Pharmacokinetics Elimination

Question 1

What are two constants for compartment models?

Answer 1

K12, K21

Question 2

Define the distribution phase (alpha phase) of elimination.

Answer 2

redistribution of drug from the plasma and vessel rich group to the less perfused tissues of the peripheral compartment.

Question 3

Explain the elimination phase (beta phase).

Answer 3

After redistribution slows, get slow continuous elimination from central compartment.

Question 4

Define Half-time.

Answer 4

time necessary for the plasma concentration to decrease to 50% during the elimination phase.

Question 5

Define half-life.

Answer 5

time necessary for 50% of the drug to be removed from the body after rapid IV administration.

Question 6

How many half-times is a drug considered cleared from the body?

Answer 6

5

Question 7

After 2 half times how much drug is eliminated from the body?

Answer 7

75%

Question 8

How much drug remains in the body after 3 half times.?

Answer 8

12.5%

Question 9

Define context-sensitive half-time.

Answer 9

Time necessary from the plasma concentration to decrease to 50% after discontinuing an infusion of a specific duration.

Question 10

Define zero order kinetics.

Answer 10

occurs when the plasma concentration of a drug exceeds capacity of metabolizing enzymes and results in metabolism of a CONSTANT AMOUNT OF DRUG PER UNIT TIME; regardless of plasma concentration. Linear.

Question 11

Name some drugs that automatically use zero order kinetics.

Answer 11

alcohol, aspirin, phenytoin.

Question 12

Define first order kinetics.

Answer 12

a CONSTANT FRACTION/PROPORTION OF AVAILABLE DRUG is metabolized in a given time period. DEPENDENT on plasma concentration. Most drugs use this pathway. Nonlinear.

Question 13

True/False: You can shift drugs into zero order kinetics by giving too much drug.

Answer 13

True. the body can’t metabolize=toxic doses.

Question 14

Define Clearance.

Answer 14

the volume of plasma cleared of a drub by renal excretion and/or liver metabolism by unit of time.

Question 15

Define Steady State.

Answer 15

The point when drug elimination is equal to the rate at which the drug is made available.

Question 16

What is the equation for R (liver metabolism)?

Answer 16

R=Q(C-inflow-C-outflow)

Liver metabolism= Blood flow to liver x (concentration flowing into liver - concentration flowing out of liver).

Question 17

What is a metabolic response of 0? metabolic response of 1?

Answer 17

0= no metabolism
1= maximal metabolism (Vm)

Question 18

Define hepatic clearance Extraction Ratio (ER).

Answer 18

the fraction of drug coming into the liver that is extracted.

Question 19

What is the equation for ER?

Answer 19

ER= C-inflow - C-outflow / C-inflow

Question 20

What is hepatic clearance and its equation?

Answer 20

The amount of blood completely cleared of drug per unit time. Clearance=QxER. Clearance=Blood flow x Extraction Ratio

Question 21

Define perfusion-dependent elimination in terms of hepatic ER.

Answer 21

high ER (>0.7) means depends on blood flow but minimal influence from hepatic enzymes.

Question 22

Define capacity-dependent elimination in terms of hepatic ER.

Answer 22

low ER (<0.3) means blood flow doesn’t affect clearance.

Question 23

Name drugs with low hepatic ERs.

Answer 23

Diazepam, lorazepam, methadone, phenytoin, rocuronium, theophylline, thiopental

Question 24

Name drugs with intermediate hepatic ERs.

Answer 24

alfentanil, methohexital, midazolam, vecuronium

Question 25

Name drugs with high hepatic ERs.

Answer 25

Bupivacaine, diltiazem, Fentanyl, Ketamine, Lidocaine, Meperidine, Metoprolol, Morphine, Naloxone, Nifedipine, Propofol, Propranolol, Sufentanil

Question 26

Name the three methods of renal clearance.

Answer 26

Glomerular filtration, Passive tubular reabsorption, active tubular secretion.

Question 27

Explain glomerular filtration.

Answer 27

Nephrons push things from blood into tubular fluid. amount of drug entering depends on amount bound to plasma proteins. Needs to be low MW and can’t be protein bound

Question 28

Explain passive reabsorption.

Answer 28

Section of nephron allowing it to reabsorb into blood from tubular fluid, trying to cross lipid membrane, affected by lipophillic drugs, pH, ionization, and conc. gradient.

Question 29

Explain active transport or secretion.

Answer 29

another opportunity further down the line to move into tubular fluid, involves energy

Question 30

What 2 things does renal filtration depend on?

Answer 30

Amount of free unbound drug, GFR

Question 31

What is the equation for Cr Cl?

Answer 31

CrCl (ml/min)= (140-age) x Wt in kg / 72xSerum creat. all x 0.85 if female.

Question 32

True/False. Non-ionized fraction of a drug is reabsorbed in renal tubules and ionized portion is excreted.

Answer 32

True. altering urine pH can alter renal excretion.

Question 33

Name drugs with significant renal excretion.

Answer 33

Aminoglycosides, atenolol, cephalosporins, digoxin, edrophonium, nadolol, neostigmine, nor-meperidine, pancuronium, PCN, pyridostigmine, rocuronium.

Question 34

How does old age affect clearance?

Answer 34

decreased GFR, decreased liver blood flow, increased fat (increased Vd of lipophilic drugs and increased half time)

Question 35

How does being a neonate affect clearance?

Answer 35

immature liver enzymes, low metabolic capacity, not really dependent on liver blood flow. poor renal function first year of life.