January 29, 2015

Homework Help: Pharmacology

Posted by Jade on Tuesday, September 25, 2007 at 7:35pm.

This is super confusing, I'm sorry!

The homework:
You have to administer simultaneously two drugs which are each 90% protein bound when administered separately. Please use the law of mass action to calculate how do you have to change the administered doses to obtain the same free drug concentration as in the case when each drug is administered individually. Consider free protein and total drug-bound protein concentrations unchanged (10% and 90% respectively), when both drugs are administered.

Hint: in the law of mass action, replace receptor concentration with protein concentration and drug-receptor complex concentration with drug-protein complex concentration. Instead of concentrations, use percentages. When the 2 drugs are administered together, divide the total complexed protein in two, one half for each drug. Free drug concentration will increase by the same amount that its drug-protein complex decreases.

1. Write the law of mass action separately for each drug when administered individually, indicating the concentrations for each component in the binding equilibrium 0.33 pts
2. Write the law of mass action for each drug when administered together, again indicating concentrations for each component 0.33 pts
3. Indicate how will you change doses for each drug when administered together and by how much. 0.33 pts

Observation: this is an oversimplified example. Usually protein binding sites don’t saturate so fast.

The Law of Mass Action:
L = ligand
R= receptor
D= drug
K A,L= association constant of L-R complex
K D,L= dissociation constant of L-R complex

[L] + [R] <--> [L-R]
K D,L= [L][R]/ [L-R] = 1/K A,L

(A drug interferes with Ligand binding and L-R complex formation)

[D] + [R] <--> [D-R]
K D,D= [D][R]/ [D-R]

I have no idea what to solve for, but this is what I have.

[L] + [R] <--> [L-R]
[.1] + [.9] <--> [1]

K D,L= [L][R]/ [L-R] = 1/K A,L
K D,L= [.1][.9]/[1] = 1/K A,L
K D,L = .09/1 which = 1/ K A,L
so K D,L= .09K
A, L= 11.11

...and now I'm stuck

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