HMG-CoA Reductase Inhibitors are also called
Is cholesterole water or lipid soluble?
- Very low density lipoprotein (VLDL)
- intermediate lipoprotein (ILP)
- Low density lipoprtein (LDL)
- High density lipoprotein (HDL)
Which is the "bad cholesterol" and what does it do?
It carries cholesterol from the liver to the rest of the body
Which is the "good" cholesterol and what does it do?
it carries cholesterol from the body to the liver
What does VLDL do?
carries fat from liver to adipose tissue
Total cholesterol goal
Preffered drug type for lowering LDL
Which drug class is the first-line treatment for hyperlipidemia and why?
Reduces the risk of MI, stroke, and cardiovascular death
what labs should be monitored when a patient is on statins?
LFTs, creatinine kinase, lipids
If a patient taking a statin develops persistent muscle weakness/discomfort or brown urine what labs should be done and why?
Creatinine kinase (CK) to assess for rhabdomyolysis
value will be increased
Assessing for signs of myopathy with statin use
6-12 weeks after begining regimen and every visit thereafter
When can peak effect for statins be seen?
After approximately 4 weeks
What do statins do?
decrese total cholesterol, LDL, triglycerides
How do statins work?
block the enzyme that catalyzes early cholesterol synthesis
Statin drug names
- lovastatin (Mevacor)
- pravastatin (Pravachol)
- simvastatin (Zocor)
- fluvastatin (Lescol)
- atorvastatin (Lipitor)
- rosuvastatin (Crestor)
Rapid with 24% bioavailability due to first pass metabolism
Highly protein bound
enter breast milk, placenta, and blood-brain barrier
Metabolized in liver with minimal excretion in urine
See page 125
Rule of 6
Statins are most effective at starting dose, longer dosing times only 6%
Patient education for statins
- symptoms of myopathy
- grapefruit juice increases levels (rhabdo risk)
- diet restriction and exercise
- report any muscle pain/weakness
Statin: pregnancy category
Statin side effects: CV
DERM side effects: Statins
EENT side effects: statins
Statin side effects: GI
liver toxicity (elevation in LFTS)
Statin side effects: MS
(rhabdomyolysis, depletion of CoQ10, mylagias)
Statin side effects: NEURO
drugs that increase serum concentration of Statins
CYP450 enzyme inhibitors
drugs that decrease effectiveness of statins
St. John's wort
bile acid sequestrants
why would you coadminister statins and CoQ10
decrease muscle symptoms
When a patient is on statins, which drugs should you be extremely cautious with?
- protease inhibitors
Purpose of bile acid sequestrants
lower LDL, not triglycerides
(may worsen if triglycerides elevated)
lowers LDL by only 13-30%
How do bile acid sequestrants work?
Bind to bile acids and form an insoluble complex that is excreted in the feces
Bile acid sequestrant drug names
cholestryramine (Questran, Prevalite)
Contraindications for statins
persistent unexplained elevated LFT
Pregnancy category of bile acid sequestrants
Common side effect of cholestyramine
Bile resin side effects: EENT
irritation of tongue
BIle resin side effects: GI
Bile acid sequestrants can lead to deficiencies in what vitamins?
A, D, E, K
Bile acid sequestrant side effects: NEURO
lightheadedness, weakness, insomnia
Why do patients often stop using bile acid sequestrants?
GI side effects
Bile resins and triglyceride levels
Not for monotherapy if triglycerides > 400mg/dL
OK as monotherapy if triglycerides < 200mg/dL
Patien education of bile resins
Powder: how to prepare
Tablets: swallow dont chew
increase fiber to avoid constipation/bloating
more effective if taken before meals
Bile resins prevention absorption of which medications?
fat soluble vitamins
How can interactions between bile resins and other medications be avoided?
take 1 hour before or 4 hours after meals
Bile resin contraindications
caution with history of constipation or bowel obstruction
Nicotinic acid is also known as
When is use of B3 indicated for cholesterol treatment?
