Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
121 Cards in this Set
- Front
- Back
|
how the body works on drugs
|
pharmacokinetics
|
|
|
pharmacokinetic properties
|
absorption
distribution metabolism elimination |
|
|
how drugs work on the body
|
pharmacodynamics
|
|
|
how will we deliver meds in the OR?
|
iv or inhalation
|
|
|
properties of an ideal anesthetic
|
rapid onset
cadaveric relaxation rapid emergence |
|
|
main goal of us giving anesthetic
|
acute actions, timing the coarse of our anesthetic
|
|
|
factors affecting the speed at which a drug will reach its effect site
|
a. blood flow to the effect side (this is our UPS)
b. concentration gradient c. protein binding volume of distribution (how much will move around) d. tissue capacity e. receptor/drug complex |
|
|
apparent volume into which a drug has been distributed
|
volume of distribution
|
|
|
formula for volume of distribution
|
total dose of drug administered/plasma conc of that drug
|
|
|
how is the volume of distribution different in an elderly person?
|
decreased CO, decreased blood volume, sm mm mass, larger fat mass, smaller central volume of distribution
you would need a smaller loading dose |
|
|
someone w/ a larger volume of distribution would need what type of loading dose?
|
larger
|
|
|
causes for high volume of distribution
|
high solubility or binding of drug in tissues other than plasma
|
|
|
all elimination happens from which compartment?
|
central compartment
|
|
|
what is contained in the central compartment, the VRG?
|
plasma volume (blood)
brain, heart, lungs, liver, kidney |
|
|
characterisitcs of the VRG?
|
receives 75% of CO
10% of body mass equilibration time is almost instantaneous |
|
|
are we always targeting just the VRG?
|
no, b/c our NMB's target the muscles in the VPG
|
|
|
what does the VPG consists of?
|
tissue
muscle, skin, fat (bone) |
|
|
characteristics of the VPG?
|
receives 25% of CO
70% of body mass |
|
|
how does the drug move b/t the central and peripheral compartment?
|
back and forth by diffusion, following its concentration gradient
|
|
|
what type of drug flows freely b/t peripheral and central compartment?
|
non protein bound
unionized lipid soluble |
|
|
when does drug metabolism start?
|
immediately after injection
|
|
|
what is responsible for the first dramatic decrease in plasma concentration after a drug is given?
|
distribution from the central compartment to the tissues
|
|
|
after iv injection, what happens to the plasma conc of the drug?
|
it instantaneously rises
|
|
|
which is faster, distribution of the drug or elimination?
|
distribution is, right at the beginning
|
|
|
3 types of receptors that we discussed
|
voltage gated
ligand gated transmembrane proteins |
|
|
3 properties of the drugs we give
|
all are ligands
all are chemicals all work at ligand gated receptors or ligand mediated receptors |
|
|
do drugs trigger voltage gated receptors?
|
no, but the nerve stimulator does though :) bzzzz
|
|
|
5 categories of ligang gated receptors
|
a. acetylcholine receptors (nACHR)
b. serotonin receptors (5HT3) c. Gamma-aminobutyric acid receptors (GABAa) d. Glycine e. Glutamate family |
|
|
ligand gated receptors that are cation selective and excitatory?
|
acetylcholine and serotonin receptors (nACHR and 5HT3)
|
|
|
ligand gated receptors that are anion selective and inhibitory?
|
Gamma-aminobutyric acid receptors (GABAa) and Glycine
|
|
|
main excitatory NT?
|
glutamate
|
|
|
glutamate family
|
NMDA, AMPA, Kainate
|
|
|
what is receptor occupancy: margin of safety?
|
you have to elicit a certain amount of receptors to produce the action. To stop the action from happening, you have to stop a certain amt of receptors, so that the amount needed to produce the action can't slip through. Most organs have a margin of safety, if they lose their receptors, it can still fxn.
|
|
|
what happens to the amount of receptors over the course of an anesthetic?
|
it changes from moment to moment
|
|
|
what is tissue capacity?
|
tissues in each compartment have a different capacity to hold onto a drug, drug is always moving and equilibrating
|
|
|
properties that affect how much that each drug compartment can hold
|
size, ph, solubility, protein binding
|
|
|
how long the drug will hang around depends on?
|
how much is absorbed by the peripheral compartment
|
|
|
what is considered a reservoir for drugs reentering circulation?
|
VPG
|
|
|
what is responsible for the termination of effect of many anesthetic?
