Pharm Flashcards
Km - michaelis constant
substrate concentration @ 1/2 vmax
high Km
low affinity of enzyme for substrate***
high Vmax
high enzyme concentration
if a reaction follows michaelis-menten kinetics, what kind of curve will it have?
hyperbolic
enzymatic reactions that follow cooperative kinetics - what is an example and what type of curve will they have
EX: hemoglobin
sigmoid curve
michaelis-menten kinetics graph
Velocity (reaction rate) vs. substrate concenration
lineweaver-burk plot graph
1/V vs. 1/[S]
increasing the y-intercept of lineweaver-burk plot
decrease Vmax
increase to the right x-intercept of lineweaver-burk plot
increase Km = decrease affinity
lineweaver-burk plot y-intercept
1/Vmax
lineweaver-burk plot x-intercept
1/-Km
lineweaver-burk plot slope
Km/Vmax
inhibitors and crossing
competitive inhibitors cross eachother competitively, whereas non-competitive inhibitors do not (on 1/v vs. 1/[s] graph)
which enzyme inhibitors resemble substrate
competitive inhibitors
which enzyme inhibitors overcome by increase [S]
competitive inhibitors
which enzyme inhibitors bind active site
competitive inhibitors
which enzyme inhibitors have an effect on Vmax, and what is the effect
noncompetitive inhibitors decrease Vmax
which enzyme inhibitors have an effect on Km, and what is the effect
competitive inhibitors increase Km (decreasing affinity for substrate)
which enzyme inhibitors decrease potency
competitive inhibitors
which enzyme inhibitors decrease efficacy
noncompetitive inhibitors
fraction of administered drug that reaches systemic circulation unchanged
F = bioavailability
bioavailability for IV dose
F = 100%
bioavailability for oral dose
F < 100% - incomplete absorption and first-pass metabolism
theoretical fluid volume req to maintain the total absorbed drug amount at the plasma concentration
volume of distribution
how to alter vd of plasma protein-bound drugs
liver and kidney disease
decreased protein binding’s effect on Vd
increases Vd
Vd equation
Vd = amount of drug in body/ plasma drug concentration
low Vd (4-8L) distribution and drug types that cause this
blood - large/charged molecules; plasma-protein bound
medium Vd distribution and drug types that cause this
ECF - small hydrophilic molecules
high Vd distribution and drug types that cause this
all tissues - small lipophilic molecules (especially if bound to tissue protein)
the time req to change the amount of drug in body by 1/2 during elimination or constant infusion
half-life (t 1/2)
property of first-order elimination
t 1/2
drug infused at constant rate takes how long to reach steady state
4-5 t 1/2
t 1/2 equation
t 1/2 = (.7 x Vd) / Cl
of half lives –> % remaining
1 half life –> 50%
2 half life –> 25%
3 half life –> 12.5%
4 half life –> 6.25%
clearance equation
rate of elimination of drug/plasma drug concentration = Vd x Ke (elimination constant)
clearance may be impaired with what
renal, cardiac or hepatic failure
loading dose
Cp x Vd/F
maintenance dose
Cp x CL/F
Cp
target plasma concentration
renal/liver disease
maintenance dose decreases (loading dose unchanged)
time to steady state
depends on t 1/2 - independent of dosing freq or size
zero order elimination
rate of elimination is constant regardless of Cp
constant AMOUNT of drug eliminated per unit time
EX of zero order kinetics
PEA - phenytoin, ethanol and aspirin(high)
capacity limited elimination
zero-order kinetics
first order elimination
rate of elimination is directly proportional to drug concentration - constant FRACTION of drug eliminated per time
how does Cp decrease with time in zero order vs. first order
zero order = linearly
first order = exponentially
flow-dependent elimination
first-order kinetics
ionized vs neutral species
ionized - trapped in urine (pee out)
neutral - can be reabsorbed
weak acids
trapped in basic env
tx overdose w/ bicarb
EX: phenobarbital, methotrexate, aspirin
weak bases
trapped in acidic env
tx overdose w/ ammonium chloride
EX: amphetamines
phase I of drug metabolism
reduction, oxidation, hydrolysis w/ cytochrome P-450 –> slightly polar, water soluble metabolites (still active)
phase II of drug metabolism
conjugation (glucuronidatoin, acetylation, sulfation) –>very polar, inactive metabolites (pee out)
geriatric patients have GAS - phase 2
which phase do geriatric patients lose first
phase I
patients who are slow acetylators
decrease rate of metabolistm –> greater side effects from certain drugs (phase II)
maximal effect a drug can produce
efficacy
amount of drug needed for a given effect
potency
high-efficacy drug classes
analgesic (pain) meds, antibiotics, antihistamines, decongestants
partial agonists vs full agonist efficacy
partial agonist - decreased efficacy
high potency
high affinity for receptors
highly potent drug classes
chemotherapy (cancer) drugs, antihypertensive (BP) drugs, antilipid (cholesterol) drugs
receptor binding curve
percent of maximum effect (efficacy) vs. agonist dose
competitive antagonist
shift curve to right –> decreases potency
overcome - increasing concentration of agonist substrate
competitive antagonist EX
diazepam + flumazenil on GABA R
noncompetitive antagonist
shift cruve down –> decreases efficacy
noncompetitive antagonist EX
NE + phenoxybenzamine on alpha-receptors
partial agonist
acts @ same site as full agonist but w/ reduced maximal effect –> decreased efficacy
potency can increase/decrease (diff variable)
partial agonist EX
morphine (full agonist) + buprenorphine (partial agonist) at opioid mu-receptors
measurement of drug safety
therapeutic index
TI equation
TILE
TI = LD50/ED50 = median lethal dose/median effective dose
safer drugs
higher TI values
drugs w/ low TI values
digoxin, lithium, theophylline, warfarin
measure of clinical drug safety
therapeutic window
range of minimum effect dose –> minimum toxic dose
