Pharmacodynamics - Part 5

Question 1

No drug produces a ______ effect.

Answer 1

single

Question 2

Another word for enzyme is what?

Answer 2

Catalytic receptor

Question 3

Enzyme dynamics:

• Binding interaction must be _____ _____ to hold the substrate sufficiently long for the reaction to occur
• Interactions must be ______ ______ to allow the product to depart
• Designing molecules with _____ binding interactions results in enzyme ________ which block the active site

Answer 3

strong enough
weak enough
stronger
inhibitors

Question 4

Write down the basic enzyme pathway.

Answer 4

E + S ES EP E+P

Question 5

Enzyme inhibitors will have what characteristics?

Answer 5

Will have structure similar to enzyme substrate

Has to bind strong enough to not be replaced easily

Question 6

Enzymes follow what kind of kinetics?

Answer 6

Michaelis-Menten kinetics

Question 7

Describe the Michaelis-Menten Plot.

Answer 7

X- substrate concentration
Y - reaction rate
v = Vmax{S]/Km + [S]
0.5 Vmax on line corresponds to Km concentration

Question 8

Example:
There are two drugs, A and B
A - Km = 10 mM
B - Km = 10 nm
Which has higher affinity?

Answer 8

B - need less of the drug to produce 50% of the maximum rate

Question 9

Describe the linear version of the Michaelis-Menten plot.

Answer 9

Lineweaver-Burk plot
1/v = Km/Vmax[S] + 1/Vmax
y = 1/v
x = 1/[S]

x-intercept = -1/km
y-intercept = 1/Vmax

Question 10

Reversible inhibitors:

• Inhibitor binds _____ to the active site
• _______ bonds are involved
• The inhibitor undergoes __ ______
• Inhibition depends on the _______ of inhibitor ______ and inhibitor ________
• ________ is blocked from the active site
• ________ substrate concentration reverses inhibition
• Inhibitor likely to be similar in ______ to what?

Answer 10

reversibly
intermolecular
no reaction
strength, binding, concentration
substrate
increasing
structure, substrate, product, co-factor

Question 11

Irreversible inhibitors:

• binds _______ to the active site
• _______ bond formed between the drug and enzyme
• ______ blocked from the active site
• ________ substrate concentration ______ reverse inhibition
• inhibitor likely similar in _______ to the ________

Answer 11

irreversibly
covalent
substrate
increasing, doesnt
structure, substrate

Question 12

Provide an example of an irreversible inhibitor.

Answer 12

Orlistat - inhibits pancreatic lipase

Question 13

Why is orlistat an irreversible inhibitor?

Answer 13

forms a stable intermediate after conversion with pancreatic lipase

Question 14

Allosteric inhibitors:

• inhibitor binds ______ to the ______ site
• ________ bonds are formed
• _______ ___ alters the ______ of the enzyme
• ______ site is _______ and no longer recognize by the substrate
• ________ substrate concentration ______ reverse inhibition
• inhibitor ______ similar in structure to the substrate

Answer 14

reversibly, allosteric
intermolecular
induced fit, shape
active, distorted
increasing, doesnt
not

Question 15

Drug target = cell membrane
Result of conformation change = ?
How would this drug work?

Answer 15

Cell membrane loses integrity –> breakup –> cell death

Non-polar region embedded in membrane; polar regions form channels in membrane

Question 16

Drug target: cell wall
Result of conformation change?
A drug of this kind would most likely target?

Answer 16

Cell wall loses integrity –> breakup –> cell death

Target transglycosidase

Question 17

Drug target: transport protein
Result of conformation change?
Give an example.

Answer 17

Inability to transport biomolecules –> altered cellular function
Cocaine
SSRI (Prozac)

Question 18

Drug target: Structural proteins
Result of conformation changes?
Example?

Answer 18

Alter normal processes of cell cycle

Taxol

Question 19

Drug target: NT receptors

Result of conformation change?

Answer 19

Alter synapse level activity –> restore or alter cellular function

Question 20

Drug target: enzymes in cellular metabolism
Results of conformation changes?
ex?

Answer 20

Alter the level of metabolite(s) –> restore or alter cellular functions
Caffeine/theophylline - inhibit cAMP phosphodiesterase

Question 21

Drug target: DNA

Results of conformation changes?

Answer 21

Alter transcription level –> restor or alter cellular function

Question 22

What is pharmacological variability due to?

Answer 22

Variation in the composition and purity of the drug
Patient conditions
- biochemical states (fever)
- Physiological states (kidney function)

Question 23

Adaptability can arise due to what?

Answer 23

Gene expression
Regulation in gene expression
Desensitization (tolerance)
Sensitization

Question 24

Adaptability could cause an undesirable outcome under what conditions?

Answer 24

1 - Prolonged drug use

2 - Drug withdrawal

Question 25

What is desensitization?

Answer 25

The drug action cannot be detected, even when the dosage is maintained or increased

Question 26

What is sensitization?

Answer 26

The drug action is detected in a greater extent when the same dosage is used

Question 27

Desensitization is often due to what?

Answer 27

Prolonged use

Question 28

Sensitization is often due to what?

Answer 28

Drug withdrawal

Question 29

Desensitization: - ____-term exposure to the drug - _______ binding of the drug could lead to change of the ________ which does not normally occur (e.g. phosphorylation) - phosphorylated _______ changes ______ and is inactivated - Dephosphorylation occurs once the drug is _________ from the receptor

Answer 29

long prolonged, receptor receptor, shape released

Question 30

What is another way, other than phosphorylation in which desensitization can occur?

Answer 30

Prolonged exposure to the drug induces receptor synthesis causing the normal dose of drug to no longer be as effective.

Question 31

How could an increase in receptors lead to sensitization?

Answer 31

This increase in receptors means that if the person stops taking the drug, cold turkey, many receptors are available and the person will experience withdrawal symptoms.