Pharmacology Flashcards
Graded dose response curve
Y- effect
X- drug concentration
EC50- concentration at 50% effect
ligand receptor binding curve
Y- DR bound
X- Drug concentration
Kd = concentration at 50% binding
Quantal dose response curve
Y- % individual responding
X- dose
graph ED50, TD50, LD50
Therapeutic index
=TD50/ED50 (bigger is better)
Margin of safety
LD1/ED99 (bigger is better)
Receptor effector coupling
transduction process between binding and effect (full–>partial–>antagonist)
Categorize competitive vs noncompetitive antagonists
Allosteric (reversible/irreversible) = noncompetitive
Active (orthosteric) irreversible = noncompetitive
Active reversible = competitive
Effect of competitive antagonist on agonist
decrease potency
Effect of noncompetitive antagonist on agonist
Decreased efficacy
noncompetitive antagonist effect on agonist WITH spare receptors
first as competitive (decrease potency)
then act as noncompetitive (decrease efficacy)
Why allosteric ligand drugs are cool.
- ceiling effect(limit with all sites bound)
- selective for tissue with endogenous active
- subtype selectivity (more varietytoo)
tachyphylaxis
repeat same dose–> decreased effect
Desensitization:
decreased receptor ability to response (homologous vs heterologous)
Inactivation:
loss of receptor ability to respond
downregulation
receptor removal from repeated stim
What is therapeutic window?
between MEC (minimal effective concentration) for desired response to MEC for adverse
How does pH change affect drug absorpption?
Decrease pH –> more protonated acids and charged bases –> charged doesnt diffuse
Henderson hasselbalch
What is bioavailability?
% of oral drug that actually reaches systemic circulation (not lost before absorption or in liver or junked up in stomach)
is the total plasma of drug over time [AUC oral]/[AUC injected]
What 3 factors impact drug distribution?
- blood flow to tissue
- capillary permeability at tissue
- binding of drug to tissues (drug reservoir)
2 compartment model of IV drug distribution
- alpha phase (fast): drug distribution to tissue (half-life 1.2 hours)
- beta phase (slow): drug metab and excretion (half-life 30 hours)
What is the volume of distribution?
Vd = [drug taken]/[drug concentration in plasma]
suggests where drug is disributed
Metabolism usually makes drug more soluble or more insoluble?
more soluble
What is phase I metabolism? Main enzyme invovled?
oxidation, hydroxylation, dealkylation, deamination cytochrome 450 (CYP)
What is phase II metabolism?
Add group (conjugation); makes compound more polar
Zero vs first order kinetics of drug elimination
First order: rate of elimination is roportional to drug concentration
Zero order: rate of elim is independent (constant) (usu at saturation)
Calculating half life
T(1/2) = 0.7Vd/CL
Which CYP metabolizes almost 1/2 drugs?
CYP3A
Which CYPs have a lot of polymorphisms?
CYP2C and CYP2A6
What is enterohepatic recirculation?
when drugs in bile is reabsorbed in small intestine (instead of excreted)
What genes are involved in warfarin?
CYP2C9 and VKORC1
antipsychotics, antidepressants, metoprolol, tamoxifen
are metabolized by what cyp?
CYP2D6
poor, intermediate, efficient, and ultrarapid metabolizers
-variance due to what cyp?
CYP2D6; ultrarapid is usu *2xn –> GOF
TPMT
Phase 2; methylation inactivation of thiopurines
Mercaptopurine and azathioprine (drugs0 are affected by which enzye gene?
TPMT; they are thiopurines and treat leukemia, IBS, RA, transplant immune supression; normally they are high activity ((ut sme are low activity)
Why does FDA recommend testing prior to azathioprine admin?
Some people have lower activity TPMT –> leukopenia (low WBC count)
