Lipid lowering drugs

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