DSA: Drugs for Lipid Disorders Flashcards
(69 cards)
1
Q
- Normally, you always start a patient off w/ diet and exercise to control lipids, what is one situation that requires drug therapy from the start?
A
Familial hypercholesterolemia
2
Q
- VLDL is increased by what four things?
A
- Total fat
- sucrose
- fructose
- EtOH
3
Q
- You advise a patient to lose weight for their lipid levels, and they successfully do so. How long does their weight have to be stable in order to draw a lipid panel to see if weight loss alone was sufficient for management?
A
- 1 month
4
Q
- What are some general dietary recommendations for a patient w/ hypercholesterolemia regarding the following:
- Calories from fat
- saturated fat
- cholesterol
A
- limit total calories from fat to 20-25% of daily intake
- saturated fats should be less than 8% of daily intake
- cholesterol intake should not exceeed 200 mg/day
*doing these things can result in a 10-20% reduction in serum cholesterol
5
Q
- Name 7 Statins we need to know for this exam
A
- Atorvastatin
- Fluvastatin
- Lovastatin
- Pitavastatin
- Pravastatin
- Rosuvastatin
- Simvastatin
6
Q
- What enzyme do statins inhibit?
- what is significant about this enzyme?
A
- They are HMG-CoA reducatase inhibitors
- HMG-CoA is the rate limiting enzyme in cholesterol synthesis.
7
Q
- What is the MOA of statin drugs?
- how much can they reduce serum LDL?
A
- Statins inhibit HMG-CoA reductase, which inhibits de novo cholesterol synthesis thus depleting intracellular supply of cholesterol.
- __this causes the cells to increase the number of LDL receptors that bind to circulating LDL, thus decreasing serum levels by 20-55%
8
Q
- Most statins have half lives of 1-3 hours, however what are the half lives of:
- Atorvastatin?
- Pitavastatin?
- Rosuvastatin?
A
- Atorvastatin: 14 hours
- Pitavastatin: 12 hours
- Rosuvastatin: 19 hours
9
Q
- Which statin drugs are metabolized primarily by CYP3A4?
A
- Lovastatin
- Simvastatin
- Atorvastatin
10
Q
- Which statin drugs are metabolized by CYP2C9?
A
- Fluvastatin
- Rosuvastatin
11
Q
- Which statin undergoes limited CYP450 biotransformation?
A
- Pitavastatin
12
Q
- Which statin drug is not metabolized by CYP450s?
A
- Pravastatin
13
Q
- Most statins have oral absorption anywhere from 40-75%
- which statin is almost completely absorbed?
A
Fluvastatin
14
Q
- **what is the order of potency of the 7 statins we need to know?**
A
- Atorvastatin=rosuvastatin>simvastatin>pitavastatin=lovastatin=pravastatin>fluvastatin
15
Q
- What are some therapeutic benefits of statin drugs?
A
- Plaque stabilization
- improvement of coronary endothelial fxn
- inhibition of platelet thrombus formation
- anti-inflammatory effects
16
Q
- Statins are taken at night except for which three drugs?
A
- Longer acting drugs
- Atorvastatin (14 hours t1/2)
- Pitavastatin (12 hours t1/2)
- Rosuvastatin (19 hours t1/2)
17
Q
- What are the adverse effect statins have on the liver?
A
- Increased serum aminotransferase activity, which can be up to 3X normal in patient w/ liver disease or hx of EtOH abuse
18
Q
- What are the adverse effects statins can have on muscles?
A
- Creatine Kinase levels may increase
- Rhabdo, leading to myoglobinuria, may rarely lead to renal injury
- Myopathy
19
Q
- Myopathy is a possible adverse effect of statin monotherapy.
- Myopathy is more likely when statins are combined with what other drug class?
A
fibrates
20
Q
- Which statin is l_east likely to increase warfarin levels thus less likely to induce bleeding complications in warfarin patients?_
- why
A
- Pravastatin, because it is not metabolized by CYPs
21
Q
- Statins are not recommended for what patient populations?
A
- Pregnant women, lactating women, or those likely to become pregnant
- not recommended in patients w/ liver disease or skeletal muscle myopathy
22
Q
- When would you use a statin in a pediatric patient?
