Med Chem - Dyslipidemia part 2

Question 1

what exactly are bile sequestrants?

are they water soluble?

Answer 1

they are anion exchange resins

water insoluble

Question 2

true or false

bile sequestrants are cation exchange resins

Answer 2

FALSE - anion

Question 3

true or false

bile acid sequestrants are not absorbed

Answer 3

true — they are inert to digestive enzymes and are water insoluble

Question 4

explain how bile sequestrants work to lower cholesterol

Answer 4

they exchange their chloride anions for anionic bile acids

this forms a strong complex and prevents their enterhepatic recirculation. since there is no more negative feedback from bile salts,

this prompts the liver to CONVERT MORE CHOLESTEROL INTO BILE ACIDS/SALTS – and to get cholesterol it is removed from the blood!!! thus lowering blood cholesterol

increased LDLreceptors, increased LDL clearance

Question 5

explain the syngery that exists between statins and bile acid sequestrants

Answer 5

when the amount of cholesterol in the liver decreases, the body compensates by making more HMG-CoA reductase to synthesize more cholesterol

however, if you give a statin, this compensatory mechanism is inhibited!

Question 6

true or false

the body’s compensatory mechanism to make more LDL when bile acid sequestrants are given is sufficient to overcome the benefits of bile acid sequestrants

Answer 6

FALSE

LDL will still be lowered, just not as much

give a statin to negate this compensatory effect

Question 7

true or false

bile sequestrants have 0% bioavailability

Answer 7

true

Question 8

in the MOA of bile sequestrants, a chloride anion from the drug is exchanged for the bile acid anion.

this allows for….

Answer 8

fecak elimination and prevents enterohepatic circulation

Question 9

*explain what PCSK9 is and how PCSK9 inhibitors work to lower cholestero;

Answer 9

PCSK9 is a protease. its function is to breakdown BOTH LDL and the LDL receptor in a lysosome

however, in a patient with high cholesterol, this isnt good bc less LDL receptors on the liver means less degradation of LDL by the liver

therefore, PCSK9 inhibitors are monoclonal antibodies that bind to PCKS9 and prevent it from binding to the LDL receptor

thus, more LDL receptors are recycled to the surface of the hepatocyte and more cholesterol is destroyed by the liver

Question 10

MOA inclisiran

Answer 10

it is siRNA (small interfering RNA) that inhibits the production of PCKS9, thus allowing more LDL receptors to be recycled and for more LDL cholesterol to be destroyed

Question 11

PCKS9 inhibitors are approved for…..

Answer 11

familial hypercholesterolemia (have hyperactive PSCK9)

and pts who cant control LDL wiht only statins

Question 12

both alirocumab and evolucumab are administered how?
they are Ig__ antibodies

Answer 12

subcutaneous

IgG