Pharm - dyslipidemia Flashcards
What are 3 risk assessment tools that can be used to assess the risk for cardiovascular dz?
- Framingham
- ASCVD risk instrument
- National lipid association risk stratification
major cardiovascular risk factors
- age: male 45 or higher, female 55 or higher
- family hx of early CHD (<55 in male first degree, <65 if female first degree relative)
- current cig smoking
- high BP (> or equal to 140/90, or on BP meds)
- low HDL (<40 in men, <50 in women)
What 3 national organizations have published guidelines for the treatment of dyslipidemias?
- national cholesterol education program(NCEP)
- american college of cardiology (ACC) / american heart association (AHA)
- national lipid association (NLA)
What 4 groups of people have demonstrated benefit of treating dyslipidemias?
- pts w/ CHD, w/ or w/o hyperlipidemia
- men w/ hyperlipidemia but no known CHD
- men w/ HTN multiple cardiac risk factors but w/o hyperlipidemia
- men and women w/ avg total and LDL levels and no known CHD
HMG-CoA reductase inhibitors, aka statins, MoA
- statins inhibits HMG-CoA reductase
- this enzyme catalyzes the rate-limiting step of cholesterol synthesis so the liver can’t make cholesterol
- the liver therefore upregulates LDL receptors, and decreases production of VLDL, IDL, and LDL
What is the lipid lowering effect of statins on LDL?
decreased by 20-55%
What is the lipid lowering effect of statins on HDL?
increased by 2-10%
What is the lipid lowering effect of statins on triglycerides?
lowered 14-40%
What is the expected LDL lowering of a low intensity statin?
lowered by about <30%
What is the expected LDL lowering of a moderate intensity statin?
lowered by 30-50%
What is the expected LDL lowering of a high intensity statin?
lowered by about 50%
low intensity statin and dose
-Simvastatin: 10mg
moderate intensity statins and doses
- Atorvastatin: 10-20mg
- Rosuvastatin: 5-10mg
high intensity statins and doses
- atorvastatin: 40-80mg
- rosuvastatin: 20 mg
clinical endpoints demonstrated by statins
- most studied drugs for dyslipidemia
- they reduce all-cause mortality, cardiovascular mortality, stroke, angina, and need for revascularization procedures
- also clear benefit in pts w/ DM
- benefits are directly associated w/ percent LDL reduction
contraindications to statins
- active liver dz
- pregnancy or lactation (class X)
- use low dose in transplant pts
- contraindicated with use of certain drugs
drug interactions with simvastatin, in which they are completely contraindicated to prescribe
- strong CYP3A4 drugs (statins are red flag drugs)
- erythromycin, clarithromycin
- gemfibrozil
- azoles
- HIV protease inhibitors
other drug interactions with simvastatin
- amiodarone, amlodipine
- grapefruit juice
what is the prescribing recommendation for drug interactions with simvastatin that aren’t completely contraindicated?
- with amiodarone/amlodipine, limit simvastatin to 20 mg
- avoid grapefruit juice
interacting drugs with rosuvastatin
-gemfibrozil
prescribing recommendation for drug interactions with rosuvastatin
-if using with gemfibrozil, limit rosuvastatin dose to 10 mg daily
drug interactions w/ atorvastatin
-clarithromycin
prescribing recommendation for atorvastatin/clarithromycin drug interaction
-limit atorvastatin to 20 mg daily
adverse effects of statins
- myopathy
- myalgia
- liver enzyme elevation
- rhabdomyolysis
- cognitive decline
- DM
patient risk factors for developing rhabdomyolysis secondary to a statin
- renal insufficiency
- age > 65
- concurrent admin of gemfibrozil, niacin or a drug that interacts w/ a statin resulting in statin accumulation
monitoring parameters for efficacy of statin therapy
- lipid profile 6 wks following initiation
- lipid profile eval 2-3 times per year once goals have been met
monitoring parameters for safety of statin therapy
- liver function tests - baseline and then as clinically indicated
- CPK: baseline (optional) and repeat w/ myalgia
What is the best time of day to take a statin?
