chpt 1 Flashcards
rx: removal of toxins during hepatic encephalopathy
lactulose
will turn into lactic acid and convert ammonia into ammonium for excretion
describe filtration of unionized and ionized drugs
both ionized and unionized are filtered. only unionized can be reabsorbed / secreted
why does sulfonamides in neonate give kernicterus? similarly, why does warfarin toxicity increase w/ sulfonamides?
sulfonamides compete with protein-binding sites (i.e. on albumin) w/ bilirubin. will displace bilirubin and make it free.
98% of warfarin = plasma protein bound. when give sulfonamides, will increase free conc of warfarin
why does Li+ and ethanol get through BBB despite being charged / polar?
bc they are small (low molecular weight!)
how to make a drug safer for pregnancy? [3]
- water soluble
- large
- protein-bound
formula for volume of distribution
volume of distribution = dose / plasma concentration at time 0
Vd = dose/[plasma]
approximate volume of distribution values (70kg man) for plasma, blood, ECF, TBW
plasma 3L
blood 5L
ECF 12-14L
TBW 40-42L
describe thiopental’s half-life
very long 9hrs, even though only has a duration of effect in the brain of <1min. bc quickly redistributes into fat
example of drug whose metabolites are active
benzodiazepines
P450 – absolute requirement for … [2]
O2 and NADPH
oxidations include [2 things]
hydroxylation and dealkylations
smoking has what effect on p450 system?
induces. need to up dose. or lower if quit
what time to reach steady state depend on?
only depends on elimination half-life (independent of dose size and freq of administration)
50% of the way to steady state after…
1 x half-life
90% of the way to steady state after…
3.3 x half-life
95% of the way to steady state after…
4-5 x half-life; considered clinical steady state
“100%” at steady state at..
> 7 x half-life
process of getting to steady state..
dose w/ fixed amount after 1 half-life. steady state oscillates between minimum toxic dose & minimum effective dose
what is steady state?
rate in = rate out
what dose the rate of infusion/maintenance dose determine?
the plasma level at steady state (amt of time needed to reach steady state is not affected by infusion rate)
if cannot wait 4-5 half-lives to achieve effective blood concentrations, what can you do?
give 1 loading dose + maintenance doses after 1 half-life
loading doses are.. formula?
one time only, estimated to put amt of drug in body that would be there at steady state. usu 2x maintenace dose. LD = Conc in plasma x volume od distribution
volume of distribution equation
Vd = Dose/C0. will be given C0 and Vd, will be asked to calculate dose.
half-life equation
t1/2 = 0.7 x Vd/Cl.
note: 1. increases Vd will increase half-life (directly proportional) 2. half-life and clearance are inversely proportional.
