Hyperlipidemia Drugs

Question 1

***What is the only class of primary Hyperlipidemia we need to know?

Answer 1

Familial Hypercholesterolemia

LDL receptor deficiency

Heterozygous and Homozygous versions - Homozygous has even crazier LDL loads

Question 2

**What is the only treatment for HLD that increases lifespan?

Answer 2

HMG-CoA Reductase Inhibitors (STATINS)

Question 3

**MOA for Statins

Answer 3

Active forms are structural analogs of the HMG-CoA reducase intermediate in mevalonate synthesis

Reduce plasma LDL by inhibiting the reductase to increase high-affinity LDL receptors

End effect = LOWER LDL, lower TGs, higher HDL

Question 4

**When should you taken statins?

Answer 4

In the evening b/c that is when de novo cholesterol synthesis occurs

Question 5

Which statins are in an inactive form?

Answer 5

Lovastatin and simvastatin (others are already active)

Question 6

**Hallmark side effects of statins

Answer 6

INCREASED SERUM AMINOTRANSFERASE (reversible, asymptomatic) —> liver damage in alcoholics and patients with existing liver problems

MYOPATHY and/or MUSCLE PAIN (increased serum CK)

RHABDOMYOLYSIS (myoglobinuria —> renal shutdown) - RARE

Question 7

What drugs are Bile Acid-binding Resins?

Answer 7

Cholestyramine (Questran)

Colestipol (Colestipol)

Colesevelam (WelChol)

Question 8

***MOA for Bile Acid-Binding Resins

Answer 8

Bind bile acids and prevent their intestinal reabsorption

Will lower LDL levels and plasma cholesterols (20%)

Unpleasant sandy/gritty (patients don’t like to take them)

Question 9

What patients should NOT take Bile Acid-Binding Resins?

Answer 9

No effect in HOMOZYGOUS familial Hypercholesterolemia

Not effective in hypertriglyceridemia (may increase VLDL)

Question 10

**Hallmark side effect of Bile Acid-Binding Resins

Answer 10

Constipation and bloating —> steatorrhea

Can also get gallstones or hypoprothrombineama

Question 11

HLD drug safe in pregnancy

Answer 11

Bile Acid-Binding Resins (b/c not absorbed)

Question 12

What types of drugs should not be taken with Bile Acid-Binding Resins?

Answer 12

Acids or fat-soluble drugs

Digitalis
Thiazides
Statins
Tetracycline
Thyroxine
Aspirin

Question 13

What is the MOA for Niacin

Answer 13

Lowers plasma VLDL and LDL by inhibiting VLDL secretion

Also inhibits hepatic cholesterologenesis

*****Increases HDL (most effective agent)

Question 14

**What drug is most effective for increasing HDL?

Answer 14

Niacin (Vitamin B3)

Question 15

**What are the hallmark adverse effects of Niacin?

Answer 15

CUTANEOUS VASODILATION (flushing) - prostaglandin dependent so take some aspirin before it

IMPAIRS GLUCOSE TOLERANCE

Nausea and abdominal discomfort

Hyperuricemia

Rarely - hepatotoxicity

Question 16

What is the MOA for fibrates?

Answer 16

PPAR-alpha*** ligand, upregulates LPL and other genes involved in fatty acid oxidation

LOWERS TRIGLYCERIDES**

Question 17

*****Most effect drug for hypertriglyceridemia

Answer 17

Fabric Acid Derivatives (Fibrates)

Gemfibrozil, Fenofibrate, Fenofibric Acid

Question 18

*****Adverse effects of fibrates

Answer 18

GALLSTONES/CHOLELITHIASIS (esp with younger women after a few pregancies)**

May increase LDL in patients with combined Hyperlipidemia

Inhibits metabolism of statins (DO NOT COMBINE)***

Increased LFTs

Potential anticoagulant action of warfarin**

Question 19

Drug that selectively blocks the intestinal absorption of cholesterol and related phytosterols

Answer 19

Ezetimibe (Zetia)

Question 20

Indications for Zetia

Answer 20

Moderate reduce LDL but NO decrease in CV endpoints

Only used in combo therapy (work synergistically with statins)

Question 21

What is the main downside of PCSK9 inhibitors

Answer 21

$$$$$

Monthly SC injections

Question 22

What class of drug are Alirocumab and Evolocumab?

Answer 22

PCSK9 inhibitors