learning objectives
· describe mechanism of action of statins
· side effects and controversies with statin use
· describe mechanism of action of fibrates
· describe mechanism of action of PCSK9 inhibitors
· describe mechanism of action of cholesterol absorption inhibitor
Atheroma
underlies pathology of :
modifiable risk factor :
· heart attack ·
hypertension
Stroke
· ·
dyslipidemia
·
Ischaemic heart disease
Dyslipidemia
primary disorder :
secondary disorders :
·
familial hypercholesterolaemia ·
hypothyroidism
·
polygenic lipid disorders ·
type 2 diabetes
· alcohol abuse
· thiazide diuretics and beta blockers
cholesterol
risk of heart disease increase with
high (DL ,
low HDL and high triglycerides
higher (DL Cholesterol - higher risk of CUD
greater reduction in LDL -
greater reduction in cu risk
, lipoproteins
chylomicrons ,
VLDL ,
LDL , IDC ,
HDL
apolipoproteins
· small proteins which binds lipids and allow transport
· act as
ligands for interaction with receptors
·
can be
enzyme co-factors (e g
. .
for lipoprotein lipase
lipids
exogenous
·
sources
-
absorbed from intestines as chylomicrons
·
endogenous sources
- made in the liver
-
secreted as vLDL
·
lipoprotein lipase begins to remove Ths
endogenous cholesterol synthesis
· 50 % of cholesterol made in the body is
by the liver
·
Acetyl-con precursor
· cholesterol produced from Acetyl Co-A
>
-
many steps
EOb
* important step
-
HMG-coA reductase is the rate
limiting step
· describe mechanism of action of statins
· side effects and controversies with statin use
· describe mechanism of action of fibrates
· describe mechanism of action of PCSK9 inhibitors
· describe mechanism of action of cholesterol absorption inhibitor
Atheroma
underlies pathology of :
modifiable risk factor :
· heart attack ·
hypertension
Stroke
· ·
dyslipidemia
·
Ischaemic heart disease
Dyslipidemia
primary disorder :
secondary disorders :
·
familial hypercholesterolaemia ·
hypothyroidism
·
polygenic lipid disorders ·
type 2 diabetes
· alcohol abuse
· thiazide diuretics and beta blockers
cholesterol
risk of heart disease increase with
high (DL ,
low HDL and high triglycerides
higher (DL Cholesterol - higher risk of CUD
greater reduction in LDL -
greater reduction in cu risk
, lipoproteins
chylomicrons ,
VLDL ,
LDL , IDC ,
HDL
apolipoproteins
· small proteins which binds lipids and allow transport
· act as
ligands for interaction with receptors
·
can be
enzyme co-factors (e g
. .
for lipoprotein lipase
lipids
exogenous
·
sources
-
absorbed from intestines as chylomicrons
·
endogenous sources
- made in the liver
-
secreted as vLDL
·
lipoprotein lipase begins to remove Ths
endogenous cholesterol synthesis
· 50 % of cholesterol made in the body is
by the liver
·
Acetyl-con precursor
· cholesterol produced from Acetyl Co-A
>
-
many steps
EOb
* important step
-
HMG-coA reductase is the rate
limiting step
