Dyslipidemia & Agents Flashcards
Kaplan Pharm
Lipoproteins: What are there functions?
Lipid transport (not H2O soluble)
Classes of ”chylomicrons”
VLDL, LDL, HDL
Classes of ”chylomicrons”: Very-Low-Density Lipoproteins VLDL
What are they made up of?
Lipid core = TGs
VLDL particles contain triglycerides as their major component, along with cholesterol and other lipids.
Classes of ”chylomicrons”: Very-Low-Density Lipoproteins VLDL
What are they responsible for?
Responsible for transporting triglycerides synthesized in the liver to various tissues in the body for energy or storage.
Classes of ”chylomicrons”: Very-Low-Density Lipoproteins VLDL
What is the risk with elevation of VLDL?
Increased VLDL ~ increase in TGs
Link to atherosclerosis not firmly established
> 500mg/dL ~ pancreatitis
Classes of ”chylomicrons”: Low-Density Lipoproteins LDLs
By-products of VLDL metabolism
Classes of ”chylomicrons”: Low-Density Lipoproteins LDLs:
What are they directly related to?
Directly related to ASCVD risk, target of TX
Classes of ”chylomicrons”: Low-Density Lipoproteins LDLs:
What are they directly related to?
Directly related to ASCVD risk, target of TX
Classes of ”chylomicrons”: High-Density Lipoproteins HDLs:
What are they directly related to?
Reduces ASCVD risk
Dyslipidemia: Complications
Atherosclerosis
HTN, CAD, PVD
Stroke
Dyslipidemia: Familial dyslipidemia
↑ liver production of cholesterol
Approach to Drug Therapy for Dyslipidemia:
Primary target ↓ LDL
Approach to Drug Therapy for Dyslipidemia:
Primary target ↓ LDL: What med is initiated first?
HMG-CoA reductase inhibitors initiated 1st
Approach to Drug Therapy for Dyslipidemia:
Primary target ↓ LDL: What med is an add on?
Add-on bile acid sequestrant
Approach to Drug Therapy for Dyslipidemia:
What are fibrates used for?
Fibrates primarily for TGs, not LDL
Drug Classes Used for Dyslipidemias & ASCVD PX include:
HMG-CoA Reductase Inhibitors (Statins)
Bile-Acid Sequestrants
Ezetimibe
Fibric Acid Derivatives (Fibrates)
PCSK 9 Inhibitors (Monoclonal Antibodies)
HMG-CoA Reductase Inhibitors end in?
(Statins)
HMG-CoA Reductase Inhibitors: What are they most effective for?
Most effective for ↓ LDL & total cholesterol
HMG-CoA Reductase Inhibitors: What can they aid in?
Evidence for possible benefits for osteoporosis
HMG-CoA Reductase Inhibitors: When is cholesterol synthesis greatest in the day? What does this mean about when med should be taken?
increases Cholesterol synthesis @ night ~ QHS
HMG-CoA Reductase Inhibitors:
MOA: What does it inhibit?
Inhibition of HMG-CoA reductase (enzyme for cholesterol synthesis)
HMG-CoA Reductase Inhibitors:
MOA: What does it increase?
Increase hepatocyte production of LDL receptors
HMG-CoA Reductase Inhibitors:
MOA: What does it decrease?
↓ production of apolipoprotein B-100 ~ VLDL & TGs
HMG-CoA Reductase Inhibitors (Statins)
ADEs:
Generally well tolerated-Transient HA, rash, GI disturbances
Hepatotoxicity
Cataracts
Myopathy
Rhabdomyolysis
Teratogenic
HMG-CoA Reductase Inhibitors (Statins)
ADEs: Myopathy
What is a sign of this?
Muscles aches, tenderness, weakness
HMG-CoA Reductase Inhibitors cont.
ADEs: Rhabdomyolysis
What are risk factors?
Advanced age, small body frame, frailty
Multisystem DX ~ chronic renal insufficiency & DM
High doses & rosuvastatin
**Low vitamin D & coenzyme Q, supplement **
Concurrent fibrates
Concurrent agents that statins
HMG-CoA Reductase Inhibitors cont.
Drug interactions:
Concurrent lipid-lowering drugs
CYP-3A4 inhibitors
HMG-CoA Reductase Inhibitors cont.
Drug interactions: CYP-3A4 inhibitors:
increase lovastatin & simvastatin
increase atorvastatin
Bile-Acid Sequestrants:
What do they do to LDLs? VLDL (what does this mean for people with very high VLDLs)?
decrease LDL ~ 20%
Mild transient increases VLDL in some (Avoid if VLDL already high)
Bile-Acid Sequestrants:
Mode of Action:
Bile acids –> intestine –> XX –> reabsorbed
increases bile acid secretion excretion –> increase synthesis (requires cholesterol)
increases LDL receptors on hepatocytes = increase LDL uptake from plasma
Bile-Acid Sequestrants
ADE
Mainly issues w/ cholestyramine, colestipol
Constipation
decrease uptake of fat-soluble vitamins ADEK
GI upset bloating, indigestion, nausea
Bile-Acid Sequestrants
Interactions
Insoluble complex w/ PO meds
Bile-Acid Sequestrants
Interactions: How should it be taken with thiazides, digoxin, warfarin, certain antibiotics?
Thiazides, digoxin, warfarin, certain ABX
1h before, 4h after
Ezetimibe: How is it used?
Used as add-on w/ statin, or monoTX
Ezetimibe:
MOA: Actions on brush border cells (small intestine)
Inhibits dietary cholesterol absorption
Inhibition of cholesterol reabsorption secreted in the bile
Ezetimibe:
MOA: Lipoprotein effects
decrease total cholesterol, LDL, TGs, apolipoprotein B.
Small increase in HDL
No evidenced of decrease ASCVD
Ezetimibe:
ADE: Who should it be avoided in?
Avoid in moderate-severe hepatic impairment
Ezetimibe:
ADE:
Gallstones ~ increase bile cholesterol
Fibric Acid Derivatives (Fibrates) ~ -fibr
Effects on lipoproteins?
Most effective for decreasing TG 40-55%
Can increase HDL 6-10%
Little or no effect on LDL (may actually increase)
No evidenced of decreasing ASCVD
Fibric Acid Derivatives (Fibrates) ~ -fibr:
When is it used?
Considered 3rd line
Fibric Acid Derivatives (Fibrates) ~ -fibr
Activation of PPAR-alpha receptor (liver & brown adipose tissue)
Accelerated clearance of VLDLs ~ increases TGs
Increase apolipoproteins A-I & A-II ~increasing HDL
Fibric Acid Derivatives (Fibrates) ~ -fibr
ADEs:
Gallstones
Myopathy
Hepatotoxicity ~ periodic LFTs
Fibric Acid Derivatives (Fibrates) ~ -fibr
Interactions
Displacement of warfarin from albumin
PCSK9 Inhibitors- end in what?
mab
PCSK9 Inhibitors-
MOA:
Monoclonal antibodies that inhibit PCSK9 (protein)
“Frees-up” receptor for LDL uptake ~ decrease in plasma LDL
Fish Oil & Omega-3 Agents
Contains omega-3 fatty acids ~ EPA & DHA
Reduces risk of CAD progression & PX arrythmia
Contains omega-3 fatty acids ~ EPA & DHA: What is it not effective for?
OTC Fish oil is NOT effective for
Lowering LDL
Direct protection for ASCVD