|
redistribution from the VRG, pt becomes awake even though drug is still present in the body, just not enough in the brain
|
|
|
1/2 time of equilibration b/t drug conc in the plasma and the drug effect that can be measured
|
effect-site equilibration (onset)
|
|
|
explain steady state
|
compartments will have different amts of drug, but the same concentration, most drugs are studied in steady state concentrations, it compares the potency of one drug w/ that of another
|
|
|
how do you achieve steady state
|
use iv infusions to get loading dose on board, then continue infusion at a rate equivalent to the elimination rate until whole body is at same concentration
|
|
|
why does steady state take out the variables of pharmacokinetics?
|
b/c each person is different
and movement b/t each compartment is individual for each drug |
|
|
constant fraction of drug that will be cleared from the plasma during the 1/2 life
|
1/2 time
|
|
|
1/2 life is clearance from?
|
the body
|
|
|
1/2 time is clearance from the?
|
plasma
|
|
|
equation for clearance
|
amt totally cleared from plasma/time
|
|
|
how many 1/2 lives does it take for 97% of the drug to be gone from the body?
|
5.5
|
|
|
the time it takes to decrease plasma concentration by 50% after an infustion has been turned off
|
context-sensitive 1/2 time
|
|
|
what can give us an idea of when the pt will wake up?
|
context-sensitive 1/2 time
|
|
|
if you redose before drug is cleared from body, what do you get?
|
drug accumulation
|
|
|
how many 1/2 lives til steady state?
|
5.5
|
|
|
3 things that can tell us when the effect might wear off
|
a. context sensitive 1/2life
b. therapeutic range c. MAC awake |
|
|
what is MAC?
|
minimum alveolar concentration where 1/2 of your pts will not move on surgical incision, gives you a dose range
|
|
|
when does the pt actually wake up?
|
when the concentration drops below therapeutic level
|
|
|
parts of the context sensitive half time that gives us anidea of when the pt will awake
|
a. plasma conc decreases by 1/2
b. drug moves away from the receptors back into the plasma c.pt wakes when conc drops below therapeutic level d. kinetics of drug, dose and duration of infusion |
|
|
proteins of the lung tissue really like what type of drugs?
|
lipid soluble
|
|
|
after drug is given iv, how much is filtered by lungs?
|
65%
|
|
|
when the lungs filter out drugs after they are given, is it considered 1st pass?
|
no, b/c it is not eliminated or metabolized
|
|
|
what is responsible for renarcitization in post op period?
|
lungs serving as a "reservoir"
|
|
|
what is the relationship b/t plasma conc and effect site conc of a drug?
|
there is a lag b/t plasma conc and effect of drug initially, at steady state, both plasma conc and drugs' effect are parallel, once infusion is stopped...effect will again lag behind as plasma conc start to fall
|
|
|
how much drug one compartment will hold vs how much drug another will hold, a ratio
|
partion coefficient
|
|
|
which has the highest partition coefficient?
morphine meperidine fentanyl sufentanil |
sufentanil, gets to effector site quicker due to high lipid solubility
morphine 1:1 meperidine 32:1 fentanyl 955:1 sufentanil 1727:1 |
|
|
what is the relationship b/t lipid solubility and protein binding?
|
the more lipid soluble, the more protein binding
|
|
|
what is the pH like at the tissue level?
|
more acidic b/c that is where metabolism is occurring
|
|
|
pH at which exactly 50% of a weak acid or base is present in each of ionized and unionized forms
|
pKa
|
|
|
factors affecting how well each compartment can hold onto the drug
|
saturation
size temp ph protein binding solubility |
|
|
what form of a drug is more lipid soluble and easily transfers across cell membrane
|
nonionized
|
|
|
HH for an acid drug
|
pH-pKa
|
|
|
HH for a basic drug
|
pKa-pH
|
|
|
what tells you the different amts of drugs in diff compartments at steady state?
|
partition coefficient
|
|
|
nice negative numbers are ???
|
non-ionized drug
|
|
|
acid drugs like to bind to things like:
|
Na, K, Ca, Mg
|
|
|
basic drugs like to bind to things like:
|
Cl, sulfates
|
|
|
more acidic drugs tend to accumulate in the ?
|
plasma, high affinity for plasma proteins
|
|
|
more basic drugs like to accumulate in the ?
|
tissue, b/c that is where the pH is lower
|
|
|
what happens when there is a pH gradient across the membrane, and the drug is trapped on the side with higher ionized fraction?
|
ion trapping: only the nonionized drug is diffusible
|
|
|
the more lipid soluble a drug, it more likely it to be....
|
highly protein bound
|
|
|
Alpha1-acid glycoproteins (AAG) prefer ?
|
basic drugs
|
|
|
what has to happen before a change in protein binding will make a difference in efficacy or dosing?
