Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
107 Cards in this Set
- Front
- Back
|
What is hyperlipidemia?
|
The presence of excess fats or lipids in the blood.
|
|
|
What is dislipidemia?
|
A condition marked by abnormal concentrations of lipids or lipoproteins in the blood.
|
|
|
What are lipoproteins?
|
Macromolecular assemblies that contain fat and proteins.
|
|
|
What is the lipid component of lipoproteins comprised of?
|
Free and esterified cholesterol, triglycerides, and phospholipids
|
|
|
What is the protein component of lipoproteins comprised of?
|
Apolipoproteins (or apoproteins), which function as structure and as ligands
|
|
|
What do lipoproteins do?
|
Transport lipids/cholesterol (water-insoluble) through bloodstream (water-based)
|
|
|
How do lipoproteins differ?
|
In lipid content and type of apolipoproteins
|
|
|
What are the four lipid components? Define.
|
1. Cholesterol - precursor to steroid hormones and bile salts
2. Triglycerides (TG) - storage form of energy 3. Phospholipid - contains hydrophilic and hydrophobic component 4. Cholesterol Esters - more hydrophobic than cholesterol |
|
|
What are the five lipoprotein components? Define.
|
1. Chylomicrons (CM) - synthesized from fatty acids of dietary TGs and cholesterol
2. Very Low Density Lipoprotein (VLDL) - synthesized by the liver. 3.Intermediate Density Lipoprotein (IDL) - VLDL remnants 4. Low Density Lipoprotein (LDL) - transports cholesterol to liver; peripheral cells 5. High Density Lipoprotein (HDL) - transports cholesterol from tissue to liver |
|
|
Rank the different types of lipoproteins from bad to good.
|
Chylomicron>VLDL>IDL>LDL>HDL
|
|
|
What is the major lipid constituent, the site of synthesis, and the mechanism of catabolism for Chylomicrons and remnants?
|
MLC: Dietary triglycerides and cholesterol
SOS: Intestine MOA: Triglyceride hydrolysis by lipoprotein lipase (LPL), uptake by liver |
|
|
What is the major lipid constituent, the site of synthesis, and the mechanism of catabolism of VLDL?
|
MLC: Hepatic triglycerides
SOS: Liver MOA: Triglyceride hydrolysis by LPL |
|
|
What is the major lipid constituent, the site of synthesis, and the mechanism of catabolism of IDL?
|
MLC: Cholesterol esters and hepatic triglycerides
SOS: Product of VLDL catabolism MOA: Converted to LDL by hepatic lipase (HL), uptake by liver |
|
|
What is the major lipid constituent, the site of synthesis, and the mechanism of catabolism of LDL?
|
MLC: Cholesterol Esters
SOS: Product of VLDL catabolism MOA: Uptake by LDL receptor |
|
|
What is the major lipid constituent, the site of synthesis, and the mechanism of catabolism of HDL?
|
MLC: Phospholipids, cholesterol esters
SOS: Intestine, Liver, Plasma MOA: Transfer of cholesterol ester to VLDL and LDL, uptake by hepatocytes |
|
|
Describe the construction of a basic lipoprotein.
|
The very inside core is lipid component made up of cholesterol esters and triglycerides. The outside is more hydrophilic and comprised of un-esterified cholesterol and phospholipids.
|
|
|
What is the site of synthesis and function of ApoA-1?
|
SOS: Liver, Intestine
Function: Structural in HDL; reverse cholesterol transport |
|
|
What is the site of synthesis and function of ApoB-100?
|
SOS: Liver
Function: Structural protein of VLDL, IDL, LDL; LDL receptor ligand |
|
|
What is the site of synthesis and function of Apo-B48?
|
SOS: Intestine
Function: Structural protein of chylomicrons |
|
|
What is the site of synthesis and function of ApoC-II?
|
SOS: Liver
Function: Lipoprotein lipase (LPL) cofactor |
|
|
What is the site of synthesis and function of ApoE?
|
SOS: Liver, Brain, Skin, Gonads
Function: Ligand for LDL receptor and receptors binding remnants; reverse cholesterol transport |
|
|
Describe the exogenous lipid transport system.
