Hyperlipidemia Flashcards
Follow the following steps
1. a nascent chylomicron from the small intestine
2.????
3.????
- a chylomicron stored in the adipose tissue as fatty acids using lipoprotein lipase
- chylomicron remnant stored in the liver
follow the following steps
1. VLDL released from the liver
2.??????
3.??????
4.??????
- free fatty acids stored in adipose tissue using lipoprotein lipase
- IDL that turns into LDL
- LDL that is rather stored in the liver or used by the muscles
what are the normal levels of the following
LDL,HDL,cholesterol, triglycerides
triglycerides <150
LDL <130
HDL 60<
cholesterol <200
what are the causes of hyperlipidemia
- Individual lifestyle (lack of exercise and high
consumption of fatty acid). - Inherited gene defect in lipoprotein metabolism
- More commonly, combination of genetics and lifestyle
factors.
what causes atherogenicity?
LDL>HDL
what is the HMG COA Reductase Inhibitors (statins) MOA?
- HMG CoA reductase inhibitors
- increase the number of cell surface LDL receptors.
- decrease TG and increase HDL
what are the therapeutic uses for HMG CoA reductase inhibitors
Effective in lowering plasma cholesterol levels in all types of
hyperlipidemias.
reduced coronary events, ischemic stroke, & death from heart
failure.
It has become standard practice to initiate reductase inhibitor
therapy immediately after acute coronary syndromes, regardless
of lipid levels.
Atorvastatin, rosuvastatin, & simvastatin are the most effective
LDL cholesterol–lowering statin drugs.
Because cholesterol synthesis occurs predominantly at night,
reductase inhibitors should be given in the evening if a single
daily dose is used, except atorvastatin and rosuvastatin because
they have much longer t1/2
Absorption is generally enhanced by food (with the exception of
pravastatin).
Simvastatin is given in doses of 5–80 mg daily.
However, patients who are homozygous for familial
hypercholesterolemia lack LDL receptors and, therefore, benefit
much less from treatment with these drugs.
Use of statins is linked to ~50% reduction in several forms of
cancer (American Society of Clinical Oncology 2005 Annual
Meeting).
Statins have been shown to prevent bone loss.
What are the side effects of statins
1) Biochemical abnormalities in liver function evaluate
liver function and measure serum transaminase levels
periodically (LFTs)
2)Myopathy and rhabdomyolysis
-In most of these cases, patients usually suffered from renal
insufficiency or were taking drugs such as cyclosporine,
itraconazole, erythromycin, gemfibrozil, or niacin,Plasma creatine kinase levels should be determined
regularly
3)• Teratogenic Contraindicated during pregnancy and in
nursing mothers.
4) Hepatic insufficiency can cause drug accumulation
5) They also should not be used in children and teenagers except selected patients.
What are the drug drug interactions for statins
Statins elevate warfarin levels monitor INR.
• Statins are metabolized by the cytochrome P450 system; drugs or foods (eg. grapefruit juice) that inhibit cytochrome
P450 activity increase the risk of hepatotoxicity and
myopathy.
What is the MOA for niacin (vitamin B3 nicotinic acid)
strongly inhibits lipolysis in adipose tissue by inhibiting hormone sensitive lipase
the primary producer
of circulating free fatty acids, which is the major precursor for triacylglycerol synthesis in the liver. Liver triacylglycerol is
required for very low density lipoprotein (VLDL) production.
Thus, both plasma triacylglycerol (in VLDL) and cholesterol (in VLDL and LDL) are lowered.
What are the side effects of niacin
1) intense cutaneous flush (accompanied by an
uncomfortable feeling of warmth) and pruritus
-Tolerance to the flushing reaction usually develops within a few days.
-administration of aspirin or another NSAID prior to taking niacin decreases the flush, which is prostaglandin-mediated.
2)Niacin inhibits tubular secretion of uric acid and, thus, predisposes
to hyperuricemia (in about 20% of patients) and gout.
3)Some hepatotoxicity.
4)Severe myopathy and rhabdomyolysis have been reported with
concomitant use of statins and niacin (major interaction). This
interaction is much higher in the Chinese descent
Note:The sustained-release formulation of niacin, which is taken once daily at bedtime, reduces bothersome initial adverse effects.
What are fibrates ?
Gemfibrozil & Fenofibrate are derivatives of fibric acid.
Fenofibrate is more effective than gemfibrozil
What’s the MOA of fibrates
PPARs agonist
Peroxisome proliferator activated receptors (PPARs) are nuclear receptors that regulate lipid metabolism.
Fibrate binding to these receptors (activates PPARα) results in reduction
of plasma triacylglycerol concentration by increasing the expression
of lipoprotien lipase (partly extracellular).
What are the sides effects for fibrates
a. The most common adverse effects are mild gastrointestinal disturbances like nausea.
b. Lithiasis: because these drugs increase biliary cholesterol excretion, there is a predisposition to the formation of cholesterol gallstones.
Don’t use in patients with previous gallbladder disease.
c. Myositis (inflammation of a voluntary muscle) can occur with these
drugs; thus, muscle weakness or tenderness should be evaluated.
-4) Severe myopathy and rhabdomyolysis have been reported during
concomitant use of statins and fibric acid derivatives, especially gemfibrozil generally avoid (major interaction). Yet, not an absolute contraindication.
What are the drug drug interactions with fibrates
Fibrates compete with the warfarin for binding sites on plasma proteins (major interaction)
Some experts recommend that the anticoagulant dose be reduced by approximately one-third to one-half initially, then gradually adjusted as necessary according to INR monitoring
