Dyslipidemia Flashcards
Describe how lipids and lipoproteins function as fuel within our bodies
Fatty acids break down to form acetyl CoA, NADH, FADh2
- when attached to glycerol, fatty acids are stored as triglycerides
What makes up the lipid cell membrane?
- Phospholpids
- Glycolipids
- Cholesterol
What are the lipid-derived steroid hormones?
- Sex hormones
- Glucocorticoids
- Mineralocorticoids
Describe the function of bile salts within our bodies, and what is the main bile salt?
Function as detergents to emulsify fats
- Glycocholate is the main bile salt
Describe the function of prostaglandins within our bodies
Diverse hormone-like fxn
- smooth muscle contraction, platelet aggregation, and inflammatory response
What are the fat-soluble vitamins?
A, D, E, K
Lipids combine with what?
Carbs: Glycolipids
OR
Protein: Lipoproteins
What is the physiology of cholesterol and triglycerides? and what are they associated with?
Both are insoluble in water (hydrophobic core) and must be transported in association w/ protein (ie lipoprotein)
What are the functions/key roles of lipoproteins?
- Absorption and transport of dietary lipids by small intestines
- Transport of lipids from the liver to peripheral tissues
- Transport of lipids from the peripheral tissues to the liver (ex: HDL)
- Transport toxic foreign hydrophobic and amphipathic compounds from areas of invasion and infxn.
The intestines make what particles? and what are they?
Chylomicrons: Large triglyceride rich particles
Chylomicrons are involved in what transport?
Transport of dietary triglycerides and cholesterol to peripheral tissues and liver
Very Low Density Lipropteins (VLDL) are produced by what? and is rich in what?
- Liver
- Triglyceride rich
VLDL particles contain what? and what it is?
Apo B-100: a core structural protein (1 per VLDL particle)
What is Low Density Lipoptroein (LDL)? and what does it carry?
- Bad cholesterol
- Carried the majority of the cholesterol in the circulation.
LDL particles contain what?
Apo B-100, each LDL particle has Apo B-100 molecule
Compared to large LDL, small dense LDL are more what?
More pro-atherogenic
- longer duration, easily enters the arterial wall, and binds to intraarterial proteoglycans
What is High Density Lipoprotein (HDL)? and what does it enhance?
- Good Cholesterol
- Enhance deposition of cholesterol into the liver vice the blood vessels (reserve cholesterol transport)
What is the potential mechanism of HDL? and how do you increase HDL levels?
- Anti-athrogenic
- Increase via exercise and moderate consumption of alcohol.
What other properties does HDL have that may contribute to their ability to inhibit atherosclerosis?
- Anti-oxidant
- Anti-inflammatory
- Anti-thrombotic
- Anti-apoptotic
What levels of HDL are considered high risk, intermediate, and protective?
- High: <40 mg/dL
- Intermediate: 40-60 mg/dL
- Protective “neg CV risk factor”: >60 mg/dL
What are the 4 functions of apolipoproteins (Apo B-48, ApoB-100, Apo E)
- Structural role
- Acts as a ligand for lipoprotein receptors
- Guide formation of lipoproteins
- Serve as activators or inhibitors of enzymes involved in lipoprotein metabolism
Elevated LDL is a major risk factor for what?
CAD and cerebrovascular dz
What is the most important and modifiable risk factor for CAD and what does it cause?
Hyperlipidemia
- accelerated atherosclerosis
What medication are risk factors for elevated cholesterol?
- Thiazides: increase LDL, TC, TG (VLDL)
- Beta blockers (Propanolol): increase TG (VLDL) and lower HDL levels
- Estrogens: increased TG levels in pts w/ hypertriglyceridemia
- Corticosteriords and HIV protease inhibitors can increase serum lipids
Do you want a high or low total cholesterol to HDL ration?
Low, want a ratio of less than 4.5
5.0 is average/standard risk
Xanthelasmas are a severe hyperlipidemia manifestation, what is it?
Yellow plaques on eyelids
Xanthomas are a severe hyperlipidemia manifestation, what is it?
Hard, yellowish masses found on tendons (finger extensors, Achilles tendon, plantar tendons)
What level of total cholesterol is a high risk for CAD?
