Unit 4-Hypolipidemics

Question 1

Niacin

Drug class

Answer 1

Nicotinic acid

Question 2

Niacin

Mechanism

Answer 2

Reduction of liver triglyceride synthesis, leading to less hepatic VLDL (thus, LDL) production; decreases lipolysis in adipose tissue, leading to lowered FFA transport to liver (thus, less triglycerides); reduced hepatic clearance of ApoAI (raising HDL)

Question 3

Niacin

Uses

Answer 3

Best agent to increase HDL (30-40%); as good as fibrates and statins at lowering triglycerides (35-45%); lowers LDL (20-30%); hypertriglyceridemia and low HDL

Question 4

Niacin

Side effects

Answer 4

Flushing, pruritis of face and upper trunk, rashes, acanthosis nigricans (hyperpigmentation)

Hepatotoxicity, hyperuricemia, hyperglycemia; dyspepsia/reactivation of peptic ulcer disease; rarely, toxic ambylopia, tachyarrhythmias, a-fib (in elderly) and myopathy

Water soluble B vitamin complex at [low]; hypolipidemic at [high]; side effects limit compliance (<50% eligible patients follow on it); contraindicated in DM and gout patients; prevent flushing and pruritus with ASA

Question 5

Clofibrate

Drug class

Answer 5

Fibric Acid Derivatives (Fibrates)

Question 6

Clofibrate

Mechanism

Answer 6

Unknown; may interact w/peroxisome proliferator-activated receptor (esp. PPARα) to stimulate LPL synthesis (enhance TG-rich lipoprotein clearance); inhibit apoC III expression (enhance VLDL clearance); stimulation of apoAI and apoAII (increase HDL)

Question 7

Clofibrate

Uses

Answer 7

Marked reduction in VLDL (thus, triglycerides); variable and small effect on LDL; small increase in HDL (10%); severe hypertriglyceridemia

Question 8

Clofibrates

Side effects

Answer 8

Potentiate oral anticoagulants (displace from albumin), increase bile lithogenicity; myositis flu-like syndrome in 5%, other effects in 10% (not serious)

Combination w/statin inadvisable due to higher myositis risk

Question 9

Gemfibrozil

Drug class

Answer 9

Fibric Acid Derivatives (Fibrates)

Question 10

Gemfibrozil

Mechanism

Answer 10

Unknown; may interact w/peroxisome proliferator-activated receptor (esp. PPARα) to stimulate LPL synthesis (enhance TG-rich lipoprotein clearance); inhibit apoC III expression (enhance VLDL clearance); stimulation of apoAI and apoAII (increase HDL)

Question 11

Gemfibrozil

Uses

Answer 11

Marked reduction in VLDL (thus, triglycerides); variable and small effect on LDL; small increase in HDL (10%); severe hypertriglyceridemia

Question 12

Gemfibrozil

Side effects

Answer 12

Potentiate oral anticoagulants (displace from albumin), increase bile lithogenicity (less than clofibrate); myositis flu-like syndrome in 5%, other effects in 10% (not serious)

Combination w/statin inadvisable due to higher myositis risk

Question 13

Fenofibrate

Drug class

Answer 13

Fibric Acid Derivatives (Fibrates)

Question 14

Fenofibrate

Mechanism

Answer 14

Unknown; may interact w/peroxisome proliferator-activated receptor (esp. PPARα) to stimulate LPL synthesis (enhance TG-rich lipoprotein clearance); inhibit apoC III expression (enhance VLDL clearance); stimulation of apoAI and apoAII (increase HDL)

Question 15

Fenofibrate

Uses

Answer 15

Marked reduction in VLDL (thus, triglycerides); variable and small effect on LDL; small increase in HDL (10%); severe hypertriglyceridemia

Question 16

Fenofibrate

Side effects

Answer 16

Potentiate oral anticoagulants (displace from albumin), increase bile lithogenicity (less than clofibrate); myositis flu-like syndrome in 5%, other effects in 10% (not serious)

Combination w/statin inadvisable due to higher myositis risk

Question 17

Colestipol (Colestid); Cholestyramine (Questran); Colesevelam (Welchol)

Drug class

Answer 17

Bile acid sequestrants

Question 18

Colestipol (Colestid); Cholestyramine (Questran); Colesevelam (Welchol)

Mechanism

Answer 18

Very positively charged resins binds negative charged bile acids, inhibiting reabsorption and increasing cholesterol loss; leads to increase in LDL receptors in liver (to make more cholesterol), decreasing LDL in blood

Question 19

Colestipol (Colestid); Cholestyramine (Questran); Colesevelam (Welchol)

Uses

Answer 19

Decrease LDL (25%), but slight increase (5%) in TG and HDL

Question 20

Colestipol (Colestid); Cholestyramine (Questran); Colesevelam (Welchol)

