Applied Pharmacokinetics

Question 1

Therapeutic window

Answer 1

Effective concentration but below (too) toxic concentration.

Question 2

Steady state

Answer 2

Rate of drug in=rate of drug out
IV infusion: 4 half lives
Amt of drug infused dosn’t change time to reach steady state, onlythe concentration at which steady state is achieved.

Question 3

Constant rate of infusion

Answer 3

IV drip
Takes four or more half-lives to achieve this steady state (~93%)
*For every drop in, one drop out

Question 4

Drug accumulation graph

Answer 4

Is the drug elimination graph flipped over

Question 5

Accumulation to steady state:

Answer 5

After 1 half life= 50% steady state
“” 2 half-lives=75% ss
3 hh=87.5% ss
4 hh=93% ss

Question 6

Oral steady state

Answer 6

Still four half-lives

Concentration of drug at steady state is related both to the dose given and to its bioavailability.

Question 7

Steady state of oral administration (graph wise)

Answer 7

Between low points (b4 next dose) and high pts (after previous dose was absorbed).

Question 8

Peak concentration

Answer 8

The highest [blood] after dosing.

Question 9

Trough concentration

Answer 9

lowest [blood] after dosing. Just before next dose

Question 10

Fluctuation

Answer 10

variation between peak and trough.

After a single dose, [peak] is about 70% steady state.

Question 11

Loading dose

Answer 11

Give twice as much drug to reach [target] moe quickly, then give regular doses

Question 12

Maintenance dose

Answer 12

Regular doses after loading dose

Question 13

Loading dose calculation

Answer 13

Dose=VdC0
Adjust for bioavailability (F):
Dose=(VdC0)/F

Question 14

What determines [drug] at SS? (Css)

Answer 14

Equals dosing rate divided by amt and frequency and bioavailability

Question 15

Concentration of drug at SS (Css)?

Answer 15

Css=[(DRF)/Cl] or DR=(CssCl)/F
Cl=proportional to half life
Dr: dosing rate
F=for IV drugs is 1.

Question 16

Drug given to [blood]

Answer 16

Proportional: 2xdose=2x concentration

1/2 dose= 1/2 concentration

Question 17

Slower the drug is eliminated, higher the concentration in blood

Answer 17

Inversely proportional.

Cl is 1/2= 2x [blood]

Question 18

Faster drug is cleared, lower the [blood]

Answer 18

Clx2= 1/2[blood]

Question 19

ppl issues for therapeutic window

Answer 19

Absorption @different rates
Different metabolisms, renal functions.
Sick, age, genetics, gender
Concurrent meds affect absorption, distribution, or elimination.
Differen sensitivities to effective and toxic concentrations.

Question 20

Drugs hard to keep w/in therapeutic window are:

Answer 20

Drugs w/narrow windows
Drugs w/short half-lives
Drugs w/long intervals between doses.
Erratic drug formulations.

Question 21

Drugs easy to keep inside therapeutic window:

Answer 21

Drugs with broad windows
Drugs with long half-lives
Short intervals between doses.

Question 22

Guidelines for staying within the therapeutic window

Answer 22

1. More often the dose, steadier balance between in and out.
2. Shorter the half-life of a drug the greater the degree of fluctuation in blood concentrations.
3. "”may have to give them more often to limit fluctuating

Question 23

More frequent dosing, why not toxic?

Answer 23

Give a smaller dose more often to achieve same {blood}

Question 24

Lengthen half life of short lived drugs by

Answer 24

Pegylation (attaches polyethylene glycol)
Timed-release
Depot preparations
Enterehepatic cycling

Question 25

Dosing rate:

Answer 25

[(Target concentration ss)x Cl]/F

Question 26

Therapeutic [drug] monitoring can tell us:

Answer 26

Are plasma concentrations of drug in therapeutic/toxic range? Is the pt adequately eliminating the drug? Is pt adhering to the dose regimen? Why is therapy failing? What does regimen needs to be given?

Question 27

Data given: [concentrations] at two different point two half-lives apart, and info on current dosing schedule. You can conclude?

Answer 27

Vd, F, Cl and t1/2

Question 28

Synergy:

Answer 28

when one drug increases effect of another by pharmacodynamic action or by increasing [blood] of second drug.

