulating statins in the bloodstream (toxicity)

Question 5

What is the MOA of statin myopathy

Answer 5

Decreased cholesterol synthesis alters membrane fluidity and electrical properties
- causes more rigid cell membrane

Question 6

Fibrates MOA. effect of lipid homeostasis? (4)

Answer 6

• Activates peroxisome proliferator-activated receptor alpha in liver & adipose
• inc LPL (reduce TG)
• inc ApoA-1 and ApoA-2 (inc HDL)
• Reduced VLDL

Question 7

Fibrates ADRs

Answer 7

• GI side effects
• elevation liver transaminases
• gall stones

Question 8

Bile acid sequestrants

Answer 8

• Large
• Anion exchange resins
• are positively charged
• not absorbed from GI tract

Question 9

Bile acid sequestrants MOA

Answer 9

• Bind negatively charged bile acid in lumen
• hepatic bile acid synthesis increases to decrease cholesterol content (inc LDL receptors, decrease LDL levels)
• CAN increase TG production

Question 10

Why are bile acid sequestrants, and ezetimibe more effective when given in combination with a statin

Answer 10

When cholesterol is lost, there is an increase production of HMG-CoA reductase

Question 11

Bile acid Sequestrants ADRs? How to minimize it?

Answer 11

• Constipation, bloating
• giving psyllium fibre

Question 12

Ezetimibe MOA

Answer 12

Blocks NPC ILI
- which is a transport protein required for cholesterol uptake
- Works for both dietary and bile cholesterol

Reduces cholesterol incorporation into chylomicrons
- inc LDL receptor, decrease LDL from bloodstream

Question 13

Niacin B3 MOA. Effect on lipid profiles?

Answer 13

Converted to nicotinamide to make NAD/NADP
- INC HDL
- REDUCE LpA
- reduce TG
- Reduce LDL

Question 14

Evolucomab MOA

Answer 14

IgG2 monoclonal antibody that inhibits proprtein convertase subtilisin/kexin type (PCSK9)

PCSK9 normally destroys LDL receptors
- inhibiting it allows LDL receptor to be recycled back to cell surface instead

• Dec LDL

Question 15

Cholesteryl ester transfer protein inhibitors MOA
Drugs?

Answer 15

Blocks transfer of cholesterol from HDL particles to lipoproteins
- inc HDL particles

Drugs
- Evacetrapib
- anacetrapib
- dalcetrapib

Question 16

ATP citrate lyase inhibitors MOA
Drug?

Answer 16

Bempedoic acid
- inhibit a step-in cholesterol synthesis that occurs before the rate-limiting step

Question 17

Angiopoietin-like 3 inhibitors MOA
Drug?

Answer 17

prevents lipase enzymes
- reduces LDL

Evinacumab

Question 18

Nucleic acid based therapies MOA
Drug?

Answer 18

Small RNA fragments and antisense oligonucletodies

Inclisiran, TCJ320

Question 19

Lomitapide MOA

Answer 19

Inhibitor of microsomal triglyceride transfer protein that adds TG to VLDL and chylomicrons which results in
- reduced VLDL & LDL