general Flashcards
Km?
Km = [S] at 1/2 Vmax
how is Km related to enzyme affinity for substrate?
inversely
how is Vmax related to enzyme concentration?
directly proportional
what does a sigmoid enzymatic curve mean?
cooperative kinetics (e.g. hemoglobin/O2 binding)
what are the intercepts on the Lineweaver-Burk plot?
y intercept = 1/Vmax - as moves up, Vmax decreases
x intercept = 1/-Km - as moves closer to 0, Km increases (affinity decreases)
how do reversible competitive inhibitors affect enzyme kinetics?
increase Km, Vmax unchanged
decrease potency
** can be overcome by increase in [S]
how do irreversible competitive inhibitors affect enzyme kinetics?
decrease Vmax, Km unchanged
decrease efficacy
** cannot be overcome by increase in [S]
how do noncompetitive inhibitors affect enzyme kinetics?
decrease Vmax, Km unchanged
decrease efficacy
** cannot be overcome by increase in [S]
formula for Vd?
Vd = (amt of drug in body) / (plasma drug concentration)
what drug types have low Vd?
large/charged molecules
bound to plasma proteins
–> confined to blood compartment
what drug types have medium Vd?
small hydrophilic molecules
–> confined to ECF
what drug types have high Vd?
small lipophilic molecules
especially those bound to tissue protein
–> distrib to all tissues, including fat
formula for clearance?
CL = (rate of drug elim) / (plasma drug concentration) CL = Vd * Ke Ke = elimination constant
how many half lives does it take for a drug to reach steady state (with constant infusion)?
4-5
(takes 3.3 half lives to reach 90% steady state)
** independent of dosage or dose frequency
formula for half life?
T1/2 = (0.693 * Vd) / CL
formula for loading dose?
LD = (Cp * Vd) / F
formula for maintenance dose?
MD = (Cp * CL * t) / F
t = time between doses
which drugs exhibit zero order elimination?
PEA = zero-shaped
phenytoin
ethanol
aspirin
which drugs are weak acids? what does this mean clinically?
phenobarb
MTX
aspirin
TCAs
** “trapped” in basic environment: OD can be tx’ed with bicarb
which drugs are weak bases? what does this mean clinically?
amphetamines
** “trapped” in acidic environment: OD can be tx’ed with ammonium chloride
phase I of drug metabolism?
CYP450: reduction, oxidation, hydrolysis
usually yields slightly polar water-soluble metabolites
products often still active
** lost first in geriatric pts
phase II of drug metabolism?
conjugation: glucuronidation, acetylation, sulfation
yields very polar, inactive metabolites –> renal excretion
** slow acetylators: increased SEs from drugs
efficacy vs potency?
efficacy = maximal effect produced by drug - Vmax potency = amt of drug needed for given effect - EC50
relationship bw diazepam and flumazenil?
diazepam = agonist
flumazenil = competitive antagonist
(GABA rcptr)
relationship bw NE and phenoxybenzamine?
NE = agonist
phenozybenzamine = noncompetitive antagonis
(alpha rcptr)
relationship bw morphine and buprenorphine?
morphine = full agonist buprenorphine = partial agonist
formula for therapeutic index?
TI = TD50 / ED50
higher TI = safer
** dig, lithium, theophylline, warfarin - LOW TI, less safe
