Prodrugs

Question 1

What is a prodrug?

Answer 1

INACTIVE compound metabolized into an active agent via bioactivation

Question 2

T/F

Bioactivation is mostly enzymatic but NOT exclusively

Answer 2

True

Question 3

When should prodrugs be utilized?

Answer 3

To address shortcomings of otherwise useful agents

Question 4

Equation for therapeutic index?

Answer 4

TD50 / ED50

Question 5

What is a hard drug?

Answer 5

Contain characteristics required for activity and NOT susceptible to metabolism

Question 6

What is the opposite of a prodrug?

Answer 6

Soft drug

Question 7

What is a soft drug?

Answer 7

Synthesized as active compounds and readily undergo metabolic inactivation

Question 8

What are the classes of prodrugs?

Answer 8

1. Simple/carrier-mediated

2. Bioprecursor

Question 9

What is a simple/carrier-mediated prodrug?

Answer 9

RX that are COVALENTLY attached directly or thru STRATEGICALLY selected and METABOLICALLY LABILE chemical linkage to another molecule designated as PROMOIETY

Question 10

For simple or carrier mediated prodrugs, what is the most common rxn for bioactivation?

Answer 10

Hydrolysis

Question 11

What is a bioprecursor prodrug?

Answer 11

They DON’T contain auxiliary promoiety

Question 12

How is a simple prodrug created?

Answer 12

Bioreversible chemical alteration of target (parent)

Question 13

What is the most common prodrug form?

Answer 13

Ester (forward rxns)

Question 14

Why are esters used as prodrugs?

Answer 14

Make RX less polar to allow it to cross cell membranes more easily

Question 15

How can you make prodrugs prolong the activity?

Answer 15

1. Mask polar groups

2. Add hydrophobic groups