Unit 05: Hyperlipidemia

Question 1

what is hyperlipidemia

Answer 1

increased amount of lipids and/or lipoproteins in the blood- risk factor for cardiovascular diseaselike atherosclerosis

*most deaths in westernized world are related to atherosclerosis which si due to cholesterol and/or lipid plaques that form in arterial blood

Question 2

What increased plasma lipoproteins are associated with atherosclerosis

Answer 2

low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL), as well as decreased high density lipoprotein (HDL) levels.

* a decrease in plasma LDL is associated with a decrease in atherosclerosis

Question 3

what condiitons result from atherosclerosis

Answer 3

Coronary artery disease, stroke and peripheral artery disease are sequelae (pathological condition resulting from disease, injury or trauma) to atherosclerosis.

Question 4

what is thoguht to cause development of atherosclerotic lesions

Answer 4

• thought to originate and develop in variety of ways - including from an intimal cell mass
• Tunica intima which is the innermost layer of an artery or vein is composed of a layer of endothelial cells (endothelium) and is supported by an internal elastic membrane
• below that is the tuna media consisting of several alyers fo smooth muscle cells and connective tissue

Question 5

what can occur upon smooth muscle proliferation in layers of vessels

Answer 5

can result in a cell mass

• LDLs cross the endothelium and make their way into mass where they can accumulate
• macrophages then enguld the LDL and become activated which prouces “foam cells” resulting in an early lesion
• damage to endothelium ensues, platelets adhere nd growth factors stimulate further vascular smooth muscle proliferation
• eventually results in fibrous plaque formation along with more lipid accumulation

Question 6

what are statins

Answer 6

structural analogs to 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA)

HMG- CoA = liver enzyme that is responsibel for producing cholesterol - statins used to lower cholesterol by inhibiting HMG CoA

Question 7

what is lovastatin and simvastatin

Answer 7

part of statin drug class

• most effective and best tolerated therapy for hyperlipidemias
• can be used as monotherapy due to high efficacy but also in combination with other drug classes
• in regards to metabolism they have a high hepatic first pass effect
• partially inhibit HMG-CoA reducing cholesterol levels but also inc LDL receptors

*result is an increase in LDL clearance and decrease ni plasma LDL

Question 9

adverse effects of statins

Answer 9

• increase in liver enzymes and risk of teratogenic effects (statinsa re contraindicted in pregnancy_
• drug interactions may be possile due to altered CYP45- enzymes

Question 10

what are VLDL secretion inhibitors?

Answer 10

• ex: niacin
• one of oldest drugs to treat hyperlipidemias
• naicin or nicotinic acid acts as a vitamin (vit B3) when converted to nicotamide adenine dibulceotide (NAD)
• unconverted niacin produces lipid lowering effects, inhibit VLDL productiona nd secretion -> thus inhibits LDL levels via effects on liver
• also inc lipoprotein lipase activity resulting in increased clearance of VLDL
• noted as best agent for raising HDLs

Question 12

formulation of niacin and adverse effects

Answer 12

• comes in rapid and slow release ablets
• those taking it may experience cutaneous flushing and pruritus (itching), mediated by prostaglandin release
• aspirin can be used to alleviate these symptoms
• elevated liver enzymes might occur although not a major concern
• GI distress and ulcers also possible

Question 13

what are bile acid sequestrants

Answer 13

cholestryamine and colestipl (colestid)

• large and highly positively charged resins that bidn to neg charged bile acids in GI tract lumen - prevents reuptake in jejunum and ileum

0 throughr eduction of bile acids, bile production increases in the liver from cholesterol -> inc in cholesterol turnover and overall increase in LDL uptake and clearance form the plasma

Question 14

when are bile acid sequestrants used? how are they formulated? what are side effects?

Answer 14

• used as second agents if statins are inffective
• available as granule packets or tabs that can be taken orally and are insolible in water and not abs by GI tract
• should eb taken with meals when bile secretion is at its highest
• constipation and bloating are common adverse effects - drug interactions may also occur due to poritive charges

Question 15

what are fibrates

Answer 15

class of amphipathic carboxylic acid sued to treat hypercolesterolemia or high colesterol

• peroxisome proliferator- activated receptors (PPARs) are pharmacologically related to fibrates and can be seud to lower lipid levels

Question 16

What is Gemfibrozil

Answer 16

Activator of PPAR

MOA unclear but thoguht to act as ligand for the nuclear transcription receptor PPAR-α.

The PPAR-α.gene receptor is found alrely in the liver and activation results in an increase in lipoprotein lipase levels which yields a decrease in VLDLs

Also decreases VLDL secretion in the liver and a modest dec in LDL often occurs as well

Question 17

what can happen following activation of PPARs

Answer 17

moderate increase in HDLs is possible

• agents are considered safe and can be used in combination with lother lipid loering agents
• should eb aovided in patietns with liver disease and their use has been shown to inc risk of cholesterol callstones

Question 18

what is Ezetimibe

Answer 18

aka zetia

• sterol absorption inhibitor
• inhibts interestinal absorption of phytosterols and cholesterol whcih decreases LDL levels
• sterol absorption inhibits target or inhibt a transport protein called NPC1L1 found in the jejuna enterocytes and is used to uptake cholesterol
• hepatic LDL receptors are also inc as is removal of LDLs from plasma
• ezetimibe is excreted in bile following ab and met and used primarily as an adjuncy with statins - appears to be very safe

Question 19

what should exetimble not be taken with

Answer 19

• do not take in combination with bile aid sequestrants bc they inhibit absorption of ezetimbe

Question 20

overview of drugs used in hyperlipidemias

Answer 20