Hyperlipidemias Flashcards
Name the 6 groups used in the treatment of hyperlipidemias
- Statins
- Fibrates
- Resins/ Bile Acid Sequestrians
- Cholesterol absorption inhibitors/ Ezetimibe
- Niacin
- PCSK9 Inhibitors
Statins Examples
ATORVASTATIN FLUVASTATIN ROSUVASTATIN SIMVASTATIN
Stains MOA
Blocks enzyme HMG-COA reductase
Decreases intracellular total cholesterol because mevelonate needs this to become cholesterol. Decreases cholesterol makes the liver increase LDL receptors to increase cholesterol therefore bringing in LDL from blood.
(HMG-COA won’t be converted to Mavulonic acid (precursor of cholesterol) → Upregulates LDL-r
Statins S/Es
Liver Toxicity Increased liver enzymes/ aminotransferases Headache Nausea Skin Rashes Hepatotoxicity GI disturbances
Myopathy Rhabdo ( Rhabdo occurs when damaged muscle tissue releases its proteins and electrolytes into the blood.)
Contraindications of Statins
Unexplained elevated levels of aminotransferase
Pregnancy/ Teens/ Kids
Active hepatic disease
History of liver disease
Niacin MOA
Strongly inhibits lipolysis in adipose tissue, thereby reducing production of free fatty acids
Reduced liver triglyceride levels decrease hepatic VLDL production, which in turn
reduces LDL-C plasma concentrations
Decreases catabolism of apoA-1
Reduces VLDL secretion from liver
Increased HDL cholesterol
Niacin USES
● Familial hyperlipidemias
● severe hypercholesterolemia
● Low HDL cholesterol
● Elevated VLDL and LDL
Niacin Side/Effects
Intense cutaneous flushing
Hyperurcemia and Goat
Incr. risk of hyperuricemia
Niacin CONTRAINDICATIONS
Diabetes,
kidney and liver disease
hypertension
Fibrate examples
Gemfibrozil
Fenofibrate
Fibrate MOA
● PPAR-ɑ(alpha) agonist
● Peroxisome proliferator–activated receptors (PPARs) are members of the nuclear
receptor family that regulate lipid metabolism.
● PPARs function as ligand-activated transcription factors
● Upon binding to their natural ligands (fatty acids or eicosanoids) or antihyperlipidemic
drugs, PPARs are activated.
● They then bind to peroxisome proliferator response elements, which ultimately leads to
decreased triglyceride concentrations through increased expression of lipoprotein lipase (Figure 22.9) and decreased apolipoprotein (apo) CII concentration
Similarly it binds to ppr-a found in adipose tissue and when bound it inactive dates certain genes involved in fat metabolism
Fibrates USES
● Hypertriglyceridemias
● type III hyperlipidemia (dys-beta-lipo-protein-emia
decreases triglycerides
Fibrates ADVERSE EFFECTS
● mild gastrointestinal (GI) disturbances
● Formation of cholesterol gallstones- d/t increased biliary excretion
● Myositis
● Myopathy - for patients taking gemfibrozil and statins together
● Rhabdomyolysis - for patients taking gemfibrozil and statins together
● Both fibrates may increase the effects of warfarin
Leukopenia
Decreased hematocrits
Pancreatitis
Fibrates CONTRAINDICATIONS
● renal insufficiency
● gemfibrozil is contraindicated with simvastatin
● gemfibrozil with any statin should be avoided
● severe hepatic or renal dysfunction
● patients with preexisting gallbladder disease
● biliary cirrhosis
Pregnancy
Hepatorenal dysfunction
Gallbladder
Bile acid sequestrants/ Resins EXAMPLE
CHOLESTIPOL CHOLESTYRAMINE CHOLESEVALAM
Bile acid sequestrates/ Resins MOA
Bind to bile acids preventing their reabsorption back into blood because they function as anion exchange resins –> An insoluble resin/bile acid complex–> leading to no reabsorption because bile acids are made from cholesterol so hepatocytes increase ldl receptors to replace the lost cholesterol by bringing in more cholesterol leading to a decreased blood LDL
● anion-exchange resins that bind negatively charged bile acids and bile salts in the small intestine
● The resin/bile acid complex is excreted in the feces, thus lowering the bile acid concentration
● This causes hepatocytes to increase conversion of cholesterol to bile acids, which are essential components of the bile.
