Term
| what are the methods of drug input (10) |
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Definition
oral
buccal
sublingual
rectal
intramuscular
subcutaneous
IV
inhalation
topical
transdermal |
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Term
| oral drugs: benifits (3), downfalls (5) |
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Definition
benfitis: most common, safest, economical
downfalls: slow, less complete, first pass effect, absorption affected by stomach contants, most absorbed in intestines |
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Term
| buccal drugs: benifits (2), downfalls (1) |
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Definition
benifits: direct absorption into venous circulation, no first pass
downfalls: fast or slow depending on the drug |
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Term
| sublingual drugs: benifits (2), downfalls (1) |
|
Definition
benifits: direct absorption into venous circulation, no first pass
downfalls: fast or slow depending on the drug |
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Term
| what drugs are commonly siblingual, what are they for |
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Definition
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Term
|
Definition
| drug must first pass through the liver where some is metabolized or less active when it leaves |
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Term
| rectal drugs: benifits (3), downfalls (1) |
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Definition
benifits: partial escape from first pass, can give higher dose, good for vomiting or nausea
downfalls: can cause irritation |
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Term
| intramuscular drugs: benifits (3) |
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Definition
| fast, complete, can give large volumes |
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Term
| subcutaneous drugs: benifit and downfall |
|
Definition
benefit: large doses ok
downfall: slow absorption |
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Term
| IV drugs: benifits and downfalls |
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Definition
benifits: bioavaility 100%
downfalls: dangerous because if administration is too rapid, blood levels can become too high |
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Term
| topical drugs: locations, effect radius, downfulls |
|
Definition
skin or mucous membranes
local effects
rate of absorption depends on area but is usually slow |
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Term
| transdermal drugs: benifits (2), downfalls (3) |
|
Definition
benifits: systemic effect, first pass avoidance
downfalls: apply to skin, slow absorption, drug must be potent or the patch has to be huge |
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Term
| what are the three different types of absorption |
|
Definition
passive diffusion
facilitated diffusion
active transport |
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Term
| passive diffusion: power source, MOA, saturatble, specificity |
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Definition
driven by concentration gradient
ions flow down concentration gradient without a carrier
unable to saturate
low specificity |
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Term
| facilitated diffusion: power source, MOA, saturatble, specificity |
|
Definition
driven by concentration gradient
involves a carrier protein
able to saturate
specific |
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Term
| active transport: power source, MOA, saturatble, specificity |
|
Definition
moves against concentration gradient via ATP
needs carrier proteins
able to saturate
specific |
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Term
| define pKa, what does the number mean if it is high or low |
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Definition
strength of the acid/base
higher is basic
lower is acidic |
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|
Term
| how is pKa and pH related mathmatically |
|
Definition
log (A-)/(HA) = pH - pKa for acids
log (B)/(BH+) = pH - pKa for bases |
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|
Term
| in a sentence relate pH to pKa |
|
Definition
| if drug is in pH equal to its pKa, it will be 50% ionized |
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|
Term
| what type of molecules are most drugs |
|
Definition
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|
Term
| how is the concentration of a drug that will be ionized on each side of a membrane determined |
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Definition
| pH and pKa which change wether the drug is charged or uncharged |
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|
Term
| how can drug movement be determined, what is the best mode for a drug to be in for movement |
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Definition
wether the drug is charged or uncharged, and thus the pH/pKa
uncharged |
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Term
| write the weak acid / weak base ionization equations and explain why they would shift left or right |
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Definition
| BH+ -> B + H+
HA -> A- + H+
shift left when pHpKa
equlibrium when pH=pKa |
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Term
| why is a weak base better absorbed in the intestines rather than the stomach |
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Definition
| the intestines are more basic so it will be non-ionized and thus uncharged, allowing bettwer movement and thus absorption |
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Term
| what are physical factors that affect absorption |
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Definition
blood flow to the absorption site: different in each tissue and body situations
SA for absorption
contact time at the absorption site: during travel drug will get stuck in some areas and go fast through others |
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Term
|
Definition
| fraction that reaches systemic circulation |
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Term
| what is bioavilavility influenced by |
|
Definition
first pass metabolism
solubility of the drug: hydrophillic drugs have less
chemical instability |
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Term
| what are the 4 areas of the plasma curve, explain their boundries and significance |
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Definition
