Dyslipemia Drugs (cholesterol) Flashcards
HMG coA reductase inhibitors (statins) PCSK9 inhibitors Lamitopide Bile acid sequestrants Niacin Fibrates Ezetimibe Omega 3 fatty acids Herb and natural products
Drug therapy options
Statins
MOA: inhibits the enzyme HMG-CoA reductase which inhibits/slows down the production of cholesterol in the liver.
- flat dose response curve
- 5-6% more LDL lowering by doubling dose
- dose at bedtime when liver makes most of the Cholesterol which will maximize effect
- Lipitor can be given in am: long t1/2
Statin
Adverse effects
- muscle toxicity: myalgia, myopathy/ Rhabdomyalgia
- heart burn/ dyspepsia
- headache
- taste disturbances
- diabetes?
Statin: risk factors for muscle toxicity
High statin/blood conc Drug inx SLCO1B1 genotype (pump) Hyperthyroidism Increase age Hypoxia Lots of exercise
PCSK9 Inhibitors
*injectable
MOA: inhibits activity of LDL-r to return to cell surface
1) Alirocimab (praluent)- 75-100mg SQ every 2 week
2) Evolocumab (repatha)- 140 mg every 2 weeks or 420 mg one a mth
* >40->60% LDL reduction with each
- effective with or without other therapy
Lamitapide (Juxtapid)
MOA: inhibits assembly of apo-B containing lipoproteins (VLDL and chyromicrons)
- LDL: ⬇️ 40-50%, TG: ⬇️45%
- close monitoring*
- homozygous familial cholesterolemia
- high risk of hepatotoxicty; monitor LFTs
- > 90% with diarrhea, heart burn or N/V
- drug/dietary interaction risk
- > $3000 a month
Bile Acid Sequestrants
MOA: bind with cholesterol containing bile acids in the intestines and then are eliminated in the stool.
- ⬇️ TC, ⬇️ LDL, ⬆️ HDL, ⬆️⬇️ TG
- start with low dose and increase as needed and as tolerated
- may interfere with the absorption of other drugs
- Colesevam- may be tolerated better
- AEs: constipation, bloating, abd pain, unpleasant taste/texture (sand)
Niacin
MOA
Inhibition of:
- free fatty acid release from adipose tissue
- cAMP accumulation
- VLDL and LDL synthesis
- ⬆️ LPL activity
- effect on lipids: ⬇️⬇️TC, ⬇️⬇️⬇️LDL, ⬆️⬆️ HDL, ⬇️⬇️⬇️TG
Niacin
Adverse effects
Flushing, pruitis, headache, fatigue, gastritis, abd pain, aggrevation of PUD
- impaired glucose control (hyperglycemia)
- ⬆️ Uric acid concentrations
Niacin
Drug inx
Alcohol: ⬆️ risk of hepatotoxicty
* statins, fibrates: ⬆️ risk of hepatotoxicty and myalgias
*hepatotoxicty: with SR niacin, cut dose by 50% or limit to 2mg a day
Fibrates
MOA
Inhibition of cholesterol synthesis
- ⬇️ TG synthesis
- inhibition of lipolysis in adipose tissue
- ⬇️ production of VLDL/increase clearance
- ⬆️ plasma and hepatic LDL activity
- effects on lipids: ⬇️ TC, ⬇️ LDL, ⬆️⬆️ HDL, ⬇️⬇️⬇️ TG
Fibrates
Dosing
Gemfibrozil: 600mg BID
Fenofibrate: dosing varies by product (fenofibrate, choline fenofibrate, fenofibric acid)
Fibrates
Adverse effects
Inx
Nausea, diarrhea, gallstones, phototoxcity
- statins: increase risk of hepatotoxicty/myalgias with station or niacin use
- protein binding displacement (warfarin)
Ezetimibe
MOA
Designed for use with statins
- cholesterol absorption inhibitor
- ⬇️ LDL and ⬆️ HDL, little effect on TG
- 10mg a day
- absorbed- undergoes phase 2 metabolism
- low drug inx risk
Ezetimibe
-when combined with a statin
Superior lowering of LDL
Statin x2= 5-6% additional LDL lowering
*adding ezetimibe = 20-25% additional LDL lowering!!
