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.
infusion rate equation:
infusion rate = Cl x Conc at steady state
loading dose equation
LD = (Vd x conc in plasma) / f, or bioavailability
note: renal fxn is not considered
maintenance dose equation
MD = (Cl x Conc at steady state x dosing interval, or tau)/ f, or bioavailability. note: renal fxn (clearance) is considered
definition of an antagonist
binds to receptor and prevents agonist from binding / functioning
affinity
like Km. inversely related to Kd (amount needed for half maximal binding). can only be compared on dose response curve if parallel (meaning they work on same receptor)
efficacy
like Vmax
potency
can only be compared on dose v. response curve if lines do not cross. if they cross, can specific specific doses where one is more potent than the other.
competitive antagonist on drug
decrease in potency, will shift dose v. response curve to right.
it is safe to assume that most drugs = competitive antagonists. name some noncompetitive antagonists (5)
phenoxybenzamine, digoxin, allopurinol, PPI, aspirin. decreased efficacy
competitive antagonist on pharmacodynamics? noncompetitive antagonist?
competitive antagonist, alters drug potency. noncompetitive antagonist, alters drug efficacy.
drugs w/ low therapeutic index (TD50/ED50) (4)
theophylline, digoxin, warfarin, lithium
intracellular receptors (4)
glucocorticoids, thyroid hormones, gonadal hormones, vitamin D
cGMP and NO. 4 drugs that use this pathway
facilitates dephosphorylation of myosin light chain in vasculature, preventing their intxn w/ actin. nitrates, muscarinic agonists, bradykinin, histamine (via protein kinase G)
JAK STAT signals (4 stimuli) and intracellular signal transduction
- cytokines like EPO, somatotropin, and interferons. membrane spanning receptors that activate cytoplasmic tyrosine kinases (JAK). JAK go on to phosphorylate signal transducers and activators of transcription (STATs). STATs dimerize then dissociate, cross nuclear membrane, and modulate gene transcription. like an insulin receptor + steroid receptor combined.
clinical trials: preclinical
safety & biological activity (animal)
phase 1 clinical trial
50 healthy volunteers, safety & dosage
phase 2 clinical trial
200 patients, effectiveness
phase 3 clinical trial
2000 patients. confirm effectiveness & common side-effects
phase 4 clinical trial
post-marketing surveillance, after FDA approval. common and rare side effects.
FDA classification of teratogenicity
A (no risks – folic acid)
B (some evidence for risk in animals, none in humans, so considered safe)
C (risk in animals, unknown risk in humans. don’t know if safe or not)
D (teratogenic, but benefits outweigh risk; anticonvulsant)
X (teratogenic in humans & animals, absolutely contraindicated)
