Treatment Of Dyslipidemia
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Which of the following strategies is recommended as lifestyle changes for dyslipidemia?
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Diet
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Weight reduction
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Exercise
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Smoking cessation
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All of the above
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About This Quiz
This quiz discusses some of the agents used in patients with dyslipidemia.
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- 2.
Which of the following is the correct mechanism of action of statins?
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Inhibit production of cholesterol in the liver
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Decrease cholesterol absorption in the intestine
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Bind bile salts in the intestine
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Stimulate lipoprotein lipase
Correct Answer
A. Inhibit production of cholesterol in the liverExplanation
(A) is the correct answer. Statins are also known as HMG-CoA reductase inhibitors. This enzyme is the rate-limiting step in the formation of cholesterol in the liver. This directly decreases the cholesterol store in the liver and forces the liver to increase the number of LDL receptors to get more cholesterol. More receptors means less LDL in the bloodstream.
(B) is the mechanism of action of cholesterol absorption inhibitors, such as ezetimibe.
(C) is the mechanism of action of bile acid sequestrants.
(D) is the mechanism of action for fibric acid derivatives.Rate this question:
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- 3.
Which of the following is the main effect of HMG-CoA reductase inhibitors?
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Decreasing HDL
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Increasing HDL
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Decreasing LDL
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Decreasing triglycerides
Correct Answer
A. Decreasing LDLExplanation
(C) is the correct answer here. The key word is "main". As mentioned before, the liver will up-regulate LDL receptors to take up more LDL particles, which will thus decrease the levels in the bloodstream. The effect is quite nice (20-60%).
(A) is false because you wouldn't want to decrease HDL.
(B) is false because the HDL-raising effect is quite minimal.
(D) is technically true but it is not the MAIN effect of these drugs. These drugs are primarily used to lower LDL levels, which, as we have seen so far, is highly important.
Actually, these statins can be combined with other drugs from other classes to get a combined effect. For instance, Advicor, which is a combination product of lovastatin and niacin, exists. Lovastatin will help lower LDL. Recall that niacin helps raise HDL. The same is true for Simcor (simvastatin and niacin). Caduet is actually a combination of atorvastatin and amlodipine, which is a nice combination to treat both atherosclerosis and coronary artery disease (discussed later).Rate this question:
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- 4.
Which of the following is the correct mechanism of action of ezetimibe?
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Inhibits cholesterol absorption in the intestine
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Decreases cholesterol synthesis in the liver
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Stimulates lipoprotein lipase
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Inhibits lipolysis in adipose tissue
Correct Answer
A. Inhibits cholesterol absorption in the intestineExplanation
(A) is the correct answer here. Indeed, ezetimibe is a cholesterol absorption inhibitor and will thus inhibit the absorption of cholesterol in the intestine. It does this by inhibits Niemann-Pick C1-like 1 protein, a transporter protein that absorbs cholesterol from the diet. Therefore, less cholesterol comes into the bloodstream via chylomicrons. This helps lower LDL.
(B) is the mechanism of action of MHG-CoA reductase inhibitors.
(C) is the mechanism of action of fibric acid derivatives.
(D) is the mechanism of action of niacin.
Actually, ezetimibe has no effect on cholesterol sources from other places. It may decrease cholesterol absorption from the diet, but the liver can still make its own by recycling bile salts. So the liver can compensate by itself. There is a drug called Vytorin, which is a combination drug of simvastatin and ezetimibe. It will decrease the absorption of cholesterol from the diet AND decrease the compensatory synthesis of cholesterol in the liver.Rate this question:
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- 5.
Which of the following are clinical teachings regarding fibric acid derivatives?
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GI effects and myopathy may occur
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Can cause gallstones by increasing biliary cholesterol secretion
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May require reduction in warfarin dosage
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Concomitant use with statins may increase myopathy risk
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All of the above
Correct Answer
A. All of the aboveExplanation
All of the above are clinical teachings of fibric acid derivatives. The following explanation will show this.
As with almost any drug, GI effects are always there, including diarrhea, N/V, etc. It is recommended that these are taken with food to help minimize these effects. Myopathy, although less of a chance than that occurring with statins, is a concern as well (A).
Increased secretion of bile cholesterol may occur and the overload may be too much to handle, leading to gallstones (B).
