MT2_2_Dyslipidemia_Pharmacologic Therapy Flashcards
Total Cholesterol Values
Normal: less than 200
Borderline: 200-239
High: greater than 240
TG Levels
Normal: less than 150
Borderline: 150-199
High: 200-499
Very High: greater than 500
LDL Levels
Optimal: less than 100 Near/Above Optimal: 100-129 Borderline: 130-159 High: 160-189 Very High: greater than 190
HDL Levels
Low: less than 40
High: greater than 60
What are the main mechanisms of lipids?
- they stabilize high risk lesions, preserves endothelial function, and controls inflammation
Meds that induce dyslipidemia?
diuretics cyclosporine taco amio steroids
Meds that induce hypertriglyceridemia?
estrogen steroids bile acid resins protease inhibitors propofol sirolimus BB atypical antipsychotics
Cholesterol Equation
o LDL= TC – (HDL+ TG/5) fyi vldl = tg/5
o Non-HDL = TC – (HDL + TG/5)
What are fibrates good for? BARs? Fish Oil? PCSK9 Inhibitors Ezetimibe
Fibrates: high TGs
BARs: good for LDL, may increase TGs
Fish Oil may increase LDL,but can greatly lower TG
PSCK9 and Ezetimibe can greatly reduce LDL
High Intensity Statins
Lower LDL by 50%
Atorvastatin 40-80mg
Rosuvastatin 20*-40mg
Moderate Intensity Statins
Lower LDL by 30-50%
- Atorvastatin (10*-20)
- Rosuvastatin (5-10*)
- Simvastatin (20-40)
- Pravastatin (40*-80)
- Lovastatin (40*)
- Fluvastatin (40*)
How do statins work?
- inhibits HMG-COA reductase
- up regulates LDL receptors in the liver to take up more
- decreases secretion of VLDL (to make liver hang on to the cholesterol)
Which statins are metabolized by CYP 3A4? 2C9?
Which statins are lipophilic?
What to give a patient if there is a lot of DDI’s?
- 3A4: Atorvastatin, Lovastatin, Simvastatin
- 2C9:Fluvastatin, Rosuvastatin
- ALS, Fluvastatin, Pitavastatin
- Pravastatin
(CYP3A4 inducers: rifampin, phenytoin, CBZ, SJW)
(CYP3A4 Inhibitors CI: azoles, macrocodes (“cins”), protease inhibitors,cyclo, grapefruit juice) danazol, gemfibrozil, NonDHP CCB, amio
Statins with short half lives?
- Dose at night
- lovastatin, simvastatin, pravastatin, fluvastatin
Statins with longer half lives?
- atorvastain, rosuvastatin, pitavastatin
Common ADRs with statin use?
GI, DM, arthalgias, myopathy transaminitis
For myopathies, when do symptoms arise? What do we see? What happens in rhabdomyolysis?
- weeks to months after initiation
- a rise in creatinine kinase due to the breakdown of muscle
- rhabdo: MSK with elevation in CK greater than 10% with renal dysfunction
What are the risk factors of myopathies?
- greater than 75
- female, low body weight
- hypothyroidism
- sporadic heavy exercise
- comorbidities: renal and hepatic dysfunction
- hx of previous statin intolerance
How to prevent myopathies from occurring? How to deal with myopathies?
- routine CK measurements is not needed
- educate patients, use lowest dose possible, avoid CYP3A4 inhibitors
- consider the phillic statins
- no need to treat unless symptoms appear, even if mild. If pain persists, hold the statin and investigate further (hypothyroidism, renal/hepatic function)
- reintroduce when symptoms resolve, with a different statin or reduced dose.
When can transaminitis appear? Is routine monitoring needed? Can statins be continued? Is it possible to rechallenge?
- 12 weeks after initiation
- no
- yes, but dc if pt develops symptoms
- can re-challenge
Which anti-hyperlipidemic agents should not be used with statins?
niacin, gemfibrozil, fenofibrate…gemfibrozil is completely contraindicated
Max dose of amiodarone, verapamil, and dilitazem while on a simvastatin?
10mg
Max dose of amlodipine and ranolazine on a simvastatin?
20mg
max dose for danazol, diltiazem, verapamil on lovastatin
20mg
max dose for amio with lovastatin?
