Hyperlipidemia/Dyslipidemia Flashcards
definition hypercholesterolemia
increased LDL, normal TG and HDL
define mixed or combined dyslipidemia
increased LDL and TG and possibly low HDL
define hypertriglyceridemia
increased TG, normal LDL and possibly low HDL
define low HDL cholesterol
low HDL and normal LDL and TG
natural products for hyperlipidemia
niacin omega 3 fatty acids red yeast rice (mevinolin = lovastatin) green tea sitostanol beta-sitosterol EDTA chelation
statins MOA
HMG-CoA reductase inhibitors (vital step in cholesterol synthesis)
liver then increases cholesterol uptake from blood stream by increasing LDL receptors
PCSKP up regulation
which statins fall into high intensity
Atorvastatin 40-80mg
Rosuvastatin 20-40mg
which statins are moderate-intensity
Atorvastatin 10-20mg* Rosuvastatin 5-10mg* Pravastatin 40-80mg* Lovastatin 40mg* PItavastatin 2-4mg
which statins are low-intensity
Pravastatin 10-20mg
Lovastatin 20mg
statin contraindications
active liver dz
pregnancy
breast feeding
side effects
myopathy
increase in liver enzymes
nausea
HA
potential interactions btwn statins and natural therapies
red yeast rice
niacin (altho sometimes used with TG high or HDL low)
alcohol, grapefruit, St John’s wort, and Sweet Orange area ll major interactions
Ezetimibe (Zetia) MOA
Ezetimibe prevents absorption of dietary and biliary cholesterol —> interrupts enterohepatic circulation of cholesterol as well as chylomicron assembly –> upregulates LDL receptors in liver, lowering plasma LDL
Ezetimibe uses **
adjunctive therapy in homozygous hypercholesterolemia and primary hyperlipidemia
used when statin intolerant
contraindications to Ezetimibe
pregnancy
breast feeding
side effects Ezetimibe
increase liver enzymes when given with statin
Ezetimibe onset/metabolism
onset: within 1 week
metabolism: 30% undergoes glucuronide conjugation in small intestine and liver
interactions with ezetimibe and natural therapies
ezetimibe inhibits sterol absorption in the gut and would lower the effectiveness of green tea, omega 3 fatty acids, stiostanol and betasitosterol
fibrates MOA
lower production and increase clearance of VLDL
increased HDL production
lowers TG** and increases HDL but has has variable effects on LDL
fibrate indications
hypercholesterolemia or mixed dyslipidemia as adjunct therapy or monotherapy in patients who can not tolerate statins
hypertriglyceridemia first-line pharmacotherapy
contraindications to fibrates
active liver dz
severe renal impairment or ESRD
pre-existing gallbladder dz
breast feeding
side effects fibrates
dyspepsia
gallstones
myopathy (increased with statins, esp gemfibrozil)
onset and metabolism of fibrate
onset: 2-3 days (quicker than statins)
metabolism: inactivated by glucuronidation in liver or kidneys
What is phase 1 detox
Oxidation reduction and hydrolysis (CYP450)
What is phase II detox
Chemically change the drug (or P1 metabolite) into compounds that are soluble enough to be excreted in urine
Potential interactions between fibrates and natural therapies
Combined with red yeast rice might increase risk of myopathy (same as statins and fibrates)
Niacin might increase the hepatoxicity of fibrates
No interaction with green tea, omega-3 FA, sitostanol and beta-sitosterol
Two drug names of Fibrates
Fenofibrate
Gemfibrozil
Gemfibrozil increases the risk for what side effect when used with statin therapy?
Myopathy
Can we assess severity of this adverse effect?
Yes through creatine kinase
Niacin MOA
Niacin is converted to nicotinamide then to NAD+ and NADH
Increases lipoprotein lipase activity enhancing removal of triglycerides from plasma
Reduces TG synthesis
Increases HDL levels
Niacin indications
Hypercholesterolemia or mixed dyslipidemia as an adjunct therapy for patients who do not tolerate fibrates or omega-3 FAs
Monotherapy for patients who do not tolerate statins, BAS, or fibrates
Contraindications to Niacin
Active liver disease, gout or peptic ulcer dz
Potential side effects of Niacin
Hepatotoxicity (enhanced in SR formula), hyperglycemia, hyperuricemia, upper GI distress, flushing, itching
Niacin onset
Immediate
Potential interactions between niacin and other natural therapies
Hyperlipidemia: red yeast rice might interact
Alcohol
Niacin causes flushing, the extended release form has less flushing as a side effect. However, it is not used very often because of an increased risk for what major side effect?
Hepatoxicity
What is the largest benefit of omega-3 FA’s?
Lowering TG’s
Omega-3 FA MOA
Inhibits release of FA from adipose tissue Inhibits beta oxidation of hepatic FA Inhibits FA synthesis Increases VLDL clearance Lowers TG and increases HDL
Omega 3 FA indications
Hypertriglyceridemia second line pharmacotherapy
Contraindications omega 3-FA
Hypersensitivity to fish oil
Potential side effects omega 3 FA
Eructation, nausea, dyspepsia, taste changes
May increase bleeding time (use with caution with anticoagulants and antiplatelets)
Onset and metabolism of Omega 3 FA
Onset 2 weeks
Metabolized by lipid enzymes in liver and tissues
What effect does omega 3 FA have on bleeding
May impair platelet function and increasing bleeding times
Bile acid sequestrants
Resins that bind bile in intestine
Reduces enterohepatic recycling
Increases hepatic conversion of cholesterol to bile acid
Upregulates LDL receptors on the liver
BAS indications and contraindications
Indications: hypercholesterolemia for high risk patients who are stain-intolerant or are on maximal tolerated doses of statin
What two drugs share intestine as site of action?
Ezetimibe and BAS
Work in lower intestine to lower absorption of cholesterol
What change occurs in the liver to lower LDL
Increase in LDL receptors –> more uptake on blood
