pharmacokinetics/pharmacodynamics Flashcards
Michaelis-Menten Kinetics
hyperbolic curve
Km= inversely related to the affinity of the enzyme for its substrate
Vmax= directly proportional to the enzyme concentration
Km (Michaelis-Menten Kinetics)
Km= [s] at 1/2Vmax
sigmoid curve
indicates cooperative kinetics in an enzymatic rxn (i.e. hemoglobin)
Lineweaver-Burk plot
inc y-intercept, dec Vmax
further to the right the X-intercept, the greater the Km and the lower the affinity
Reversible Competitive inhibitor graph changes
unchanged Vmax
increased Km
decreased potentcy
Irreversible competitive inhibitors/noncompetitive inhibitors graph changes
dec Vmax, unchanged Km, decreased efficacy
**Volume of Distribution equation*
D/C = (amount of drug given/plasma drug concentration)
must account for weight. Should only be in L
Volume of Distribution characteristics
Blood= low ECF = medium Tissues/Fat= High
What type of drug must be used for blood Vd
large/charged molecules; protein/plasma bound
What type of drug must be used for ECF Vd
small hydrophilic molecule
What type of drug must be used for blood Vd
small lipophilic molecules, especially if bound to tissue protein
Clearance equation
(rate of elimination/plasma concentration) = [(0.7Vd)/half-life] = KeVd
Half-life (t1/2)
0.693Vd/CL in first order elimination
takes 4 halflives to reach Css in 1*
amount cleared by half-life
1st=50%; 2nd=75%; 3rd=87.5%; 4th=94%
**Loading Dose Equation*
Css*Vd
Maitenance Dose Equation
Css*CL
additive
effect of A&B is equal to sum of individual effects
permissive
presence of A is required for full effect on B
synergistic
effect of A&B is greater than sum of individual effects
tachyphylactic
acute decrease to response to drug after repeated admin
zero order elimination
Cl is linear, constant amount excreted
phenytoin, ethanol, asa(toxic)
1* order elimination
Cl is exponentially decreased, proportional amount excreted
Weak acids
phenobarbital, methotrexate, ASA
tx: na bicarb
Weak bases
amphetamines, TCAs
tx: ammonium chloride
Phase I metabolism
Hydolysis, Oxidation, Reduction
Phase II metabolism
Methylation, Acetylation, Glucuroniation, Sulfation
efficacy
maximal effect a drug can produce (Vmax, y-value);
partial agonists less than full
potency
amount of drug needed for given effect (EC50, x-value)
competitive antagonist receptor binding change
decreased potency, no change in efficacy
ex: Diazepam + flumazenil at GABA
noncompetitive antagonist receptor binding change
decreased efficacy
ex: norepi + phenoxybenzamine at a-receptors
partial agonist receptor binding
decreased efficacy
ex: morphine vs. buprenorphine
Therapeutic index
(Lethal Dose/Effective Dose)
larger the index, the better