|
Fat and cholesterol that come from the diet are absorbed into the intestine and chylomicron is made. Chylomicron can be broken up by Lipoprotein-Like-Lipase and will be free fatty acids and chylomicron remnants. Chylomicron remnants are taken up by the liver.
|
|
|
Describe the endogenous lipid transport system.
|
Cholesterol is synthesized by the liver. Liver takes free fatty acids and makes VLDL. VLDL is broken down into IDL and LDL and free fatty acids are released and can be stored or used as energy. IDL and LDL are taken up in the liver by LDL receptors.
|
|
|
Briefly describe atherosclerosis.
|
When high levels of LDL in the blood it can leak into endothelial spaces of the blood vessel. This LDL is oxidized and taken up by monocytes forming foam cells. Foam cells accumulate, form plaques, and eventually cause injury to the blood vessel. This can occlude the blood vessel.
|
|
|
What are the six available treatments for hyperlipidemia?
|
1. HMG-CoA reductase inhibitors (STATINS)
2. Bile acid sequestrants (RESINS) 3. Nicotinic Acid (NIACIN) 4. Fibric acid derivatives 5. Cholesterol absorption inhibitor (EZETIMIBE) 6. Omega-3 fatty acids (FISH OIL) |
|
|
What are the seven HMG-CoA reductase inhibitors (Statins) on the market?
|
1. Atorvastatin (Lipitor)
2. Fluvastatin (Lescol) 3. Lovastatin (Mevacor) 4. Pitavastatin (Livalo) 5. Pravastatin (Pravachol) 6. Simvastation (Zocor) 7. Rosuvastatin (Crestor) |
|
|
What is the mechanism of action for statins?
|
The rate-limiting step in hepatic cholesterol synthesis is the conversion of HMG-CoA to mevalonate via HMG-CoA reductase. Statins are structural analogs of HMG-CoA and as such, competitively inhibit the HMG-CoA reductase. The liver compensates for this by increasing the number of high-affinity LDL receptors. This increases the removal of LDL from the blood.
|
|
|
What are the six possible pleiotropic (Cardioprotective benefits) effects of statins?
|
1. Anti-inflammatory actions
2. Plaque stability 3. Antithrombotic effects 4. Reverse endothelial dysfunction 5. Antioxidant 6. Decreased platelet activation |
|
|
What effect do statins have on total cholesterol, LDL, triglycerides, and HDL?
|
Decreases in TC, LDL, and TGs
Increase in HDL |
|
|
What determines what time of day statins should be taken?
|
Half-Life
The longer half-lives can be taken any time of day. |
|
|
Rank the seven statins by half-life.
|
Atorvastatin(15-30) > Rosuvastatin(20) > Pitavastatin(12) > Simvastatin(2-3) > Lovastatin(2.9) > Pravastatin(1.3-2.8) > Fluvastatin(0.5-2.3)
|
|
|
What seven CYP3A4 inhibitors do statins have a drug interaction with?
|
1. Azole antifungals (itraconazole and Ketoconazole)
2. Ritonavir 3. Cyclosporine 4. Amiodarone 5. Macrolides (erythromycin and clarithromycin) 6. Verapamil and Diltiazem 7. Grapefruit juice |
|
|
Which CYP2C8/2C9 inhibitor do statins have a drug interaction with?
|
Gemfibrozil
|
|
|
Which transport inhibitors do statins have a drug interaction with?
|
Cyclosporine
Gemfibrozil |
|
|
True/False: Statins have no drug interactions with Red Yeast Rice.
|
False: It is a duplication of treatment
|
|
|
What is Red Yeast Rice?
|
It is an extract available as an OTC dietary supplement. It is a product of Monascus Purpureus yeast.
|
|
|
How does Red Yeast Rice work?
|
It contains monacolins which inhibit cholesterol synthesis. Monacolin K (aka Lovastation)
|
|
|
What are the issues with Red Yeast Rice?
|
The contents vary widely because not regulated by the FDA.
