pharmacokinetics Flashcards
renal excretion terminates actions of what drugs?
small hydrophilic
fully/nearly fully ionized at physiological ph
not protein bound
most pharmacologically active drugs are..
lipophilic
unionized / partially ionized
bound to plasma proteins
what is the primary determinant of duration and intensity of drug action?
rate of drug metabolism
drug metabolism mainly occurs where?
liver in er
what other organs can also metabolize substances?
gi mucosa = lower bowel kidneys lungs nasal mucosa skin
first pass effect
drugs are extensively metabolized during initial pass though the liver
what enzymes are involved in phase I ?
CYP450
oxidases
what is the most common phase ii rxn?
glucuronidation
conjugation using what?
glucorunic acid
sulphate
glutathione
what are examples of phase ii rxns?
glucuronidation
methylation
sulfation
n-acetylation
codeine, a prodrug, is demethylated to produce
morphine
inducers of metabolism
increase synthesis of p450 and reduce degradation
inhibitors of metabolism
bind to cytochrome oxidase and inhibit metabolism of other drugs
CYP2D6 affects
beta blockers –> alter effect
CYP2C9
warfarin –> change dose
CYP2C19
omeprazole –> variable response in peptic ulcers
what are the most imp routes of drug elimination?
urine and feces
what drugs follow zero order kinetics?
ethanol and aspirin
ethanol is excreted in …
sweat
what’s penicillin?
an acidic antibiotic
how are penicillin and aspirin excreted?
via proximal tubular secretion (renal excretion)
what is used in the excretion of penicillin and aspirin?
anion transport system
what may prolong effects of penicillin?
competition for secretion with probenecid
what is aspirin?
acidic salicylate
what is given to prevent gout?
aspirin is given to compete with uric acid during distal tubular active reabsorption
drug clearance
apparent volume of blood that is cleared of drug per time period
clearance equation
U x V / P
clearance equation what everything stands for
U = urine drug concentration V = rate of urine flow P = plasma drug concentration
lamda equation
drug in lung blood / drug in lung air
what does low / small lambda mean?
short DOA
rapid elimination
what does high/large lambda mean?
long DOA
slow elimination
rate of elimination equation
plasma drug concentration x clearance
general rate equation
rate = k x C ^n k = rate constant n = order if zero = 0 if first = 1
one compartment model
body is a single compartment
drug is rapidly distributed
elimination = first order
Vd equation
Vd = dose / Co
Clearance equation
CL = Vd x ke
t 1/2 equation
0.0693 / ke
ka aka
absorption
ke aka
elimination
graph of log plasma drug concentration vs time in one compartment model when drug given via IV dose looks like ?
its linear and negative slope
graph of log plasma drug concentration vs time in one compartment model when drug given via oral dose looks like ?
first it rapidly increases ( bc being absorbed) then its linear with a negative slope
true or false. t 1/2 depends of dose
false it doesn’t depend on dose
in 2 compartment model what are the two phases and what do they rep?
S phase = elimination rate constant
F phase = distribution rate constant
at steady state what’s true about about dosing rate?
dosing rate = elimination rate
dosing rate equation
dosing rate = clearance x Css ( steady state concentration)
for drugs with first order elimination what does the time to reach Css depend on?
half life of elimination
Css is a function of what?
dose
dosing interval
clearance
how many half lives to reach Css 94-97%?
4-5
infusion rate equation
CL x Css ( unit = mg/min)
dosing rate equation ( maintenance dose)
clearance x desired plasma concentration
kinetics for multiple iv ( iv bolus)
dose / T = CL x Css
kinetics after multiple oral administration
dose x f ( bioavailability) / T = CL x Css
maintenance dose equation
CL x Css x T
loading dose equation
loading dose = vd x Css
non compartmental clearance eq
cl = dose / auc or cl = Vd x kel
non compartmental t1/2 eq
0.693 / k el
non compartmental Vd eq
2
(1) dose / Co
(2) CL / kel
non compartmental bioavailablity eq
auc oral / auc IV x 100