Fibric acid derivatives displace warfarin from albumin binding sites, allowing more free warfarin to be in the bloodstream. This is undesired as the effect of warfarin would be increased. Therefore, the warfarin dosage may have to be reduced. "May" is the key word. Although the effect is real, some patients may be perfectly fine, but the clinical teaching is still relevant (C).
These drugs with many statins may increase the risk of myopathy and rhabdomyolysis. This is serious as acute kidney failure can occur with rhabdomyolysis (D).
Fibric acid derivatives.may interact with cyclosporine. Cyclosporine, if you do not already know, interacts with many, many drugs and that will be evident throoughout therapeutic modules.Rate this question:
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- 6.
Which of the following correctly describes the mechanism of action of niacin?
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Inhibits lipolysis in adipose tissue to disrupt mobilization of free fatty acids
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Decreases cholesterol synthesis in the liver
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Decreases absorption of cholesterol in the intestine
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Bind to bile salts in the intestine
Correct Answer
A. Inhibits lipolysis in adipose tissue to disrupt mobilization of free fatty acidsExplanation
The correct answer is (A).
Niacin, also known as nicotinic acid, acts on adipose cells and decreases the activity of hormone-sensitive lipase by acting on a nicotinic acid receptor. As a result, free fatty acids are not formed as much and less are in the plasma. The liver can't form triglycerides as much since there are less free fatty acid molecules to work with. Less triglycerides means less VLDL, and thus less triglycerides in the plasma. VLDL is also the precurose to LDL, so there is less LDL as well.
(B) is actually the mechanism of action for statins.
(C) is the mechanism of action of ezetimibe
(D) is the mechanism of action of bile acid sequestrants.Rate this question:
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- 7.
Which of the following components is most greatly reduced by fibric acid derivatives?
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Triglycerides
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HDL
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LDL
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VLDL
Correct Answer
A. TriglyceridesExplanation
(A) is the correct answer. As you may recall, the idea of stimulating the PPARa is to reduce triglycerides. According to the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) from 1999, the decrease of triglycerides from fibric acid derivatives was immense (31%).
HDL is actually increased due to Apo-I and Apo-II being activated.
LDL and VLDL are decreased as well. Because ApoE is more able to help bind to the LDL receptor, it can remove VLDL and reduce the about of LDL that way. However, compared to the triglyceride-lowering effect, it is not as relevant.
An easy way to remember this is thinking of the brand name of fenofibrate, which is Tricor.
TRIcor = TRIglycerides.Rate this question:
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- 8.
Which of the following correctly describes the mechanism of action of fibric acid derivatives?
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Inhibit lipolysis in adipose tissue to disrupt mobilization of free fatty acids
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Agonize peroxisome proliferator-activated receptor alpha (PPARa)
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Decrease cholesterol synthesis in the liver
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Decrease absorption of cholesterol in the intestine
Correct Answer
A. Agonize peroxisome proliferator-activated receptor alpha (PPARa)Explanation
(B) is the correct answer here. Fibric acid derivatives are agonists of PPARa. The following will explain what that means.
PPARa is a transcription factor that will transmit signals to genes. The receptor is expressed in the liver, kidney, heart, and muscle. Stimulation of the receptor leads to increased expression of lipoprotein lipase on cell membranes. Recall that this is to break down triglycerides contained in VLDL and chylomicrons into FFAs. As a result, there will be a decrease in triglycerides.
Actually, more ApoE, which helps bind to the LDL receptor, will be able to help remove VLDL from the bloodstream to also reduce triglycerides. ApoCIII is another apoprotein that would normally inhibit lipoprotein lipase and is such decreased in expression. ApoA-I and ApoA-II are activated, which are responsible to help HDL carry cholesterol.
(A) is the mechanism of action for niacin.
(C) is the mechanism of action for statins.
(D) is the mechanism of action for ezetimbe.Rate this question:
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- 9.
Which of the following correctly describes the mechanism of action of bile acid binding resins (bile acid sequestrants)?
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Decrease production of cholesterol in the liver
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Decrease absorption of cholesterol in the intestine
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Bind to bile salts in the intestine
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Inhibit lipolysis in adipose tissue
Correct Answer
A. Bind to bile salts in the intestineExplanation
(C) is the correct answer, as may have been evident from the class name. These drugs will bind to bile salts in the intestine. The drugs themselves are not absorbed. Bile salts are normally excreted in the bile and enter the intestine and then majorly recycled, conserving cholesterol. These resins will inhibit the recycling by binding to the bile salts and eliminate the cholesterol in the feces. The liver senses this loss and forms more bile salts from its own stores of cholesterol. But it still needs more cholesterol so it will increase the number of LDL receptors to get more cholesterol from LDL particles.
