Mmc Pharmacology - Antihyperlipidemic Drugs

Front 1

First line treatment for hyperlipidemia

Back 1

Diet and Lifestyle modification

Front 2

Second-line treatment for hyperlipidemia

Back 2

Pharmacologic intervention

Front 3

Drugs that increase LDL Cholesterol

Back 3

1. Progestins

2. Steroids

3. Corticosteroids

4. Cyclosporine

5. Thiazide diuretics

Front 4

Drugs that increase Triglycerides

Back 4

1. Estrogen

2. Protease inhibitors

3. Corticosteroids

4. Isotretinoin

5. Atypical psychotics

6. Thiazide diuretics

7. Beta blockers

Front 5

Drugs that decrease HDL cholesterol

Back 5

1. Progestins

2. Protease inhibitors

3. Steroids

4. Isotretinoin

5. Atypical psychotics

6. Beta blockers

Front 6

Diet therapy for Hyperlipidemia

Back 6

1. Cholesterol lowering diets

(decrease HDL and LDL)

2. Mediterranean diet

3. Vegetables and fruits

4. Foods that reduce LDL

(Oats, garlic, soy protein, vitamin C)

Front 7

Lifestyle changes to treat hyperlipidemia

Back 7

1) Weight reduction

2) Increased physical activity

3) No alcohol or smoking

Front 8

Names of Fibrates

Back 8

1) Clofibrate

2) Gemfibrozil

3) Fenofibrate

Front 9

Fibrates - Mechanism of Action

Back 9

1) Activate PPAR alpha, which increases transcription of lipoprotein lipase, apo A-I and apo A-II, and decreased levels of apo C-III

2) Increased catabolism of VLDL and IDL due to increased lipoprotein lipase levels

3) Increase plasma HDL levels via induction of apo A-I and apo A-II

4) Inhibits lipolysis via reduction in apo C-III

5) Decreases plasma VLDL and triglycerides

Front 10

Clinical use of fibrates

Back 10

Treatment of patients with type IV and V hyperlipidemia who are at greater risk for pancreatitis and who have not undergone dietary intervention

Front 11

Adverse effects of Fibrates

Back 11

1) Mild GI disturbances and distress

2) Cholelithiasis

3) Malignancy (primarily with clofibrate)

4) Myositis

5) Hypoglycemia

6) May increase LDL in patients with hypertriglycemia

Front 12

Drug interactions associated with Fibrates

Back 12

Potentiates warfarin and sulfonyurea

Front 13

Fibrates - Contraindications

Back 13

1) Patients with liver or severe renal disease

2) Primary biliary cirrhosis

3) Preexisting gall bladder disease

Front 14

Bile Acid Resins - Mechanism of Action

Back 14

1) Bind bile acids in the intestine to form complex that is excreted in feces

2) Increases conversion of plasma cholesterol to bile acids and increase expression of LDL receptors

3) Feedback inhibition of 7 alpha hydroxylase

Front 15

Clinical use of Bile Acid Resins

Back 15

1) Treat patients with elevated LDL

(used with other drugs)

2) To treat heterozygous familial hypercholesterolemia

3) To reduce itching in cholestasis

4) To bind toxicological agents like digoxin

5) As adjunctive treatment for pseudomembranous colitis

Front 16

Adverse Effects of Bile Acid Resins

Back 16

1) GI disturbances (constipation, nausea, bloating, abdominal pain)

2) Reduction of fat soluble vitamins

3) Malabsorption of vitamin K, vitamin C and folic acid

4) Interferes with absorption of other drugs (like tetracycline, phenobarbital, and digoxin)

Front 17

Bile acids - Contraindications

Back 17

1) Pregnant or lactating women

2) Patients with severe hepatic and renal dysfunction

3) Pre-existing gall bladder disease

4) Patients with elevated triglycerides

Front 18

Ezetimibe

Back 18

1) Prevents intestinal absorption of cholesterol

2) Decreases LDL (but not HDL)

3) Often used in combination with statins

Front 19

Ezetimibe - Side effects

Back 19

1) GI distress

2) Headache

3) Increased risk of hepatic toxicity

Front 20

Colesvelam

Back 20

1) Synthetic soluble fiber that reduces LDL cholesterol

2) Does not bind digoxin, warfarin or statins

3) Required to take 6 tablets a day

Front 21

Statins - Mechanism of action

Back 21

1) Inhibit HMG-CoA reductase

2) Results in decreased liver and plasma cholesterol

3) Increases HDL and cell surface LDL receptors

4) Decreases hepatic production of VLDL and apoB

Front 22

Clinical uses of Statins

Back 22

1) Primary prevention of cardiovascular disease

2) Secondary prevention of cardiovascular disease in patients with evidence of heart disease

