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what is "elimination" of a drug?
removal of an administered drug from the body
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in general, would you expect kidney failure ina patient to speed up or slow down the rate of elimination of a renally excreted drug? would this result in subtherapeutic or toxic levels of this drug?
slow down. toxic.
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in general, would you expect IV fluid administration in a patient to speed up or slow down the rate of elimination of a renally excreted drug? would this result in subtherapeutic or toxic levels of this drug?
speed up. subtherapeutic
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what 3 things do researchers need to know about a drug before they can determine the dosage interval for that drug?
blood concentration, therapeutic range, half-life or clearance.
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what do "half-life" and "clearance" measure?
the rate at which the drugs leaves the body
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what is "clearance"?
how fast a volume of blood is cleared of a drug - until the drug is completely eliminated from that volume of blood
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what is the "half-life" of a drug?
the amount of time it takes for the blood concentration of the drug to decrease by one half. determined by lab tests.
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for a particular drug, which blood concentration will drop at the fastest rate - 100 mg/dl or 20 mg/dl?
100 mg/dl
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which drug will need to be administered to the patient most often - a drug with a half-life of 4 hours or one with a half life of 24 horus?
the drug with the 4 hour half life
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name the 2 major organ routes of elimination of drugs
liver and kidney
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name 5 other organ or gland routes of elimination of drugs
- mammary glands
- lungs
- intestinal tract
- sweat glands
- salivary glands
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name the 2 main mechanisms of kidney excretion of drugs
- glomerular filtration
- tubular (active) secretion
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the kidneys can "actively secrete" certain drugs. what does this mean?
the kidneys can use active transport ot move certain drug molecules from kidney cells into the urine against a concentration gradient - from the area of low concentration of drug molecules in the kidney cells to the area of high concentration of drug molecules in the urine. this achieves high urine concentrations of the drug for excretion purposes
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what part of the kidney nephron does active secretion take place in?
the proximal tubule
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are all drug actively secreted?
no
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can active secretion cause very high urine levels of certain drugs?
yes
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once a drug has diffused into the glomerular filtrate or been excreted into the kidney tubules, does it all necessarily get excreted into the urine?
no
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besides being excreted, what else may happen to a drug in the kidney tubules?
it may be reabsorbed - passively diffuse back into the blood
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where in the nephron does reabsorption mostely take place?
from the tubules, mostly in the loop of Henle
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which is reabsorbed form the glomerular filtrate or urine most easily - a hydrophilic or lipophilic drug?
lipophilic drug
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what type of drug molecule is most likely to be reabsorbed from the kidney tubules back into the blood - hydrophilic or lipophilic?
lipophilic
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what 2 factors affect the amount of drug elimination by the kidneys?
degree of protein-binding of the drug, and renal perfusion
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which is more likely to be excreted by the kidneys - protein bound or free drug molecules?
free drug molecules
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for a patient with hypoproteinemia, will a normally protein-bound drug be excreted faster or slower thna usual?
faster
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what is a renal perfusion?
the amount of blood flowing to and through the kidneys
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if renal perfusion is less than normal, will a drug excreted by the kidneys be excreted faster or slower than usual?
slower
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what kind of patient conditions cause decreased renal perfusion?
dehydration, shock, blood loss, sympathetic stimulation
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if a drug is excreted slower than usual, will the blood concentration of this drug be higher or lower than usual?
higher
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if a drug is excreted slower than usual, should the dose be increased or decreased? alternatively, hsould the dosage interval be shortened or prolonged?
decreased or prolonged
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if our patient was suffereing from a drug toxicity, should we try to increase or decrease kidney perfusion in order to get the drug eliminated faster? how would we do this?
increase kidney perfusion by giving IV fluids
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what are 2 ways the liver can help eliminate drugs?
metabolize the drug into the more hydrophilic form easier for the kidneys or excrete, or directly excrete the drug in the bile.
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describe "enterohepatic circulation"
drug is secreted from liver into bile. bile drains into the intestines via bile durct. drug is resorbed from intestines into portal vein which carries the drug back to the liver, which starts the cycle all over again
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does it matter whether or not a drug is excreted in milk? why or why not?
yes - drug in milk can affect the patient's baby, or in the case of dairy cattle, may get into the human food supply
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what types of drugs are mainly eliminated through the lungs?
inhalant anesthetics
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list 3 ways the intestinal tract can eliminate drugs
incompletely absorbed oral drugs, biliary excretion, active excretion
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what is drug "withdrawal time"?
the period of time from the last dose of the drug to the time that the animal can be slaughtered or its products used for human consumption
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what is the purpose of drug withdrawal time?
to prevent drug residues from getting into the human food chain
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in general, is extra-label use fo drugs in food-producing animals acceptable? why or why not?
no - may result in drug residues in human food
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what does "steady - state" refer to?
after a certain number of maintenance doses of a drug are given, absorption and excretion are balanced in the therapeutic range
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in general, after how many half-lives of a drug (maintenance dose) is the steady-state achieved?
5
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how could we reach the steady-state faster?
use a loading dose
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for a patient with hypoproteinemia, how could we adjust the dose of a normall protein-bound drug so that the blood concentration would stay in the steady-state?
give a lower dose more ofen
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referring to liver excretion of drugs, do drugs passively diffuse into the bile or are drugs actively transported into the bile?
actively transported
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