pharmacokinetics in practice Flashcards
define first order kinetics
rate of elimination is proportional to the plasma drug concentration
(processes involved in elimination do not become saturate)
what happens in first order kinetics
A drug given IV is rapidly distributed to the tissues
By taking repeat plasma samples, the fall in the plasma concentration with time can be measured
Often, the decline is exponential – a constant fraction of the drug is eliminated per unit of time
define zero order kinetics
rate of elimiation is not proportional to the plasma drug concentration
(metabolism processes become saturated)
what happens in zero order kinetics
If an enzyme system that removes a drug is saturated the rate of removal of the drug is constant and unaffected by an increase in concentration
define half life
the time taken for a concentration to reduce by one half
The units of the rate constant are hard to use practically so we use half life (t1/2)
what does half life refer to in practice
normally for the elimination rate from the plasma as this is easy to measure
what is Cmax
maximum plasma concetration
what is tmax
time taken to reach Cmax
what is clearance CL
the volume of blood or plasma cleared of drug per unit time by all eliminating organs
what does half life depend on
clearance of drug from body by all eliminating organs (hepatic, renal, faeces, breath)
volume of distribution - a drug with large Vd will be cleared more slowly than a drug with a small Vd
what does half life not depend on
drug dose or drug formulation
when is half life relevant in clinical practice
- drug dosing (short half life needs more dosing)
- organ dysfunction (increases half life)
- adverse drug reactions or management of toxicity
- short half life increases risk of discontinuation/withdrawal symptoms
define bioavailability
Fraction of the administered drug that reaches the systemic circulation unaltered (F)
what is bioavailability of IV drugs
IV drugs has F=1 as 100% of drug reaches circulation
what is bioavailablity of oral drugs
Oral drugs may have F<1 if they are incompletely absorbed or undergo first pass metabolism
what is bioavailablity determined from
by measuring plasma concentration after oral and IV doses
define distribution
Rate and extent of movement of a drug into tissues from blood
what does distribution of water soluble drugs depend on
rate of passage across membranes
what does distribution of lipid soluble drugs depend on
on blood flow to tissues that accumulate the drug
define apparent volume of distribution Vd
the total amount of drug in body (dose)/ plasma concentration
describe relationshp between rate of elimiation and volume of distribution
The rate of elimination is inversely proportional to Vd
K is the rate constant of elimination
K = CL/Vd
If clearance was zero – drug would not be removed and the plasma concentration would remain at equilibrium indefinitely
define steady state
A balance between drug input and elimination (Css)
impact of slow elimination on steady state
A drug with slow elimination will take a long time to reach steady state, and it will accumulate high plasma concentrations before elimination rate rises to match drug infusion
Css = rate of infusion/ CL
what route is most long term drug adminstration
oral route
describe oral administration
Doses are intermittent so will have peaks and troughs
Rate of absorption will affect the profile; rapid = exaggerated peaks, slow = flatter peaks
define genomics
the study of the genomes of indivudals and organisms that examines both the coding and non codin regions.
the study of genomics in humans focuses on areas of the genome associated with health and disease
define pharmacogenomics
the use of genetic and genomic information to tailor pharmaceutical treatment to an individual
how do we currently prescribe
- patient diagnosed
- standard treatment at standard dose initaied
- genetic variation leads to poor response/side effects
- drug choice or dose is altered
- patient receives optimal treatment
- patients genome used to identify most appropriate dose and treatment
what is the pharmacogenetic approach to prescribing
- patient diagnosed
2.patients genome used to identify most appropriate dose and treatment