Sketchy Pharm: Statins

Question 1

Cholesterol is packaged into chylomicrons as _____________.

Answer 1

cholesteryl ester (like the cholesterol gold bars being packaged in CH-ESTs before being loaded onto the hot air balloon)

Question 2

What is on the outside of chylomicrons?

Answer 2

Triglycerides (think of the hot air balloon with the TRI-pronged pitchforks sticking out)

Also, keep in mind that chylomicrons have more triglycerides than cholesterol (just like how the hot air balloon is mostly pitchfork-wielding passengers and not so many chests)

Question 3

___________ are on the surface of chylomicrons.

Answer 3

Apolipropoteins

Question 4

Prior to being resorbed by the liver, chylomicrons deliver ________________.

Answer 4

triglycerides to peripheral tissues in the form of free fatty acids (just like the pitchfork-wielding passengers deboarding at the LipoProtein Lighthouse –LPL –above the muscle-clams on the beach)

Question 5

Remnant lipoprotein is taken up by the liver by ________________.

Answer 5

apolipoprotein E-mediated endocytosis (think of the hot air balloon landing on the LoaD –L dock)

Question 6

After being absorbed into hepatocytes, cholesterol from remnant lipoprotein can take one of two fates: ________________.

Answer 6

it can be secreted into bile acid (and then pooped out) or it can be packaged into circulating lipoproteins

Question 7

Describe the composition of VLDL.

Answer 7

Mostly triglyceride (just like the airship VLDL mostly filled with pitchfork-wielding passengers) with apolipoprotein B100 (like the B-shaped anchor)

Question 8

What is IDL?

Answer 8

Intermediate-density lipoprotein

Question 9

LDLs are formed by ______________.

Answer 9

the continual loss of triglycerides from VLDL (think of the little LDL ship with only CHESTs on it)

Question 10

What is the basic function of LDL?

Answer 10

It delivers cholesterol to the body (such as to the adrenals for steroid synthesis).

Question 11

How do cells regulate their cholesterol levels?

Answer 11

When low on cholesterol, they express more apolipoprotein B100 receptors, leading to endocytosis of LDL. When cholesterol is abundant in cells, they express fewer B100 receptors, leading to less endocytosis.

Question 12

How is LCAT depicted in this sketch?

Answer 12

As the diver moving free cholesterol bars (cholesterol) to the chests on the HDL submarine (cholesteryl ester)

Question 13

HDL helps get cholesterol back to the liver (where it can be excreted as bile) by two mechanisms: ______________.

Answer 13

directly – by absorbing cholesterol as cholesteryl ester via LCAT – and indirectly –by using CETP to package cholesterol onto LDL

(Think of the submarines directly taking chests back and adding chests onto the platforms beneath the LDL boat.)

Question 14

Statins work in a one-two mechanism: _______________.

Answer 14

they decrease the synthesis of cholesterol by inhibiting HMG co-a reductase which then stimulates the liver to reel in more circulating LDL

(Think of the Steampunk Statin pirate disrupting the gold-bar smelting and the other pirate making the sailors pull in more LDL by the B100 anchor.)

Question 15

Remember, statins are the only lipid-lowering drug shown to ____________.

Answer 15

prevent CV mortality

Question 16

It is standard practice to prescribe statins even in a patient with normal lipid levels if ___________.

Answer 16

they’ve had an MI, have diabetes, or have signs of peripheral vascular disease

(Think of the pirate playing the banjo with broken strings, the pirate eating candy, and the clogged pipe.)

Question 17

Remember an important contraindication for statins is _____________.

Answer 17

pregnancy (the teratogen tarantula on the submarine)

Question 18

Statin-induced myopathy usually presents as ____________.

Answer 18

proximal bilateral muscle soreness

Question 19

Remember to check for drug interactions with ____________.

Answer 19

CYP450-affecting drugs (because all statins except one are metabolized by CYP450)

(Think of the CYP license plate on the tank.)

Question 20

True or false: statins are idiosyncratic hepatotoxins.

Answer 20

False, but they can lead to a usually asymptomatic elevation in LFTs.