Clinical applications of Pharmacokinetics

Question 1

what is MEC

Answer 1

Minimum effective concentration

Question 2

therapeutic requirements often _____ duration ____ the MEC

Answer 2

therapeutic requirements often exceed the duration above the MEC following a single dose

• prolonging the duraction above MEC by increasing the dose may produce a peak conc that is not desirable and toxic
• prolonged efficiacy thus usually achieved by administering multple small doses

Question 3

try to make sure the drug concentration remains between ______

Answer 3

• MEC of advrese effect and MEC of desired effect

Question 4

what is the most important pharmacokinetic parameter, what is it used for and how is it expressed

Answer 4

• drug clearance
• gives indication of efficiency of elimination of a drug from plasma
• used clinically to calculate the dosing rate and maintenace doses to maintain target drug conc
• expressed in units of volume/time

Question 5

how is dosing rate calculated

Answer 5

Dosing rate (DR) = Clearance (CL) x Target Drug Concentration (TC)

Question 6

Answer 6

• there is a peak effect that occurs after onset of effect is observed
• minimum effective conc for adverse and desired effects need to be considered when determining dose
• drugs should be administered within therapeutic window to create desired effect

Question 7

what limits the rate of drug metabolism and excretion?

Answer 7

blood flow to target organ

Question 8

most drugs follow a _____ kinetics meaning ____

Answer 8

• follow first order kinetics
• constant fraction of the drug is eliminated per unit time

Half-life can be used to describe elimination (defined by time to eliminate serum drug conc by 50%)

*half life is independent of serum drug concentraton

After 1 half-life, 50% of original dose is eliminated; after 2 half-lives, 75% of original dose is eliminated; after 3 half-lives, 87.5% of original dose is eliminated and after 4 half-lives, 93.75% of original dose is eliminated.

Question 10

how is half-life calculated

Answer 10

Half-life = Ln2/k (k is elimination constant)

Question 11

what are the 3 categories of drug concentrations from a clinical perspective?

Answer 11

• subtherapeutic, therapeutic and toxic ranges
• goal of most drug-drug regimens is to maintain the drug at concentrations within the therapeutic range

Question 12

the first several doses of a drug are typically _____

Answer 12

• subtherapeutic
• occurs as the drug equilibrates to its steady state concentrations (approx 4 elimination half lives)
• Appropriate drug dosing and dosing frequency result in steady-state drug levels that are therapeutic, and the maximal and minimal concentrations of the drug remain within the therapeutic window

Question 13

describe

Answer 13

• if the initial (loading) dose is larger than the maintenance dose the drug reaches therapeutic concentrations more rapidly

Question 14

how is the magnitude of the loading dose determined?

Answer 14

• by the volume of distriubtion of the drug

Question 15

describe

Answer 15

excessive maintenance doses or dosing frequency result in drug accumulation and toxicity

Question 16

describe

Answer 16

insufficient maintenance doses or dosing frequency results in subtherapeutic steady-state drug concentrations.

Question 17

what does therapeutic dosing seek

Answer 17

• maintain the highest plasma drug concentration that is below the toxic concentration while maintaining a dose that is also above the minimally effective concentration

*drug conc divided itno subtherapeutic, therapeutic and toxic

Question 18

what is steady state

Answer 18

• occurs when the amont of drug administered is equal to the amount of drug eliminated in the same time period
• it is affected by drug bioavailability, clearance, dose and dosing interval

The time taken to achieve steady-state does not depend on the rate at which the drug is administered

*when it comes to chronic dosing, the steady-state of plasma drug concentration (Css) is directly proportional to the rate of drug administration

Question 19

how does drug administration relate to steady state when drug dosing is chronic

Answer 19

the steady-state of plasma drug concentration (Css) is directly proportional to the rate of drug administration.

If the rate of administration is doubled, the steady-state of plasma drug concentration is also doubled

Question 20

what occurs upon administration of the drug

Answer 20

• plasma conc initially inc
• drug then distributes from blood to body tissues causing plasma conc to dec
• if drug dosage does not acount for Vd then therapetc range will not be reached

Question 21

what is the purpose of the laoding dose, how is it calculated

Answer 21

• compensates for drug distribution to tissues
• dose is administered at higher dose then subsequent doses

Dose_loading = V_d x C_ss

• once steady-state drug concentratiosn are achieved

Question 22

what is a maintenace dose, how is it calculated

Answer 22

• dose needed to replace that lose through metabolism and excreation
• dependent on drug clearance

Dose_maintenance = Clearance x C_ss

*C_ss = steady state conc