Pharm 7 Dyslipidemia pt2 Flashcards
In what percentage range do Statins affect:
TC, LDL, HDL, TG?
TC: down 15%-60% LDL: down 20%-60% HDL: up 3%-15% TG: down 10%-15% (these are the numbers, not the outcomes data)
PK profile of Rosuvastatin
Relatively hydrophilic (fewer muscle aches) NO clinically significant metabolites Plasma clearance: renal & hepatic NO CY-p450 Bioavailability: 20% Half life: 19 hours
PK profile of Pravastatin
Relatively hydrophilic (fewer muscle aches) NO clinically significant metabolites Renal & hepatic clearance No CY-p450 Bioavailability: 17% Half-life: 77 hours
PK profile of Simvastatin
NOT Hydrophilic (more muscle aches) There are clinically significant metabolites Renal & hepatic clearance There is CY-P450 metabolism Bioavailability: <5% Half life: 1.9 hours
PK profile of Atorvastatin
NOT Hydrophilic (more muscle aches)
There are clinically significant metabolites
Primarily HEPATIC clearance (unique to others)
There is CY-P450 metabolism
Bioavailability: 14%
Half life: 14 hours
According to STELLAR, rank the statins from most-least potent.
How does this vary by dose?
Rosuvastatin, Atorvastatin (overall most potent), Simvastatin, Pravastatin.
This is true from 10mg-40mg
At 80mg: Only Atorvastatin & Simvastatin may be given.
Rank Statins by risk with Type 2- DM
Lowest risk: Pravastatin
Intermediate risk: Atorvastatin
Greatest risk: Rosuvastatin
(This appears to correlate with their potency)
Possible drug interactions of Statins (5)
Name 1 that is unique to Simvastatin
Erythromycin, Biaxin, Cyclosporin, anti-fungal agents, Verapamil
Amiodarone (Simvastatin)
The risk of fatal Rhabdomyolysis from a Statin:
1 in 10 million
(Of half billion, there were 42 cases)
It’s more dangerous to fly on an airplane than take a Statin.
How low should LDL go?
All moderate-risk and higher-risk patients, regardless of baseline LDL-C, experience significant benefit from a 30% to 40% reduction in LDL-C
Relative risk continues to reduce until LDL = 40
2 examples of Common Fibrates & Fenofibrates
What are they for?
Which is never used?
Fenofibrate
Gemfibrozol - Never used! These drugs have the ability to cause Rabdo. Gemfibrozil’s risk of this is 1500x higher (when combined with a statin)
Primarily to lower TG
Fenofibrate
Purpose of drug, how effective?
Route of admin?
Fenofibrate (PO QD)
Primarily to lower TG (by about half)
Ezetimibe - how does it work?
What does it do?
How well?
When would you use it?
blocks absorption of cholesterol in intestinal brush border.
Lowers LDL: 18%
if they tried everything else, and patient LDL still isn’t low enough, then give Ezetimibe a shot. No real downside if it doesn’t work.
How doubling statin’s dose affects reduction in LDL
Doubling each time reduces LDL an extra 5-6%, until the 3rd step.
Statin alone versus Statin + Ezetimibe
Statin alone after the 3rd time doubling: extra 15-18%
Statin + Eztimibe (can’t double the Statin this way): extra 25%
Omega-3 Acid Ethyl Esters
What do they do?
How do they work?
Inhibit synthesis of VLDL and TG in the liver
Increase rate of hepatic fatty acid oxidation
Reduce serum TG; lower risk of cardiac sudden death and all-cause mortality; mildly lower BP; reduce inflammatory and thrombotic risk
Can be combined with statins, no known drug interactions.
Foods that increase TG:
“If it’s white, don’t bite.” Potatoes, white bread, pasta, rice, bananas (ripe)
American Heart Association recommendations about fish. (3)
No documented coronary ds: Eat a variety of fish (preferably oily, not tuna) at least twice weekly
Documented coronary ds: Consume approximately 1 g EPA plus DHA daily, preferably from oily fish.
HyperTRIG: Consume 2-4g of EPA plus DHA daily in capsules by prescription.
A possible side effect of Omega-3 fatty acids with HyperTG
May prolong bleeding time in some patients
Niacin
Indications
Take it when?
Adjunct to diet and exercise in primary hypercholesterolemias and mixed dyslipidemias
To reduce the risk of AMI in patients with a history of AMI and hypercholesterolemia
To slow the progression or promote the regression of atherosclerosis in patients with CAD and hypercholesterolemia
Take at bedtime
Niacin Cautions/precautions: (3)
Should be utilized only in those intolerant of statins
While they lower LDL, raise HDL, they do not imporove mortality and morbidity
Can cause hepatotoxicity, especially in those with history of jaundice, hepatobiliary disease, or ETOH abuse
How to monitor Niacin patients for hepatotoxicity
Monitor LFTs prior to initiating therapy and then every 6-12 weeks thereafter for 1 year and then twice annually thereafter unless symptomatic
Niacin is the best drug at what?
What can it do to the face? What can you do about it? (3)
Best drug for raising HDL-C
Can cause facial flushing - mediate that by taking ASSA 30 min prior to Niacin, taking drug with low-fat snack, or titrating dosing upwards slowly.
New data on Niacin says:
Raises overall cardiovascular mortality. Would not prescribe this.
