Dd - Pk Excretion And Elimination Kinetics

Front 1

____is the primary organ of elimination (excretion of unaltered drugs).

Back 1

kidneys

Front 2

Filtration:

Back 2

get drugs into the urine from the blood.
• Protein-bound drugs cannot be filtered (at least by a healthy kidney).
• Can filter ionized or water-soluble drugs (notice these compounds can't cross membranes, important for reabsorption later).
• Can filter pretty large drugs, although nothing the size of albumin.

Front 3

what drugs can and cannot be filtered by kidneys

Back 3

protein bound NOT

ionized and water soluble FILTERED

large drugs (not albumin) FILTERED

Front 4

Secretion:

Back 4

secrete acids or bases into the urine from the blood.
• Only acts on ionized compounds. On them, this can speed up renal excretion considerably.

Front 5

o Reabsorption:

Back 5

reuptake of drugs out of the urine into the blood.

• Specialized barrier: drugs have to go through membranes to return to the bloodstream (thus have to be nonpolar, uncharged).
• Water-soluble, ionized, or large drugs (often conjugated or metabolized) can't be reabsorbed.
• Remember that you can raise or lower the pH of urine to trap compounds in their ionized forms (keep pH low to increase urine retention of aspirin) and thus limit their reabsorption.

Front 6

what drugs cannot be reabsorbed

Back 6

water soluble, ionized, large

Front 7

fastest renal excretion means what

what is the rate

what kind of drugs

Back 7

fastest filtration and secretion

rate is 600 ml/min

ionized, large, water soluble drugs

Front 8

slowest excretion means what

what is the rate

what kind of drugs

Back 8

meas high reabsorption rate

1 ml/min

nonpolar, small, lipid soluble

Front 9

therapeutic implications of enterohepatic recirculation of drugs.

Back 9

o Extend half-life of relatively large or charged drugs (excreted unchanged in bile to small intestine).
o Note that gluconuridated drugs can be degluconuridated in the small intestine, which means they can be absorbed again (or, for drugs that have their action in the intestine, they can act on their targets multiple times).

Front 10

gluconuriidated drugs can be degluconuridated where and what does this do

Back 10

small intestine

means drug can be absorbed again

Front 11

factors influencing drug passage from plasma to breast milk

Back 11

o Most drugs in the plasma will show up in some levels in the breast milk; but the level that makes it into the infant's plasma will generally be less than 5%.
o Drugs that pass well

non-protein-bound drugs,
weak basic drugs,
more polar or charged drugs.

Front 12

avoid these factors when giving drugs to nursing mothers

Back 12

non-protein-bound drugs,
weak basic drugs,
more polar or charged drugs.

Front 13

Clearance (Cl):

Back 13

• Clearance is, effectively, the metabolism of the drug plus the excretion of the non-metabolized drug.
• Measured in volume over time (per kilogram body weight).
• Clearance (L/hr) = ke * Vd.

Selecting maintenance dose, dosage adjustments necessitated by alteration of kidney or liver function:

Front 14

half life

Back 14

time to steady state or removal from body

after 4-5 half lives

Front 15

steady state

Back 15

drug administration rate at which the rate in equals the rate out. administration rate = clearance rate

Front 16

Fluctuation = 2x

Back 16

, where x = the number of half-lives between doses.

the more half-lives between doses, the more fluctuation in plasma concentration

Front 17

Elimination rate constant (ke

Back 17

constant for any given drug; influences how fast the drug is eliminated (higher ke = faster elimination).
• Again: Clearance (L/hr) = ke * Vd.
• Again: t1/2 = .693/ke (ie it's inversely proportional to ke

Front 18

relationship between half life and elimination rate constant (ke)

Back 18

t1/2 = .693/ke (ie it's inversely proportional to ke

Front 19

• First-order elimination kinetics:

Back 19

All drugs but three are eliminated by 1st-order kinetics.

 The rate of elimination equals a constant times the present concentration remaining. dCp/dt = -keCp.

 Thus rate of elimination starts high (with high plasma concentration) and slows down as there's less drug remaining in the plasma.

 The reason that most drugs are first-order is that hepatic and renal excretion are first-order processes.
 The reason that there's a couple of drugs that are zero-order is that they saturate the metabolism/excretion process.
 Note that you can still calculate the half-life of first-order drugs-- effectively can always predict the time it takes to eliminate 50% of the drug given regardless of initial concentration.

Front 20

hepatic and renal excretion and ___-order processes

Back 20

first order processes

most drugs are first order because they have to go through hepatic and renal

Front 21

• Zero-order kinetics:

Back 21

ethanol, aspirin

 The rate of elimination equals a constant. dCp/dt = ke.
 No real half-life-- just a constant rate of elimination, since the rate doesn't depend on the concentration in the plasma.
 As mentioned, these are only drugs that are given in such high doses that their receptors are saturated (process is going at roughly Vmax)

Front 22

ethanol and aspirin are eliminated by which order kinetics

Back 22

zero order kinetics

Front 23

pharmacokinetics vs pharmacodynamics

Back 23

PK - dose-conceentration, absorption, distribution, elimination

PD - concentration-effect, toxicity, efficacy