Some products have been found to be contaminated with toxins (citrinin). |
|
|
What are the side effects associated with statins?
|
Common:
GI disturbances Headache Fatigue Increase in LFTs Myalgia Less Common: Hepatotoxicity Myopathy Rhabdomyolysis |
|
|
What is myopathy and how could we decrease the incidence of it?
|
Myopathy is muscle aches or weakness AND subsequent increase in creatinine phosphokinase (CPK) > 10 x ULN
We can decrease the incidence by monitoring CPK levels, using cautiously or avoiding altogether in renal impairment, and teaching the patient to recognize the symptoms. |
|
|
What is rhabdomyolysis and how is it damaging?
|
Rhabdomyolysis is the breakdown of muscle due to injury (physical or chemical)
This is released into circulation and the myoglobin damages kidney cells. This can lead to acute renal failure. |
|
|
What are some predisposing conditions to rhabdomyolysis?
|
Sepsis
Hypotension Electrolyte imbalance Uncontrolled seizure disorder Surgery/Trauma Sever endocrine disease |
|
|
What are some contraindications for statins?
|
Absolute:
Hepatic disease Pregnancy Breast feeding Rhabdomyolysis Precautions: Renal disease Uncontrolled seizure disorder Alcoholism |
|
|
Give some information on the investigational new statin.
|
PPD 10558 is in Phase II clinical trials. It is being developed for patients who have experienced statin-associated myalgia.
Claims: Will not increase LFTs or CPK levels Less distribution into muscle, less systemic exposure Will have a very low risk of drug interactions (not metabolized by CYP450) |
|
|
Name three Bile acid sequestrants (resins).
|
1. Cholestyramine (Questran)
2. Colestipol HCl (Colestid) 3. Colesevelam (Welchol) |
|
|
What is the mechanism of action of bile acid sequestrants?
|
BAS are large non-absorbale polymers that bind bile acids in the intestine. This prevents the bile acid absorption and recycling and diverts hepatic cholesterol to synthesis of new bile acids. The liver compensates by increasing the number of high-affinity LDL receptor which increases the removal of LDL from the blood.
|
|
|
How do Bile acid sequestrants affect TC, LDL, TGs, and HDL?
|
Decreases TC and LDL.
Increases HDL. No change or an increase in TGs |
|
|
How are bile acid sequestrants administered?
|
For powder/granule formulations, administer as a suspension. Mix 60-180 mL of water, milk, or juice. May also mix with applesauce or soft cereal. Take within one hour of meal.
|
|
|
What measures have to be taken when administering other medications with bile acid sequestrants?
|
Other medications have to be taken at least one hour before or at least 4-6 hours after each dose of BAS
|
|
|
True/False: Bile acid sequestrants are not significantly absorbed.
|
True
|
|
|
Which seven drugs will bile acid sequestrants decrease the absorption of?
|
1. Digoxin
2. Carbamazepine 3. Mycophenolate 4. Levothyroxine 5. Warfarin 6. Beta Blockers 7. Thiazide Diuretics |
|
|
What are some side effects of bile acid sequestrants?
|
GI disturbances - bloating, nausea, vomiting, flatulence, constipation
Pancreatitis Increased TGs No systemic absorption, so no systemic effects |
|
|
What are the contraindications of bile acid sequestrants?
|
Absolute:
Biliary Obstruction TGs>400mg/dL Relative: TGs>200mg/dL Precaution: Some formulations contain aspartame, avoid in Phenylketonuria patients |
|
|
Name Nicotinic Acid (Niacin) formulations.
|
Regular-Release:
Niacor (Rx) Niacin (Supplement) Extended-Release: Niaspan (Rx) Sio-Niacin (Supplement) Combination - Simcor: Simvastatin/Niaspan and Advicor: Lovastatin/Niaspan |
|
|
What is the mechanism of action of Niacin?
|
Inhibits the lipolysis of TGs in adipose tissue.
Reduces transport of free fatty acids to the liver. Decreases hepatic TG synthesis. Increases ApoB degradation. Reduces hepatic VLDL production, LDL. Also reduces hepatic clearance of HLD, raises HDL. |
|
|
What is Niacin's effect on TC, LDL, TGs, and HDL?
|
Decreases TC, LDL, and TGs.
Increases HDL. The big effect is the decrease in TGs. |
|
|
What are the distribution and metabolism of Niacin?
|
Niacin is well absorbed and widely distributed.