> 240 mg/dL
normal is <200
What are the normal levels of HDL in males and females?
Male: >45
Females: >55
What are normal levels of LDL in pts w/ and w/o DM?
- w/o DM: <100
- w/ DM: <70
What is a normal level of triglycerides?
<150 mg/dL
What are the key difference between ATP IV and ATP III?
- Targeting specific cholesterol goals no longer recommended
- The use of non-statins meds to lower LDL is no longer recommended
- New risk calculator used to calculate the pts 10-yr risk of ASCVD
What is the recommended caloric intake to lose weight in men and women?
Men: 1,500 to 1,800 kcal per day
Women: 1,200 to 1,500 kcal per day
What tx is important before and during statin therapy?
Diet!!
- lower fat intake (esp. saturated fat) and increased omega-3 fatty acids
What is the mainstay pharmacologic therapy for hyperlipidemia? and what labs should be checked prior to starting and after starting statins?
Statins
- AST and ALT: monitor for hepatoxicity
What are the 4 guidelines for statin therapy?
- > 7.5% risk for ACVD
- Has ACVD
- Age 40-75
- Very high LDL ( >190)
When do you use high intensity statin therapy?
- Has ACVD and age < 75
- LDL >190
- Has type 1 or 2 DM (40-75 yr old) and >7.5% risk of ACVD
When do you use moderate intensity statin therapy?
- Has ACVD and age >75
- Has type 1 or 2 DM (40-75 yr old) and < 7.5% risk of ACVD
When do you use moderate to high statin therapy?
Established 10 yr ACVD risk > 7.5% and age 40-75
What is the medication effectiveness of high intensity statins?
Lowers LDL by about 50%
What is the medication effectiveness of moderate intensity statins?
Lowers LDL by 30-50%
When do you use low intensity statins and what is the effectiveness?
- In pts who cannot tolerate high or moderate dose statins
- Lowes LDL by <30%
What is the MOA of the HMG CoA reductase (statins)
Rate limiting step in cholesterol synthesis
What are the most potent LDL lower agents?
- Pitavastatin
- Rosuvastatin
- Atorvastatin
What are the intermediate potency agents?
- Simvastatin
- Pravastatin
What are the lower potency agents?
- Lovastatin
- Fluvastatin
What organ is primarily affected by statins?
Liver (marked first pass extraction)
- all hepatically metabolized
What are the CI of statins?
- Pregnancy (cat. X)
- cholesterol is an essential component of fetal development, including steroid synthesis and membrane development
What are the ASEs of statins?
- Elevated liver enzymes
- Myopathy and rhabdomyolysis
If a pt is taking a statin and comes in w/ muscle complaints what should be evaluated?
Plasma creatine kinase (CK) levels
What is the MOA of Nicotinic Acid (Niacin)?
- At gram dose, strongly inhibits lipolysis in adipose tissue thereby reducing the free fatty acid production
- renally excreted
What are the effects of HDL and triglycerides when taking Nicotinic Acid (Niacin)?
- HDL: most effective agent for increasing HDL
- Triglycerides: lowers by 20-30% at typical dose of 1.5 to 3 grams/day
Nicotinic Acid (Niacin) is useful in tx for what?
- Familial hyperlipidemias
- Lowers plasma level of cholesterol
- Lowers plasma levels of triglycerides
What are the ASEs of Nicotinic Acid (Niacin)?
- Intense cutaneous flushing w/ uncomfortable sensation fo warmth
- Pruritus
- Hepaotoxicity
What should be taken prior to Nicotinic Acid (Niacin) to decrease flushing sxs?
Aspirin, take 30 minutes prior
What are the drugs in the Fibric Acid Derivatives?
Fenofibrate and Gemfibrizol
- Feno > Gemi in lowering triglycerides
What is the MOA of Fibric Acid Derivatives?
Binds to PPAR to decrease triglycerides and increase HDL concentration.
When would you use a Fibric Acid Derivatives?
In tx of hypertriglyceridemias and familial dysbetalipoproteinemia
What are the ASEs of Fibric Acid Derivatives?
