hyperlipidemias Flashcards
1
Q
lipids
- lipids serve as energy sources, _____ precursors and _____ molecules and are packed within _____
- lipoproteins are _____ aggregates that transport _____ and _____ in the blood
- _____: large, not dense, high lipid content
- _____: smaller, less dense, moderate-high lipid content
- _____: very small, very dense, low lipid content
- _____ which deliver fatty acids to muscle for _____ synthesis and for storage in adipose tissue/hepatocytes
- -cholesterol: component of _____/ precursor to _____ and _____ compounds
- -triglycerides: main storage form of _____
-elevation of both cholesterol and triglycerides play an important role in _____ and other disorders
A
hormone signal lipoproteins macromolecular triglycerides cholesterol chylomicrons LDL HDL apolipoproteins ATP cell membrane steroid steroid fuel heart disease
2
Q
dyslipidemias cause:
- _____
- _____
- _____
- _____
- _____
- elevated _____/ low _____
- elevated _____
A
atherosclerosis hypertension MI stroke peripheral arterial occlusive disease LDL HDL triglycerides
3
Q
causes of hyperlipidemia
- diet
- diabetes
- chronic _____ failure
- _____
- _____ storage diseases
- sepsis
- physiological _____
- _____ excess
- _____
- oral _____ replacement therapy
- beta blockers, diuretics, glucocorticoids, _____- used for HIV also
A
renal hypothyroidism glycogen stress alcohol lipodystrophy hormone protease inhibitors
4
Q
LDL particles
- LDL particles not taken up by LDL receptors in tissues migrate to the _____ of _____ and bind to _____
- they are subject to _____ resulting in lipid _____
- this modified LDL is internalized by _____ in _____
- continued accumulation of oxidized LDL results in formation of _____ cells which are _____ phagocytes
- foam cells may undergo _____ and release _____
- this promotes a local _____ response
- _____ is initiated
- there is release of _____ which may destabilize atherosclerotic plaques
A
intima blood vessels peptidoglycans oxidation peroxidation scavenger receptors phagocytic monocytes foam cholesterol rich apoptosis free radicals atherosclerosis matrix metalloproteinases
5
Q
HDL formation
- HDL formation occurs in the _____ and _____
- pre-beta-HDL particles are _____ shaped and are bound to _____ (_____)
- this binding converts cholesterol into _____
- these esters migrate to the core of the molecule called _____ particles which is _____ in shape
- HDL seres as a reservoir for exchangeable _____ and plays a role in cholesterol _____
- HDL removes excessive _____ from cells and transports it to the _____
- cholesterol efflux occurs when _____ cholesterol molecules from plasma membrane of cells bind to _____ particles
- this extrahepatic cholesterol is carried by HDL to liver and this _____ explains HDL’s protective role
A
liver small intestine disk PLTP phospholipid transfer protein cholesterol esters alpha-HDL spherical apolipoproteins homeostasis cholesterol liver unesterified HDL reverse transport
6
Q
cholesterol balance
- cholesterol is converted in liver to _____ and secreted in the bile
- _____ elimination occurs but most cholesterol is recycled by _____ proteins in the _____ back to the liver and back into _____
- this is called _____
- absorption of dietary cholesterol is _____ determined and ranges from 20-80%
- studies have showed a definite link between elevated plasma lipids and _____ disease
- increase _____ and low _____ levels
A
bile acids fecal high affinity transport distal ileum bile enterohepatic circulation genetically cardiovascular LDL HDL
7
Q
HMG-CoA reductase inhibitors
- statins act by _____ inhibiting _____ (rate-limiting enzyme of the _____ pathway)
- because statins are similar in structure to _____ on a molecular level, they will fit into the enzymes active site and compete with the native substrate (HMG-CoA)
- this competition reduces the rate by which HMG-CoA reductase is able to produce _____, the next molecule in the cascade that eventually produces cholesterol
A
competitively HMG-CoA reductase mevalonate HMG-CoA mevalonate
