Lipid Lowering Drugs Flashcards
Which lipoprotein type contributes to atherosclerosis?
LDL (the most)
probably VLDL also
Cholesterol
- cell membranes, membranes of intracellular organelles, hormone synthesis
- primarily manufactured in liver, some dietary intake required
Lipoproteins
- transport cholesterol & TGs in blood
- apolipoproteins = recognition sites for cell surface receptors, allows for cellular ingestion & metabolism
- pharm apos = A-I, A-II, B-100
VLDL
- TGs as core
- B100
- deliver TGs from liver to adipose & muscle tissue
LDL
- cholesterol as core
- B100
- deliver cholesterol from liver to non-hepatic tissue
- increased cellular demand for cholesterol = increased LDL receptor #
- greatest contribution to atherosclerosis
HDL
- cholesterol as core
- A-II, A-I
- delivery of cholesterol from peripheral tissues back to liver
Which lipoprotein type protects against atherosclerosis
HDL
First line treatment for hypercholesterolemia
lifestyle measures
which drug class for hypercholesterolemia results in the greatest decrease in LDL
monoclonal antibodies (but not widely used)
**HMG-CoA reductase inhibitors (statins)
How do HMG-CoA reductase inhibitors work?
inhibit the enzyme HMG-CoA reductase = increased LDL receptors and increased LDL uptake
–> decreased free LDL
PK - HMG CoA reductase inhibitors
PO at night, hepatic met, biliary excretion, Rosuvastatin not well metabolized in Asian heritage
HMG-CoA reductase inhibitors
atovastatin, lovastatin, simvastatin, rosuvastatin
Adverse effects of HMG-CoA reductase inhibitors
myopathies (can lead to rhabdomyolysis)
hepatotoxicity
Bile acid sequestrants
colesevelam, cholestyramine, colestipol
mechanism of action of bile acid sequestrants
- remain in GI tract and bind up bile acids –> decreased absorption/increased excretion
- increases hepatocyte LDL receptor #
adverse effects of bile acid sequestrants
GI side effects (i.e. constipation)
Fibric acid derivatives / fibrates
gemfibrozil, fenofibrate, bezafibrate
mechanism of action of fibrates
inhibit hepatic production of triglycerides - decreased VLDL
(i.e. NOT LDL which holds cholesterol)
adverse effects of fibrates?
GI disturbances
gallstones
myopathy
hepatotoxicity
mechanism of action of ezetimibe
decreased dietary & biliary cholesterol absorption/reabsorption
PK: ezetimibe
PO, converted to active metabolite esetimibe glucuronide, biliary elimination
adverse effects of ezetimibe
myopathy/rhabdomyolysis
hepatitis
pancreatitis
thrombocytopenia
PCSK9 inhibitors
alirocumab, evolocumab
mechanism of action of monoclonal antibody (PCSK) inhibitors
inhibit PCSK9
PCSK9 usually binds LDL receptors in liver
free LDL receptors = increased LDL uptake & less free LDL
adverse effects of monoclonal antibody (PCSK9) inhibitors
hypersensitivity
immunogenicity
PCSK9 inhibitors: PK
subQ, dosing Q2 weeks, 11-20 day 1/2 life; used in combination w/ statins in patients w/ high risk of mortality / morbidity
ACL inhibitors
Bempedoic acid
mechanism of action of ACL inhbitors
inhibit ACL activity (enzyme higher up pathway than HMG-CoA) –> increased LDL receptor & increased uptake of LDL, decreased cholesterol synthesis
adverse effects of ACL inhibitors
increased uric acid (gout risk)
tendon rupture
When & how should patients take their HMG-CoA Reductase inhibitor medication
at night, PO
list some HMG-CoA Reductase inhibitors
“statins”
atorvastatin
lovastatin
simvastatin
rosuvastatin
s/s of myopathy that can lead to rhabdo with statin administration
muscle aches
tenderness
weakness
What is the risk if patient doesn’t call provider w/ myopathies?
progression to myositis with increased CK & K+
can lead to renal injury
What labs do we monitor upon initial therapy with HMG-CoA reductase inhibitors?
CK
at start of therapy and again if symptomatic
Name some bile acid sequestrants
colesevelam
cholestyramine
colestipol
Name some fibric acid derivatives
gemfibrozil
fenofibrate
bezafibrate
