pharmacokinetics Flashcards
what is pharmacokinetics
relationship between dose and time course of drug concentration attained in different regions of the body during and after dosing
(what the body does to the drug basically)
what is pharmacodynamics
relationship between drug conc/time profile and therapeutic and adverse effects
(basically how the drug affects the body)
why is pharmacokinetics relevent
allows prediction of time course of drug action
why are drugs with a narrow therapeutic range not good
difficult to use, patient might need to be monitored frequently (therapeutic effects, side effects, blood level)
what does ADME stand for
absorption- movement of drug form site of administration to site of measurement
distribution- reversible transfer of drug within body
metabolism- loss of drug from body by chemical conversion
excretion- loss of unchanged drug from body
what is elimination in ADME
irreversible loss of drug from body (metabolism and excretion) (ME)
what is disposition in ADME
process of elimination and distribution (distribution, metabolism and excretion) (DME)
name things that affect absorption
passive diffusion- ficks first law
lipophilicity (partition coefficient)- lipid soluble drugs have higher permeability and polar ionised compounds have lower permeability
size- small water soluble drugs can pass between cells easily, size affects diffusion rate
ionisation- pH affects ionisation and lipophiliicty, charged drugs are slower
what is bioavailability
fraction of administered dose reaching systemic circulation in an unchanged form
describe the causes of reduced bioavailability in oral administration
loss in faeces, decomposition in lumen, destruction within walls of GI tract (intestinal first pass metabolism), destruction within liver (hepatic first pass metabolism)
how is drug transported
blood
what is volume of distribution and its equation
Vd= total amount of drug in body/plasma drug concentration
describes relationship between amount of drug in body and the concentration in blood
name 1 thing that majorly determines Vd (volume of distribution)
strength of drug binding to tissue components compared to plasma proteins
name 2 main routes of elimination of drugs and where it mostly occurs
excretion and metabolism
mostly in kidney and liver
kidney- excreted unchanged
liver- metabolised then excreted
difference between drug elimination in kidney and liver
kidney- drug is excreted unchanged
liver- drug gets metabolised then excreted
name 2 major independent pharmacokinetic parameters
volume of distribution and clearance
what is clearance
volume of blood cleared of drug per unit time (L/hr, mL/min)
describes efficiency of irreversible elimination of a drug molecule from systemic circulation, can be through excretion or metabolic conversion to a metabolite (metabolite in body but parent molecule is cleared)
(uptake into tissue isnt clearance if unchanged drug eventually returns to circulation)
what is extraction ratio and its equation
E=1-(Cv/Ca)
0<E<1
0=no extraction 1=complete extraction
an organs efficiency in eliminating drug from the systemic circulation over 1 pass through the organ
what is the equation for clearance
clearance= Q x E
Q=blood flow to organs
E= extraction ratio of organ
what is clearance
volume of blood completely cleared of drug per unit of time, (can be hepatic clearance, renal clearance, pulmonary clearance etc.)
what is the equation for rate of elimination and the units
rate of elimination (mg/hr) = clearance (L/hr) x plasma drug conc (mg/L)
for most drugs the rate of elimination is directly proportional to drug concentration
what is the equation for elimination rate constant (K) and what does it depend on
K=CL/Vd
elimination rate constant depends on clearance and volume distribution
name 2 categories of iv administration
bolus (single dose) and infusion (constant rate)
bolus= injection into bloodstream
what assumptions are made for the one compartment model for iv bolus
body acts as a single and uniform compartment, entire does of drug is injected at once, drug distributes through entire body instantaneously, volume of compartment remains constant, drug elimination starts immediately
describe a blood concentration time profile for a one compartment model of iv bolus
most drugs show first order elimination kinetics, conc time data show a straight line going down on a semi log plot, on normal plot it curves down
semi log plot= one axis is logarithmic and one is linear
what is the unit for elimination rate constant
h^-1 (per hour)
what is the equation for a plasma concentration at a specific time (t) in single dose iv administrations
Ct=C0e^(-kt)
Ct= plasma conc at time t
t= time
C0= initial conc
K= elimination rate constant
what is half life and how to calculate it
time take for plasma conc to fall by a half
t1/2=0.693/k
(could be worked out from Ct=C0e^(-kt) by setting t as 0.5 and C0 as 1)
how to find clearance
take frequent blood samples after a single (bolus) iv dose and measure the drug conc in plasma and plot against time, calculate area under drug conc
clearance= dose/auc
how to find area under conc/AUC
split the graph into trapeziums and use 0.5(a+b)h
what is the equation for volume distribution
clearance/k
find k using t0.5=0.693/k on graph
describe the kinetics of oral absorption
mostly first order (curves down), rate of absorption is proportional to the amount remaining to be absorbed
the amount of drug in intestinal lumen will decrease with time, the rate of emptying of the lumen will also decrease but why
rate of emptying decreases over time because it depends on the amount of drug remaining in the intestinal lumen, rate of emptying is proportional to the amount of drug remaining and the efficiency of absorption
what is the equation for rate of absorption in first order oral absorption kinetics and its half life
rate of absorption= ka x Aa
Ka= absorption rate constant
Aa= amount remaining to be absorbed
t0.5a= 0.693/ka
how to calculate total bioavailability (F)
F= Ff x Fg x Fh
Ff= fraction entering intestinal wall tissue
Fg= fraction that survives destruction in intestinal wall
Fh= fraction that survives destruction in liver
x100 if u want %
what equation is used to compare the bioavailability of 2 drugs (A and B) and an assumption of it
F= (AUC A x Dose B) / (AUC B x Dose A)
assume clearance will be the same
if the dose/fraction of dose absorbed was increased while the other factors remained constant what would happen and how it would show on a graph
produces a proportional increase in plasma concentrations at all times
graphically the line goes taller/ increased Cmax and AUC while tmax is the same
what happens to the graph if everything remains the same but the absorption is slower
AUC remains the same, Cmax will be lower and tmax will be higher
for constant rate intravenous infusion, what happens to the amount in body (Ab) when
1) input rate < elimination rate
2) input rate> elimination rate
3) input rate=elimination rate
1) input rate < elimination rate= Ab decreases
2) input rate> elimination rate= Ab increases
3) input rate=elimination rate= Ab remains constant
what is steady state
when input rate= output rate
(when graph plateus)
how to calculate rate of elimination for constant rate iv infusion
rate of elimination= elimination rate constant (Kab) x amount in body (Ab)
how to calculate rate of change of drug in body for constant rate iv infusion
rate of change of drug in body= rate of infusion - Kab
how to calculate volume of distribution at steady state
Vd= Ab/Cpss
Cpss= plasma drug conc at steady state
how to calculate clearance at steady state
CL=K x Vd
what is the plasma drug concentration at steady state directly proportional to
rate of infusion
how to calculate infusion rate of iv infusion
Rinf= CL x Cpss
how to calculate plasma conc at time t (build up to steady state)
Ct=Cpss(1-e^(-kt))
when is a loading dose administered
to speed up time to target plasma conc (Cpss), useful for drugs with long half lifes if immediate effect is required, provides target Cpss from a single bolus injection
how to calculate bolus dose
plasma conc (Cpo) x v
how to calculate loading dose
target plasma conc (Cpss) x v
what affects volume of distribution
renal/liver failure, dehydration, age, weight
renal failure- fluid retention, increases vd
liver failure- alters body fluid and plasma protein binding, increases vd
dehydration- lowers vd
age- body composition changes as age increases, decreases vd
weight- obese has more fat, vd is greater as drug diffuses into body fat