8
Q
HMG-CoA reductase inhibitors
- by inhibiting HMG-CoA reductase, statins block the pathway for synthesizing cholesterol in the _____
- most circulating cholesterol comes from _____ rather than diet
- lowered liver production results in lover _____ levels
- cholesterol synthesis appears to occur mostly at _____
- _____ at night work bestq
A
liver internal manufacture blood cholesterol night short half life statins
9
Q
HMG-CoA reductase inhibitors
- reduced levels of liver cholesterol compensate by _____ (up-regulating) _____ receptors to draw cholesterol out of the _____
- proteases cleave membrane-bound _____, which then migrate to the nucleus and bind to the _____ which increase _____ of various proteins, most notably _____ receptor
- the LDL receptor is transported to the _____ membrane and binds to passing _____ and _____ particles, mediating their uptake into the liver (_____)
- this results in less LDL circulating in _____
A
synthesizing LDL SREBP- sterol regulatory element binding proteins SRE- sterol response element transcription LDL liver cell VLDL LDL bile blood
10
Q
HMG-CoA reductase inhibitors
statins
-enable more _____ to be delivered to the _____ resulting in a 60% reduction in serum LDL cholesterol (70% liver uptake/ 30% other tissues)
-_____ bioavailability/ good safety profile
-large extensive _____ metabolism
–lovastatin and simvastatin are prodrugs
–other statins are active compounds
-metabolized by CYP450 therefore drug interaction with other drugs metabolized by the same enzyme
-very effective in treatment of _____
A
LDL liver low first pass hypercholesterolemia
11
Q
pharmacological consequences
- decreased inflammation: decreased C-reactive protein
- reversal of endothelial dysfunction: improved _____ response to NO
- decreased thrombosis/ _____ formation
- improved _____ of _____
- decrease in cardiovascular morbidity and mortality
- fluvastatin is least potent
- atrovastatin and rosuvastatin most potent
A
vasodilator
ateroma
stability
atherothrombotic plaque
12
Q
HMG-CoA reductase inhibitors
adverse effects:
-relatively free of adverse effects
-may elevate serum levels of hepatic enzymes and can cause hepatitis
-less frequent adverse effects are:
–_____, _____, _____ (destruction of muscle cells releasing myoglobin leading to renal failure)
-increase in ALT/AST (lover homeostasis)
-hepatic toxicity wit concurrent alcohol use
A
myalgia
myopathy
rhabdomyolysis
13
Q
bile acids-binding resin
- cholestyramine
- colestipol
- _____ molecular weight _____ containing _____ ion (_____)
- chloride ion is exchanged for _____ in the _____: forming _____ complex
- resin-bile complex cannot be reabsorbed in the _____
- to obtain maximum effect, they must be taken before each _____ and at _____
- the bile acid-resin complex is excreted via the _____
A
cationic large polymer chloride Cl- bile acids gut bile acid-resin distal ileum meal bedtime feces
14
Q
bile acids-binding resin
- moderately effective
- reduce LDL by 28%
- excellent safety record
- why? bc it is not _____ and there is no _____ effect
- great for patients who cannot tolerate other drugs and for _____ patients who may require long term therapy
- bloating and dyspepsia
- decreased absorption of _____
- bind to digoxin, levothyroxine and warfarin
A
absorbed
hepatic first pass
young
fat-soluble vitamins
15
Q
inhibitors of cholesterol absorption
- reduce cholesterol absorption by _____
- includes both dietary and biliary cholesterol
- also inhibit production of hepatic VLDL
- available: plant sterols (_____: present in fruits/vegetables)
- ezetimibe: decreases cholesterol transport from the _____ into _____ reducing absorption by 50%
- does not reduce absorption of _____ and _____ or _____
- decreased plasma _____, decreased _____ cholesterol, decreased liver _____, decreased _____ production
- single daily dose may reduce cholesterol by 20%
- very effective in combination with a _____
A
small intestine stanons micelles enterocytes fatty acids triglycerides fat-soluble vitamins LDL chylomicron LDL VLDL statin
