32 - lipid lowering drugs Flashcards
steps and formation of plaque growth in vessels
vessel damage cholesterol particles inflitrate site plaque develops within artery grows as more shit is incorporated could continue to grow and occlude artery or rupture and multiple clots may form
_ _ _ and _ contribute to
plaque build up too.
LDL’s
Triglycerides
cholesterol - damaged vessel
inflammation IL4 and IL5
mechanical procedures to treat plaque build up in vessels
Balloon angioplasty to treat
blocked coronary artery
Stent placement in carotid
artery
High pressure jetting - best
Pharmacological treatments center around _ and _ componetns of plaque buildup
cholesterol (LDL and HDL) and triglycerides
stores cholesterol in the blood stream
LDL - stores in BS
HDL - regulates LDL storage and promotes excretion
“Poor Lipid Biochemistry” can contribute other health
problems
_ a cluster of biochemical and
physiological abnormalities associated with type 2 diabetes
and cardiovascular disease
Metabolic Syndrome:
insulin resistance
high BP and triglyceride levels
low HDL cholesterol
total cholesterol levels
total non-HDL
cholesterol calculated,
below _ considered
desirable
130 non HDL cholesterol is desirable
High levels of free fatty
acids are thought to
contribute to _ and lead to
a slew of health issues
insulin resistance
A disorder of lipoprotein metabolism, including lipoprotein
overproduction or deficiency.
may be manifested by elevation of the
total cholesterol, the “bad” low-density lipoprotein (LDL) cholesterol and the
triglyceride concentrations, and a decrease in the “good” high-density lipoprotein
(HDL) cholesterol concentration in the blood
Dyslipidemia
Drugs used to treat Dyslipidemia
- Derivatives of _ acid
- Nicotinic Acid
- Bile Acid sequestrants
- Inhibitors of HMG CoA Reductase (_)
- Cholesterol Absorption inhibitors
- Derivatives of fibric acid
- Nicotinic Acid
- Bile Acid sequestrants
- Inhibitors of HMG CoA Reductase (statins)
- Cholesterol Absorption inhibitors
Drugs used to treat Dyslipidemia
agonist of PPARa receptor
Increase peripheral lipolysis
decrease hepatic triglyceride
production
Major net effect: Reduce levels of triglycerides
Fibric Acid derivatives
(PPARs) function as transcription factors regulating the expression of genes. PPARs play essential roles in the regulation of cellular differentiation, development, and carbohydrate, lipid and protein metabolism. α (alpha) is expressed in liver, kidney, heart, muscle, adipose, and other tissues.
Activated PPAR alpha stimulates fatty acid
catabolism in the liver by inducing the
expression of genes controlling the betaoxidation
Derivatives of fibric acid
Activated _ stimulates fatty acid
catabolism in the liver by inducing the
expression of genes controlling the betaoxidation
PPAR alpha
Derivatives of fibric acid
are primarily used for lowering _ (~50%)
triclycerides
side effects - abdominal discomfort, diarrhea, nausea, etc
Drugs used to treat Dyslipidemia
Agonist for GPR 109A (and 109B) receptor
Inhibitor of diacylglycerol acyltransferase
GPR109A activation inhibits lipolysis and atherogenic
activity(formation of fatty plaques)
increase HDL cholesterol
block triacyl glycerol (triglyceride) production
Nicotinic acid
*Both niacin and
niacinamide are
suitable as vitamin B3
Only niacin (nicotinic acid) is suitable to treat dyslipidemia. Has
nothing to do with vitamin B3 activity and requires doses that are
much higher
major benefits of niacin (nicotinic acid
increase _
decrease _
increase HDL
decrease triglyceride
niacin (nicotinic acid) side effects
flushing vasodilation is due to _ release
also have pruritus (itching)
GI distress
due to histamine release
and arachidonic acid - PGs on SM
Drugs used to treat Dyslipidemia
blocks reabsorption of bile acids
Liver removes cholesterol by converting it to bile acid
keep bile
acids from getting
absorbed as they pass
through the intestine
bile salts via enterohepatic circulation stimulate hepatocytes to secrete more bile salts (which break down fat)
Bile Acid sequestrants
Bile acids = A family of
cholesterol like acids
Does more of this if bile acid is prevented from
recirculating
In the liver, cholesterol is converted to bile acid which is excreted to
the intestine through the action of C7H. By preventing bile acid
resorption, the sequestrants increase cholesterol metabolism to _
cholesterol gets converted to bile acid
Drugs used to treat Dyslipidemia
Diminish cholesterol by inhibiting HMG CoA reductase
inhibition of the cholesterol biosynthetic pathway
statins
Statins lower cholesterol.
They are helpful for people at risk of having a heart attack.
Men and women over 65 who are at risk for cardiovascular
disease but don’t have any known heart problems might
benefit from cholesterol-lowering drugs, a new study suggests
The task force recommends the use of low- to moderate-dose of _ in adults without a history of heart disease and who
don’t have current signs of problems but who have one or
more risk factors, including high cholesterol, diabetes, high
blood pressure or smoking, and a calculated 10 percent risk of
a heart attack in the next 10 years
statins
Drugs used to treat Dyslipidemia
_ drugs - inhibit LDL formation, NPC1L1: a transport protein moving cholesterol from lumen into enterocyte (and ultimately back into the blood) This transport protein is blocked
inhibit absorption of dietary cholesterol
inhibt reabsorption of biliary cholesterol
lower LDL cholesterol
Cholesterol Absorption inhibitors
selectively inhibs intestinal absorption
NO CHANGE IN HDL
side effects - unique because no bloating or farting
reduction of cholesterol absorption results in less _
less LDL