40mg
Meds CI with lovastatin?
similar to simvastatin, including boceprevir, telaprevir, nefazodone
- avoid cyclosporine and gemfibrozil and a lot of grapefruit juice
When are stains CI?
- acute liver disease
- pregnant (category X)
- breastfeeding
- concurrent use of CYP3A4 inhibitor
What to monitor for when a patient is on a statin?
FLP at baseline, 4-12 weeks after initiation or adjustment, q3-12 months
Baseline transaminases and CK..only get repeat levels if there is a concern for stain toxicity
Check 3 months if pt is taking niacin or vibrate
routeine DM screening
For fibrates, what do we have to monitor for?
- might have to renally adjust due to excretion through urine
What is the general MAO of fibrates?
activates PPARalpha, increases synthesis of apoCIII, increases synthesis of LDL receptors
ADRs of fibrates?
GI, Rash, Cholelithiasis, Cr increase w/o renal dysfunction, myopathy
What are the main CI of fibrates?
- severe hepatic or renal dysfunction
- biliary cirrhosis or preexisting gallbladder disease
may enhance anticoag effect of warfarin, hypoglycemic effect on sylfonylureas
What to monitor for fibrates?
- renal function at baseline, q3 months, q6months therefore after
- transaminases at baseline and 3 months after initiation
for fenofibrate, what is the monitoring parameter?
CrCl less than 30, DC
greater than 30-80, limit dose to max 54mg/day
For gemfibrozil what are the parameters?
less than 10, avoid or admin 50% of the dose
10-60, admin 75% of the dose
What are the MOAs of bile acid resins?
- bile acids facilitate digestion and absorption of lipids from the GI tract, synthesized in the liver
- BARs sequester bile acids in the GI tract, increasing elimination, so the liver is then stimulated to produce more bile acids, and the reduced cholesterol concentrations upregulate LDL receptors.
Major ADR with bile acid resins?
GI, improve adherence by taking apple or orange juice
What are the complete CI for BAR?
- hypertriglyceridemia
- biliary or bowel obstruction
- reduces the absorption of warfarin, levothyroxine, thiazide, BBs, therefore give drugs time apart
- can decrease absorption of fat-soluble vitamins
What is the main monitoring parameter for BARs?
- TGs, repeat q4-8 weeks
- use w caution if TG is over 250, do not initiate if over 300
- dc if TG is over 400
What is the MOA of niacin?
- inhibits the mobilization of FFA from peripheral adipose to liver
- reduces synthesis and secretion of VLDLC, and LDLC
- promotes HDL retention of apolipoprotein AI
What are the ADRs of Niacin?
- Based on the metabolic pathway. Amidation follows hepatotoxicity, and conjugation causes vasodilatory effects.
How to deal with flushing with Niacin?
- start at a low dose w food
- premedicate with aspirin 325mg 30 min prior
- avoid hot things
CI for Niacin
- active hepatic disease, transaminitis
- active peptic ulcer disease
- severe gout
- consider: BARs can decrease [niacin], niacin may enhance myopathic effects of statins, may interact w anticoags and antiplatetlets
Monitoring parameters for niacin?
- hepatic trans aminases
- uric acid
- diabetes
at baseline and repeat when dose is changed or every 6 months
ADRs of Omega 3 fatty acids?
- GI, fishy burps
- increase in bleeding time, abnormal plate function (therefore watch out for DDIs with anti-platelets and warfarin)
How do PCSK9 inhibitors work? (alirocumab, evolocumab)
inhibiting PCSK9 will allow more LDL receptors to remain in the membrane to uptake more lipids
Main ADRs associated with PCSK9 inhibitors?
- respiratory, injection site reaction, myalgia, increased transaminases w alirocumab
How does ezetimibe work?
blocks NPC1L1 (a cholesterol absorption blocker) stimulating hepatic cholesterol and bile acid synthesis, and up regulates LDL receptor expression
What are ADRs with exetimibe?
- GI, arthalgias, cough, fatigue
- transaminases greater than 3x
CI to ezetimibe?
- hypersensitivity
- concomitant use with a statin in patients with hepatic disease or transaminits
- severe hepatic disease (class C)
What to monitor for ezetimibe?
- hepatic transaminases baseline, routine if on use with statin or fenofibrate
- DC if transaminits is greater than 3x
for diet, what should be avoided to improve LDL levels?
reduce both saturated and trans fats
