Pharmacokinetics Flashcards
What is the “theoretical” volume necessary to account for the total amount of drug in the body in the same concentration as in the plasma?
Volume of distribution
What is the “theoretical” volume of plasma that is completely cleared (100%) of drug in a given period of time?
Clearance
What is elimination half-time (T1/2B)?
The time it takes for PLASMA CONCENTRATION of a drug to fall by one-half.
What is elimination half-life?
The time it takes for the total amount of drug IN THE BODY to decrease by one-half
How is the volume of distribution calculated?
by dividing the amount of drug injected by the plasma concentration; Vd= Q/C, where C is the plasma concentration
What drugs in anesthesia have relatively small volumes of distribution?
water soluble
ex) muscle relaxants (ionized and restricted to extracellular space)
What drugs in anesthesia have relatively large volumes of distribution?
fat soluble
ex) induction agents (readily dissolves in adipose tissue), opioids
What is pharmacokinetics?
What the body does to drugs
What is different about a neonate or infants body composition compared to an adult?
they have an expanded extracellular fluid volume (plasma volume plus interstitial fluid volume)
How does distribution of muscle relaxants differ in the neonate than the adult?
muscle relaxants are ionized and restricted to the extracellular space–> they have VoD that are greater in the neonate because the neonate has a greater extracellular fluid volume on a weight/kg basis
SUX increase–> immature junctions, more water
NDMB–> give same, immature needs less inhibition; this cancels the more H2O out
Give 2 reasons neonates require more sux? For how long?
1) > VOD
2) immature junctions
* extracellular fluid volume is twice that of the adult (40% vs 20%) up to ~ 18 months old
What is zero order kinetics?
a constant amount of drug is eliminated per unit of time
ex) 2mg per min
straight decreasing line graph (linear trend with negative slope)
What are 3 primary drugs that exhibit zero order kinetics at therapeutic concentrations?
1) alcohol
2) dilantin (phenytoin)
3) aspirin
“ADA ZERO”
Most drugs are eliminated by _____ order kinetics.
first
What is first order kinetics?
a constant fraction of drug is eliminated per unit of time
A constant amount over time=
zero order
A constant fraction over time=
first order
What is the look of the line graph for first order one compartment?
linear trend with negative slope… but there will be a LOGARITHM (LOOK FOR THIS)
What is the look of the line graph for first order two compartment?
Has a distribution or alpha phase (small curve) and an elimination or beta phase (linear trend with negative slope)
Name a drug that is eliminated by first order one compartment kinetics.
albumin
Where is volume of distribution calculated from on a first order two compartment kinetic model?
from the equilibrium point (between the alpha and beta phase)
Drugs will be eliminated rapidly if: (2)
1) their clearances are high
and/or
2) their volumes of distribution are small
How many half-times does it take to eliminate 98% of a drug?
6
Name the 4 types of phase I reactions.
1) oxidation
2) reduction
3) methylation
4) hydrolysis
“HORM”
*phase I reactions involve chemical biotransformation of a molecule, usually to a more water soluble and often inactive metabolites
Name 4 types of phase II reactions.
1) glucuronidation
2) glutathione conjugation
3) sulfation
4) acetylation
Phase II reactions involve ______ of a drug or its metabolite with endogenous molecules.
conjugation
Acetylation (a phase II reaction) is an important pathway for metabolism of agents such as __________, __________, and _________.
procainamide, hydralazine, isoniazid
Phase III reactions are elimination that involve ____________ transport proteins.
ATP-binding cassette (ABC) trasport proteins
What is the most abundant plasma protein, therefore binding the majority of injected drugs?
albumin
_______ drugs do not leave circulation, only the _____ drugs diffuses across capillary walls to target cells.
protein bound drugs
free (unbound)
Only ______ and _______ drug crosses the placental and BB barriers.
free (unbound) and nonionized
How does hypoproteinemia (hypoalbuminemia) affect injected drugs?
patients with hypoalbuminemia are more sensitive to injected drugs because protein binding is reduced; more of the injected drug are in the free form.
How does hypoproteinemia (hypoalbuminemia) affect the volume of distribution of injected drugs?
increases VoD