(A) describes the mechanism of action of statins.
(B) describes the mechanism of action of cholesterol absorption inhibitors, such as ezetimibe.
(D) describes the mechanism of action of niacin.
Examples of bile acid binding resins (aka bile acid sequestrants) are cholestyramine and colestipol.Rate this question:
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- 10.
Which of the following is the main effect of bile acid sequestrants?
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Decrease LDL
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Decrease VLDL
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Decrease triglycerides
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Decrease HDL
Correct Answer
A. Decrease LDLExplanation
(A) is the correct answer. BEcause the liver must compensate for the loss of cholesterol, it will increase the number of LDL receptors to take up more LDL particles.
(B) is technically true as well, but the decrease in LDL is honestly the most clinically important.
(C) is actually false, but the decrease in LDL is much more relevant.
(D) is a trick answer as lowering HDL is not desirable when treating dyslipidemia.
While some answers are technically true, the clinical importance of LDL, as seen by guidelines from 2004, is evident. LDL reduction is an important part of treatment of dyslipidemia.Rate this question:
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- 11.
According to the 2013 American College of Cardiology/American Heart Association (ACC/AHA) Prevention Guidelines, which of the following is true?
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Emphasis is now placed on assessing cardiovascular risks rather than cholesterol goals
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There are "Four Statin Benefit Groups"
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Patients over 75 should receive high-intensity statin therapy
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Weight management and lifestyle changes are still recommended
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All of the above
Correct Answer
A. All of the aboveExplanation
(E) is the correct answer here. In the latter part of 2013, new guidelines for the management of dyslipedmia were released. The previous guidelines, called Adult Treatment Panel III, were released in 2004 and contain the information with which we are most likely familiar. These new guidelines actually abandon LDL goals and instead focus more on cardiovascular risks.
(A) is correct. Assessment of cardiovascular risk, especially with dyslipidemia, is important. The ACC/AHA have put out an online calculator which helps determine cardiac and stroke risks. The guidelines set thresholds for a 10-year risk of heart disease and a 7.5% or higher stroke risk, with treatment options from that. The emphasis really has been shifted away from LDL goals.
(B) is also very true. These statin groups are the following:
1. Patients with clinical atherosclerotic cardiovascular disease (ASCVD) without New York Heart Association (NYHA) Class II-IV heart failure or hemodialysis. ASCVD is very all-encompassing, including history of stroke and MI)
2. Individuals with LDL >190 mg/dL
3. Individuals aged 40-75 with diabetes with LDL of 70-189 mg/dL without clinical ASCVD
4. Individuals without clinical ASCVD or diabetes but aged 40-75 and LDL of 70-189 mg/dL AND have 10-year ASCVD risk of 7.5% or higher.
These groups help direct treatment. the guidelines, if you ever decide to read them, also delineate treatment if NOT in one of these groups.
(C) is also true. This might be surprising because there is a risk of using high-intensity statins, which is a "high-dose" statin, such as atorvastatin 80mg, in the elderly. High-intensity statins are daily doses that lower LDL by greater than 50% This risk is from the adverse effects associated with statins. Guidelines now state that if you are greater than 75 and you need a statin, give a high-intensity one.
(D) is very much true. As with any guidelines, weight management and lifestyle changes (exercise, smoking cessation, etc.) are always recommended.
While this question is intended to have the student think about the guidelines, it cannot be substituted for the guidelines themselves. A true understanding of the guidelines can only come from reading them altogether. There are numerous sources of guideline summaries that other organizations and groups have published to help streamline understanding.Rate this question:
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- 12.
Which of the following are adverse effects of niacin?
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Flushing
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Exacerbation of peptic ulcer
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Hyperglycemia
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Myopathy
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All of the above
Correct Answer
A. All of the aboveExplanation
(E) correctly describes the adverse effects of niacin. The following explains why.
One of the major adverse effects of niacin is flushing. Prostaglandin synthesis mediated via nicotinic acid, which is coupled to cyclooxygenase. Prostaglandin D is released from macrophages and causes cutaneous vasodilation. This can be remedied with aspirin, ibuprofen, etc. Aspirin 81 mg PO is commonly used to prevent the flushing, but the flushing may go away on its own in a few weeks.
