Flashcards in Lipid Metabolism, Dyslipidemias and Treatment 3 Deck (16):
Adipose tissue, especially adipose cells around visceral organs can contribute negatively to CV health, name some of its adverse endocrine effects.
increase insulin resistance (increased glucose)
increased leptin (increased appetite)
increased SNS (HTN)
increased angiotensin (HTN)
increased inflammatory mediators
increased FAs (increased atherosclerosis)
** esp. important as adipose cells get larger
How does insulin resistance contribute to dyslipidemia?
in insulin resistance, HSL is not inhibited and FFAs and glycerol are shuttled to the liver via VLDL, leading to greater numbers of VLDL in circulation
6. List 3 drugs that function to raise HDL and to lower TG.
niacin (also lowers LDL-C)
note that alcohol and estrogens can uncouple the relationship between HDL and TG
6. What are the effects niacin (B3) on cholesterol synthesis?
niacin B3 reduces VLDL production (reduces TG and then also less LDL, at high doses) and blocks catabolism of HDL
modest evidence for CVD reduction; long-term safety
6. Name 3 mechanism for the action of niacin to reduce.
1. reduces lipolysis from adipocytes
2. reduces diaclyglycerol acyltransferase (responsible for VLDL synthesis)
3. reduces apo A-1 catabolism, while permitting removal of cholesterol from HDL
6. Why aren't all patients on niacin given its efficacy and safety?
major side effects:
flushing and itching (reduced with aspirin)
abdominal pain, ulcers
hyperglycemia (contraind. with DM2)
hepatotoxicity (contraind. with liver disease)
myalgia/myopathy esp with statins (esp among Asians)
contraind. with pregnancy
6. What are the major actions of fibrates on lipid metabolism?
decrease VLDL production
increase lipolysis of VLDL and IDL
end result is reduced TG, increased HDL_C [maybe decrease in LDL-C, depending on TG]
What is the mechanism of action for fibrates?
activation of PPAR-a synth of apo A-I and A-II
activation of LPL and reduces apo CIII (LPL inhibitor)
stimulates hepatic FA uptake and B-oxdaiton (reduces TG syn)
6. What adverse effects should you consider when using fibrates?
stomach aches are pretty common
concentration of bile pool can lead to call stones
phenylfibrate is best with statins, lower risk of myalgia/myopathy
possibly blocks active secretion of creatine
contraindications: liver disease, sever kidney disease, pregnancy
6. How do omega-3-fatty acid's effect lipid levels?
reduces TG (20-50%)
modest effects on HDL-C related to TG reduction
LDL-C may increase or not change
6. Discuss the mechanism and safety of omega-3 FA.
complex mechanism: inhibits DGAT, reduces lipolysis, stimulates hepatic fatty acid catabolism by B oxidation (less TG)
long history of safety with adverse effects including eructation, flatulence, abdominal pain and bruising/bleeding
Broadly speaking describe the process of deciding on lipid medications.
1. estimate the 10 yr risk to the patient of developing CVD
2. intensity of therapy is adjusted to patient's risk of CVD, currently recommendations have gotten away from using hard numerical guidelines
What is the most severe risk to those patients with TG over 500mg/dL.
high risk of pancreatitis
6. What is the first line treatment of patients with dysilipidemia and TG<500mg/dL
STATINS! and more statins!
note with increasing TG, it can be helpful to add niacin as a secondary treatment
Which disease of dyslipidemia is known to cause xanthomata?
familial hypercholesteroliema (fatty deposits in the tendons)