A
- kids who have homozygous and some patients with heterozygous familial hypercholesterolemia
23
Q
- What is the MOA of NIAICIN (nicotinic acid, vitamin B3)?
A
- Niacin inhibits the lipolysis of triglycerides in adipose tissue, which is the primary producer of circulating ffa’s
24
Q
- By reducing circulating free fatty acids, Niacin has what four subsequent effects?
A
-
liver produces less VLDL
- LDL decreases subsequently
- catbolic rate for HDL is decreased
- fibrinogen levels are reduced
- tissue plasminogen activator levels are increased (clot busting *after clot formed* by activating plasminogen, which makes plasmin, which breaks apart fibrin cross linking)
25
* What is the most commonly experienced side effect of Niacin, and what can be done to alleviate this presentation?
* an intense cutatneous flush accompanied by an uncomfortable feeling of warmth that occurs after each dose when drug is started, or when the dose is increased.
* can take NSAID (aspirin, ibuprofen)
26
* What side effect is likely to happen if a diabetic patient is started on Niacin?
* **Hyper**glycermia due to _niacin-inducled insulin resistance_
* __patients w/ insulin resistance often show signs of acanthosis nigricans due to elevated insulin levels
27
* What is the most effective drug to increase serum HDL?
Niacin (sketchy)
28
* Niacin can reduce excretion of uric acid and cause hyperuricemia
* what drug should it be given with in patients at risk for gout?
allopurinol
29
* Niacin should be avoided in patients with what two diseases?
* hepatic disease
* active peptic ulcer
30
* what are the two fibric acid derivatives (fibrates)?
* Gemfibrozil
* Fenofibrate
31
* What is the half life of gemfibrozil?
* What is the half life of fenofibrate?
* gemfibrozil: 1.5 hours
* fenobibrate: **20** hours
32
* Fibrates are well absorbed (\>90%) when they are taken with?
food
33
* What is the MOA of fibrates?
* agonists for peroxisome proliferator-activated receptor alpha (PPARa, a nuclear receptor)
34
* When PPARa is activated
* what does it regulate?
* what things are increased, what things are decreased?
* it binds to DNA and regulates the expression of genes encoding proteins involved in lipoprotein structure and function.
* lipoprotein lipase, apo A-1, apo A-II expression increased
* apo C-III expression is decreased
35
* What are the major effects of fibrates?
* six
* increased oxidation of fatty acids in liver and striated muscle
* increased lipolysis of TG via lipoprotein lipase
* intracellular lipolysis in adipose tissue is decreased
* VLDL levels decrease
* LDL levels modestly decrease in most
* HDL levels increase modestly
36
* Which lipid-lowering agent is _useful for treating hypertriglyceridemia that results from treatment with viral protease inhibitors_? (eg. saquinavir, indinavir, or nelfinavir)
* Fibric acid derivatives
* Gemfibrozil
* Fenofibrate
37
* Which lipid-lowering agent is indicated for use in patients with type III familial hyperlipoproteinemia (_dysbetalipoproteinemia)_?
* AKA deficiency of ApoE
* Fibric acid derivatives
* Gemfibrozil
* Fenofibrate
38
* Which lipid-lowering agent would you use in management of a patient with _hypertriclyceridemia_ where _VLDL predominates_?
* Fibric acid derivatives
* Gemfibrozil
* Fenofibrate
39
* What medication should you be careful when prescribing it to this woman?
* why?
* Fibrates
* They increase the risk of cholelithiasis due to an increase in the cholesterol content of bile
* Native americans, women are already at higher risk of this, so fibrates increases this risk further
40
* What are some other contraindications for the use of fibrates?
* Myopathy, **especially when combined with statins**
* fibrates can potentitate anticoagulants
* avoided in hepatic or renal dysfunction patients
* can rase LFTs 3x normal
* pregnancy safety has not yet been established
41
* What are they three bile acid sequestrant drugs that we need to know? (Resins)
* Colestipol
* Cholestyramine
* Colesevelam
42
* What class of drugs is described as: _large polymeric cations, insoluble in water, totally excreted in feces without alteration?_
resins
43
* What is the MOA of Resin drugs?
