Pharmacology

Question 1

major site of biotransformation at the tissue level and at the cellular level

Answer 1

Tissue = Liver and Cellular = ER
If pt has compromised liver, they won’t metabolize that drug as quickly and levels of the drug will build up in their body

Question 2

Definition of biotransformation and 2 phases.

Answer 2

Biotransformation = conversion of compounds from lipophilic to polar. This facilitates elimination from the body.

• Phase I = subtle change to make more polar. Addition or unmasking of a polar functional group.
• Phase II = much bigger change! Conjugation of large, endogenous (already in the body) polar group

Question 3

What is important to remember about the 2 phases of biotransformation?

Answer 3

Names Phase I and Phase II don’t reflect the order in which they occur. Drugs can go through Phase II metabolism first, then Phase I. They can also undergo only one or the other. And some drugs can’t undergo either one at all!

Question 4

Name the (4) P450 DEpendent rxns of Phase I biotransformation

Answer 4

HOOD
Hydroxylations: add hydroxyl (-OH); 
Oxidative dealkylations: lose alkyl (-RCH3, -CH3); 
Oxidations (net addition of O); and 
Deaminations: lose amine (NH2)

Question 5

Name the (3) P450 INdependent reactions

Answer 5

Dr. H. Waters is an independent dr (= DRH, also b/c all rxns related to -H and water)
Dehydrogenation (loss of -H)
Reductions (gain of an -H)
Hydrolysis (breaking a molecule in two by adding H2O)

Question 6

What is P450 anyways (w/ regards to Phase I reactions)

Answer 6

Cytochrome P450s are proteins in the liver that regulate (i.e. rate-limiting step) liver oxidation. These proteins bind tot he drug and regulate its oxidation state.

Question 7

How do Phase II reactions work?

Answer 7

Transferases are enzymes that transfer the (endogenous) polar group from its source in the body onto the drug.

Question 8

Name 7 different Phase II rxns and their substrates in ( )

Answer 8

II Gangsters GAG Me With Soap (Phase II)
G: Glucuronidation (UDP glucuronic acid)
G: Glutathione conjugation (glutathione)
A: Acetylation (acetyl CoA)
G: Glycine conjugation (glycine)
M: Methylation (s-adenosyl methionine)
W: Water conjugation (water)
S: Sulfate conjugation (phosphosulfate)

[Also 4 conjugations, acetylation, methylation and glucuronidation]

Question 9

Volume of Distribution (Vd) eqn

[plasma concentration eqn]

Answer 9

Vd = [amt of drug in body] / [plasma conc of drug]

plasma [ ] = dose / Vd. Just switch up above eqn!

Question 10

Clearance (Cl) eqn

Answer 10

Cl = [rate of elimination] / [concentration]

Question 11

Half life eqn

Answer 11

t1/2 = (0.693 x Vd) / Cl

Question 12

Henderson-Hasselbach eqn

Answer 12

pKa - pH = log (protonated / UNprotonated)

Question 13

What do you do with the following:

-2 = log (prot / unprot)

Answer 13

1) subst X/(100-x) for (prot/unprot)
2) anti-log of both sides

x/(100-x) = .01

So ratio of prot:unprot = 1/100. Thus, 99% will be charged and 1% will be absorbed

Question 14

Why is the rate of elimination at the target concentration important?

Answer 14

rate of elimination of the target concentration = the dosing rate. i.e. rate in = rate out

Question 15

Eqn for bioavailability related to oral dose and iv dose

Answer 15

Oral dose = IV dose / F(oral)

F(oral) might be listed as “Oral availability” = 95%. Thus, do IV dose / 0.95

Question 16

How (and why) can you use Vd to calculate loading dose? What’s the next step if calculating for oral dose?

Answer 16

If you’ve been given the target concentration and Vd, then you can use the Vd eqn to solve for the “amount of drug in body” needed to get to that target concentration.
Vd = amount of drug in body / target [ ]

This answer gives you the IV loading dose. If oral, then divide this answer by the oral %.
Ex. oral dose = 150 mg/95% = 158 mg

Question 17

Infusion Rate eqn

Answer 17

IR = Css x Cl

Remember that Css = amt/volume. So this eqn makes sense b/c you’re multiplying target [ ] by the rate at which it is cleared. IR = amt/time (ex. mg/hr)