Cardio: Lipid Lowering Agents Flashcards
HMG-CoA reductase inhibitor drugs:
- Lovastatin
- Pravastatin
- Simvastatin
- Atorvastatin
- Rosuvastatin
Effect of HMG-CoA reductase inhibitors
- ↓↓↓ - LDL
- ↑ - HDL
- ↓ - TG
Mechanism of Action for HMG-CoA reductase inhibitors:
Inhibit conversion of HMG-CoA to
mevalonate (a cholesterol precursor)
Side Effects of HMG-CoA reductase:
- 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’
Effect of Niacin (Vitamin B3):
- ↓↓ LDL
- ↑↑ HDL
- ↓ TG
- ↓ Lp(a)
Mechanism of Action of Niacin (Vitamin B3)
- Decreases the production and secretion of VLDL in the Liver
- Inhibits Lipolysis in Adipose tissue
- which leads to reduction of Hepatic VLDL synthesis
Side Effects of Niacin (Vitamin B3)
- Red, flushed face (due to PGD2), which is ↓ by aspirin or longterm use
- Hyperglycemia (Acanthosis Nigricans)
- Hyperuricemia (exacerbates gout)
Bile acid resin (sequestraints) drugs:
- Cholestyramine
- Colestipol
- Colesevelam
Effect of Bile acid resins:
- ↓↓ LDL
- Slightly ↑ HDL
- Slightly ↑ TG
Mechanism of Bile acid resins:
- Prevent intestinal reabsorption of bile acids
- Therefore the Liver must use Cholesterol to make more
Side Effects of Bile acid resins:
- Patients HATE IT - it tastes bad and causes GI discomfort
- ↓ Absorption of Fat-soluble vitamins
- Cholesterol gallstones
Cholesterol absorption blocking drugs:
- Ezetimibe
Effects of Cholesterol Absoprtion blockers (Ezetimibe)
- ↓↓ LDL
- No effect HDL
- No effect TG
Mechanism of Action of Cholesterol absorption blockers
- Prevent cholesterol absorption at small intestine brush border
Side Effects of Cholesterol absorption blockers
- Rare ↑ LFTs
- Fatigue, Abdominal pain, and Diarrhea
Fibrate drugs:
- Gemfibrozil
- Clofibrate
- Bezafibrate
- Fenofibrate
Effect of Fibrates:
- ↓ LDL
- ↑ HDL
- ↓↓↓ TG
- They ↓ the incidence of MI and CHD
Mechanism of Fibrates:
- 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
Side Effects of Fibrates:
- Myositis (↑ risk with concurrent statins)
- Hepatoxicity (↑ LFTs)
- Cholesterol gallstones (esp. w/ concurrent Bile acid resins)
Cardiac Glycosides drugs:
- Digoxin (Lanoxin)
- Digitoxin (discontinued in the United States)
- Ouabain - glycoside plant not used clinically
Mechanism of Cardiac glycosides:
- 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
Clinical use of Cardiac glycosides:
- CHF (↑ contractility)
- Atrial Fibrillation (↓ conduction at AV node and depression of SA node)
- Administer Potassium-sparing diuretics to avoid Potassium depletion
Toxicity of Cardiac glycosides:
- 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)
