Test 2 - definitions Flashcards
3 major physiologic factors that affect drug distribution
blood flow, body composition, protein binding
3 major drug factors that affect drug distribution
lipophiliicity, size, ionization
2 major plasma protiens
albumin & alpha 1 glycoprotien
albumin
prefers acidic binding & hydrophobic; typically constant levels
alpha 1 acidic glycoprotien
binds to basic drugs; stressed induced
plasma protein binding is ___ & ___
saturable and reversible
amount of drug bound to a plasma protein is determined by
drug concentration, # of available binding sites, affinity of drug for protein
what causes pharmacological effect
free drug
ion trapping
when an ionized species of drug accumulates in a specific tissue or organ, more drug ionized on one side than the other, accumulation of drug in a specific tissue that doesn’t reflect the plasma concentration
Vd
hypothetical volume; apparent volume of distribution
Vd ___ describes _____
indirectly; the extend to which a drug distributes outside of the plasma compartment which is one of the water compartments within the body; proportionally constant related to the amount of drug in the body to the plasma concentration
Vd is a ____ pharmacokinetic paramater
independent; it is dictated by the characteristics of the DRUG such as ionization, lipophilicity, size, etc
Vd is always a ___ divided by ___
mass over volume
C0 must be assumed to be
instantaneous distribution
total body water = __ X body weight
.6
ECF = __ X body weight
.2
ICF = ___ X body weight
.4
ECF = ___(3/4) & ___(1/4)
Interstital fluid / Plasma
Vd (once divided by kg): less than .6 = drug in ___ more than .6 = drug in ___
plasma tissues
smaller Vd means more drug is in the
plasma bc of protein binding
pericytes
have tight junctions between cells to limit diffusion of drug into CNS
PgP also work to
pump out toxins and drugs from the brain
what could hinder a drug from passing through BBB
large, charged, hydrophillic
metabolism
refers to the process by which the administered drug is biochemically altered producing a metabolite
metabolites typically have ___ activation
little but some can have significant
pro-drug
inactive but upon metabolism release or form active drug
excretion
removal of drug from body
___ is the primary organ for excretion
kidney, but some drug can be eliminated through bile
when a drug is renally excreted, we mean that ____ is eliminated
unchanged parent drug
the purpose of drug metabolism is to
increase water solubility, increase polarity, and increase H-bonding partners
hepatocytes work through what 2 functions
passive diffusion & carrier transporters
OATP enzymes
shuttle drug across membrane into hepatocye taken from GI tract
MRP1 / P3 / P4 ABCC1 / C3 / C4
work to shuttle drug out of hepatocyte into the blood stream
MDR3 / R1 / P2 ABCB4 / B1 / C2
filter blood into bile canaliculus for excretion
what are the two types of hepatic metabolism
Phase 1 and phase 2
phase 1
introducing or exposing a functional group to increase polarity; these can be redox, hydroxylation, hydrolysis typically removing methyl and adding NH or OH to prepare metabolite for phase 2
phase 2
conjugating reactions, adding a molecule or large functional group, hydrophilic
CYP450 are examples of phase 1 or 2
1
UGT are examples of phase 1 or 2
2
CYP450 enzymes
involved in many biochemical reactions involving endogenous substrates, including steroids, fatty acids, prostaglandins, and bile acids. they are critically involved in the removal of drugs, carcinogens, insecticides, plant toxins, and environmental pollutants
CYP2D6 2 represents ___ & what percent homology D represents ___ & what percent homology 6 represents ___ & what percent homology
family (40%) subfamily (55%) gene product (different unless identical)
CYP1, CYP2, CYP3 substrates?
drugs, other xenobiotics
CYP4, CYP5, CYP8 substrates?
fatty acids, prostaglandins, thromboxanes
CYP7, CYP11, CYP17, CYP21, CYP24, CYP27 substrates?
steroid hormones
what CYP accounts for 34% in drug metabolization
3A4/5
1A1, 1A2, 2E1, 3A3, 3A4,5
nutrition
1A1, 1A2
smoking
2E1
alcohol
1A1, 1A2, 2A6, 2B6, 2C, 2D6, 3A3, 3A4,5
drugs
1A1, 1A2, 2A6, 1B, 2E1, 3A3, 3A4,5
environment
1A, 2A6, 2C9,19; 2D6, 2E1
genetic polymorphism
phase 2 relationship to CYP
phase 2 occurs after CYP450 has metabolized drug but can also work independently of phase 1
phase 2 almost always
inactivated the parent drug molecule, but there are some instances where a phase 2 metabolite could still have activity
excretion by the kidney is determined by what 3 factors
filtration reabsorption secretion
filtration
occurs in glomerular capillary; cut off point is 5000 daltons
reabsorption
from filtrate back into the blood happens in the peritubular capillaries (works against drug removal!!!)
properties that assist reabsorption
nonionized & lipophilic
secretion
from peritubular capillaries into the tubular space
properties that assist secretion
lipophilic; transporters
amount excreted by kidney =
amount filtered - amount reabsorbed + amount secreted
what percent of blood actually gets filtered
20%
amount
X, amount given to the patient at the start time of dosing, dose is frequently called X0, mass amount gms, mgs, etc
concentrations
C; always amount divided by a volume; mg/L, mcg/mL
rate
a change is something per unit time; can be first or zero order
rate constant
k, constant rates, do not change with time, determined by slope
K for zero order rate is
constant
elimination rate in zero order is
constant
zero order characteristics
concentration independent elimination; high substrate concentrations
K for a first order is
a rate constant
elimination rate of drug removal is
variable
first order characteristics
concentration dependent elimination; low substrate concentrations
