Pharmacokinetics and dynamics Flashcards
Michaelis-Menten Kinetics
Velocity on Y-axis, [S] on X-axis
Km, Vmax are found on this
Km
inversely related to the affinity of the enzyme for the substrate
Vmax
directly proportional to the enzyme concentration
half of Vmax is how you find Km on the X-axis
Lineweaver-Burk Plot
Plotted line crossed the Y-axis
1/V on Y axis; 1/[S] on X-axis
1/(Vmax) is when plotted line touches Y-axis
1/-Km on X-axis
Pharmacokinetics
The effects of the body on the drug
Absorption, Distribution, Metabolism, Excretion
Pharmacodynamics
The effects of the drug on the body
includes concepts of receptor binding, drug efficacy, drug potency and toxicity
Bioavailability (F)
Fraction of administered drug that reaches systemic circulation unchanged
Bioavailability for IV dose
F = 100%
Volume of Distribution (Vd)
(amt drug in body)/([plasma drug])
Vd for large/charged molecules; plasma protein bound
Low Vd, in blood compartment
Vd for small hydrophilic molecules
Medium Vd, in ECF
Vd for small lipophilic molecules, esp if bound to tissue protein
High Vd, in all tissues including fat
Half lives to reach steady state
need 4-5 t1/2
Eqtn for T1/2
(0.639*Vd)/(CL)
Clearance
CL = (rate of elimination of drug)/([plasma drug])
Zero Order Elimination
Plasma concentratino decreases linearly with time
Constant amount of drug eliminated per unit time
Phenytoin, Ethanol, Aspirin
First Order Elimination
Rate of elimination is directly proportional to drug concentration
Weak Acid Drugs
Phenobarbital, Methotrexate, Aspirin
Trap in basic environments so tx overdose with bicarbonate
Weak Base Drugs
Amphetamines
Trap in acidic environments so tx overdose with ammonium chloride
Phase I drug metabolism
Reduction, Oxidation, Hydrolysis with cyto P450
Geriatrics lose phase I first
Phase II drug metabolism
Conjugation (Glucuronidation, Acetylation, Sulfation)
yields very polar, inactive metabolites
Slow acetylators
Great S/E from drugs because decreased rate of metabolism
Efficacy
Maximal Effect a drug can produce
Partial Agonists
less efficacy than full agonists
Potency
Amount of drug needed for a given effect
Competitive Antagonist
shifts curve to right (decreases potency), no change in efficacy. Can be overcome by increase conc of agonist
Noncompetitive Antagonist
Shifts curve down to decrease efficacy.
Cannot be overcome with increase agonist substrate
Irreversible competitive antagonist
Shifts curve down to decrease efficacy.
Cannot be overcome with increase agonist substrate
Partial Agonist
Acts on same site as full agonist but with lower efficacy. Potency is variable.
Therapeutic Index
Measurement of Drug Safety
between ED50 and TD50 on graph or = TD50/ED50
High Therapeutic Index
safer drug
Low therapeutic Index
more dangerous drug
LD50
median lethal dose
TD50
median toxic dose
Therapeutic Window
measure of clinical drug effectiveness
ED
effective dose