* Prevent intestinal reabsorption of bile acids; **liver must** **use cholesterol to make more**
44
* Resins cause increased bile acid excretion, which causes the liver to _enhance the conversion of cholesterol to bile acids via 7a-hydroxylation_
* **_the decline in hepatic cholesterol stimulates which hepatic receptor?_**
* LDL receptor, which enhances LDL clearance and lowers levels, but is partially offset by the enhanced cholesterol synthesis due to loss of bile acids bound to resins
45
* Which drug class can be prescribed as _monotherapy_ or in _combination with niacin_ for treatment of _Type IIa and Type IIb hyperlipidemia?_
* Resins
* Colestipol
* Cholestyramine
* Colesevelam
46
* Which drug would you use to relieve the symptoms of pruritus in patients w/ bile acid accumulation?
resins
47
* Bile acid sequestrants (resins) can be used for primary hypercholesterolemia, and reduce levels by approximately what percentage?
20% reduction
48
* High doses of resin drugs can induce a deficiency of what vitamins and why?
* impairs absorption of fat soluble vitamins
* reduced ADEK
49
* What are some of the numerous drugs that interact with bile acid sequestrants?
* tetracycline
* phenobarbital
* digoxin
* warfarin
* pravastatin
* fluvastatin
* aspirin
* thiazide diuretics
50
* Bile acid resins should be given **at least 1 hour before, or at least 2 hours after** most drugs
* what is the exception?
* can be given with niacin
51
* The use of bile acid resins should be avoided in patients with what conditions?
* diverticulitis, prexisting bowel diseae, cholestatis
52
* What is the first and only approved member of the cholesterol aborption inhibitor drug class?
* Ezetimibe
53
* Pharmacokinetics of Ezetimibe
* solubility in water
* excretion
* half life
* highly water **in**soluble
* majority excreted in feces
* 22 hour half life
54
* What is the MOA of Ezetimibe
* which transport protein is inhibited?
* Selectively inhibits intestinal absorption of cholesterol and phytosterols (plant sterols)
* inhibits NPC1L1
55
* Which drug is effective at lowering cholesterol even in the absence of dietary intake?
* why?
* Ezetimibe
* because it inhibits reabsorption of cholesterol excreted in bile
56
* Ezetimibe is indicated for use in various causes of elevated cholesterol levels: how is it used in the following situations
* primary hypercholesterolemia?
* homozygous familial hypercholesterolemia?
* mixed hyperlipidemia?
* primary--\> monotherapy or in combo w/ statin (does not say which)
* homozygous--\> combo with _atorvastatin_ or _simvastatin_
* mixed--\> combo with _fenofibrate_
57
* What is the only known contraindication for administration of ezetimibe?
* don't give with bile acid sequestrant due to impaired absorption of eszetimibe
58
* Which drug class is most effective at lowering LDL?
* Statins
59
* Drug class that has the highest lowering effect on TGs?
fibrates
60
* drug class that has the highest increase in HDL?
Niacin
61
* Drug class w/ minimal effect on TGs?
* Resins
62
* What is Lomitapide used for?
* treatment of homozygous familial hypercholesterolemia
63
* What is the MOA of Lomitapide?
* what does it inhibit
* inhibition prevents?
* Inhibits microsomal triglyceride transfer protein (**MTP**) in the lumen of the ER
* prevents the assembly of apo-B containing lipoproteins in enterocytes and hepatocytes
* results in reduced production of chylomicrons and VLDL and subsequently reduces plasma LDL [cholesterol]
64
* Lomitapide is a substrate and inhibitor of which enzyme?
CYP3A4
65
* Adverse effects of Lomitapide
* cost?
* due to CYP3A4 metabolism, interacts with lots of drugs
* most common adverse effects are gi symtpoms
* increased LFTs, _hepatic fat accumulation_
* _Cost is \>$250,000 a year_
66
* What is Mipomersen used for?
homozygous familial hypercholesterolemia
67
* What is the MOA of Mipomersen?
* it is an antisense oligonucleotide that _targets apolipoprotein B-100 mRNA and disrupts its function._
68
* Adverse effects of Mipomersen?
* Cost?
* when shouldit be discontinued
* pain at injection site (1 inj per week)
* flu-like symptoms
* ^LFTs greater/= to 3x normal limit
* $176,000 a year
* discontinue if elevations persist or are accompained by clinical symptoms such as hepatic steatosis
69
Good review slide
