Pharmacokinetics (AS) Flashcards
What is pharmacokinetics?
quantitative description of changes in conc of drug in body over time after dosing
ADME
interaction between fluoxetine and amitriptyline
- fluoxetine increases plasma concentration of amitriptyline
- fluoxetine inhibits metabolism of amitriptyline and inc its plasma conc
-> pharmacokinetic interaction
interaction between fluoxetine and tramadol
- serotonin syndrome can occur
- both inc availability of serotonin
- happens without change in the conc of either drug
-> pharmacodynamic interaction
drugs that need regular pharmacokinetic monitoring
theophylline lithium methotrexate ciclosporin cardioselective agents (digoxin) aminoglycosides (gentamicin) anti-convulsants (phenytoin)
TDM
therapeutic drug monitoring
why to indicidualise dosage regimens
- therapeutic index of drug is small
- standard dose doesn’t always produce expected results
- signs of toxicity may be hard to recognise
- metabolites may be effective AND toxic
- inter-patient variability factors
- disease states can alter patients’ PD parameters
- social habits can alter parameters
- protein binding
- non-compliance
- overdoses
- route of admin
- drug interactions
drug that smoking effects
theophylline
factors that affact absorption of drugs
- pH/surface tension
- food/mucus/other drugs
- emptying time
- motility
- disease
- posture (maybe)
- brand substitution
factors that affect distribution of drug
- perfusion (blood supply)
- binding (to R/plasma proteins)
- membrane (can drug cross?)
- drug (physiochem properties)
What does k stand for?
elimination rate constant
- > FRACTION of drug eliminated per unit time
- > unit = minute-1 or hr-1
What does K=0.25 per hour mean?
25% is eliminated from the body per hour
What does V stand for?
volume of distribution
-> hypothetical vomume of fluid in which the total amount of drug in the body would need to be distributed to give a conc equal to the conc measured in plasma
What does high vol of distribution mean?
- drug distributes better to the peripheries
- need large vol to contain the total amount of drug
- distributes everywhere
- will need go give a high dose of drug to get the plasma conc
How to calculate dose based on vol of distcibution?
conc required x V
vol of distribution for drug that binds tightly to tissues
high V
- small proportion found in plasma
V for drug that binds tightly to plasma proteins
low V
-> large proportion found in plasma
What is clearance (Cl)?
describes efficiency of irreversible elimination of drug from body
removal of drug from plasma in a given unit of time
formula for clearance
Cl = K x V
elimination rate constant x vol of distribution
2 most important parameters for determining drug pharmacokinetics
clearance
volume of distribution
What is half life?
time taken for the conc of drug to be reduced by one half
How many half lives for drug to be effetively eliminated?
approx 5 - 7 half lives
equation for half life
half life = 0.693/k
ln2/k
PK changes in elderly patients
- altered absorption
changes in distribution - hepatic metabolism
- renal excretion
PK changes in paediatrics
- drug response
- oral drug absorption
- distribution
- metabolism
- excretion
