Chapter 12

Question 1

Which enzyme and pathway do statins act on?

Answer 1

Melavonic pathway for cholesterol synthesis

HMG CoA Reductase

Question 2

Benefits of Statins

Answer 2

Decrease LDL cholesterol
Increased HDL cholesterol
Decrease triglycerides

Question 3

Primary Prevention vs. Secondary Prevention

Answer 3

Primary prevention - preventing development of cardiovascular disease

Secondary prevention - prevent recurrence of cardiovascular events

Question 4

Pharmacokinetics of Atorvastatin

Answer 4

Also known as Lipitor
Low oral bioavailability
Large fraction of dose extracted by liver
Distributed to liver, spleen, adrenal glands and skeletal muscle
Metabolized by CYP3A4
Eliminated in feces predominantly

Question 5

Pharmacokinetics of Rosuvastatin

Answer 5

Also known as Crestor
Low oral bioavailability
Large fraction of dose extracted by liver
Distributed to liver and skeletal muscle
Not extensively metabolized
Predominantly eliminated in feces
Asians experience 2x higher concentrations (initial dose should be 5 mg)

Question 6

Adverse effects of statins

Answer 6

Generally well tolerated
Most common event is myopathy
Rhabdomyolysis - muscle lysis with severe pain - measure creatine kinase blood levels (10x higher = yes) - accompanied with hyperkalemia
Low incidence of hepatotoxicity - liver function tests should be performed
Should not be given to females trying to get pregnant because cholesterol is important for cell membranes

Question 7

What does Nicotinic Acid (Niacin) do?

Answer 7

Inhibits hepatic secretion of VLDL and thus LDL because VLDL degradation forms LDL
Increases blood levels of HDL
Side effects: facial flushing, hepatotoxicity, hyperglycemia, skin rash and increase uric acid levels

Question 8

Bile acids are __ charged molecules that are produced in the ___ by ____ (CYP enzyme)

Answer 8

Negatively

Produced in liver by CYP7A1

Question 9

__% of bile acids undergo enterohepatic recycling

Answer 9

95

Question 10

What do bile acid sequestrants do?

Answer 10

Because they are large and positively charged they bind to bile acids and prevent absorption - excreted in feces
This causes an increased demand for bile acid synthesis and this requires LDL cholesterol

Question 11

Adverse effects of bile acid sequestrants

Answer 11

Bile acid sequestrants are not absorbed at all and therefore do not have any systemic side effect
Side effects limited to to GI tract - constipation and bloating
May decrease absorption of some drugs: thiazide diurects, digoxin, warfarin and antibiotics

Question 12

What do cholesterol absorption inhibitors do? Name an example cholesterol inhibitor

Answer 12

They inhibit the transporter NPC1L1 which is responsible for intestinal uptake of dietary cholesterol

Example: ezetimibe (Zetia)

But it often causes a compensatory increase in hepatic cholesterol synthesis so it is usually prescribed with a statin

Question 13

What is vytorin?

Answer 13

contains a statin with ezetimibe

Question 14

What do fibric acid derivatives (fibrates) do?

Answer 14

Most effective drug at lowering plasma triglyceride levels
Increase HDL but have NO effect of LDL levels
Bind to and activate a receptor in the liver called PPAR(alpha) which causes:
1. increased lipoprotein lipase
2. decreased apolipoprotein C3 which inhibits lipase
3. increased apolipoprotein A1 and A2 which increase HDL levels

Question 15

Adverse effects of fibrates

Answer 15

Gallstones
Myopathy
Hepatotoxicity

Question 16

What do VLDLs do?

Answer 16

Deliver triglycerides from liver to adipose tissue and muscle

Question 17

What do LDLs do?

Answer 17

Deliver cholesterol to non-hepatic tissue

Question 18

What do HDLs do?

Answer 18

Deliver cholesterol from non-hepatic tissue back to the liver