Lecture 4: Pharmacokinetics Flashcards
pharmacokinetics
how drugs are handled by the body
goal of pharmacokinetics
predicting time course of active drug in blood that is available at receptor sites
the time course of a drug’s action allows a determine of ___
the intensity of the drug effect as a function of time
ADME
absorption
distribution
metabolism
elimination
absorption
movement of drug from site of administration to the blood
distribution
movement of drug from blood to rest of body
metabolism
breakdown of drug
elimination
removal of drug’s metabolic waste products from the body
therapeutic index (TI)
in animals: ratio of the dose that causes death in 50% of the population (LD50) to dose that is effective in 50% of population
TI = (LD50)/(ED50)
therapeutic ratio (TR)
in humans: ratio of dose that causes toxicity in 50% of population (TD50) to dose that is effective in 50% of the population (ED50)
TR = (TD50)/(ED50)
Cmax
max concentration of drug
Tmax
time at which Cmax is reached
T1/2
half life
AUC
area under the curve; total exposure to drug
half life
time it takes to remove half of current concentration of drug from the body
enteral routes
oral, rectal
drugs enter the capillaries and blood through ____
passive diffusion down concentration gradients
4 disadvantages of oral admin
- stomach distress
- hard to know how much will be absorbed
- stomach acid
- slow onset
path to brain for inhaled drugs
rapid absorption into blood through lungs, pulmonary capillaries carry drug to left side of heart and into arteries
benefits of transdermal administration
continuous absorption over hours or days
2 types of IM injections
- rapid onset/short duration (aqueous solution
2. slow onset/prolonged duration (oily solution)
2 types of IM injections
- rapid onset/short duration (aqueous solution
2. slow onset/prolonged duration (oily solution)
pulmonary circulation
circulation of blood from heart to lungs for oxygenation and back to heart (artery = from heart, vein = to heart)
systemic circulation
between heart and all other body tissues
function of right side of heart
veins flow to it; blood flows from it to brain
function of left side of heart
oxygenated blood goes from there to rest of body; oxygenated blood goes from there to brain
blood returning to the heart from the ____ enters the ___ and flows to the ___ ventricle
- systemic venous system
- right atrium
- right ventricle
with contraction of the heart, blood is pumped into the ___, leading to the ___. once in pulmonary capillaries, ___ is lost and replaced with ____
- pulmonary arteries
- lungs
- CO2 is lost and replaced with O2
oxygenated blood returns to the heart in the ___ veins, which empty into the ___. with heart contraction, blood is pumped from ____ into ___ and is carried to ___
- pulmonary
- left atrium
- left ventricle
- aorta
- body tissues and brain
3 places drug molecules can be found in blood
- plasma (free; water-soluble drugs)
- attached to proteins like albumin (bound)
- platelets (lipid soluble drugs)
4 membranes that affect drug distribution
- cell membranes
- capillary walls
- BBB
- placental barrier
cell membranes are made of a ____ and therefore only permeable to ___
- phospholipid bilayer
2. small lipid-soluble molecules
experimental methods allow small therapeutic agents to pass thru BBB by turning off ___
P-glycoprotein
drugs cross placenta by ___
passive diffusion
5 compartments
- blood
- fat
- extracellular fluid
- intracellular fluid
- other
when drugs move into a new compartment…
some of that drug is sequestered by binding to proteins within that compartment
Kc
equilibrium constant; number showing whether balance is in forward or backward direction
Kc is dep on (3)
- permeability of barriers
- pH of compartments
- binding capacity
Vd
volume of distribution: total amt of drug in the body/conc of drug in plasma
synonym for metabolism
biotransformation
____ drugs are hard for kidneys to hold on to, so they ___ before excretion
- lipid soluble
2. cross back into circulation
the kidneys change molecules from ____ to ____
highly lipid soluble
less lipid soluble; can also change to another lipid soluble molecule, active metabolite
main category of enzymes
cytochrome P450
location of enzymes
hepatocytes (liver cells)
two enzymes that metabolize over 50% of drugs
CYP2D6
CYP3A
two enzymes that metabolize over 50% of drugs
CYP2D6
CYP3A4
4 potential results of metabolism
- active drug to inactive metabolite
- active drug to active metabolite
- inactive prodrug to active metabolite
- active drug to toxic metabolite
grapefruit juice inhibits ___
CYP3A4
enzyme induction
liver “learns” and creates more enzymes for a specific drug
graphs for 0, first, and second order kinetics
page 53
plasma concentration is plotted as ___
log concentration
what kind of function describes terminal decay?
exponential decay
a quantity is subject to exponential decay if it decreases at a rate proportional to its…
current value
in how many half lives is elimination achieved?
6
4 routes through which drugs can leave the body
- kidneys
- lungs
- bile
- skin
diagram of kidney
page 61
three types of tolerance
- metabolic
- cellular-adaptive or pharmacodynamic response
- behavioral conditioning (conditional stimuli elicit compensatory conditional response)
