Pharmacodynamics - Part 5 Flashcards
No drug produces a ______ effect.
single
Another word for enzyme is what?
Catalytic receptor
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
strong enough
weak enough
stronger
inhibitors
Write down the basic enzyme pathway.
E + S ES EP E+P
Enzyme inhibitors will have what characteristics?
Will have structure similar to enzyme substrate
Has to bind strong enough to not be replaced easily
Enzymes follow what kind of kinetics?
Michaelis-Menten kinetics
Describe the Michaelis-Menten Plot.
X- substrate concentration
Y - reaction rate
v = Vmax{S]/Km + [S]
0.5 Vmax on line corresponds to Km concentration
Example: There are two drugs, A and B A - Km = 10 mM B - Km = 10 nm Which has higher affinity?
B - need less of the drug to produce 50% of the maximum rate
Describe the linear version of the Michaelis-Menten plot.
Lineweaver-Burk plot
1/v = Km/Vmax[S] + 1/Vmax
y = 1/v
x = 1/[S]
x-intercept = -1/km y-intercept = 1/Vmax
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?
reversibly intermolecular no reaction strength, binding, concentration substrate increasing structure, substrate, product, co-factor
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 ________
irreversibly covalent substrate increasing, doesnt structure, substrate
Provide an example of an irreversible inhibitor.
Orlistat - inhibits pancreatic lipase
Why is orlistat an irreversible inhibitor?
forms a stable intermediate after conversion with pancreatic lipase
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
reversibly, allosteric intermolecular induced fit, shape active, distorted increasing, doesnt not
Drug target = cell membrane
Result of conformation change = ?
How would this drug work?
Cell membrane loses integrity –> breakup –> cell death
Non-polar region embedded in membrane; polar regions form channels in membrane