Exacerbation of a peptic ulcer is another big gastrointestinal issue with niacin. The issue is large enough that in those who have a history of peptic ulcers, niacin is contraindicated.
Hyperglycemia is mainly a problem in those that are uncontrolled.
Myopathy is a problem with statins for some. While the myopathy for niacin is not as problematic, the concern is still there. Actually, for patients who cannot take statins for whatever reason, niacin is a good choice.Rate this question:
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- 13.
Which of the following are concerns of statins?
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AST/ALT elevations
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Myopathy
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Drug-drug interactions
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A and B
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All of the above
Correct Answer
A. All of the aboveExplanation
(E) is the correct answer here. All of the above are concerns regarding statins.
AST/ALT elevations are indicators of liver toxicity. This is very rare but it can occur. The levels of these enzymes are based on upper limit of normal (ULN). If a patient is 50x normal, there is a problem. This is known as rhabdomyolysis. Skeletal muscle cells break down so much that acute kidney failure becomes a grave concern. In this situation, the statins may be stopped. For the curious ones, the urine turns a dark brown. Therefore, it's important to obtain a baseline CK just to keep track.
Drug-drug interactions are huge and that is due to CYP enzyme metabolism. This will be discussed in greater detail, but the information is important to have when dealing with certain statins.
With all this discussion about adverse effects, it may seem that statins are bad. On the contrary, for many, statins are well-tolerated and actually work. These are effects of which clinicians must be aware.Rate this question:
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- 14.
Which of the following correctly characterizes homozygous familial hypercholesterolemia?
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Individuals cannot make HDL
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Individuals cannot make LDL receptors
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Individuals cannot absorb cholesterol
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Individuals live long, healthy lives
Correct Answer
A. Individuals cannot make LDL receptorsExplanation
(B) is the correct answer. These are individuals who cannot make LDL receptors. So these drugs that ultimately increase LDL receptors (statins, bile acid sequestrants, etc.) will not work in these individuals.
(D) is an interesting false statement. Individuals with this condition die young and extract LDL for blood. This is a very rare disease and quite difficult to manage.
There are some drugs that can help manage this condition. The main problem of this disease is the diet. Since LDL receptors cannot be made, the diet must be very strict. Lomitapide (Juxtapid) prevents the assembly of Apo-B-containing lipoproteins, such as LDL and VLDL. This drug changes the fat content in the liver, leading to fat-soluble nutrient deficiency. Therefore, these individuals must have daily supplements of vitamin E, linoleic acid, DHA, and others. It can't be taken with food and the individual must have a low-fat diet. On top of that, it is contraindicated with inhibitors of 3A4, such as azole antifungals and HIV protease inhibitors.Rate this question:
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- 15.
Which of the following is false regarding the uses of niacin?
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It decreases VLDL and LDL
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It decreases triglycerides
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Its vitamin effect requires higher doses
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It increases HDL
Correct Answer
A. Its vitamin effect requires higher dosesExplanation
(B) is the false statement here. Niacin is also known as vitamin B3, and it is an important vitamin. However, the dose of niacin required for the vitamin effects is significantly lower than the cholesterol-lowering effects. For reference, the dose for the vitamin effect is in the milligrams, whereas the dose for the cholesterol-lowering effect is in the grams (approximately 1-2 grams). The difference is enormous.
The other statements are correct. As mentioned through the mechanism of action, because the liver has less of a store of free fatty acids to make triglycerides (B), it cannot make as much VLDL and thus less LDL (A).
Actually, the liver reduces it uptake of HDL and leaves it into the blood, thereby increasing HDL. This is one of the major benefits of niacin as few agents can actually do this. The increase is about 10-30%!Rate this question:
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- 16.
Which of the following is false regarding simvastatin?
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It is contraindicated with azole antifgunals
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Its maximum dosage is 10 mg qhs with diltiazem or verapamil
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Its maximum dosage is 20 mg qhs with amlodipine
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80 mg qhs should be the start dose in every patient
Correct Answer
A. 80 mg qhs should be the start dose in every patientExplanation
(D) is the false statement. 80 mg qhs is "dangerous". The risks of adverse effects, such as myopathy are quite great. this dosage is reserved for those who have been taking it that high for at least 1 year. It shouldn't be the starting dose.
(A) is true. Azole antifungals (fluconazole, itraconazole) are potent inhibitors of CYP enzymes. They are strictly contraindicated with simvastatin.
(B) is also true. When taking either diltiazem or verapamil, the maximum dose of simvastatin is 10 mg qhs.