It has extensive first-pass metabolism. |
|
|
When are the peak concentrations of regular-release and extended-release Niacin?
|
Peak Concentrations:
Regular-release: 45 minutes Extended-Release: 4-5 hours |
|
|
What causes the flushing with Niacin?
|
The flushing can occur within 20 minutes with regular-release and can last an hour. The extended-release version slows down flushing and decreases severity. Niacin binds to receptors on epidermal cells and elicits arachidonic acid response which makes prostaglandins which go through the dermis and bind to receptors there.
|
|
|
Is there anything that can block the flushing reaction?
|
Aspirin taken 30-60 minutes before Niacin can block the COX pathway and prevent this from happening.
|
|
|
What are three drug interactions with Niacin?
|
1. Alcohol
2. Bile acid sequestrants 3. Warfarin |
|
|
How does alcohol interact with niacin?
|
May exacerbate flushing
|
|
|
How do bile acid sequestrants interact with niacin?
|
May decrease niacin absorption. Need to separate dosing.
|
|
|
How does warfarin interact with niacin?
|
May increase INR
|
|
|
What are five side effects of niacin?
|
1. Cutaneous flushing
2. GI effects 3. Hepatotoxicity 4. Hyperglycemia 5. Hyperuricemia |
|
|
Can you develop a tolerance to the flushing with niacin?
|
Tolerance can happen in 7-14 days
|
|
|
What are the GI effects of niacin?
|
Nausea
Dyspepsia Vomiting Diarrhea (Taking with food improves tolerance) |
|
|
What are the contraindications and precautions with niacin?
|
Contraindications:
Hepatic disease Arterial bleeding Precautions: Surgery Diabetes Gout |
|
|
What are the fibric acid derivatives (fibrates)?
|
Fenofibrate (Tricor)
Gemfibrozil (Lopid) |
|
|
What is the mechanism of action of fibrates?
|
Fibrates are ligands for the PPAR-alpha protein. PPAR-alpha regulates transcription of genes involved with lipid metabolism. The mechanism of action is not fully understood, but fibrates:
- Increase expression of Apo-AI, increases HDL - Increases synthesis of LPL, decreases TGs - Reduces expression of ApoC-III, decreases hepatic TGs, synthesis of VLDL |
|
|
What is the effect of fibrates on TC, LDL, TGs, and HDL?
|
Decreases TC, LDL, and TGs (patients with high TGs can have low LDL. Fibrates would normalize LDL cholesterol content and increase the size making it more easily cleared - so the LDL could increase)
Increases HDL |
|
|
What are the pharmacokinetics of fibrates?
|
Fibrates are metabolized via glucuronidation. A majority of the dose is excreted renally, so it requires renal dosing and precautions. Fibrates are not metabolized by CYP450, but they are inhibitors.
|
|
|
What does fenofibrate inhibit?
|
Weakly inhibits CYP2C8, CYP2C19, and mildly inhibits CYP2C9.
|
|
|
What does gemfibrozil inhibit?
|
Inhibits CYP2C8, CYP2C9, and also inhibits OATP1B1.
|
|
|
What five drugs have interactions with Fibrates?
|
1. Statins
2. Bile acid sequestrants 3. Cyclosporine 4. Ursodiol 5. Warfarin |
|
|
What is the drug interaction between fibrates and statins?
|
Increased risk of rhabdomyolysis (gemfibrozil)
|
|
|
What is the drug interaction between bile acid sequestrants and fibrates?
|
BAS decrease absorption of fibrates.
Separate dosing |
|
|
What is the drug interaction between cyclosporines and fibrates?
|
May potentiate renal dysfunction.
|
|
|
What is the drug interaction between ursodiol and fibrates?
|
Fibrates may counteract the effects of ursodiol.
|
|
|
What is the drug interaction between warfarin and fibrates?
|
Fibrates may potentiate warfarin's effects.
|
|
|
What are side effects of Fibrates?
|
Fibrates are generally well tolerated.