- Gallstone formation d/t increase biliary cholesterol excretion
What 2 drug combo are CI?
Gemfibrizol + Simvastatin
What drug is apart of the Bile Acid Binding Resin class?
- Cholestyramine
- Colesevelam
- Colestipol
What is the MOS of Bile Acid Binding Resins?
The bound complex is excreted in feces which lowers the bile acid [ ] and causes hepatocytes to increase conversion of cholesterol to bile acids
What are the therapeutic use of Bile Acid Binding Resins?
- Treating different types of hyperlipidemias
What is the therapeutic use of Cholestyramine?
Relieve pruritis related to bile acid accumulation in pts with biliary stasis
What is the therapeutic use of Colesevelam?
Indicated for DM type 2 d/t glucose lowering effects
What are the ASEs of Bile Acid Binding Resins?
GI effects: constipation, nausea, and flatulence
What drug is apart of the Cholesterol Absorption Inhibitors? and what is the MOA?
Ezetimibe
- a selective inhibitor of dietary and biliary cholesterol in small intestine
What are the use of omega 3 fatty acids (PUFAs)?
Essential fatty acids used mainly for lowering triglyceride levels
What is the best tx for lowering LDL?
Statins
What is the best tx for increasing HDL?
Nicotinic acid (Niacin)
What is the best tx for lowing triglycerides?
Fibrates
What is the primary tx for hypertriglyceridemia?
Diet and exercise
What is the secondary tx for hypertriglyceridemia?
- Fibric acid derivatives (most effective) and Nicotinic acid
- Omega-3 fatty acids in adequate dose may be beneficial
What are the complications of Hyperlipidemias?
- Impotence (good for pt education)
- MI
- CVA
- Retinopathies
- NEphropathies
- Rhabdomyolysis and renal failure related to statins
What is the primary organ at risk for hypoglycemia?
Brain
- unlike other tissues, the brain cannot use free fatty acid as an energy source
What usually causes hypoglycemia?
An imbalance between insulin and glucagon
What is the first line of defense for more severe hypoglycemia? and then what hormone is used to combat hypoglycemia?
- Glucagon is the first line
- Epinephrine is the next hormone
What is factitious hypoglycemia?
If a pt tool insulin there will be high blood insulin levels and low blood C-peptide level
(exogenous insulin does not contain C-peptide)
Ethanol ingestion is a cause of what and why?
- Hypoglycemia
- Poor nutrition leads to decrease glycogen
- Metabolism of EtOH lower nicotinamide adenine dinucleotide levels and decreases gluconeogenesis
What is reactive (idiopathic) hypoglycemia?
- Sxs that occur 2-4 hrs after a meal
- Rarely indicates a serious underlying disorder
What are insulinomas? and what are they associated with?
- Insulin-producing tumor arising from beta cells of the pancreas
- Usually benign
- Associated with MEN 1 syndrome
Insulinoma can cause what?
- Sympathetic activation
- Neuroglycopenic sxs
What are sxs of sympathetic activation?
- Diaphoresis
- Palpitations
- Tremors
- HTN
- Anxiety
What are the Neuroglycopenic sxs?
- HA
- Visual disturbances
- Confusion
- Seizures
- Coma
How do you dx an Insulinoma?
72 hr fast
- pt becomes hypoglycemic and insulin does not respond appropriately to hypoglycemia (may increase, decrease or may not change at all)
What is the Whipple triad used as a diagnostic tool in a pt with Insulinoma?
- Hypoglycemia sxs brought on by fasting
- BG <50 mg/dL during symptomatic attack
- Glucose administration bring relief of symptoms
What is the tx of Insulinoma?
Surgical resection of tumor
What levels of BG usually cause sxs of hypoglycemia?
40 to 50 mg/dL
What diagnostic tool is used to dx TRUE hypoglycemia?
Whipple triad
What is the acute tx of hypoglycemia?
- If able to eat: give sugar-containing foods
- if not: administered 1/3 to 3 ampules of D50W IV
What is the management of reactive hypoglycemia management?
Dietary intervention
What is the management of a pt in an alcoholic or suspected alcohol?
Give Thiamine before administration of glucose to avoid Wernicke encephalopathy