(C) is true. When taking either amlodipine, amiodarone, or ranolazine, the maximum dose of simvastatin is 20 mg qhs.
Just a quick note here. You may have noticed that the dosages of simvastatin are "qhs". This is obviously deliberate. Simvastatin should be taken at bedtime because cholesterol synthesis goes up between meals (problematic during sleep). Simvastatin is at night because it has a relatively short half-life (about 3 hours). This is contrasted with atorvastatin, which has a 14-hour half-life and thus can be taken any time during the day.Rate this question:
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- 17.
Which of the following statins is NOT metabolized by CYP3A4?
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Simvastatin
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Fluvastatin
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Atorvastatin
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Lovastatin
Correct Answer
A. FluvastatinExplanation
(B) is the correct answer here. Fluvastatin is metabolized by 2C9.
The point of this question is to understand that three statins: simvastatin, atorvastatin, and lovastatin, are metabolized by 3A4. 40% of drugs have some sort of interaction (metabolized, inducer, inhibitor) with 3A4 and makes the interaction relevant. For instance, the HIV protease inhibitor, ritonavir, is one of the most potent inhibitors of 3A4. Concomitant administration of ritonavir and simvastatin is so dangerous (less metabolism of simvastatin and thus higher risk for adverse effects) that it is contraindicated. The same is true for drugs such as cyclosprine, erythromycin, and even gemfibrozil.
Fluvastatin is not without interactions. A fair amount of drugs use 2C9 in some way, such as phenytoin and amiodarone.Rate this question:
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- 18.
Which of the following is the most relevant adverse effect of bile acid sequestrants?
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Systemic toxicities
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Decreased absorption of other drugs
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Myopathy
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Abdominal discomfort
Correct Answer
A. Decreased absorption of other drugsExplanation
(B) is the correct answer. Because these are resins, they can bind to other drugs and decrease their natural absorption. This is a problem if the drug is already poorly absorbed. To account for this, other drugs should be taken 1 hour before or 4 hours after. This does include statins.
(A) is false because bile acid sequestrants are not absorbed and systemic toxicities are not relevant.
(C) is false because myopathy, relevant in other classes, is not relevant here.
(D) is actually an important side effect, but the MAIN one. While abdominal discomfort is a common side effect, it tends to disappear as a person takes the drugs for a good amount of time.Rate this question:
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- 19.
Which of the following is false regarding omega-3 fatty acids?
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They help decrease triglyceride synthesis from the liver
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Belching and altered taste are examples of adverse effects
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They are clinically proven to protect individuals from atherosclerosis
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They may potentially increase bleeding times
Correct Answer
A. They are clinically proven to protect individuals from atherosclerosisExplanation
(C) is the false statement. Omega-3 fatty acids are NOT proven to protect against atherosclerosis. The outcome studies are lacking and the evidence is not yet convincing.
(A) is true. that is one of the hallmarks of these drugs. The lowering effect is on par with fibrates and niacin (30-40%). There are no changes to a slight increase in BOTH HDL and LDL.
(B) is true. The "fishy" taste after taking a "fish oil tablet" is what is meant here.
(D) is surprisingly true. These drugs interact with anticoagulants and may potentially lead to an increased bleeding time.Rate this question:
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- 20.
Which of the following is true regarding ezetimibe?
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It is synergistic with statins for LDL-lowering effects
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There are some GI effects associated with it
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It interacts with bile acid sequestrants
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It interacts with cyclosporine
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All of the above
Correct Answer
A. It is synergistic with statins for LDL-lowering effectsExplanation
(E) is the correct answer. All of the above are true regarding ezetimibe. The following will explain why that is the case.
(A) is true, as mentioned before. The combination effect of these two drug classes will help decrease teh compensatory cholesterol synthesis by the liver due to the loss of cholesterol from ezetimibe. The synergistic effect grants about a 21% decrease in LDL.
(B) is also true. Most drugs have some sort of GI adverse effect of nausea or vomiting. This is relatively uncommon, though.
(C) is true because bile acid sequestrants can decrease the absorption of drugs due to its resins. That is indeed the case here.
(D) is true. It seems that cyclosporine interacts with many drugs, and that is the case. That is the same thing here as concentrations of ezetimibe may increase in the presence of cyclosporine.Rate this question:
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Mar 21, 2023Quiz Edited by
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Jun 02, 2014Quiz Created by
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