What is the benefit of combining B3 with a statin?
decreased progression of atherosclerosis
reduce CHD events
Maximum dose of Niacin
2mg for ER
5mg for immediate release
Ways to reduce flushing with Niacin
ASA or NSAID 30 minutes prior
take with food
avoid hot liquids
A patient taking Niacin long term should be instructed to report
darkening of urine
light colored stools
severe stomach pain
(signs of hepatotoxicity)
How does niacin work?
inhibits fatty acid release from adipose tissue
inhibits fatty acid ang triglyceride synthesis in the liver
prevents recurrent MI
rapid and extensive
widely distributed after converted to niacinamide
must be converted to niacinamide, which concentrates in liver, kidneys, and adipose tissue
side effects of niacin: CV
side effects of niacin: DERM
side effects of niacin: EENT
side effects of niacin: GI
upper GI distress
hepatotoxicity with long term use
side effects of niacin: HEM
Niaspan ER is associated with platelet count reduction
side effects of niacin: META
can interefere with BG in diabetics
can exacerbate gout
side effects of niacin: NEURO
caution with diabetes, peptic ulcer disease, hyperuricemia
Cholesterol absorption inhibitor:
What does Zetia do?
reduce total cholesterol, LDL, apo B, and triglycerides
How does Zetia work?
inhibits absorption of cholesterol in small intestine. This lowers the amount of cholesterol available to the liver which reduces circulating cholesterol and hepatic stores
easily absorbed and conjugated to an active phenolic complex (ezetimibe-glucuronide)
highly distributed bound to plasma protein
in intestine and liver
biliary and fecal
Coadministration of zetia and statins or fenofibrates
May be taken at the same time
Coadministration of Zetia and bile resins
2 hours before or 4 hours after bile resin is taken
Side effects of zetia: DERM
side effects of zetia: GI
side effects of zetia: HEM
MAY CAUSE ANGIOEDEMA
side effects of zetia: META
side effects of zetia: MS
when is zetia most effective?
when given with statins
which medications does zetia interact with?
zetia/statin combo is contraindicated with liver disease or unexplained elevated LFT
What do fibric acids do?
increase size and decrease density of LDL
What is the most effective type of drug for lowering triglycerides?
Why is fenofibrate preferred when used in combination with a statin?
Because of better renal clearance
Fibric acid drug names
benefits of fibric acids
prevents cardiovascular disease
how do fibric acids work?
activate a nuclear receptor which inhibits triglyceride synthesis
(also facilitates liver uptake of LDL)
What is heightened with coadministration of fibric acids and statins?
risk for rhabdomyolysis
fibric acids: absorption
reduced by bile resins
fibric acids: distribution
unknow: upt to 99% protein bound
fibric acids: metabolism
converted to fenofibric acid (active metabolite) which is metabolized in the liver
fibric acids: excretion
fibric acid side effects: CV
fibric acid side effects: DERM
fibric acid side effects: GI
dyspepsia, abdominal pain, diarrhea, gas, liver dysfunction, gall bladder disease, pancreatitis
when are GI side effects of fibric acids increased?
when coadministered with statins
fibric acid side effects: MS
muscle pain, myopathy, rhabdomyolysis
fibric acid side effects: NEURO
fatigue, weakness, headache
coadministration of a fibrate and warfarin
increased bleeding risk
coadminstration of a fibrate and statin
increased risk of rhabdomyolysis
fibric acid contraindications
gall bladder, liver, or kidney dysfunction
fibric acids in pregnancy
safety not determined use only if necessary
When is combination therapy indicated?
when goals are not reached with statin monotherapy and lifestyle modifications
which 2 drugs make up Vytorin?
Considerations with Vytorin
slightly increased risk of rhabdomyolysis
64% reduction in LDL
adjunt to diet
What 2 drugs make up Simcor?
Considerations with Somcor
watch for flushing. pruritis, GI distress
single dose at half strength with low fat snack
used in patients with hypercholesterolemia and dyslipidemia
NCEP guidelines: screening
should be done with fasting labs every 5 years in patients over 20
NCEP guidelines: goal for LDL (all patients)
NCEP guidelines: LDL goal for those at risk for or with coronary or vascular disease