Exam 3

Question 1

Lecture 1: Applied PK:Digoxin

digoxin molecular weight

Answer 1

780.95

Question 2

Lecture 1: Applied PK:Digoxin

bioavailability of diff dosage forms

Answer 2

tabs: 0.7
elixir: 0.8

Lanoxicaps: 1

Question 3

Lecture 1: Applied PK:Digoxin

digoxin binding

Answer 3

high tissue binding

Question 4

Lecture 1: Applied PK:Digoxin

digoxin distribution

Answer 4

binds very tightly to Na/K atpASE, IN COMPETITION WITH K+.

high tissue binding

Question 5

Lecture 1: Applied PK:Digoxin

digoxin pk variability

Absorption

Answer 5

increased:
erythromycin
tetracycline

decreased:
diarrhea

Question 6

Lecture 1: Applied PK:Digoxin

digoxin pk variability

distribution

Answer 6

increased:
hypokalemia

decreased:
hyperkalemia
renal failure

Question 7

Lecture 1: Applied PK:Digoxin

digoxin pk variability

elimination

Answer 7

increased:–
decreased: renal fialure
p-GP substrates

Question 8

Lecture 1: Applied PK:Digoxin

therapeutic range for digoxin

Answer 8

0.5-2.0 ng/mL

Question 9

Lecture 1: Applied PK:Digoxin

digoxin adverse effects

Answer 9

cardiac effect: av block, premature ventricular contractions (PVCs), atrial tachycardia, sinus bradycardia

etc.

Question 10

Lecture 1: Applied PK:Digoxin

why use pk individualization for digoxin?

Answer 10

high interpt. variability in disposition

low TI

poor accuracy in prediction of pk PARAMETERS FROM PATIENT CHARACTERISTICS

Limitations:

• poor correlation of Cp to effect/ toxicity
• poor selectivity inclniical assay

Goals: achieve desired Css, av concentration

Question 11

Lecture 1: Applied PK:Digoxin

estimation of volume of distribution equations

Answer 11

A. from ‘pt characteristics

if renal insufficiency(when CrcL<30 mL/min):
V(L)= 3.8xTBWxCLcr(in ml/min)

no renal sufficiency(when CrCL>30 ml/min, or is not available):
V=7.3L/kg x TBW

B: from plasma conc: NEVERRR!!!

Question 12

Lecture 1: Applied PK:Digoxin

estimation of CL prior to dosing

Answer 12

if pt doesn’t have CHF:
0.8 mL/min/kg x TBW + CLcr (in mL/min)

if pt has CHF: 0.33 ml/kg/min x TBW + CLcr x 0.9

Question 13

Lecture 1: Applied PK:Digoxin

estimation of CL: pk analysis of Cp

Answer 13

1. determine if pt is at steady state (have they been on it for >/= 1 week?
2. determine if the plasma conc. was collected greater than 6 hrs after the last dose.
3. use Css av eq. to determine CL:
4. if want to calculate a new dose to get a new (desired) Css, rearrange css eq. to solve for dose

Question 14

Lecture 1: Applied PK:Digoxin

method of superposition for atypical dosing. what is it?

Answer 14

loading dose is calculated

pt given 50% of dose as IV bolus

pt given next 25% dose

then pt given next 25%

then starts maintenance dose

used to find remaining concentration of drug in blood before initiation of maintenance dose

Question 15

Lecture 1: Applied PK:Digoxin

how to calculate cp using method of superposition for atypical dosing

Answer 15

1. calculate PK parameters:
   CL: (use eq.. based on whether pt has CHFor not)

V: (use eq. based on if pt has renal failure or not)

K: CL/V

2. create a table with dose/ admin times.

titles for each column:
Dose, ug, time, hrs, t(time from last dose to measurement), F (consider different F for different dosage forms)

3. calculate the cp for each dose given after decay using eq.
   Cp= (Dose x F)/V x e ^-kt
4. add up the concentrations

Question 16

Lecture 2: Applied PK:Digoxin pt 2

evaluation of digoxin toxiicity

when do we use ADF (antidigoxin immune fab)

Answer 16

LIFE THREATENING digoxin intoxication…

1. V. tachycardia, or V. fib
2. 2nd/3rd degree block (not responsive to atropine)
3. acute ingestion of > 10 mg digoxin (adults), > 4 mg children)
4. K+> 5 mEq (in setting of digoxin intoxication

Question 17

Lecture 2: Applied PK:Digoxin pt 2

info on ADF

Answer 17

specific activity: 0.8

Question 18

Lecture 2: Applied PK:Digoxin pt 2

how to calculate ADF dose

Answer 18

1. estimate V
2. calculate amount of digoxin in body (in ug): AB= Cp/V
3. convert to molar quantity using molecular weight (780.95 g/mol)(must first convert from ug to g )
4. calculate equimolar quantity of ADF using specific activity (0.8)
   Active quantitiy[[of digoxin in moles]= dose x specific acttivity
   solve for dose (answer is in mol)
5. convert mol to mg using ADF molecular weight of 50000 g/mol.

Question 19

when do you give a repeat dose of ADF?

Answer 19

only if life threatening symptoms return or got worse following first ADF. if pt is feeling better, do not give ADF again.

