Flashcards in lecture 2- pharmacokinetics con't Deck (77):
creatinine clearance is based on
why is it significant if you have too much creatinine in your blood
mean your kidneys aren't functioning properly
creatinine clearance definition
s the volume of blood plasma that is cleared of creatinine per unit time. from Cockcroft and Gaul
females have a correction factor for cc and this does what
makes it lower, 85%
in calculating IBW for a female, compare actual body weight to ideal body weight and use which one ?
the lower value
more accurate calculation for excessive body weight and renal dysfunction , but really not practical/ used
what qualifies a patient as being obese
30% over their IBW
if a patient is obese, use
adjusted body weight
dialysis diffusion vs ultrafiltration
diffusion moves across the barriers. ultrafiltration is taking off a lot of fluid.
during dialysis, med will be removed if unbound volume is
<3.5L/kg. so if highly bound to albumin, it wont be removed.
during dialysis, med will be removed if clearance is
<10ml/min/kg. if highly renal eliminated, its already a med that is hydrophilic and small so it will move easily through dialysis filters
if the med has a dosing interval longer than its half life
you can expect it might be removed during dialysis
if a med has a molecular weight less than 1000 daltons
it will be removed during dialysis
when you put someone on dialysis, you assume that they have a creat clearance of about
single dose concentration graph
med peaks and then eliminates slowly at consistent rate.
continuous IV infusion
if you want to maintain something that has a short half life, redistributes quickly
get to therapeutic, wears off.
we cannot tell the effect of a med until
that med is ate steady state
amount of drug administered over time = amount of drug eliminated during the same time period. rate in = rate out. how quickly are you taking it in vs how quickly are you eliminating it.
how to do half life percentages
1 half life is 50%, and then each next one is halfway between the previous and 100%.... 50, 75, 87.5, 93.75, 96.875
does a loading dose shorten the time to ready steady state
NO. loading doses bring you to therapeutic but elimination hasn't caught up
would you reach steady state faster if the dose was given at one half of the medications life?
no. you cant just change the dosing interval. have to account for elimination. rate in vs rate out.
tips for interpreting drug levels
never treat an isolated number and check the dosing history. treat the pt not the #!
is the lowest concentration reached by a drug before the next dose is administered
he highest concentration of a drug in the patient's bloodstream.
if an elderly person has reduced first pass metabolism
more drug gets to general circulation, can lead to toxicity
elderly fat % and free water
increased rat, reduced free water
what is the impact of the elderly having reduced albumin concentration and/or increased alpha1 acid glycoprotein ?
increased toxicity because reduced carrier proteins so more free levels
gastric pH and emptying time in neonates and infants
CYP450 in neonates and infants
protein binding in neonates and infants
renal clearance in neonates/infants
the effects of drugs and mechanisms of their actions
drugs will either..
find their target cell, or be distributed, metabolized, and excreted.
most drugs bind to
what do drugs do on cellular receptors
initiate biochemical reactions that alter the cell's physiology
where do drugs exert their primary action
the cellular level
drug receptors are generally made up of what
proteins or glycoproteins present on the cell surface, on an organelle within the cell or in the cytoplasm
receptor mediated responses plateau once...
....receptor saturation occurs. (you can give a med, not get the effect you want, and doesnt matter how much more you give. you only have so many receptors.
although we have a finite number of receptors on a given cell, how does the body compensate?
thru up and down regulation. defense mechanism. body will produce more receptors. so you can't just d/c a drug without considering this. must taper
once a drug has bound to a receptor, what are the 3 things that could occur?
