Drugs used in Dyslipidemia Flashcards by Barrett Thompson

Fibric Acid Derivatives
• MOA
• Name them

MOA:
• Act as Ligands to for PPARa nuclear receptor
• PPARa turns on processes that help to get rid of TGs

(increased FA use in muscle, inc. apoA1/2, dec. apo CIII, inc. LDL-R)

Drugs:
• Gemfibrozil
• Fenofibrate
• Fenofibric Acid

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**Statins
• MOA
• Name them

Blockage of Cholesterol Synthesis
• Competitive inhibitor of HMG-CoA Reductase

Increased LDL receptors
• causes SREBP to go from ER to Golgi and Finally to act as a transcription factor to up regulate LDLR synthesis

Drugs = Lo-SPAR:
• Lovastatin
• Simvastatin
• Pravastatin
• Atrovastatin
• Rosuvastatin

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**Bile Acid Resins
• MOA
• Name them

MOA:
• Anionic ion exchange resins (they are Positively charged)
• Bind up bile acids and prevent recycling
• Cholesterol must then be pulled out of the blood to make new bile acids

Drugs:
• Colestipol
• Cholestyramine
• Coleevelam

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**Ezetimibe
• MOA
• Method of administration

MOA:
• Prevents uptake of CHOLESTEROL itself in SMALL INTESTINE and leaves the bile alone
• Decreased Cholesterol uptake cause liver to UPREGULATE LDL Receptors

*Given as a pill

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**Niacin
• MOA
• Name them

MOA:
• Reduces Hepatic Triglyceride Synthesis
• Reduces Hepatic ApoB synthesis
• Enhances Macrophage transfer of Cholesterol to HDL
• Promotes VLDL conversion to LDL

Name:
• Niacor - IR
•Niaspan - ER

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How much can statins lower LDL compared to other drugs such as Bile acid resins, ezetimibe, or niacin?

Statins lower LDL by 25-60% while other drugs lower it by ~20%

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Which statins are acted on by CYP3A4?
• Note any important differences

• Lovastatin

• Simvastatin

• Atorvastatin

**Atorvastatin is also metabolized by ß-oxidation so CYP3A4 interactions typically aren’t an issue

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Which statins are the most effective at lowering cholesterol?

How effective are they?
What type of patients would you typically give these to?

• Atorvastatin
• Rosuvastastin

*Can give AT LEAST a 50% reduction in cholesterol **Typically given to patients who have lots of risk factors such as those with diabetes or heart disease**

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What statin would you consider giving to a patient with renal dysfunction?
• if this drug were not available, what backup would you use?
• Metabolism of these drugs?

Atorvastatin (only 2% renal excretion)
• ß-oxidation and CYP3A4 metabolized

Fluvastatin (only 5% renal excretion)
• CYP2C9, hydoxylation, and ß-oxidation

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What statins are acted on by CYP2C9?

Rosuvastatin
• CYP2C9, Fecal excretion

Fluvastatin
• CYP2C9, Hydroxylation, ß-oxidation

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Of the statins which are most susceptible to drug-drug interactions and why?

Simvastatin and Lovastatin
• Both are metabolized primarily by CYP3A4

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What are some drugs that inhibit CYP3A4?

• Macrolides
• Azole Antifungals
• Calcium Channel Blockers
• Grapefruit
• HIV protease Inhibitors
• Immunosuppressants

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What is the risk of Rhabdomyolysis other than severe muscle pain?
• indicators that this is happening

Indicators:
• Very High Levels of CPK
• Tea colored Urine

Risk:
• Myoglobin released from damaged muscle is nephrotoxic and can damage Kidneys

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What are some drugs that inhibit p-glycoprotein mediated intestinal reabsorption?

• Cyclosporin
• Grapefruit Juice

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What drug should you not use with any of the statins and why?

Gemfibrozil - contraindicated
• Inhibits glucuronyltranserase-1 and glucuronidation used as one of the methods of elimination for almost all of the statins

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How does myositis differ from Rhabdomyolysis?

Both result in high CPK and muscle pain, but Rhabdomyolysis is so severe that it can cause increased risk of Renal failure and death

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Which of the statins has the lowest risk of drug-drug interactions and why?

Pravistatin

• Eliminated via Sulfation, Oxidation, and Gluroonidation

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Lovastatin Simvastatin
• Metabolism
• Systemic Bioavailability

Metabolism
•CYP3A4
• Glucoronidation

Bioavailability:
• 5% (lowest)

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Pravastatin
• Metabolism
• Systemic Bioavailability

Metabolism
• Sulfation
• Oxidation
• Glucoronidation

Bioavailability:
• 17%

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Fluvastatin
• Metabolism

• Systemic Bioavailability

Metabolism
• CYP2C9
• Hydroxylation
• ß-oxidation

Bioavailability
• 24%

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Atorvastatin
• Metabolism

• Systemic Bioavailability

Metabolism
• ß-oxidation
• CYP3A4
• Glucoronidation

Bioavailability
• 14%

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Rosuvastatin
• Metabolism
• Systemic Bioavailability

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Metabolism
• CYP2C9

• Fecal Excretion

Bioavailability
• 20%

Besides muscle pain what are 4 other side effects of statins?

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Pregnancy Category X
Sleep Disturbance, Memory Loss, Reduced daytime Vigilance
Increased Liver Enzymes (rarely Hepatitis)
Mild GI distress

If a patient has liver disease or another disease where they can’t handle drugs in their system, what options are available to lower their cholesterol?

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Bile Acid Sequesterants
• No systemic effect because they never even enter the circulation

How will your **lipid profile** change after taking a **bile acid sequestran**t?

• **ONLY LDL decreases** - there is **NO EFFECT ON TRIGLYCERIDES**

What are the **3 bile acid sequestering drugs?** • how are they administered?

