Lipoprotein Drugs

Question 1

Cholestyramine; side effects

Answer 1

Dose-dependent Most common - constipation, bloating Effects absorption of other drugs - statins, thiazide, digitalis

Question 2

Cholestyramine; uses

Answer 2

hypercholesterolemia w/out hyperTAGs - second agent after statins; 11-20 year olds

Question 3

Statin; side effects

Answer 3

Major - myopathy, rhabdomyolysis Hepatotoxic - increased enzymes Minor - GI

Question 4

Statins; lipid profile

Answer 4

Decrease TAGs - the higher the baseline level, the stronger the lowering effect Decrease LDL Increase HDL

Question 4

Niacin; lipid profile

Answer 4

TAG/LDL/Lp(a) = decrease HDL = increase

Question 5

Statin; pharmacokinetics

Answer 5

Life-long treatment 1st pass effect - necessary for accumulation in liver High plasma protein binding Metabolism - CYP3A4

Question 6

Niacin; CI

Answer 6

Peptic ulcer Gout Liver disease Diabetes

Question 7

Hypertriglyceridemia treatment

Answer 7

Fibrates - first-line Niacin

Question 7

Niacin; uses

Answer 7

Hypercholesterolemia and hypertriglyceridemia

Question 8

Cholestyramine; mechanism

Answer 8

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

Question 9

Myopathy/rhabdomyolysis; risk factors

Answer 9

Genetic - SCLO1B1 polymorphisms Dose - direct relationship CYP3A4 inhibition Gemfibrozil - blocks OATP1B1 - increased statin in circulation Female sex, old age Renal sufficiency Hypothyroidism

Question 10

Niacin; pharmacokinetics

Answer 10

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

Question 12

Statins; CI

Answer 12

Hypersensitivity - lovastatin, simvastatin Liver disease Pregnancy/breast feeding

Question 13

Only drug that can lower Lp(a) levels

Answer 13

Niacin/nicotinic acid

Question 14

Bile acid binding resins

Answer 14

Cholestyramine

Question 15

Niacin; mechanism

Answer 15

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

Question 16

List statins

Answer 16

Atrovastatin - Lipitor; active, highest half-life Lovastatin - Mevacor; prodrug; hypersensitivity Simvastatin - Zocor; prodrug; hypersensitivity

Question 18

Statin mechanism

Answer 18

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

Question 19

Myopathy/rhabdomyolysis; symptoms

Answer 19

Major SE of statins Signs - myalgia, fatigue, elevated CK levels Myopathy - pain w/out increased CK Rhabdomyolysis - pain w/ increased CK

Question 20

Niacin; side effects

Answer 20

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

Question 21

Hypercholesterolemia treatment

Answer 21

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

Question 22

Cholestyramine; lipid profile

Answer 22

TAGs - transient increase; return to baseline >250mg/dl = signficant increase