Pharmacokinetics

Question 1

Clearance

Answer 1

Rate of elimination / [Drug] plasma

Question 2

First order elimination

Answer 2

Usual for dosage at which drugs are given
when the rate of elimination is proportional to the concentration of drug

Zero order elimination is when there is not a dependance of rate of concentration on clearance and you get drug buildup and potential severe toxicity

Question 3

T1/2

Answer 3

0.693 * Vd / Cl

Question 4

Bioavailability

Answer 4

fraction of unchanged drug reaching the systemic circulation by any route
not changed by percent bound to transport protein
IV= 100%
Oral = 100- stuff that is not absorped - stuff that is metabolized in first pass to liver (because ab into portal circulation) = can bypass this sublingually or partially sub-rectally (practically get about 50% to bypass and 50% ab into veins that go into portal system), or transdermally

Question 5

Henderson Hasselbach equation

Answer 5

pH= pKa + log [U]/[P]

Weak acid = H+ + A- –> HA
Weak base = H+ + B –> HB+

Question 6

C50

Answer 6

concentration of a drug that produces 50% of the max effect

want the initial concentration to key high in relationship to the C50

Question 7

Peak drug concentration

Answer 7

= dose/ Vd

Question 8

Steady state concentration

Answer 8

Rate of drug in / clearance

Question 9

Concentration max drug

Answer 9

[steady state] + 1/2[bolus]

min = [steady state] - 1/2[bolus]

Question 10

Vd

Answer 10

Hypothetical volume to take up drug dose at plasma concentration
Vd = dose / [Drug]plasma

Question 11

Where does drug metabolism occur?

Answer 11

Mostly in the SER of the liver (duel blood supply)
First pass - oral or 50% rectal (superior rectal veins to IMA to Portal)
Drug absorbed = drug does * bioavailability

Question 12

What are the most common phase I enzymes?

Answer 12

cytochrome p450 oxidases (CYP 450)
more than 50% are CYP 3A4
CYP 2D6 (polymorphisms which can result in rapid conversion of codeine to morphine)

Question 13

What is the basic phase I rxn?

Answer 13

Drug + Fe –> + oxidized flavoprotein (oxidized by NADPH) –> Drug-Fe-O2 –> Drug-O + H20

Question 14

What are the most common phase II enzymes?

Answer 14

UGT (UDP glucuronosyl transferase)
NAT (N-acetyl transferase)
GST (glutathione-s transferase)
SULT (sulfotransferase)

Question 15

What drug is heavily metabolized by phase II enzymes?

Answer 15

Tylenol/ acetamenaphine - 95% excreted
BUT if you have altered hepatic fn or other drugs that compete for detox you can get toxic problem
treat with N-acetylcysteine

Question 16

What is gray baby syndrome and how is it caused?

Answer 16

Infants lack some of the liver enzymes that adults do (UGT) and so can’t metabolize chloramphenicol (anti-bacterial) the way adults do and so get toxicity (cyanosis, ashy skin, floppy, hyothermia, cardiovascular collapse, hypotension)

Question 17

What metabolism enzymes do the elderly loose?

Answer 17

Preferentially loose phase I enzymes unless they are malnurished /cachetic and then they don’t have the substrates for phase II rxns

Question 18

What are some co-morbidities that can effect drug metabolism?

Answer 18

Altered hepatic function (has to be very severe to decrease metabolism)
Altered hepatic perfusion
Nutritional status
Cancer/cachexia

Question 19

Competitive antagonist

Answer 19

no change in Emax at high enough agonist concentrations
right shift in the curve, but same Emax
C’ = C(1+ [I]/K) where [I] is a fixed concentration of antagonist and K is the dissociation constant of the antagonist
Ex: propranolol (beta antagonist, cleared differently with different people) so [I] will vary and so effect of C does of epi/ne will have a different C’ effect depending on the person ; also depends on C so if you give propranolol for a resting dose of epi and then you exercise, can see you overcome the effect of the anatgonist (reach the same pt on the y axis by moving across to the right enough on the x)

Question 20

Non competitive antagonists

Answer 20

irreversible so agonists cannot increase [ ] to surmount inhibition ; so lower Emax unless a huge no of spare receptors, but can have the same Ec50
ex: phenoxybenzamine (a adrenergic receptor antagonist) to control HT of a pheo so will control HT even in face of large doses of epi from the tumor, but can’t overcome the block either if something goes wrong

Question 21

Nicotinic receptor

Answer 21

5 subunits, ach binds to two a units (beta, gamma, and delta are other)
Non specific cation receptor, Enernst = 0, membrane potential -70 so cations (Na) physiologically flow in

Question 22

Therapeutic window

Answer 22

TD50/ ED50

50% toxic/ 50% effective (want toxic dose to be much higher), want a large therapeutic window

Question 23

4 beta lactam antibiotic families

Answer 23

1. ) PCN
2. ) cephalosporin
3. ) carabepenems
4. ) monobactam

Question 24

What is the effect of a beta lactamase on PCN

Answer 24

penicilloic acid which is not antibacterial