**Colestipol** - Powder or Tablet **Cholestyramine -** Powder **Colesvelam** - Tablet

What are some common **adverse effects/**down sides of the **Bile Acid Sequestrants**?

* Gritty Texture * Constipation, Nausea, Flatulence **• Fecal Impaction** **• HYPERtriglyceridemia**

What problems do the **bile acid sequensterants** pose when taking **other drugs** with them? • how can this be avoided?

Problems: • **Prevents absorption** of other drugs \*take other drugs 1 hour before or 3 to 4 hours after bile sequesterant

What conditions are **bile sequestrants contrainidicated** with?

**• Hypertriglyceridemia • Complex Drug Regimens • Hx of Constipation**

What is the most **common use of Ezetimibe**?

• Given along **with Statins** to achieve **extremely low LDL levels** required in **patients with CV risk factors**

What drugs can be given the BOTH **LOWER LDL** and **RAISE HDL**?

• **Fibric Acid Derivatives (fibrates) • Nicotinic Acid (niacin)** **• Omega-3 (fish oil)**

What is the **relationship** between **triglycerides** and **HDL-C?**

**Inverse** Relationship, if **HDL falls** then **TGs go** up and vise vesa

T or F: adding drugs besides Ezetimibe to Statins has proven to be highly effective.

False, using Niacin, Fibrates, or Fish Oil has shown little effect

What group of drugs **activates PPARalpha** and what is the effect? • Name drugs

**Fibrinates** PPARa • **Decreased ApoCIII** synthesis • **Increased Apo AI** and **AII** synthesis • **Increased LPL synthesis** Drugs: **• Gemfibrozil** **• Fenofibrate** **• Fenofibric Acid**

How do the **Fibrates** effect **Lipids**? • Adverse effects?

Lipid Effects: • **Reduced TGs up to 50%** * Reduced VLDL, **Increased HDL** * **LDL relatively unaffected** Adverse Effects: • **GI upset** • **Increased Creatinine or Liver enzyme** • **Gallstones**

**Gemfibrozil** • Drug Class • Metabolism

Drug Class: • Fibrinates Metabolism: **• LIVER - (oxidation and glucuronidation by UGTA1) - do not give other drugs that are elminated by glucoronidation (most statins) with this drug**

**Fenofibrate** • Drug Class • Metabolism

Drug Class: • Fibrinates Metabolism: • **Hepatic** to become Fenofibric acid then **Renally** Excreted

Between the fibrinates which do you think would be **safer** to give to a patient in renal failure? • Liver disease?

Best for **renal failure**: Gemfibrozil - almost **entirely hepatically metabolized** Best for **Liver disease**: • Fenofibric acid because it **doesn't have to undergo activation in the liver** like fenofibrate

**Fenofibric Acid** • Drug Class • Metabolism

Drug Class: • Fibrinates Metabolism: • Almost Exclusively Renally Excreted

Which of the **Fibric Acid** derivatives is **contraindicated with statins**? why?

**Gemfibrozil** - both gemfibrozil and statins are extensively metabolized in the liver and can lead to inhibition of statin effect

Do fibrinates show a benefit when added to statins?

NO, BUT due to discrepancies in studies it might be worth trying in your own patients to get them to safe cholesterol levels

What are the 2 different preparations of niacin and how should they be administered? • Dose?

**Niacor - (IR)** - immediate Release • must incrementally increase dose over time to minimize flushing • 6 grams/day **Niaspan - (ER)** - Extended Release • Less Flushing and usually given before bed to minimize flushing • 1-2 grams/day

What are some adverse **side effects of Niacin**?

• Cutaneous **Flushing** • **Elevated Hepatic Enzymes (also caused by statins)** • **GI irritation** • Hyperuricemia/**Gout** • Dry Skin **• Insulin Resistance**

taking niacin with statins does not significantly reduce the risk of a CHD event

What are some food sources for **Omega-3** and **Omega-6** fatty acids?

**Omega-3** • Walnuts, Flaxseed, Soybean • Canola Oil • Fatty fish **Omega-6** • Corn, Safflower, soybean, sunflower oils • meat, poultry, and eggs

What is the effect of **Omega-3** fatty acids on lipid profile?

* **Reduced Plasma Triglycerides** * Little to **NO effect on HDL or LDL cholesterol** \* \*May also have antiplatelet, hypotensive, and hypolidemic effects

Omega-3 • MOA

Increased **Fatty acid oxidation via PPARa** PPARa • Decreased ApoCIII synthesis • Increased Apo AI and AII synthesis • Increased LPL synthesis

T or F: statins have a large effect on triglycerides

False

What drugs have a significant effect on triglycerides?

* Niacin * Fish Oils * Fibrinates

If someone is **under 75** and has **known atherosclerotic CV disease** what should you prescribe them? • what is **older than 75**

* Under 75 - **HIGH intensity statins** (if no safety concerns) * Over 75 or have safety concerns - **Moderate intensity** statin

What is the protocol for treatment of someone with **LDL-C level is greater than 190 mg/dl?**

* If over 21 = **HIGH intensity statin** * Consider adding an a**dditional drug** to lower cholesterol

What treatment should you give someone with **diabetes and no vascular disease age 40-75** with **LDL 70-189 mg/dl?**

• **High intensity** statin if at **High (\>7.5%)** 10 yr risk of CV disease **• Moderate intensity** statin if at **Lower risk of CV** disease

What treatment should you give someone **without diabetes or CV disease** if they are 4**0-75 and have LDL 70-189?**

* **Moderate or High Intensity statin** for patients with (\>7.5%) 10 yr risk of CV disease * Moderate intensity statin for patients with (5%-7.4% risk)

Drugs used in Dyslipidemia Flashcards

(54 cards)