Side Effects: GI effects - nausea, vomiting, dyspepsia, diarrhea Risk of myopathy, rhabdomyolysis when combined with statin (gemfibrozil) Cholelithiasis (gallstones) |
|
|
What are the contraindications and precautions of fibrates?
|
Contraindications:
Biliary cirrhosis Gallbladder disease Hepatic disease Renal failure Simvastatin+Gemfibrozil Precautions: Renal impairment/disease Pregnancy (category C) Breast Feeding Cholelithiasis |
|
|
What is ezetimibe (Zetia)?
|
A cholesterol absorption inhibitor.
|
|
|
What is the mechanism of action of ezetimibe?
|
Ezetimibe acts at the brush border of the small intestine and inhibits the NPC1L1 mediated uptake of cholesterol. This prevents absorption of dietary cholesterol and cholesterol excreted in bile. The liver compensates by increasing the number of high-affinity LDL receptors which increases the removal of LDL from the blood.
|
|
|
What is the effect of ezetimibe on TC, LDL TGs, and HDL?
|
Decreases TC, LDL, and TGs.
Increases HDL. |
|
|
What are the pharmacokinetics of ezetimibe?
|
Ezetimibe has extensive conjugation via glucuronidation. It undergoes enterohepatic circulation.
|
|
|
True/False: Ezetimibe absorption is affected by the presence of a fatty meal.
|
False
|
|
|
What is the half-life of ezetimibe?
|
Approximately 22 hours
|
|
|
Do we have to adjust dosing of ezetimibe in the elderly?
|
Plasma concentrations are higher in elderly patients, but no dose adjustment is recommended.
|
|
|
What four drugs have interactions with ezetimibe?
|
1. Bile acid sequestrants
2. Cyclosporine 3. Warfarin 4. Gemfibrozil |
|
|
What is the interaction between bile acid sequestrants and ezetimibe?
|
BAS reduce ezetimibe absorption. Should take ezetimibe at least 2 hours before or 4 hours after BAS.
|
|
|
What is the interaction between cyclosporine and ezetimibe?
|
Concentrations of both may increase (mechanism not clear)
|
|
|
What is the interaction between warfarin and ezetimibe?
|
There have been case reports of INR increases.
|
|
|
What is the interaction between gemfibrozil and ezetimibe?
|
The safety of this combination has not been established.
|
|
|
What are the side effects of ezetimibe?
|
Ezetimibe is generally well-tolerated.
There are rare allergic reactions. Cholecystitis (inflammation of gallbladder) and cholelithiasis (gallstones) have been reported |
|
|
What are the precautions with ezetimibe?
|
Pregnancy (Category C)
Breastfeeding Elderly Hepatic disease Myopathy |
|
|
What are the active ingredients in Omega-3 fatty acids?
|
Eicosapentaenoic acid (EPA 465mg)
Docosahexaenoic acid (DHA 375mg) |
|
|
What is the only licensed Omega-3 fatty acid pharmaceutical?
|
Lovaza (formerly Omacor)
|
|
|
What is the mechanism of action of fish oil?
|
The mechanism of action is not fully understood. Fish oil decreases fatty acids by increasing degradation and decreasing synthesis. They also decrease TG and VLDL synthesis, act as PPAR agonist (alpha and gamma), and increase LPL activity.
|
|
|
What effect does fish oil have on TC, LDL, TGs, and HDL?
|
There is no change or a modest raise in TC and LDL.
Decreases TGs. No change in HDL. |
|
|
What are the pharmacokinetics of fish oil?
|
Fish oil (Omega-3 fatty acids) appear to be well-absorbed orally. Serum concentrations of EPA/DHA increase with dietary consumption. Fish oils are broken down into polyunsaturated fatty acids (PUFAs) and then oxidized to CO2 and water. Unclear if PK is affected by hepatic or renal impairment.
|
|
|
What are the two drug interactions with fish oil?
|
1. Warfarin
2. Antihypertensives |
|
|
What is the interaction between warfarin and fish oil?
|
Omega-3 fatty acids are known to inhibit platelet aggregation, so there is a theoretical risk of bleeding. There are case reports of INT increases.
|
|
|
What is the interaction between antihypertensives and fish oil?
|
Case reports of blood pressure reductions in hypertensive patients.
|
|
|
What are the side effects of fish oil?
|
GI effects - nausea, burping, bad breath, taste disturbance
Prolonged bleeding time Elevated hepatic enzymes |
|
|
What are the contraindications and precautions of fish oil?
|
Contraindications:
Fish hypersensitivity Precautions: Anticoagulant therapy Bleeding Surgery |
|
|
What effects does fish oil have on TC, LDL, TG, and HDL?
|
Only decreases TGs
|
