Cardio-Lipid Disorders Flashcards
What is the effect of fibrates with anticoagulants
Potentiate their effect
What are the adverse effects of the mipomersen
- Injection site reactions
- flu-like symptoms
- elevation of the liver enzymes to as high as 3x normal
- Expensive at 176,000 a year
How is most of the absorbed dose of statins excreted
In bile
What are the pharmacokinetics of bile acid sequestrants aka resins
Large cationic resins that are insoluble in water
-Completely excreted in feces as it is neither absorbed or altered/metabolized
What is the effect of firbrates on the muscle
Myositis, myopathy, rhabdomyolysis
What are the pharmokenetics of NIACIN
Converted into nicotinamide adenine dinucleotide (NAD)
- Extensive first pass, so half life is 60 minutes (2-3 times a day)
- Distributed to hepatic, renal, and adipose tissue
Which drug class will be ineffective with a patient with familial hypercholesterolemia
Statins because they rely on a functions LDL receptor, but that is not the cause in familial hypercholestermia
Which conditions can be exacerbated by niacin use
Gout and glucose intolerance
What drug class is colesevelam
Bile acid sequestration (resins)
What is the effect of firbrates on the liver
Elevated aminotransferases
What is the mechanism of metabolism for simvastatin
CYP3A4
What is the result of statins on muscle
- Creatine kinase levels increased
- Rhabdomyolysis
- increases myopathy if taken with fibrates
What drug class is Ezetimibe
Cholesterol absorption inhibitors
What are the most potent statins
Atorvastatin and rosuvastatin
What are the conditions that mipomersen can be used
Familial hypercholesterolemia
What are the adverse effects of limitapide
- Substrate and inhibitor of CYP3A4
- GI symptoms
- Increased liver aminotransferases levels
- hepatic fat accumulation
- Expensive at 250,000 a year
What are the conditions that lomitapide can be used
Familial hypercholesterolemia
When is treatment with fibrates very warranted
In those with very high VLDL, or those with treatment with viral protease inhibitors (such as HIV treatment)
What is the mechanism of metabolism for atorvastatin
CYP3A4
Which drug class has the highest effect on lowing the levels of triglycerides
Fibrates
What is the mechanism of action for mipomersen
-antisense oligonulceotide that targets and disrupts the ApoB100 mRNA
What is the mechanism of action of NIACIN
- inhibits the lipolysis of TGs in the adipose tissue, which decreases free circulating free fatty acids
- Decreased FFAs result in decreased VLDL and LDL, increased HDL
- Fibrinogen levels are decreased and tPA are increased
Why are statins primarily taken at night
Most cholesterol synthesis occurs at night
Which statins are more likely to be used when using another drug affecting CYP450s
- Pravastatin
- Pitavastatin
What is the mechanism if action for bile acid sequestrants aka resins
1) Because they are positively charged, binds to the negative charged bile acids and increases the excretion (almost tenfold)
2) INcreased bile acid excretion results in the increased conversation of cholesterol to bile acids via 7alpha hydroxylation
3) LDL receptors increase, along with the clearance of LDL from the blood
Which of the drug classes has the highest effect on lowering the LDL levels
Statins
What is an adverse effect seen on the liver as a result of statins
Elevated serum liver aminotransferases
What is the mechanism of action for fibrates
- Agonist for peroxisome proliferator-activated receptor alpha (PPARalpha), which regulates the DNA for lipoprotein structure and function
- increases the oxidation of FFA, greatly decreases VLDL and slightly LDL
What is the mechanism of metabolism for pitavastatin
Limited CYP450 activity
What is the result of statins with warfarin
Increases the levels of warfarin
What is the mechanism of action for PSCK9 monoclonal antibodies (evolocumab and alirocumab)
Forms complexed with the PCSK9 and inhibits the catabolism of LDL receptors, so more LDL is cleared from the blood
