Pharmacokinetics III

Question 0

What three factors affect drug elimination via the kidney and how do they relate to each other?

Answer 0

Glomerular filtration + tubular filtration - tubular reabsorption = kidney elimination

Question 1

What is the most important organ in drug elimination?

Answer 1

Liver

Question 2

What is the equation for clearance (CL)?

Answer 2

CL = Rate of elimination of drug (mg/hr) / Plasma drug concentration (mg/L)

Question 3

What is clearance?

Answer 3

the amount of plasma that is cleared of a drug per unit time

rate of drug elimination

Question 4

How do drugs get cleared?

Answer 4

• zero-order kinetics

- first-order kinetics

Question 5

What is zero-order kinetics?

Answer 5

the rate of elimination is constant regardless of concentration (i.e., ethanol and high doses of aspirin and phenytoin)

*fixed amount of drug that can be handled at any one time

Question 6

What is first-order kinetics?

Answer 6

the rate of elimination is proportionate to the concentration (i.e., the higher the concentration, the greater the amount of drug eliminated per unit time)

• a constant fraction of drug is metabolized per unit of time
• majority of drugs cleared via first-order kinetics

Question 7

Log transformation of first-order kinetics gives a linear relationship and helps easily determine what?

Answer 7

the drug’s half-life

Question 8

How do you get initial plasma concentration (C0)?

Answer 8

back-extrapolate from linear portion of log graph

*DON’T FORGET THIS

Question 9

How does half-life relate to volume of distribution (Vd) and clearance (CL)? (units = time)

Answer 9

half time = 0.693 * Vd / CL

• take two points on the linear portion of the curve, determine half-life
• remember, Vd = dose (mg) / Cp (mg/L) ; CL = elimination (mg/hr) / Cp (mg/L)

*back-extrapolate for C0, this is Cp

Question 10

Why do you back-extrapolate?

Answer 10

To overcome for the initial distribution phase of the drug

*we are assuming that is the concentration of the drug if it had initially completely dissociated

Question 11

What is multicompartment distribution?

Answer 11

after absorption, many drugs undergo an early distribution phase followed by a slower elimination phase

Question 13

When do you reach steady state concentration (C_ss)? What is the significance of Css?
(drug accumulation with repeated dosing)

Answer 13

• after about 5 half-lives

- amount of drug delivered is equal to the amount metabolized and eliminated

Question 13

Half-life determines the rate at which _____ concentration rises during constant infusion.

Answer 13

blood

Question 14

What is the equation for Average Plasma Concentration at Plateau?

Answer 14

Average Plasma Concentration at Plateau = F/CL * Dose/Dosing Interval

Question 15

What will increase the plasma half-life?

Answer 15

• increase Vd (take longer to get drug back out of all the tissues and clear)
• decrease CL

Question 16

What are two conditions which reduce the clearance of drugs?

Answer 16

• renal disease
• reduced cardiac output
• corrected dose = average dose * patient’s creatinine clearance / (100 ML/min)
• normal creatinine clearance

Question 17

Is drug elimination the same as saying drug termination?

Answer 17

no

drug can be terminated before getting eliminated (ex: inhibition?)

Question 18

What is the normal creatinine clearance?

Answer 18

100 mL/min = 6 L/hr

• men: 97-137 mL/min
• women: 88-128 mL/min
• each decade of age corresponds to a decrease of about 6.5 mL/min

Question 19

Can a drug with a half life of 30 minutes still have effects 48 hours after administration?

Answer 19

• depends on metabolites - it may have a longer half life; is active for longer than parent drug
• irreversible binding to a receptor, body has to make new receptor, so effect can be extended out longer than drug’s half-life

Question 20

What is dose regimen?

Answer 20

a plan for drug administration over a period of time

- need to achieve therapeutic levels of the drug in the blood, without exceeding the minimum toxic concentration

Question 21

After giving loading dose, how do you maintain patient at desired plasma concentration?

Answer 21

maintenance dose

Question 22

How does large Vd affect loading dose? What is equation for loading dose?

Answer 22

if therapeutic dose must be achieved rapidly and the Vd is large, a large loading dose may be needed to onset therapy

Loading Dose = Vd * Cp,desired / bioavailability

Cp,desired = desired plasma conc = Cpss = plasma conc at steady state

Question 23

What is maintenance dose?

Answer 23

maintenance rate of drug administration is equal to the rate of elimination at steady state, the maintenance dose is a function of clearance

maintenance dose = CL * desired plasma concentration / bioavailability

Question 24

What does biotransformation typically accomplish?

Answer 24

typically results in conversion of the foreign compound into a form that is more water soluble and can be excreted in the urine

*mostly occurs in liver

Question 25

What is the most important organ for excretion of drugs and their metabolites?

Answer 25

kidney

Question 26

In zero-order kinetics, when the drug dose is increased, what happens to the elimination half-life?

Answer 26

it increases
(if there is more drug, it will take longer to eliminated because rate of elimination is constant)

Question 27

When steady state is reached and rate of input equals elimination, what is the equation for plasma concentration at steady state (Css)?

Answer 27

Plasma concentration at steady state (Css) = Rate of Input / CL

Question 28

For patients with reduced elimination of a drug (ex, due to impaired renal or liver function), what changes should be made to the rate of input?

Answer 28

Rate of input may need to be decreased in order to achieve the same plateau level

*time to steady state may be prolonged in these patients due to a longer half-life