may be
stored
oxidised
to
bile acids
secreted
in
the bile
unaltered
EXOGENOUS
PATHWAY for lipids
ENDOGENOUS
PATHWAY for lipids
HEPATOCYTE
CHO
Fig.1a
GIT
bile acids
Bile duct
CHO
bile acids
v.portae
Fat
+ CHO
+ fatty acids
ENDOGENOUS
PARTHWAY
chylomicr
remn
CHO TG
chylomicr
TG CHO
Peripheral tissues
Fatty acids
CHO can return to plasma from the tissues in HDL particles and the
resulting cholesteryl esters are subsequently transferred to VLDL or LDL
One species of LDL lipoprotein - is associated with atherosclerosis
(localised in atherosclerotic lesions). LDL can also activate platelets,
constituting a further thrombogenic effect
ENDOGENOUS
PATHWAY for lipids
Fig.1b
EXOGENOUS
PATHWAY for lipids
GIT
HEPATOCYTE
ACoA
MVA
CHO
bile acids
Bile duct
bile acids
CHO
v.portae
CHO
LDL
receptors
CHO
HDL
CHO
CHO
from cells
CHO
VLDL
TG CHO
LDL
CHO
Uptake
of CHO
lipase
Fatty
acids
Peripheral tissues
Dyslipidemia
Dyslipidemia can be primary or secondary.
The primary forms are genetically determined
Secondary forms are a consequence of other
conditions
such as diabetes mellitus, alcoholism, nephrotic
syndrome, chronic renal failure, administration
of drug
Lipid-lowering drugs
Statins
Fibrates
LIPID-LOWERING
DRUGS
Others
Resins
ENDOGENOUS
PATHWAY for lipids
EXOGENOUS
PATHWAY for lipids
Fig.1c
GIT
GIT
HEPATOCYTE
STATINS
ACoA
Bile duct
MVA
STATINS
FIBRATES
CHO
bile acids
bile acids
CHO
v.portae
FIBRATES
CHO
HDL
CHO
CHO
from cells
CHO
LDL
receptors
VLDL
Chylomikr remn
TG CHO
FIBRATES CHO TG
LDL
CHO
RESINS
fat
+ CHO
+ fatty
acids
Chylomikr
TG CHO
lipase
Uptake
of CHO
Fatty
acids
Fatty
acids
Peripheral tissues
LIPID-LOWERING DRUGS
Statins
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A)
reductase inhibitors. The reductase catalyses the conversion
of HMG-CoA to mevalonic acid
Rosuvastatin>atorvastatin>simvastatin=lovastatin>pravastatin>fluvastatin
Statins
Statins
Pharmacokinetics
- well absorbed when given orally
- extracted by the liver (target tissue), undergo
extensive presystemic biotransformation
Simvastatin is an inactive pro-drug
Statins
A d v e r s e e f f e c t s:
-
LIPID-LOWERING DRUGS
Fibrates
stimulate the beta-oxidative degradation of fatty acids
- liberate free fatty acids for storage in fat or for metabolism in
-
striated muscle
- increase the activity of lipoprotein lipase,
hence increasing hydrolysis of triglyceride in chylomicrons
and VLDL particles
- reduce hepatic VLDL production and increase hepatic LDL
uptake
Fibrates
Other effects:
improve glucose tolerance
inhibit vascular smooth muscle inflammation
fenofibrate clofibrate
gemfibrozil ciprofibrate
Fibrates
A d v e r s e e f f e c t s:
in patients with renal impairment myositis (rhabdomyolysis)
myoglobulinuria, acute renal failure
Fibrates should be avoided in such patients and also in alcoholics)
mild GIT symptoms
LIPID-LOWERING DRUGS
A d v e r s e e f f e c t s:
GIT symptoms - nauzea, abdominal bloating,
constipation or diarrhea
resins are unappetising. This can be minimized by
suspending them in fruit juice
interfere with the absorption of fat-soluble vitamins
and drugs (chlorothiazide, digoxin, warfarin)
These drugs should be given at last 1 hour before or 4-6 hours after a resin
LIPID-LOWERING DRUGS
Others
Nicotinic acid inhibits hepatic TG production and VLDL
secretion
modest reduction in LDL and increase in HDL
A d v e r s e e f f e c t s:
flushing, palpitations , GIT disturbances
LIPID-LOWERING DRUGS
Others
Fish oil (rich in highly unsaturated fatty acids)
the omega-3 marine TG
- reduce plasma TG but increase CHO (CHO is more strongly
associated wih coronary artery disease)
-the effects on cardiac morbidity or mortality is unproven
( although there is epidemiological evidence that eating fish
regularly does reduce ischemic heart disease)
Reduced VLDL, reduced TG. May increased LDL in some
patient.
TLC Diet:
Saturated fat <7% of calories, cholesterol <200 mg/day
Consider increased viscous (soluble) fiber (10-25 g/day)
and plant stanols/sterols (2g/day) as therapeutic options
to enhance LDL lowering
Weight management
Increased physical activity
CARDINAL POINT OF
TREATMENT
Decreased LDL is primary target
Statin are the preferred initial treatment choice, shuld be used at
sufficient to lower LDL by 30%-40%.
If maximal dose of statin is unable to achieve goal of LDL, then
statin + ezetimibe or statin + bile acid sequester are useful
combination
If TG are 200 to 499 mg/dl after LDL goal has been reached,
consider adding niacin or fibrate.
If TG > 500 mg/dl, use fibrate or niacin to lower TG and prevent
pancreatitis
If HDL ow after LDL goal reached, consider adding niacin or fibrate
Case One:
Mark Guttman is a 39 year old white
male living in Stamford, Connecticut.
Mr. Guttman is here to see you for a
follow up to an initial routine health
care maintenance exam.
Case One:
What treatment strategies for hyperlipidemia
should be offered to Mr. Guttman?
1.?
2.?
3.?
4.?
5.?
6.?
Case 2
Maria De Los Santos is a 67 year old
Dominican female living in Washington
Heights. She has been your patient for 8
years and is here to discuss the results of
her fasting lipid panel.
Case 3
Nelson Nguyen is a 43 year old Vietnamese
male living in Castro Valley, CA. He has been
your patient for 5 years and is here to discuss
the results of his fasting lipid panel. He had been
lost to follow up to your practice for 2 years. He
was taking only hydrochlorathizide (was buying it
on own over past 2 years you added a second
hypertension med at the last visit)
Case 3
What treatment strategies for
hyperlipidemia should be offered to Mr.
Nguyen?
Step 8
Identify metabolic syndrome and treat, if
present, after 3 months of TLC.
Clinical Identification of the Metabolic
Syndrome Any 3 of the following must
be present:
LDL Goal
(mg/dL)
100>
130>
160>
160>
190>
130>
Treat hiperTG
If triglycerides 200-499 mg/dL after LDL goal is reached, consider
adding drug if needed to reach non-HDL goal:
intensify therapy with LDL-lowering drug, or
add nicotinic acid or fibrate to further lower VLDL.
If triglycerides 500 mg/dL, first lower triglycerides to prevent
pancreatitis:
very low-fat diet (15% of calories from fat)
weight management and physical activity
fibrate or nicotinic acid
when triglycerides >500 mg/dL, turn to LDL-lowering therapy.