pharmacokinetics Flashcards by Zoe Chan

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)

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what is pharmacodynamics

relationship between drug conc/time profile and therapeutic and adverse effects

(basically how the drug affects the body)

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why is pharmacokinetics relevent

allows prediction of time course of drug action

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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)

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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

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what is elimination in ADME

irreversible loss of drug from body (metabolism and excretion) (ME)

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what is disposition in ADME

process of elimination and distribution (distribution, metabolism and excretion) (DME)

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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

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what is bioavailability

fraction of administered dose reaching systemic circulation in an unchanged form

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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)

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how is drug transported

blood

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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

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name 1 thing that majorly determines Vd (volume of distribution)

strength of drug binding to tissue components compared to plasma proteins

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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

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difference between drug elimination in kidney and liver

kidney- drug is excreted unchanged
liver- drug gets metabolised then excreted

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name 2 major independent pharmacokinetic parameters

volume of distribution and clearance

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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)

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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

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what is the equation for clearance

clearance= Q x E

Q=blood flow to organs
E= extraction ratio of organ

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what is clearance

volume of blood completely cleared of drug per unit of time, (can be hepatic clearance, renal clearance, pulmonary clearance etc.)

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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