Question 20

Lecture 3: Phenytoin 1: ADME and PK-PD

dosage forms of phenytoin

Answer 20

phenytoin sodium:IV or capsules. has 92% phenytoin by weight

Phenytoin acid: chewable tablets, oral suspension

fosphophenytoin: only parenteral(IV).

Question 21

Lecture 3: Phenytoin 1: ADME and PK-PD

how to increase solubility of phenytoin sodium

Answer 21

ethanol and propylene glycol assed to admin vehicle

Question 22

Lecture 3: Phenytoin 1: ADME and PK-PD

phenytoin infusioin rate

Answer 22

limit of infusion for adults and pets, with lower and children

Question 23

Lecture 3: Phenytoin 1: ADME and PK-PD

side effect of phenytoin sodium injection

Answer 23

hypotension and ready cardia

Question 24

Lecture 3: Phenytoin 1: ADME and PK-PD

fosphenytoin dosing

Answer 24

to avoid confusion, fosphenytoin is prescribed in terms of phenytoin sodium equivalents (PE)

Question 25

Lecture 3: Phenytoin 1: ADME and PK-PD VM KM:

Answer 25

Vm: max rate of elimination km: concentration at which saturation is likely to occur

Question 26

Lecture 3: Phenytoin 1: ADME and PK-PD therpeutic range of phenytoin target phenytoin fup:

Answer 26

10-20 mg/mL 1-2 mg/L

Question 27

Lecture 3: Phenytoin 1: ADME and PK-PD affect of 10% chain in max depends on what

Answer 27

depends on Km and steady state. As css becomes much greater than km, the maintenance dose approaches max, and a small change in either the maintenance dose or max can result in disproportionate changes in the new Css

Question 28

Lecture 3: Phenytoin 1: ADME and PK-PD phenytoin skin special situations Pregnancy liver disease:

Answer 28

serum phenytoin conc. tend to fal; during pregnancy due to enhanced metabolism Liver disease: increased conc. due to impaired metabolism renal disease: reduced phenytoin conc due to binding to serum proteins is reduced

Question 29

Lecture 3: Phenytoin 1: ADME and PK-PD why do TDM for phenytoin

Answer 29

undergoes saturable metabolism TI is narrow great interpt. variability

Question 30

Lecture 4: Phenytoin calculations Estimation of pk parameters proper to dosing

Answer 30

V: always = 0.65 Vm: use 7 mg/kg/day Km: use 4mg/day

Question 31

Lecture 4: Phenytoin calculations note about fup

Answer 31

fun of phenytoin is fup=0.1 total=bound+unbound

Question 32

Lecture 4: Phenytoin calculations how to find out true phenytoin conc. w. decreased protein binding

Answer 32

normal albumin is 4.4 if albumin is below that, must rearrange and find the conc if the person had normal protein binding. use those 2 eq. 1. if pt has low albumin and CrcL>25mL/min 2. if pt has normal or low albumin and pt receiving dialysis

Question 33

Lecture 4: Phenytoin calculations how to decide regimen of pt who has not received phenytoin

Answer 33

start with a low dose and increase based on pt response and plasma concentrations. not able to predict pk parameters from pt characteristics initial calculated doses are probably not gonna yield safe effective ocncentrations

Question 34

Lecture 4: Phenytoin calculations when increasing phenytoin, how to do so

Answer 34

never increase more than 25% when vm and km not known

Question 35

Lecture: Carbamezapine and Valproic Acid Carbamezapine as a drug

Answer 35

used for tonic clinic (grand mal), partial or secondarily generalized prophylactic agent moa: blocks Na channels in their inactive conformation, which prevents repetitive and sustained firing of an action potential

Question 36

Lecture: Carbamezapine and Valproic Acid carbamezapine absormption

Answer 36

no first pass metabolism rate of absorption is slow, erratic, and unpredictable, due to slow rate of dissolution and or/ anticholinergic properties also circadian variation: evening doses absorb more slowly than morning dose secondary peaks in drug conc. due to slow and constant rate of absorption in the upper and lower intestine

Question 37

Lecture: Carbamezapine and Valproic Acid carbamezapine distribution

Answer 37

distributes rapidly and uniformly to various organs crosses placenta and accumulates in fetal tissues of

Question 38

Lecture: Carbamezapine and Valproic Acid carbamezapine metabolism

Answer 38

met. by cyp3a4 metabolite is therapeutically active and toxic as well. it is a potent inducer and can induce its own enzyme, causing auto induction that's why you must start low

Question 39

Lecture: Carbamezapine and Valproic Acid cl of carbamezapine in initial conc. vs chronic doising

Answer 39

different clearance

Question 40

Lecture: Carbamezapine and Valproic Acid carbamezapine ddi

Answer 40

induces cyp3a4, (own enzyme) and inhibit cyp219

Question 41

Lecture: Carbamezapine and Valproic Acid tDM

Answer 41

tdm not usually done, but conc. of >15 is associated with toxic effects. start low and go slow

Question 42

Lecture: Carbamezapine and Valproic Acid carbamezapine dosing rate and titration

Answer 42

no loading dose short dosing intervals.