lag time: time from drug administration to appearance in the blood
onset of activity: time from administration to minimin effective concentration
duration of action: time plasma concentration remains above MEC
elimination: changing elimination of the drug changes its duration of action |
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Term
| if you take an antacid what happens to absorption on the plasma curve for a weak acid and weak base |
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Definition
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Term
| what is distribution of a drug determined by |
|
Definition
size of organ
blood flow
capillay permeability
hydrophobic or hydrophillic drugs (lipid soluble can go more places like CNS)
size of drug: smaller can go through BBB |
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|
Term
| what is the relationship between drugs and protein binding, why do they do this, what situations, what does it mean for the drug |
|
Definition
most drugs bind to albumin in the blood to hitch a ride because they are lipid soluble
if the drug binds proteins in the tissue compartment it can increase concentration in that compartment |
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|
Term
|
Definition
volume distribution
volume of fluid a drug is put into
the volume it would require to contain all the drug in the body at the same concentration in the plasma
relates amount of drug in the body to the plasma concentrations |
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|
Term
| what is Vd dependent on, give values |
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Definition
water compartments in the body
plasma 6%
ECF 20% (plasma and IF)
TBW 60% |
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Term
| what does it mean if Vd is larger than TBW |
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Definition
| it rapidly leaves the vascular compartment |
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|
Term
|
Definition
| Vd = amount in the body / amount in the blood |
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Term
| what happens to Vd if the drug was not eliminated? if the drug is eliminated? what about graphically |
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Definition
if not eliminated: the plasma concentration stays the same
if eliminated; the curve is extrpolated to ge the plasma concentration of the drug you need the calculation |
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|
Term
| how is Vd used, what does it mean if it is big, what other factors is it related to |
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Definition
tells the amount of drug needed to achieve a desired plasma concentration
large Vd means most of the drug isnt in the extraplasmic space
Vd is related to half life and can extend duration |
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|
Term
| what are the drug reservoirs (4) |
|
Definition
bound to plasma protein
cellular reserviors
fat
bone |
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Term
| when a drug is bound to a plasma protein that mean the drug structure is like what, what protein is it bound to |
|
Definition
acidic bind albumin and basic bind 1-a-glycoprotein
not hydrophillic or neutral |
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|
Term
| what does it do to the drug when it binds to a plasma protein |
|
Definition
inactive, cannot cross membranes
dont worry its reversible |
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Term
| what qualifies a tissue to be a cellular reserve, give examples |
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Definition
if binding of the drug within the cell is reversible, the tissue can be a drug reservior
muscle, ECF, etc |
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Term
| what is cellular reserve in fat not awesome, what types of drugs do this |
|
Definition
it can be a toxin risk in obease people
lipid soluble ones |
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Term
| what drugs accumulate in bones, why is this in particular bad |
|
Definition
tetracyclines, heavy meatals
can cause slow release of toxins like lead over time |
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Term
| what types of drugs enter fetal circulation, by what method |
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Definition
lipid soluble, non-ionized
simple diffusion |
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Term
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Definition
| disppearance of a drug by chemically changing it another compound |
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Term
| what normally happens to lipid soluble drugs in metabolism |
|
Definition
absorbed well but removed slow from the body because they are reabsorbed in the renal tubule
drugs are metabolized to a less lipid soluble form to help elimination |
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|
Term
| metabolism can inactivate drugs: explain this |
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Definition
drug is metabolized to be biologically inactive, becoming more polar and less lipid soluble
less lipid soluble means less renal reabsorption and more excretion |
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Term
| define prodrug, give two examples, what is an exception that still fits into the prodrug category |
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Definition
inactive drugs that must be metabolized to activate agents
levodopa
methyldopa
some drugs are active when administered but other parts become active through metabolism (sometimes toxic parts) |
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Term
| some drugs dont need to be metablized, why, what is happening to them |
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Definition
lithium isnt modified in the body
these drugs act up until the time they are excreted |
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Term
| 1st order kinetics of metabolism: laws, definition |
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Definition
follows michalis-Menten kinetics
rate of drug metabolism is proportional to concentration of free drug
a constant fraction of the drug is metabolized per unit time
enzymes not saturated |
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Term
| zero order kinetics of metabolism: when is it used, what is the law |
|
Definition
drugs with very large doses saturate metaboling enzymes
constant amount of drug metabolized per unit time |
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Term