in the evening as that is when the most cholesterol is produced
lipid lowering effects of niacin on LDL
decrease 5-25%
lipid lowering effects of niacin on HDL
increase of 15-35%
lipid lowering effects of niacin on TGs
decrease 20-50%
contraindications of niacin
- liver dz
- severe gout
- active peptic ulcer
- arterial bleeding
drug interactions of niacin
- statins: this is a caution
- antihyperglycemic agents (DM meds)
monitoring parameters for efficacy of niacin
-fasting lipids q 4-6 weeks during dose titration then q 4-6 mos
monitoring parameters for safety of niacin
- LFTs at baseline, q 6-12 weeks X 1yr, then periodically
- blood glucose in DM
- CPK baseline and w/ muscle sx if on statin
- uric acid
lipid lowering effects of fibric acid derivatives (aka fibrates) on LDL
- variable
- in many pts: decrease of 5-20%
- usually LDL increases in pts w/ very high TGs
lipid lowering effects of fibric acid derivatives on HDL
-increase 10-35%
lipid lowering effects of fibric acid derivatives on TGs
decrease 20-50%
contraindications of fibric acid derivatives
- pre-existing gallbladder dz
- hepatic dysfunction
- severe renal impairment
drug interactinos of fibrates
- statins - avoid gemfibrozil in combo w/ statins, fenofibrate can be used if needed.
- exetimibe - cholelithiasis risk
monitoring parameters for efficacy in fibric acid therapy
- these drugs take 3 mos to see full effect
- fasting lipids q 4-6 mos
monitoring parameters for safety in fibric acid therapy
-LFTs at baseline then periodically
MoA of ezetimibe
- cholesterol absorption inhibitor
- inhibits cholesterol absorption at the brush border of the small intestine from bile and dietary intake
- results in reduced hepatic cholesterol stores and increases cholesterol clearance in the blood
lipid lowering effects of ezetimibe on LDL
-decrease of 20%
lipid lowering effects of exetimibe on HDL and TGs
- negligible
- HDL increased 0-5%
- TG decreased 5-11%
MoA of bile acid sequestrants (BAS)
- bile acids are normally reabsorbed in the jejunum and ileum then return to cholesterol cycle
- BASs are resins that complex w/ the bile acids preventing reabsorption
- liver recognizes the reduction and increases hepatic uptake and catabolism of LDL
lipid lowering effects of BAS on LDL
-15-30% (modest at best)
lipid lowering effects of BAS on HDL
3-5%
lipid lowering effects of BAS on TG
-they actually can increase the TGs 0-10%
contraindications to using BASs
- bowel obstruction
- complete biliary obstruction
- hypersensitivity
precautions to using BASs
- malabsorptions disorders
- chronic constipation
- TGs > 200 mg/dL
drug interactions with BASs
- they bind many drugs (too many to list) and impair absorption to varying degrees
- most clinically relevent to drugs w/ narrow therapeutic window (warfarin)
- separate the doses of BASs from other drugs (1 hr before or 4-6 hrs after)
ADRs of BASs
- contipiation/flatulence/bloating
- steatorrhea
- increased TG concentration
- malabsorption of fat soluble vitamins
long-chain omega-3 FAs
- EPA
- DHA
- essential
- sources: anchovy, halibut, herring, kipper, mackerel, mullet, salmon, sardine, sturgeon, trout, tuna
ADRs of omega-3 FAs
fishy aftertaste - fishy burp
-use enteric coated or refrigerate capsules
lipid lowering effects of fish oil on LDL
-can see an increase by 40% when TGs >500
lipid lowering effects of fish oil on TGs
-20-50% (similar to fibrates)
The AHA recommends eating how much fatty fish?
-two servings per week
dosing of fish oil for hypertriglyceridemia
2.0 - 4.0 gm of DHA plus EPA daily
dosing of fish oil for very high triglycerides
Lovaza 4 gm daily or 2.0 gm BID
NLA recommendations for LDL goals
<70 or 100 mg/dL
NLA recommendations for non-HDL goals
<130 or 100 mg/dl
