CVS - Lipid Lowering Drugs Flashcards Preview

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Flashcards in CVS - Lipid Lowering Drugs Deck (14):
1

Classes of lipid lowering drugs used & examples

1. HMG-CoA Reductase Inhibitors (Statins - Simvastatin)
2. Fibrates (Gemfibrozil, Fenofibrate)
3. Niacin (Nicotinic acid, Vitamin B3)
4. Bile Acid Sequestrants (Bile Acid-Binding Resins - Colestipol, Cholestyramine)

+ Diet, Exercise

2

Mechanism of action of statins

Reduces cholesterol synthesis + increases peripheral clearance of cholesterol

1. Competitive inhibition of HMG-CoA reductase (rate limiting step in cholesterol synthesis)
2. Depletion of intracellular cholesterol - increased number of LDL receptors - increased LDL uptake - lowers plasma LDL

3

Uses of statins (2)

1. Hyperlipidemia - lowers plasma cholesterol levels
2. Ischemic Heart Disease - reduces risk of coronary events & mortality

4

Toxicity of statins (3+3)

Most common
1. GIT-related (cramps, dyspepsia, flatulence, constipation)
2. Headache
3. Rash

Serious but rare
1. Myotoxicity
2. Hepatotoxicity
3. Lenticular Opacities - Cataracts

5

Contraindications of statins (3)

1. Drug Interactions
- CYP3A4 Inhibitors (eg erythromycin) - increases blood levels of simvastatin
- Amlodipine (CCB, anti-HTN) - increases risk of simvastatin toxicity - should reduce dose
- Fibrates - increased incidence/severity of muscle/liver injury & renal damage

2. Pregnant/lactating mothers - can enter breast milk

3. Children/teenagers - HMG-CoA reductase is important for development - morphological defects

6

Mechanism of action of fibrates

Increases peripheral clearance of VLDL

1. Binds to nuclear PPAR-α (mainly in liver & brown adipose tissue)
2. Enhances synthesis & activity of endothelial LPL - increased breakdown of plasma TGs + clearance of VLDL
3. Induces increased apolipoproteins I & II production - facilitates hepatic production of HDL - increases HDL

7

Uses of fibrates (1)

Hypertriglyceridemia associated with VLDL elevation, esp dysbetalipoproteinemia

8

Toxicity of fibrates (6) + Contraindications (1)

1. GIT-related (nausea, abdominal pain)
2. Musculoskeletal (backache)
3. Skin Rash
4. Rhabdomyolysis/Myositis - tender, weak muscles
5. Hepatotoxicity - Gemfibrozil
6. Gall Stones - long term

1. Warfarin - displaced from plasma protein binding - bleeding

9

Mechanism of action of niacin

Reduces VLDL production

1. Reduces hepatic lipase activity - decreased liver VLDL production - decreased IDL - decreased LDL
2. Inhibits lipolysis in adipose tissue + enhances LPL activity (increased TG breakdown) - lowers plasma TG & LDL
3. Increases HDL-cholesterol levels
4. Decreases circulating fibrinogen & increases tissue plasminogen activator - less risk of thrombosis (associated with hypercholesterolemia & atherosclerosis)

10

Uses of niacin (2)

1. Hyperlipoproteinemia type IIb & type IV
2. Thrombosis associated with hypercholesterolemia & atherosclerosis

11

Toxicity of niacin (4) + Contraindications (3)

1. Intense (facial) cutaneous flush + Pruritus (esp with immediate release prep) - mediated by PGs, minimise by pre-treating with aspirin
2. GIT-related (nausea, vomiting, diarrhea)
3. Hepatotoxicity - more with long acting prep Niaspan
4. Metabolic disorders (hyperuricemia & gout, hyperglycemia) - rare

1. Hepatic Disease
2. Gout/Hyperuricemia
3. Diabetes Mellitus

12

Mechanism of action of resins

Decreases fat absorption

1. Cationic resins bind to negatively charged bile acids/salts in the small intestine - prevents reabsorption into hepatocytes
2. Hepatocytes generate more bile acid via hydroxylation of cholesterol - depletes intracellular cholesterol conc
3. Compensatory upregulation of LDL receptors - increased hepatic uptake of cholesterol-containing LDL - decreased plasma LDL

13

Uses of resins (2)

1. Primary Hypercholesterolemia (type IIa)
2. Combined Hyperlipoproteinemia (type IIb) (+niacin)

14

Toxicity of resins (2)

1. GIT-related (constipation, abdominal discomfort, nausea, vomiting, flatulence)
2. Impaired absorption of fat soluble vitamins A, D, E, K and folic acid