8. What Separates Drug from the Poison

Question 1

Selectivity

Answer 1

THE MOST IMPORTANT ATTRIBUTE THAT
SEPARATES THE DRUG FROM THE
POISON…BUT NOT ALL DRUGS HAVE
THIS

Question 2

death from cold damp Northern climates comes mainly from

Answer 2

respiratory infections

Question 3

death from hot southern climates come from

Answer 3

gut infections

Question 4

1993 infectious diseases accounted for ____of deaths in developed world and ____ of deaths in developing world

Answer 4

1.2% & 41.5%

Question 5

Tuberculosis

Answer 5

• Has killed more than 1 billion people
• Developed resistance to antibiotics

Question 6

Drug sensitive TB

Answer 6

*Requires 6 months of treatment
*Cure rate 85%

Question 7

Multi-drug resistant TB
(2017: 580,000 new cases)

Answer 7

*Requires 18 months of treatment
*Cure rate 48%
*14,000 pills and injections

Question 8

Extensively drug resistant TB
(2017: 50,000 cases)

Answer 8

*Cure rate 34% (much less in some studies)

Question 9

When dealing with bacteria __________ is not difficult, ___________ is our main concern

Answer 9

1. selectivity
2. permeability

Question 10

Tuberculosis cell wall have a barrier with the consistency of ….

Answer 10

candle wax at room temperature (therefore needs assistance from our silicon-based drugs)

Question 11

A.I. and machine-learning hare helpful to identify:

Answer 11

• Compounds which will be active against bacterial targets
• Compounds which will penetrate bacterial cell walls
• Compounds as clever as those we stumbled on accidentally taking advantage of unusual opportunities

Question 12

Mycobacterial KatG

Answer 12

This is technically a poison but since it is in the bacterium (not in the location of the human cell), it can not effect human cells because we do not have this enzyme

Question 13

Small changes can be the difference between a drug and poison that is why we need

Answer 13

a crystal structure to guide what we are doing

Question 14

GPCR receptors

Answer 14

the most common class of drug target

Question 15

The biggest challenge for drug development

Answer 15

metabolic stability and the liver
- The liver contains enzymes called cytochrome P450s (CYP450s) which often oxidize drugs into an inactive
analogue

Question 16

We must find and rule out every_______ in order to make sure the drug will work

Answer 16

metabolite

Question 17

Usually want drug to remain effective
for at least _______(for convenience)

Answer 17

8 hours

Question 18

Bioavailability (looking for about 50%):

Answer 18

How much of the drug will distribute through the body
cardiotoxicity, mutagenicity, general non-specific toxicity
(“cytotoxicity”)

Question 19

penicillin has a _____ therapeutic window thus, has _____ side effects

Answer 19

large

low

Question 20

cytotoxic cancer drugs have a ______ therapeutic window and come with _______ effects

Answer 20

small

high/ likely adverse

Question 21

Drugs must dissolve in the ____ in order to be absorbed

Answer 21

gut

Question 22

_____ and ______ drugs are better at dissolving in the digestive tract

Answer 22

Polar and Charged

Question 23

lipophilic

Answer 23

tending to combine/ dissolve in lipids or fats.

Question 24

______ drugs are better at passing through biological membranes

Answer 24

Lipophilic

Question 25

A poision

Answer 25

a non selective drug

Question 26

The drug binding pocket of a GOOD drug target will be a mixture of which characteristics?

Answer 26

Enclosed, with a mixture of polar and lipophilic spaces

Question 27

Which of the following is a reason that we usually try to increase the potency of a drug during its development?

Answer 27

We hope it will improve the selectivity