● intracellular cholesterol concentrations decrease, which activates an increased hepatic uptake of cholesterol-containing LDL-C particles, leading to a decrease in plasma LDL-
Bile acid sequestrates/ Resins USES
● type IIA hyperlipidemias
● type IIB hyperlipidemias
● Pruritus
● type 2 diabetes
Bile acid sequestrants/resins SIDE EFFECT
- Bloating
- Constipation
- GI disturbances, such as constipation, nausea, and flatulence,
- Decreased absorptions of fat soluble vitamins ADEK + Folate
Decreased absorptions of thiazide diuretics
Decreased absorptions of warfarin
Decreased absorptions of digoxin
Bile acid sequestrants/resins CONTRAINDICATIONS
hypertriglyceridemia
Cholesterol absorption inhibitors: EXAMPLE
EZETIMBE
Cholesterol absorption inhibitors: USE
Hyperlipidemia
Good for those unresponsive to statins
Elevated LDL cholesterol
Phytosterolemia
Cholesterol absorption inhibitors: EZETIMBE
MOA
Cholesterol binds to NPC1L1 and undergoes endocytosis with CLATHRIN-AP2 before releasing cholesterol endocytosis is blocked.
Reduces intestinal uptake of cholesterol by inhibiting sterol transporter NPC1L1
inhibits absorption of dietary and biliary cholesterol in the small intestine, leading to a decrease in the delivery of intestinal cholesterol to the liver
his causes a reduction of hepatic cholesterol stores and an increase in clearance of cholesterol from the blood
Similarly, ezetimibe inhibits intestinal uptake of dietary and biliary cholesterol at the level of the brush border of the intestine.
This happens by the interaction with NPC1L1 without affecting the absorption of fat soluble nutrients
By inhibiting cholesterol absorption ezetimibe decreases amount of cholesterol delivered to the liver hence the liver is unregulated LDL-r expression leading to higher clearance of LDL from blood
Cholesterol absorption inhibitors: EZETIMBE
SIDE EFFECTS
Diarrhea Myalgia Increased LFT Gi distress Hepatic dysfunction Myositis Abdominal pain Non-specific backspin
Cholesterol absorption inhibitors: EZETIMBE
CONTRAINDICATIONS
homozygous familial hypercholesterolemia
moderate to severe hepatic insufficiency
PCSK9 inhibitors: EXAMPLES
ALIROCUMAB
EVOLOCUMAB
PCSK9 inhibitors: USE
● heterozygous or homozygous familial hypercholesterolemia
● clinical ASCVD
● statin intolerance
PCSK9 inhibitors: MOA
Inhibits PCSK9 (enzyme) from breaking down LDL receptors
PCSK9 inhibitors are monoclonal antibodies that bind to and inactivate PCSK9 (propprotein converts subtilisin 9)
● —> more LDL receptors available for removal of LDL in circulation
● —> decreased LDL
PCSK9 inhibitors: SIDE EFFECTS
Neurocognitive problems reactions at injection site flu-like symptoms
● Expensive ● Injection site reaction ● Nasopharyngitis ● Flu like symptoms 3rd line of therapy = They are indicated as a third option after statins, and if statins don't work, Ezetimibe with a decreased concentration of statins or Ezetimibe alone. You can also try Cholestyramine/ Cholestelevel and derivatives. Where could it be given first - genetic conditions such as familial hypercholesterolemia and if patient has statin intolerance)
PCSK9 inhibitors: CONTRAINDICATIONS
Pregnancy
Angioedema
What is the first line treatment in hyperlipidemia
Statins
What is the second line treatment treatment of hyperlipidemia
Fibrates
What is the main side effect of drugs use in hyperlipidemia
Myopathy
Hepatotoxicity
Headaches
GI Disturbances
*Leukopenia and pancreatitis are specific to Fibrates
What is the best drug too reduce triglycerides
Statins
ESPECIALLY ARTOVASTATIN & RORTURVASTATIN
WHAT IS THE BEST DRUG TO REDUCE ALL HYPERLIPIDEMIAS
STATINS
Dyslipidemia group 1
Group 1= Primary Hyperchylomicronemia
-High level o chylomicrons
Dyslipidemia Group 2a
G2a= Familial Hypercholesterolemia
High LDL levels
Dyslipidemia group 2B
G2B= Familial mixed hyperlipidemia
High; VLDL, TGs, LDL
Dyslipidemia Group 3
G3= Familial Dyslipoproteinemia
Increase IDL, TG, TC
Dyslipidemia Group 5
G5= Mixed hypertriglyceridemia
Mainly increased TG & CYLOMICRONS (CHM)
Dyslipidemia Group 4
G4= Hypertriglyceridemia
Increase VLDL, TG
What is the formula used to measure lipids
Friderwald Formula
LDL-c = TC- HDL -C
_______________ mg/dL
TG/5
Stains Indication
All Hyperlipidemias ( Drastically decreases triglycerides)
Discuss the pleiotropic effect of statins
Statins may be used to treat MI because :
- It increases Nitric Oxide leading to vasodilation
- Has antithrombin effects
- Has antiinflammatory effects
- Stabilises plaque formation
- Used in patients with increased risk of stroke or MI
- Improvement of endothelial dysfunction,
- A ntioxidant properties