Question 29

Antagonism:

Answer 29

One druge decreases the effect of another

Question 30

Pharmacodynamic Synergy of toxicity

Answer 30

Two drugs add to or have a synergistic action through a shared mechanism or pathway SSRI's and sumatriptan Beta-agonist plus a vasodilator

Question 31

Pharmacodynamic antagonism

Answer 31

Other drugs having opposing effects: fighting for same receptor Indirectly: glucocorticoids and insulin. Cisapride slows HR and conduction, adrenergic increases automaticity at other sites in heart tissue.

Question 32

Pharmacokinetic synergy of toxicity through metabolism:

Answer 32

Inducer of P450 increases activation rate of a prodrug. Or increase creation of toxic metabolites An inhibitor of P450 decreases elimination of drug***most common toxicity reason.

Question 33

Pharmacokinetic synergy of action: renal and absorption

Answer 33

``` One drug can either decrease or increase renal elimination of a second drug. Thiazide diuretics increase lithium Other increase reabsorption. Probenecid inhibits aspirin secretion. Cholinergic speed gastric emptyingtime. ```

Question 34

Pharmacokinetic synergy of toxicity through distribution

Answer 34

One drug displacing a second from plasma proein binding, inreasing [free/active] of the drug. Occasionally, one drug will increase the distribution of another. Manitol opens BBB

Question 35

Pharmacokinetic antagonism through elimination or decreased activation:

Answer 35

One drug can speed up elimination of another: 1. Inductions: phenobarbital and birth control 2. 2a to diuresis: help wash out many drugs 3. Ion trapping: carbonic anhydrase inhibitors and barbiturates. One drug can slow down activation of a prodrug: Cimetidin and sulndac

Question 36

Pharmacokinetic antagonism through decreased or delayed absorption:

Answer 36

A few bind to many others in GI and prevent absorption. Sucralfate and cholestyramine (inhibits digoxin absortpion) Calcium carbonate and several drugs. Others slow down GI or speed up GI altering absorption.

Question 37

Drugs most commonly involved in Toxic Interactions

Answer 37

Narrow therapeutic window. Drugs that boost them to toxic level or lowerthem to subtherapeutic levels. Others add to pharmacodynamic effect. Toxicity triggered by bullydrugs.

Question 38

Worst bully drugs: inhibitin P450

Answer 38

``` Ketoconazole Cimetidin Ritonavir Cyclosporine Spironolactone ```

Question 39

Worst bully's that activate P450

Answer 39

Rifampin Phenytoin Phenobarbital Carbamazepine

Question 40

Block renal secretion/reuptake

Answer 40

Probenecid | Aspirin

Question 41

Cause increased renal elimination

Answer 41

Diuretics w/renally eliminated drugs.

Question 42

Victim drugs; become toxic easily

Answer 42

``` Theophylline LIthium Digoxin warfarin Coumarin Tolbutamide MAOI ```

Question 43

Victims due to reduced action

Answer 43

Low bioavailability: digoxin | Easily eliminated byP450 inducers: birth control

Question 44

Most common drug interactions occur with: (victim drugs)

Answer 44

``` Theophylline Lithium Digoxin Warfarin Coumrin Tolbutamide MAOI ```

Question 45

4 mechanisms by which victim drugs become toxic:

Answer 45

1. Pharmacodynamic interactions: Add adrenergic to Theophylline or MAOI; add second blood thinner to warfarin. 2. P450 inhibition: ketoconazole increases warfarin, tolbutamide, theophyllne. 3. INteract with diuretics: LIthium increased, digoxin increased by hypo-kalemic inducing diuretics. 4. INteracting with protein binding: warfarin, tolbutimide, coumarin are highly bound but: Sulfonamides, aspirin and others can displace them.

Question 46

Ketoconazole Increases:

Answer 46

Warfarin Tolbutamide Theophylline

Question 47

Diuretics increase

Answer 47

LIthium and digoxin

Question 48

Adrenergics interact with:

Answer 48

MAOI and Theo

Question 49

Sulfonamides and aspirin displace what from proteins

Answer 49

Warfarin Tolbutamide Coumarin

Question 50

Birth control easily eliminated by

Answer 50

P450 inducers