Midterm 1 Flashcards
(84 cards)
what are 4 factors that can influence bioavailability?
- first-pass hepatic metabolism
- solubility of the drug
- chemical instability
- nature of the drug formulation
pharmacokinetics
ADME (absorption, distribution, metabolism, elimination)
Class I drug
dose less than the binding capacity of albumin, very little unbound drug
Class II drug
given in doses that greatly exceed the number of albumin binding sites, high proportion of the drug is not bound
what are 5 factors that influence the distribution of a drug?
- protein binding
- blood flow
- membrane permeability
- tissue solubility
- pKa (intrinsic to drug properties)
(apparent) volume of distribution (Vd)
Vd = amount of drug in body/concentration of drug in blood or plasma
what is the volume of distribution if the drug is evenly distributed and unbound?
volume of distribution = body volume (42L)
what is the volume of distribution if the drug is sequestered in plasma?
Vd = about 7L
what is the volume of distribution if the drug accumulates in specific tissues outside of the vascular system?
Vd = very large
if Vd is large, what is the fate of the drug after it is released from binding proteins (albumin)?
large Vd = easily displaced from albumin
- the drug displaced from the albumin distributes to the periphery
- the change in free-drug concentration in the plasma is not significant
if Vd is small, what is the fate of the drug after it is released from binding proteins (albumin)?
- the newly displaced drug does not move into the tissues as much
- the increase in free drug in the plasma is more profound
amount of drug metabolized in a half life is dependet on:
concentration (always cut in half) with the exception of alcohol (constant rate of 10mL/hour)
what is the relationship between time to reach steady state and dose?
Time is independent of dose. Time depends on the interval between doses.
If dosed at an interval equal to half-life, how long will it take to reach steady state?
after 4-6 half-lives
what is the steady state LEVEL determined by?
dose, interval, half-life
steady state
rate of administration equals rate of elimination
dissociation constant formula
Kd = k off/k on = { [ligand]*[receptor]} / [ligand * receptor]
what is the law of mass action? what is an assumption of the law of mass action?
Law of mass action: interactions between drug and receptor is due to diffusion and random collisions, the higher the concentration of both, the more frequent the interactions. Assumes that the reaction is reversible
when the concentration of ligand equals the Kd (dissociation constant), what percentage of receptors will be occupied?
50% of receptors will be occupied at equilibrium (high affinity = low Kd=low concentration of ligand to bind half the receptors because less likely to dissociate)
quantal dose effect curve
exhibits a Guassian distribution (bell shape) when plotted as cumulative responses, exhibits a quantal “yes” or “no” response
potency
refers to the amount of a particular drug required to elicit a specific response (lower EC50 = more potent), not necessarily clinically useful
efficacy
maximal asymptotic response, greater efficacy = larger max effect, clinically relevant
range
the difference between the biggest dose to give NO EFFECT and the smallest dose to give a MAX EFFECT, shallow slope = more working range
variability
differences due to individual responses