3) Treatment of type IIa, IIb, III and IV hyperlipidemias

4) Treatment of primary dysbetalipoproteinemia

5) Treatment of homozygous and heterozygous familial hypercholesterolemia

Front 23

Side Effects of Statins

Back 23

1) Liver toxicity --> increased aminotransferase activity

2) Muscle disintegration

3) Renal insufficiency--> increased creatine kinase

4) Systemic lupus erythrematosus (SLE)-like syndrome

5) Decreased ATP synthesis

Front 24

Statins - Key Drug Interactions

Back 24

1) Enhanced toxicity with P450 inhibitors (especially those that compete with CYP3A4 and CYP2C9)

2) Increases coumadin (warfarin) levels

3) Interacts with the drugs amiodarone, amlodipine and ranolazine

4) Increased catabolism of statins by drugs that induce CYP3A4

Front 25

Statins - Contraindications

Back 25

1) Pregnancy and nursing mothers

2) Children and teenagers

3) Patients with liver disease

Front 26

Niacin - Mechanism of Action

Back 26

1) Inhibits lipolysis in adipose tissue, resulting in decreased hepatic VLDL and LDL synthesis

2) Activates lipoprotein lipase, resulting in enhanced VLDL clearance

3) Decreases plasma VLDL, LDL and triglycerides

4) Increases plasma HDL levels

5) Increase tPA and decreases fibrinogen

Front 27

Clinical Uses of Niacin

Back 27

1) Adjunctive treatment of dyslipidemias

2) Used in combination with other anti-dyslipidemic agents (such as bile acid resins and reductase inhibitors)

3) Treatment of hypertriglyceridemia in patients at risk for pancreatitis

4) Treatment of peripheral vascular disease and circulatory disorders

5) Treatment of pellagra

6) Also used as a dietary supplement

Front 28

Adverse effects of Niacin

Back 28

1) Intense cutaneous flush and pruritus

2) Nausea and abdominal pain

3) Predisposes to hyperuricemia and gout

4) Hyperglycemia

5) Hepatotoxicity (RARE)

6) GI ulcer exacerbation

Front 29

Niacin - Contraindications

Back 29

1) Patients with liver disease

2) Active peptic ulcer disease (PUD)

3) Arterial bleeding

4) Use with caution in patients with diabetes and gout

5) Interacts with statins; use niacin+statin combination with caution

Front 30

Rimonabant

Back 30

1) Endocannabinoid receptor blocker that increases HDL and reduces triglycerides

2) Side effects include nausea, vomiting, diarrhea, headache, dizziness and anxiety

3) Contraindicated in patients with depression and those on antidepressant medication

Front 31

Orlistat

Back 31

1) Inhibitor of pancreatic, gastric and carboxylester lipase enzymes

2) Reduce intestinal absorption of fat, LDL cholesterol and triglycerides

3) Increases HDL

Front 32

Sibrutamine

Back 32

1) Monoamine uptake inhibitor

2) Increases HDL and reduces triglycerides

(NO effect on LDL cholesterol!)

Front 33

Omega-3-Fatty Acids

Back 33

1) Reduce VLDL particle synthesis

2) Used as treatment for hypertriglyceridemia or adjunct to diet in type IV hyperlipidemia

3) Used in combination with statins to treat type IIb hyperlipidemia

Front 34

Plant Sterols

Back 34

1) Reduces LDL cholesterol by up to 15%

2) Used along with diet to treat patients with hypercholesterolemia

Front 35

Surgery (Partial Ileal Bypass)

Back 35

1) Potential therapy for hypercholesterolemia

2) Side effects include diarrhea, renal calculi, gallstones and intestinal obstruction

Front 36

Combination therapies used to reduce LDL

Back 36

1) Statins + ezetimibe

2) Statins + bile acid resin

3) Bile acid resin + ezetimibe

Front 37

Combination therapies used to increase HDL and lower triglycerides

Back 37

1) Statins + niacin

2) Statins + fibrate