Side effects

Answer 20

Very safe (only hypolipidemic indicated for children) because not systematically absorbed; impairs fat soluble vitamin absorption, binds other drugs (e.g., cardiac glycosides, coumarins)

Bloating, dyspepsia, constipation, gritty/unpleasant taste

Standard treatment in combo w/statin; contraindicated in hypertriglyceridemia

Question 21

Lovastatin

Drug class

Answer 21

HMG-CoA reductase Inhibitors (statins)

Question 22

Lovastatin

Mechanism

Answer 22

Inhibits HMG-CoA reductase formation of mevalonate; leads to activation of SREBP, a membrane-bound transcription factor that increases LDL-R synthesis and lessens degradation; reduction in cholesterol decreases VLDL synthesis, lowering TG

Question 23

Lovastatin

Uses

Answer 23

Reduce LDL (20-55%) and TG (25%), while increasing HDL (5-10%); treatment of dyslipidemia (reduces fatal & nonfatal CHD, strokes; total mortality reduction is 20%)

Question 24

Lovastatin

Side effects

Answer 24

Very few; hepatic dysfunction in 1% (serious hepatotoxicity rare); myopathy/rhabdomyolysis (reduced if factors inhibiting statin catabolism lacking)

Lactone prodrug (modified in liver to hydroxy acid form); must be taken in evening; Advicor = niacin + lovastatin

Question 25

Simvastatin Drug class

Answer 25

HMG-CoA reductase Inhibitors (statins)

Question 26

Simvastatin Mechanism

Answer 26

Inhibits HMG-CoA reductase formation of mevalonate; leads to activation of SREBP, a membrane-bound transcription factor that increases LDL-R synthesis and lessens degradation; reduction in cholesterol decreases VLDL synthesis, lowering TG

Question 27

Simvastatin Uses

Answer 27

Reduce LDL (20-55%) and TG (25%), while increasing HDL (5-10%); treatment of dyslipidemia (reduces fatal & nonfatal CHD, strokes; total mortality reduction is 20%)

Question 28

Simvastatin Side effects

Answer 28

Very few; hepatic dysfunction in 1% (serious hepatotoxicity rare); myopathy/rhabdomyolysis (reduced if factors inhibiting statin catabolism lacking) Lactone prodrug (modified in liver to hydroxy acid form); must be taken in evening; Vytorin = ezetemibe + simvastatin

Question 29

Pravastatin (Pravachol); Fluvastatin (Lescol) Drug class

Answer 29

HMG-CoA reductase Inhibitors (statins)

Question 30

Pravastatin (Pravachol); Fluvastatin (Lescol) Mechanism

Answer 30

Inhibits HMG-CoA reductase formation of mevalonate; leads to activation of SREBP, a membrane-bound transcription factor that increases LDL-R synthesis and lessens degradation; reduction in cholesterol decreases VLDL synthesis, lowering TG

Question 31

Pravastatin (Pravachol); Fluvastatin (Lescol) Uses

Answer 31

Reduce LDL (20-55%) and TG (25%), while increasing HDL (5-10%); treatment of dyslipidemia (reduces fatal & nonfatal CHD, strokes; total mortality reduction is 20%)

Question 32

Pravastatin (Pravachol); Fluvastatin (Lescol) Side effects

Answer 32

Very few; hepatic dysfunction in 1% (serious hepatotoxicity rare); myopathy/rhabdomyolysis (reduced if factors inhibiting statin catabolism lacking) Must be taken in evening

Question 33

Ezetimibe Drug class

Answer 33

Inhibits enterocyte absorption of cholesterol in intestine

Question 34

Ezetimibe Mechanism

Answer 34

Decreases LDL-C alone (15-20%) or in combination w/statin (60%)

Question 35

Ezetimibe Uses

Answer 35

Inhibits cholesterol absorption by enterocytes in jejunum (70% in mice), leading to less cholesterol in chylomicrons; reduction in chylomicron remnant cholesterol delivery to liver; may also decrease atherogenesis directly (remnants very atherogenic)

Question 36

Ezetimibe Side effects

Answer 36

None (rare allergies) Long-term decrease in endpoints not seen yet (questionable effectiveness)

Question 37

Alirocumab; Evolucumab Drug class

Answer 37

PCSK9 inhibitors

Question 38

Alirocumab; Evolucumab Mechanism

Answer 38

Inhibits an endopeptidase (PCSK9) responsible for LDL-R degradation, resulting in higher numbers of LDL-Rs on hepatocytes

Question 39

Alirocumab; Evolucumab Uses

Answer 39

2nd line therapy for hypercholesterolemia not controlled by diet and statins

Question 40

Alirocumab; Evolucumab Side effects

Answer 40

Injection site reactions; flu-like symptoms; nose and throat irritation; muscle pain; diarrhea