Pharm 7 Dyslipidemia pt2

Question 1

In what percentage range do Statins affect:

TC, LDL, HDL, TG?

Answer 1

TC: down 15%-60%
LDL: down 20%-60%
HDL: up 3%-15%
TG: down 10%-15%
(these are the numbers, not the outcomes data)

Question 2

PK profile of Rosuvastatin

Answer 2

Relatively hydrophilic (fewer muscle aches)
NO clinically significant metabolites
Plasma clearance: renal & hepatic
NO CY-p450
Bioavailability: 20%
Half life: 19 hours

Question 3

PK profile of Pravastatin

Answer 3

Relatively hydrophilic (fewer muscle aches)
NO clinically significant metabolites
Renal & hepatic clearance
No CY-p450
Bioavailability: 17%
Half-life: 77 hours

Question 4

PK profile of Simvastatin

Answer 4

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

Question 5

PK profile of Atorvastatin

Answer 5

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

Question 6

According to STELLAR, rank the statins from most-least potent.
How does this vary by dose?

Answer 6

Rosuvastatin, Atorvastatin (overall most potent), Simvastatin, Pravastatin.
This is true from 10mg-40mg
At 80mg: Only Atorvastatin & Simvastatin may be given.

Question 7

Rank Statins by risk with Type 2- DM

Answer 7

Lowest risk: Pravastatin
Intermediate risk: Atorvastatin
Greatest risk: Rosuvastatin
(This appears to correlate with their potency)

Question 8

Possible drug interactions of Statins (5)

Name 1 that is unique to Simvastatin

Answer 8

Erythromycin, Biaxin, Cyclosporin, anti-fungal agents, Verapamil
Amiodarone (Simvastatin)

Question 9

The risk of fatal Rhabdomyolysis from a Statin:

Answer 9

1 in 10 million
(Of half billion, there were 42 cases)
It’s more dangerous to fly on an airplane than take a Statin.

Question 10

How low should LDL go?

Answer 10

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

Question 11

2 examples of Common Fibrates & Fenofibrates
What are they for?
Which is never used?

Answer 11

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

Question 12

Fenofibrate
Purpose of drug, how effective?
Route of admin?

Answer 12

Fenofibrate (PO QD)

Primarily to lower TG (by about half)

Question 13

Ezetimibe - how does it work?
What does it do?
How well?
When would you use it?

Answer 13

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.

Question 14

How doubling statin’s dose affects reduction in LDL

Answer 14

Doubling each time reduces LDL an extra 5-6%, until the 3rd step.

Question 15

Statin alone versus Statin + Ezetimibe

Answer 15

Statin alone after the 3rd time doubling: extra 15-18%

Statin + Eztimibe (can’t double the Statin this way): extra 25%

Question 16

Omega-3 Acid Ethyl Esters
What do they do?
How do they work?

Answer 16

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.

Question 17

Foods that increase TG:

Answer 17

“If it’s white, don’t bite.” Potatoes, white bread, pasta, rice, bananas (ripe)

Question 18

American Heart Association recommendations about fish. (3)

Answer 18

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.

Question 19

A possible side effect of Omega-3 fatty acids with HyperTG

Answer 19

May prolong bleeding time in some patients

Question 20

Niacin
Indications
Take it when?

Answer 20

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

Question 21

Niacin Cautions/precautions: (3)

Answer 21

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

Question 22

How to monitor Niacin patients for hepatotoxicity

Answer 22

Monitor LFTs prior to initiating therapy and then every 6-12 weeks thereafter for 1 year and then twice annually thereafter unless symptomatic

Question 23

Niacin is the best drug at what?

What can it do to the face? What can you do about it? (3)

Answer 23

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.

Question 24

New data on Niacin says:

Answer 24

Raises overall cardiovascular mortality. Would not prescribe this.