Antihyperlipidemics

Question 1

What are the HMG Co reductase inhibitors and MOA

Answer 1

rosuvastatin and other “statins”

MOA: inhibit HMG CoA –> Mevalonate (cholesterol percursor)

Decreased liver cholesterol
Increased LDL-receptor expression
Decreased plasma LDL

Decreased VLDL synthesis results in: ↓triglyceridemia

Question 2

HMG Co reductase inhibitors side effects and drug interactions

Answer 2

Side effects:
– Myalgia,myopathy (check creatine kinase)
– Rhabdomyolysis
– Hepatotoxicity (check liver function tests)

Drug interaction:
– Gemfibrozil (fibrates) ↑rhabdomyolysis
– CytochromeP450 inhibitors enhance toxicity of statins

Question 3

What are the Bile Acid Resins and MOA

Answer 3

cholestyramine, colestipol, colesvelam

Prevent intestinal reabsorption of bile acids; liver must use cholesterol to make more

Question 4

Bile Acid Resins side effects and drug interactions and contraindications

Answer 4

Side effects:
– Increase VLDL and triglycerides
– Gastrointestinal disturbances
– Malabsorption of lipid-soluble vitamins
– Hyperglycemia

Drug interactions with orally administered drugs (warfarin, thiazides, digoxin, etc.)

Contraindication: hypertriglyceridemia

Question 5

Ezetimbe MOA and side effect

Answer 5

Prevent cholesterol absorption at small intestine brush border (NPC1L1) results in ↓ LDL

GI distress

Question 6

PCSK9 inhibitors and MOA

Answer 6

Alirocumab, evolocumab

Inactivation of LDL-receptor degradation, increasing LDL receptor number and amount of LDL removed from bloodstream

Question 7

PCSK9 inhibitors side effects

Answer 7

Myalgias, delirium, dementia, other neurocognitive effect

Question 8

Niacin, Vitamin B3 MOA and side effect

Answer 8

Inhibits lipolysis (hormone- sensitive lipase) in adipose tissue; reduces hepatic VLDL synthesis

inhibition of VLDL synthesis, results in:
– Decreased plasma VLDL
– Decreased plasma LDL
– Increasedplasma HDL

Side effects:
Red, flushed face, which is decreased by NSAIDs or long-term use
Hyperglycemia
Heptatoxcitiy

Question 9

Fibrates and the MOA and side effects

Answer 9

Gemfibrozil, bezafibrate, fenofibrate

Upregulate LPL to stimulate TG clearance,
Activates PPAR-α to induce HDL synthesis

upregulation of LPL, apoA-I, apoA-II, and for downregulating apo CIII (inhibitor of lipolysis)

– Decreased VLDL and IDL
– Modest ↓LDL (however,in some patients with combined hyperlipidemias, ↑ LDL)
– Increased HDL (most patients)
– Used in hypertriglyceridemia

SE: Gallstones, myositis (increase risk with statins)

Question 10

Statins are contraindicated in

Answer 10

Pregnant/lactating women and persons >8y/o

Question 11

Omega 3 Fatty Acid

Answer 11

decrease hepatic TG synthesis

Question 12

Rx for Familial Hypercholesterolemia

Answer 12

Lomitapide - microsomal TG transfer protein inhibition

Mipomersen - destroy Apo B 100 mRNA

Question 13

Orlistat

Answer 13

weight loss
inhibit pancreatic lipase which decreases TG breakdown

SE: oily stool