Cardio: Lipid Lowering Agents

Question 1

HMG-CoA reductase inhibitor drugs:

Answer 1

• Lovastatin
• Pravastatin
• Simvastatin
• Atorvastatin
• Rosuvastatin

Question 2

Effect of HMG-CoA reductase inhibitors

Answer 2

• ↓↓↓ - LDL
• ↑ - HDL
• ↓ - TG

Question 3

Mechanism of Action for HMG-CoA reductase inhibitors:

Answer 3

Inhibit conversion of HMG-CoA to
mevalonate (a cholesterol precursor)

Question 4

Side Effects of HMG-CoA reductase:

Answer 4

• Hepatotoxicity (↑ LFTs) - minor elevations in serum aminotransferase levels during the 1st month of use: use reduced dosage for patients with hepatic parenchymal disease)
• Rhabdomyolysis (esp. when used with Fibrates and Niacin)
• Pregnant women should use Bile acid resins and should never use ‘Statins’

Question 5

Effect of Niacin (Vitamin B₃):

Answer 5

• ↓↓ LDL
• ↑↑ HDL
• ↓ TG
• ↓ Lp(a)

Question 6

Mechanism of Action of Niacin (Vitamin B₃)

Answer 6

• Decreases the production and secretion of VLDL in the Liver
• Inhibits Lipolysis in Adipose tissue
• which leads to reduction of Hepatic VLDL synthesis

Question 7

Side Effects of Niacin (Vitamin B₃)

Answer 7

• Red, flushed face (due to PGD₂), which is ↓ by aspirin or longterm use
• Hyperglycemia (Acanthosis Nigricans)
• Hyperuricemia (exacerbates gout)

Question 8

Bile acid resin (sequestraints) drugs:

Answer 8

• Cholestyramine
• Colestipol
• Colesevelam

Question 9

Effect of Bile acid resins:

Answer 9

• ↓↓ LDL
• Slightly ↑ HDL
• Slightly ↑ TG

Question 10

Mechanism of Bile acid resins:

Answer 10

• Prevent intestinal reabsorption of bile acids
• Therefore the Liver must use Cholesterol to make more

Question 11

Side Effects of Bile acid resins:

Answer 11

• Patients HATE IT - it tastes bad and causes GI discomfort
• ↓ Absorption of Fat-soluble vitamins
• Cholesterol gallstones

Question 12

Cholesterol absorption blocking drugs:

Answer 12

• Ezetimibe

Question 13

Effects of Cholesterol Absoprtion blockers (Ezetimibe)

Answer 13

• ↓↓ LDL
• No effect HDL
• No effect TG

Question 14

Mechanism of Action of Cholesterol absorption blockers

Answer 14

• Prevent cholesterol absorption at small intestine brush border

Question 15

Side Effects of Cholesterol absorption blockers

Answer 15

• Rare ↑ LFTs
• Fatigue, Abdominal pain, and Diarrhea

Question 16

Fibrate drugs:

Answer 16

• Gemfibrozil
• Clofibrate
• Bezafibrate
• Fenofibrate

Question 17

Effect of Fibrates:

Answer 17

• ↓ LDL
• ↑ HDL
• ↓↓↓ TG
• They ↓ the incidence of MI and CHD

Question 18

Mechanism of Fibrates:

Answer 18

• Acts as a ligand at Peroxisome Proliferating Activating Receptors - **PPAR-α receptors **
• Upregulate LPL → ↑ TG clearance → ↑ VLDL and Chylomicron catabolism → ↓ VLDL secretion and by Liver
• Reduces Hepatic synthesis of Cholesterol
• Activates PPAR-α to induce HDL synthesis → ↑ ApoA-1 synthesis

Question 19

Side Effects of Fibrates:

Answer 19

• Myositis (↑ risk with concurrent statins)
• Hepatoxicity (↑ LFTs)
• Cholesterol gallstones (esp. w/ concurrent Bile acid resins)

Question 20

Cardiac Glycosides drugs:

Answer 20

• Digoxin (Lanoxin)
• Digitoxin (discontinued in the United States)
• Ouabain - glycoside plant not used clinically

Question 21

Mechanism of Cardiac glycosides:

Answer 21

• Are carbdenolides that contain a lactone rein and a steroid moiety attached to sugar molecules.
• Direct inhibition of Na^₊ / K⁺ ATPase leads to indirect inhibition of Na⁺ / Ca²⁺ exchanger / antiport
• ↑ [Ca2+] → each action potential produces a greater release of Ca²⁺→ net result is a positive inotropic effect
• Increase stroke volume and enhance cardiac output
• Stimulates Vagus nerve → inhibition of SA node and delayed conduction of AV node → ↓ HR

Question 22

Clinical use of Cardiac glycosides:

Answer 22

• CHF (↑ contractility)
• Atrial Fibrillation (↓ conduction at AV node and depression of SA node)
• Administer Potassium-sparing diuretics to avoid Potassium depletion

Question 23

Toxicity of Cardiac glycosides:

Answer 23

• Cholinergic - nausea, vomiting, diarrhea, blurry yellow vision (think of Van Gogh’s Starry Night)
• ECG - ↑ PR, ↓ QT, ST scooping, T-wave inversion, arrhythmia, AV block
• Can lead to Hyperkalemia, which indicates poor prognosis
• Predisposing factors: Renal failure (↓ excretion), Hypokalemia (permissive for digoxin binding at K⁺ -binding site on Na⁺ / K⁺ ATPase) Verapamil, Amiodarone, Quinidine (↓ digoxin clearance; displaces digoxin from tissue-binding sites)