|
drug must be very highly protein bound (>90%)
|
|
|
a competitive drug at protein binding sites?
|
coumadin
|
|
|
for protein binding, consider which three things:
|
competition (>90%)
saturation low protein states |
|
|
effects of renal failure on protein binding?
|
normal albumin on labs
uremia changes albumin's ability to bind more free drug available |
|
|
Phase I
|
exposing water soluble group
Oxidation Reduction Hydrolysis |
|
|
Phase II
|
adding water soluble grp to make it polar
Conjugation |
|
|
Do you have to go through Phase I rxn before Phase II?
|
no
|
|
|
constant Fx of drug is cleared (%)
|
first order, dependent on blood flow to the liver
|
|
|
constant amt of drug is cleared
|
zero order. Enzymes are saturable
low clearance drugs clear this way ETOH is example |
|
|
alternate sites of metabolism
|
plasma, lungs, intestines, renal, pH
|
|
|
enzyme responsible for most anesthesia drug metabolism
|
cytop450
|
|
|
what is genetic polymorphism?
|
people metabolize different b/c of their genetics
|
|
|
CYP3A4/5
|
most abundant
>50% of all drugs women have more than men |
|
|
CYP2D6
|
25% of drugs
|
|
|
NON-CYP drugs
|
esters: conj or hydrolysis
plasma & tissue cholinesterases: -succ, atricurium, cisatracurium, ester locals, mivacurium, esmolol **good for pts w/ enzyme induction |
|
|
Flavin containing monooxygenase
|
less common oxidizer
nitrogen, phos, sulfur can be inhibited by tricyclic antidepressants |
|
|
All transferases are what type of metabolism?
|
phase II
|
|
|
metabolism in infant
|
fetal liver is fully fxnal, but not enzymes
-increase in enzyme levels start w/i a day -avg adult levels at 1yr -overshoot from age 2-15 drug chewing up machines, need a higher dose or increase freq |
|
|
extraction rates of hepatic clearance of anesthesia drugs
|
blood flow to liver affects drugs that have a high clearance: flow dependent
low flow: low extraction rate, little dependence if you change flow, you change rate of metabolism |
|
|
Drugs w/ high hepatic clearance:
|
Etomidate, propofol, ketamine, bupivicaine, fentanyl, sufentanil, remifentanil, meperidine, morphine, naloxone
|
|
|
CO to the liver
|
30%:
25% hepatic artery 75% portal vein |
|
|
study of a drug's specific traits as it relates to a genome wide DNA sequence variation
|
genomics
|
|
|
population analysis of a single gene effect
|
genetics
|
|
|
biologic systems are stereospecific: meaning...
|
drug receptor
drug enzyme drug protein binding |
|
|
all natural drugs are:
|
stereospecific and are all one enantiomer: not racemic mix's
|
|
|
drug that binds to a receptor but does not activate it, but may prevent another drug from occupying same receptor
|
antagonist
|
|
|
drug that binds to receptor at the active site, w/o activating receptor, and is reversible
|
competitive antagonism
|
|
|
how well a drug produces a desired effect
|
efficacy
|
|
|
how much of a drug is needed to produce 50% of max effect
|
potency
|
|
|
how titrateable is a drug?
|
therapeutic window, we prefer it to be steep
|
|
|
What is responsible for arousal?
|
RAS: thalamic branch/cholinergic
hypothalamic branch: monoaminergic |
|
|
The RAS sends what NT"s up to the upper cortex for arousal?
|
Ach, steroids, histamines, NE, serotonin
|
|
|
What suppresses the RAS?
|
VLPO:ventrolateral preoptic nucleus: suppresses the awareness center and we go to sleep
|
|
|
what can override GABA VLPO suppression?
|
external and internal (mental/physical) stimuli
|
|
|
during anesthesia, they are usually having what type of sleep?
|
non-Rem
|
|
|
describe REM sleep
|
rapid eye movement
restorative to brain brain is active comes from pontine reticular nuclei active process |
|
|
describe non-REM sleep
|
physically restorative
very little thought, very little EEG you want this for anesthesia, b/c in REM, brain is metabollically active, using oxygen, glucose...etc |
|
|
alpha waves
|
8-13hz, awake-resting
|
|
|
beta waves
|
14-80 hz, awake-active
|
|
|
theta waves
|
4- 7 hz
beginning of sleep in adult most sleep in a child non-rem & anesthesia |
|
|
delta waves
|
<3.5 hz- deep sleep in adult
|
|
|
what pattern in brain wave activity will you see first?
|
increase in Beta wave activity
|
