Pharm - Cholesterol Flashcards
Drugs that are primarily used to lower cholesterol
Statins Ezetimibe Resins PCSK9 inhibitors ApoB antisense MTP inhibitor
Drugs that are primarily used to lower triglycerides
Fibrates
Drugs that are primarily used to lower both cholesterol and triglycerides
Niacin
Drugs to lower LDL cholesterol:
Statins
MOA
- Inhibit biosynthesis
- Induce LDL receptors to increase removal of LDL
- binds to HMG CoA reductase
1st line drugs for both primary and secondary prevention of ASCVD
Statins
-monotherapy or combined with resins or ezetimibe
What is the most potent statin?
Rosuvastatin
Adverse effects of statins
Mild GI disturbances Reversible memory loss Headache Rash Diabetes ***Myopathy (common) Rhabdomyolysis (rare)
Contraindications for statins
Pregnant and lactating women
Serious illness, trauma, major surgery, or liver disease
Drug-drug interactions of statins
Any drug that affects
CYP3A4 (lovastatin, simvastatin, atorvastatin) or
CYP2C9 (fluvastatin, rosuvastatin)
Ezetimibe
MOA
- Inhibits intestinal sterol absorption (NPC1L1)
- inhibits expression of hepatic LDL receptors
For patients who can’t tolerate statins
For primary and secondary preventions of ASCVD
Ezetimibe
Resins
MOA
Increase bile acid excretion
induce up regulation of LDL receptors
*not absorbed orally
Resins:
Examples
Colestipol
Cholestyramine
Colesevelam
Primary and secondary prevention of ASCVD
antitoxic agents for cardiac glycosides
Bile malabsorption caused diarrhea
Resins
___ can be used to treat hyperlipidemia in pregnant women
Resins
Side effects of resins
Relatively safe
Constipation and bloating
Increase VLDL
Side effects of ezetimibe
Few
Contraindications for resins
Diverticulitis
Elevated VLDL
Drug-drug interactions for resins
Absorption of some oral drugs may be reduced
PCSK9 inhibitors
Examples
“Proprotein convertase subtilisin hexin 9”
- alirocumab
- evilocumab
Used as an adjunct to diet and maximally tolerated statin in patients with HeFH when require additional lowering of LDL cholesterol
PCSK9 inhibitors
Side effects of PCSK9 inhibitors
Injection site reaction
Myalgia
Standard treatment for HoFH (homozygous familial hypercholesterolemia)
- low fat diet, high dose statin
- ezetimibe
- bile acid sequestrants
- niacin
- LDL apheresis
2 orphan drugs for HoFH
Mipomerson
Lomitapide
Adverse effects of Mipomerson and Lomitapide
- both: Liver toxicity (transaminase elevations and hepatic steatosis)
- lomitapide: GI side effects
- mipomerson: injection site rxns
MOA
- Mipomerson
- Lomitapide
- Binds to apoB to decrease expression
- Binds to MTP to inhibit it
* both inhibit synthesis
Drug-drug interactions for lomitapide
CYP3A4 inhibitors
P-glycoprotein substrates
Major contraindications for lomitapide and mipomerson
Hepatic diseases
*lomitapide: pregnant and lactating women
Fibrates
MOA
Bind to PPAR alpha
- increase LDL expression, increases lipolysis of triglycerides, lowers VLDL
- oxidizes FFA, lowers VLDL synthesis
- increases apoA1 expression, increases HDL
Fibrates examples
Gemfibrozil
Fenofibrate
Drug of choice for hypertriglyceridemia
Fibrates
Adverse effects of fibrates
Rare
Rashes
GI effects
*risk of myopathy and rhabdomyolysis increases when used with statins
Contraindications for fibrates
Hepatic dysfunction
Renal dysfunction
Drug-drug interactions for fibrates
- gemfibrozil: myopathy with statins
- fenofibrate: nephrotoxic drugs
- both can potentiate the anticoagulation effects of warfarin and the antihyperglyceremic effects of pioglitazone
Drugs used to lower LDL and VLDL
Nicotinic acid
MOA
- niacin, vitamin B3
- reduces Lp(a)
- increases HDL and tPA
Uses of nicotinic acids
Hypercholesterolemia by combining with resins and statins
Hypertriglyceridemia
Adverse effects of nicotinic acids
Flush (PGE2 and PGD2) and dyspepsia
-high dose=GI distress, liver dysfunction, insulin resistance, hypotension, hyperuricemia
Contraindications of nicotinic acids
Hepatic dysfunction and active peptic ulcer
True or false: if one statin is not working well enough we should add another statin
False
Never!
Which statins are prodrugs?
Lovastatin
Simvastatin
Statins are analogues of ___and inhibit ___
HMG-CoA
HMG-CoA Reductase
*rate limiting step of synthesis
Medications that inhibit CYP3A4 or CYP2C9 can ____ statins concentrations, while medications that induce them ____ statins concentrations
Increase
Decrease
____ is the first drug that inhibits intestinal absorption of cholesterol.
It is absorbed and conjugated in the intestine to an active glucuronide
Ezetimibe
Ezetimibe’s duration of action is ___
Long
22 hour half life
____ binds to NPC1L1 on GI epithelial cells to reduce absorption. What else does this drug do?
Ezetimibe
Increases expression of hepatic LDL receptors thus promoting uptake
Examples of resins:
Colestipol
Cholestyramine
Colesevelam
Resins enhance the conversion of cholesterol to ____
They also do what?
Bile acids in the liver by 7 alpha hydroxylation and increasing excretion from feces
*also induce up regulation of LDL receptors
___ can be used for pregnant women with hyperlipidemia
What else can they be used for?
Resins
Digitalis toxicity
PCSK9 inhibitors are human monoclonal antibodies that prevent PCSK9 from binding to ___
LDL receptors and degradation of LDL receptors thus increasing hepatic uptake and metabolism of LDL-C
___ are given subcutaneously once every two weeks or every month
PCSK9 inhibitors
Apo B-100 synthesis inhibitors are used to treat ___
Homozygous familial hypercholesterolemia
___ binds to and cleaves apoB mRNA in the nucleus of hepatocytes, which inhibits apoB protein leading to reduced production of VLDL and LDL
Mipomersen
Administration route of mipomersen
Subcutaneous injections once a week
Administration route of Lomitapide
Metabolism
Orally once a day
CYP3A4
True or false:
Mipomersen has no interactions with simvastatin from, ezetimibe, or warfarin
True
Fibrates decrease VLDL by ___
- Increase LPL expression
- Reducing synthesis of VLDL
- Increasing HDL
True or false: fibrates do not pass the placenta
False. They easily pass it
___ is the most effect be agent for increasing HDL and is the only agent for reducing Lp(a)
Niacin
These drugs lower LDL
Statins Resins Ezetimibe PCSK9 inhibitors ApoB antisense MTP inhibitor Nicotinic acid
These drugs lower VLDL
Fibrates
Omega 3 PUFAs
Nicotinic acid
___ acts as a PPAR alpha agonist to lower trigs
Gemfibrozil
