Lipoprotein Drugs Flashcards
Cholestyramine; side effects
Dose-dependent Most common - constipation, bloating Effects absorption of other drugs - statins, thiazide, digitalis
Cholestyramine; uses
hypercholesterolemia w/out hyperTAGs - second agent after statins; 11-20 year olds
Statin; side effects
Major - myopathy, rhabdomyolysis Hepatotoxic - increased enzymes Minor - GI
Statins; lipid profile
Decrease TAGs - the higher the baseline level, the stronger the lowering effect Decrease LDL Increase HDL
Niacin; lipid profile
TAG/LDL/Lp(a) = decrease HDL = increase
Statin; pharmacokinetics
Life-long treatment 1st pass effect - necessary for accumulation in liver High plasma protein binding Metabolism - CYP3A4
Niacin; CI
Peptic ulcer Gout Liver disease Diabetes
Hypertriglyceridemia treatment
Fibrates - first-line Niacin
Niacin; uses
Hypercholesterolemia and hypertriglyceridemia
Cholestyramine; mechanism
Dose-dependent Quaternary amine; Anion-exchange w/ bile acid; positively charged resin binds w/ negatively charged bile Increased bile excretion = increased bile synthesis = decreased hepatic cholesterol = increased LDL-R expression = decreased LDL levels
Myopathy/rhabdomyolysis; risk factors
Genetic - SCLO1B1 polymorphisms Dose - direct relationship CYP3A4 inhibition Gemfibrozil - blocks OATP1B1 - increased statin in circulation Female sex, old age Renal sufficiency Hypothyroidism
Niacin; pharmacokinetics
o Oral – doses much higher than those used as vitamins o Three types Immediate release – 2-3 times a day Long-acting release Extended release – once a day
Statins; CI
Hypersensitivity - lovastatin, simvastatin Liver disease Pregnancy/breast feeding
Only drug that can lower Lp(a) levels
Niacin/nicotinic acid
Bile acid binding resins
Cholestyramine
Niacin; mechanism
o In adipose – inhibits FFA mobilization; niacin receptor 1 in adipose tissue; Activates niacin receptor 1 = decreased cAMP = no PKA activation = no perilipin/HSL phosphorylation = no TAG is broken down = decreased FFA release o In liver – decreased synthesis of VLDL-TAGs Inhibits DGAT2 – catalyzes final reaction in TG synthesis Increased ApoB degradation o Inhibits uptake of HDL-apoAI Increase in HDL-apoA1 levels = good thing
List statins
Atrovastatin - Lipitor; active, highest half-life Lovastatin - Mevacor; prodrug; hypersensitivity Simvastatin - Zocor; prodrug; hypersensitivity
Statin mechanism
HMG-CoA analogs Competitive, reversible inhibitors of HMG-CA reductase = bind w/ higher affinity Decrease de novo cholesterol synthesis = increase in LDL-R expression (SREBP/Scap) = decreased LDL levels
Myopathy/rhabdomyolysis; symptoms
Major SE of statins Signs - myalgia, fatigue, elevated CK levels Myopathy - pain w/out increased CK Rhabdomyolysis - pain w/ increased CK
Niacin; side effects
o Major – intense cutaneous flush/pruritus Soon after taking drug – poor compliance Mediated by vasodilatory PGs – PGD2 Tolerance over time Treat w/ NSAIDs o Severe GI effects – avoid in patients with peptic ulcer Elevated liver enzymes – MAJOR CONCERN WHEN COMBINED W/ STATINS • Increased risk of myopathy Hyperurecemia – avoid w/ gout Increased fasting glucose/insulin resistance – avoid w/ diabetes
Hypercholesterolemia treatment
Statins - first line; life-long; >12 years of age Cholestyramine - second agent after statins; 11-20 years of age Niacin - not first line PCSK9 - future Statins + niacin = hepatotoxicity risk
Cholestyramine; lipid profile
TAGs - transient increase; return to baseline >250mg/dl = signficant increase