What is the mechanism of metabolism for lovastatin
CYP3A4
What is the mechanism of metabolism for rosuvastatin
CYP2C9
What are the pharmacokinetics of ezetimibe
- A cholesterol absorption inhibitor
- Highly water insoluble,so most is excreted in the feces
- 22 hour half life
Which patients are statins contraindicated in
- Liver failure
- Pregnancy or lactating
- skeletal muscle myopathies
What drug class is gemifibrozil
Fibril acid derivatives (fibrates)
What are the contraindications for fibrates
- Pts at risk or with biliary tract diseases (women, obese, Native Americans)
- Hepatic dysfunction
What are the three statins with the longest half life
Atorvastatin (14 hrs)
Pitavastatin (12 hrs)
Rosuvastatin (19 hrs)
What is the mechanism of action for Statins
1) Decreased production of cholesterol via inhibition of HMG-CoA reductase
2) Increased LDL receptors and LDL uptake
3) Decreased blood levels of LDL
What are the adverse affects of bile acid sequestrants aka resins on the GI system
- Constipations, nausea, and flatulence most common
- Impaired absorption of fat soluble vitamins (A,D,E,K)
- Impaired absorption of many common drugs
What are the contraindications for using bile acid sequestrants aka resins
Pts with:
- Diverticulitis
- Preexisting bowel disease
- cholestasis
What drug class is colestipol
Bile acid sequestration (resins)
What is the mechanism of metabolism for pravastatin
Not involved with CYP450
What drug class is cholestryamine
Bile acid sequestration (resins)
What is the result of LDL receptors levels, LDL serum levels, and activity of the HMG-CoA reductase activity as a result of administration of bile acid sequestrants aka resins
- Increased LDL receptors and LDL clearance
- Increased HMG-CoA activity
What ar ethe some of the drugs that are impacted by bile acid sequestrants aka resins
- tetracycline
- Phenobarbital
- Digoxin
- warfarin
- Pravastatin, fluvastatin
- Aspirin
- Thiazides
What is the mechanism of metabolism for fluvastatin
CYP2C9
What are some secondary benefits of statins
- Plaque stabilization
- Improved coronary endothelial function
- Inhibition of thrombus formation
- Anti-inflammatory effects
What is the mechanism of action of Exetimibe
- Inhibits the intestinal absorption of cholesterol and the plant sterol, phytosterol via inhibiting the transport protein NPC1L1.
- Works even if there is dietary cholesterol by inhibiting the uptake of cholesterol from the bile that is excreted
What are the serum level changes with NIACIN (aka nicitinic acid, vitamin B3)
Decreases TGs, LDL
Increases HDL
In a patient taking bile acid sequestrants aka resins, when should other drugs be taken
-at least 1 hour before or 2 hours after
What drug class is fenofibrate
Fibril acid derivatives (fibrates)
Which statins are not taken at night like the others
- Atorvastatin
- pitavastatin
- rosuvastatin
What are the contraindication so NAICIN
- DM patients and can induce insulin resistance
- Liver or peptic ulcer disease
Which of the statin drug in contrast to others is almost completely absorbed when taken orally
Fluvastatin
What are the adverse effects of NIACIN
- intense cutaneous flush when first started or dose is increased
- rash, dry skin or mucous membranes
What is a combination that is commonly used with bile acid sequestrants aka resins and what is the reasoning
Statins, because the resins increase the activity of HMG-CoA reductase activity, so statins can help limit the amount of new cholesterol synthesized
What situations are PSCK9 monoclonal antibodies (evolocumab and alirocumab) used
Familial hypercholesterolemia that is not responsive to oral therapy
What is the mechanism of action for lomitapide
1) binds to and inhibits the triglyceride transport protein (MTP)of the ER
2) Inhibition leads to Prevention of the Apo-B
3) Decreases the levels of LDL, VLDL
Which drug class has the highest effect on raising the levels of HDL
Niacin
What are the adverse effects of fibrates on the GI
Increased risk of cholelithiasis (increased bile cholesterol level)
