Pharmacodynamics and Pharmacokinetics Flashcards
michaeles menten
velocity of rxn vs. [substrate]
Km
= 1/2 Vmax
inversely related to affinity of enzyme for substrate
Vmax
direct proportional to enzyme concentration
lineweaver burke plot
1/V vs. /[S]
y-intercept = 1/Vmax
x-intercept - = 1/-Km
slope of lineweaver burke
= Km / Vmax
noncompetitive inhibitor
decreased Vmax
no effect Km
decreased efficacy
competitive inhibitor - irreversible
no overcome by increasing [substrate]
decreased Vmax
no change Km
decreased efficacy
competitive inhibitor - reversible
overcome by [S]
Vmax unchanged
increased Km
decreased potency
bioavailability
fraction admin drug reaching systemic circulation unchanged
= F
IV - 100%
oral - typically
volume of distribution =
Vd = amount of drug in body / plasma drug concentration
Vd of different tissues
blood - low
ECF - medium
fat - high
clearance =
CL = rate of elimination of drug / plasma drug concentration
V= Vd x Ke (elim constant)
half life =
t1/2 = 0.693 x Vd / CL
remaining after 1, 2, 3, 4 half lives
1 - 50%
2 - 25%
3 - 12.5%
4 - 6.25%
loading dose =
LD = Cp x Vd / F
Cp - target plasma concentration at steady state
F - bioavailability
maintenance dose =
MD = Cp x CL x t / F
Cp - target plasma concentration
CL -clearance
t - dosage interval
F - bioavailability
LD and MD with renal and liver disease
MD - goes down
LD - no change normally
MD = maintenance dose LD = loading dose
zero order elimination
rate - constant regardless of desired [plasma] of drug
constant amount of drug eliminated per unit time
linear
first order elimination
rate - proportional to [drug]
constant fraction of drug eliminated per unit time
exponential curve
drugs eliminated with zero order elimination
PEA
phenytoin
ethanol
aspirin
ionized species
trapped in urine - cleared faster
weak acid elimination
trapped in basic environment
tx OD with bicarb
weak base elimination
trapped in acid environment
tx OD with ammonium chloride
weak acid drugs
phenobarbitol
methotrexate
aspirin
TCAs
tx OD - bicarb
phases of drug metabolism
1 - reduction, oxidation, hydrolysis - CYP450
-yield polar, water soluble metabolites - may be active
2 - conjugation - glucuronidation, acetylation, sulfation
-yield very polar inactive metabolite - lost in urine
slow acetylators
more side effects certain drugs
- decreased phase 2 metabolism
- intermediates build up
efficacy
max effect drug can produce
represented by Vmax
partial agonist - lower efficacy
potency
amount drug needed for given effect
EC50 - effective concentration for 50% max effect
- shift to left - more potent
- shift to right - less potent
competitive antagonist
decreased potency - can be overcome
ex/ flumazenil - benzo antagonist
noncompetitive antagonist
decreased efficacy - cannot be overcome
ex/ phenoxybenazmine - NE antagonist alpha receptors
partial agonist
lower efficacy
therapeutic index
measure of drug safety
TD50/ED50
median toxic dose vs. median effective dose
safer drug - higher TI