1) an ion channel is opened or closed
2) biochemical messengers, often called second messengers are activated
3) a normal cellular function is physically inhibited or initiated
biochemical messengers aka second messengers
(cAMP, cGMP, Ca+++, inositol phosphates) these initiate a series of chemical reactions within the cell, and transfuce the signal stimulated by the drug.
strength of binding between a drug
and its receptor. makes the receptor do what it normally does
dissociation constant (Kp)
the measure of a drug’s affinity for a given receptor. The concentration of drug required in solution to
achieve 50% occupancy of its receptors.
drugs which alter the physiology of a
cell by binding to plasma membrane or
agonist's stop the normal effect
an agonist which causes
maximal effects even though it may only occupy a small fraction of receptors on a
an agonist which must
be bound to many more receptors than
a strong agonist to produce the same
inhibit or block actions caused by agonists.
competes with agonist for
-During the time that a receptor is occupied by an
antagonist, agonists cannot bind to the receptor. Because the antagonism can be overcome by high
doses of agonists, competitive antagonism is said to
binds to a site
other than the agonist-binding domain. Induces a conformational change in the receptor such that the agonist no longer “recognizes” the agonist-binding domain.
§ “Insurmountable” because even high doses of
agonist cannot overcome this antagonism.
with the receptor.
-Rate of antagonism can be slowed by high
concentrations of antagonist.
-Once an irreversible antagonist binds to a
particular receptor that receptor cannot be
“reclaimed” by an agonist.
with agonists for the agonist-binding receptor.
-Irreversible antagonists combine permanently
The degree to which a drug is able to cause maximal effects.
- If Drug A reduces blood pressure by
20mmHg and Drug B reduces blood pressure by 10mmHg, then Drug A has greater efficacy than Drug B.
the amount of drug required to produce 50% of the maximal response that the drug is capable of causing. potency has more to do with dosing
potency is used to compare drugs that are..
in the same chemical class. drugs within the same chemical class will usually have similar maximal efficacy if a high enough dose is given.
used to compare drugs with different mechanisms. like toradol (NSAID) and morphine (narc)
dose response curves show
the magnitude of drug action against the concentration/dose of drug required to induce those actions.
-the curve represents the effects and dose of a drug within an individual animal or tissue rather than in the population
effective concentration50% EC50
The concentration of drug which induces a specified clinical effect in 50% of
the subjects to which the drug is administered.
Lethal Dose 50% LD50
the conc of drug which induces death in 50% of the subjects to which the drug
a measure of the safety of a drug. calculated by dividing the LD50 by the ED50
margin of safety
the margin between therapeutic and lethal doses of a drug
Drugs may inhibit absorption of other
drugs across biologic membranes (antiulcer agents that
coat the stomach may decrease GI absorption of other
Clinically important drug interactions
can occur when the P450 isoenzymes are inhibited or
Plasma protein competition:
Drugs that bind to plasma
proteins may compete with other drugs for the protein
binding sites. Displacement of drug ‘A’ from plasma
proteins by drug ‘B’ may increase the concentration of
unbound drug ‘A’ to toxic levels.
Drugs may act on the
kidney to reduce excretion of specific
agents (e.g. probenecid competes with
sulfonamides for the same carrier,
increasing the risk of sulfonamide toxicity).
the response elicited by combined drugs
is EQUAL TO the combined responses of the
individual drugs. 1+1=2
the response elicited by combined
drugs is GREATER THAN the combined responses of
the individual drugs. 1+1=3
A drug which has no effect enhances
the effect of a second drug. 0+1=2
Drug inhibits the effect of another
drug. Usually, the antagonist has no inherent activity.
Midazolam is a significant substrate of
CYP3A4. Erythromycin is a CYP3A4 inhibitor.
How would you manage this drug interaction?
substrate means metabolized by.
so too much free versed... this patient may be hard to wake up
use a different drug than erythromycin.
propofol is a strong CYP3A4 inhibitor. What
types of side effects would you expect from
sedatives that are metabolized by this
enzyme when given together?
so if you give prop with versed... more sedated, longer emergence
inhibition causes buildup
Carbamazepine is a very strong inducer
of CYP3A4. How might you have to
alter the dose of midazolam if given
you'll need more versed because its getting metabolized faster
represents a deresponsed to a drug. Clinically, this is observed when the dose of a drug must be increased to achieve the same effect.
tolerance can be ___ or ___ in nature
metabolic(drug metabolized more rapidly after chronic use) or cellular(decreased number of receptors, "downregulation"
patient needs drug to function normally. noted when cessation produces withdrawal symptoms.
dependence maybe physical and/or psychological