| phase 1 metabolism: location, main driving reaction / mechanism |
|
Definition
on surface of SER
conversion of lipophillic molecules into polar molecules by adding or unmasking a polar functional group (NH2, OH) |
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Term
| in phase 1 metabolism, once the molecule is polar what happens to it (5) |
|
Definition
cytochrome P450 dependent oxidation
cytochrome P450 independent oxidation
reduction
hydrolysis of esters
hydrolysis of amides |
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Term
| cytochrome p450 dependent oxidation: 4 types and their examples |
|
Definition
hydroxylation: ibprofin, phenytoin
N or O dealkylation: morphine, codeine, caffiene
N or S oxidation: tylenol, nicotine, ametidine
deamination: diazepam, amphetamines |
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Term
| cytochrome p450 independent oxidation: 2 types and their examples. just checking... what does this even have to do with |
|
Definition
amine oxidation: epinepherine
dehydrogenation: ethanol
phase 1 metabolism reaction after conversion into a polar molecule |
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Term
| in phase 1 metabolism give example of a drug that is reduced |
|
Definition
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Term
| in phase 1 metabolism give example of a drug thats ester is hydrolyzed |
|
Definition
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Term
| in phase 1 metabolism give example of a drug thats amide is hydrolyzed |
|
Definition
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Term
| where does phase 2 metabolism take place, what is the initial reaction that takes place, what is the goal here |
|
Definition
cytoplasm
endogenous substrate is conjugated to the drug increasing the size and decreasing lipophilicity
size keeps it in the kidney tubule helping elimination |
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|
Term
| what is different in phase 2 metabolism in neonates |
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Definition
| they dont have transferase enzyme so drugs accumulate fast and can be toxic |
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Term
| what reactions occur in phase 2 metabolism (6) |
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Definition
glucuronidation
sulfation
acetylation
glycine conjugation
glutathione conjugation
methylation |
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Term
| phase 2 metabolism glucuronidation MOA |
|
Definition
| addition of glucuronic acid to the drug vua glucuronosyl transferase |
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Term
| phase 2 metabolism sulfation MOA |
|
Definition
| adding sulfate to the drug via sulfotransferase |
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Term
| phase 2 metabolism acetylation MOA, why is this reaction different than the others |
|
Definition
add acetyl group to the drug
some people are slow or fast acetylators. slow acetylators are a genotypic variation that can cause lupus) |
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|
Term
| phase 2 metabolism glycine conjugation MOA and examples |
|
Definition
add glycine to the drug
asprin and niacin |
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Term
| phase 2 metabolism glutathione conjugation MOA and example |
|
Definition
add acetylcysteine to the drug
acetaminophen (toxic metabolite) |
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|
Term
| phase 2 metabolism methylation MOA |
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Definition
| add methyl group to the drug |
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|
Term
| name the sites of metabolism (9) intracellular and system levels |
|
Definition
| liver, kidney, GI, skin, lungs, SER, cytoplas, mitochondria, cell membrane |
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|
Term
| where are most drugs metabolized |
|
Definition
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Term
| what is a drug metabolizing initiator isoenzyme, what does this mean for the drug in the body |
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Definition
| makes you less able to metabolize drugs. adding drug will give side effects stopping drug from being broken down |
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Term
| drug metabolizing initiator examples |
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Definition
| cimetidine, erythromycin, ketonasole, grape fruit |
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Term
| what is a drug metabolizing inducer isoenzyme, what does this mean clinically |
|
Definition
increase production of enzymes via gene expression
make plasma levels lower via more enzymes
you may need to increase dose if they are on an inducer |
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Term
| give examples of drug metabolizing indicers and their MOA |
|
Definition
bensopyrine: p460 1As family in the liver
chronic ethanol: p450 2E1 family
phenytoin, carbamepine, rifampin, barbituates: p450 3A4 family |
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|
Term
| what are the drugs that follow zero order kinetics, under what conditions |
|
Definition
asprin, ethanol, penytoin
when in high dose, except ethanol |
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|
Term
| what determines the interaction of a drug |
|
Definition
| rate of elimination and dosage |
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|
Term
| what is the relationship between elmination and excretion |
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Definition
| there is none, drug can be eliminated by metabolism before excretion |
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|
Term
| how is a drug eliminated if it is not metabolized |
|
Definition
|
|
Term
| where are the areas in the kidney excretion occur |
|
Definition
|
|
Term
| what types of drugs are filtered in the glomerulus |
|
Definition
free unbound
filter by size, not by pH or solubility |
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|
Term
| what drugs are filtered in the PCT, how |
|
Definition
drugs not filtered in the glomerulus that pass into capillary plexus
active transport for specific anions (deprotinated WA) and cations (protinated WB) |
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|
Term
| how does PCT drug excretion cause hypernatremia |
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Definition
| drug is WA and competes for uric acid in PCT causing side effects |
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|
Term
| what is the down side of PCT filtration |
|
Definition
low specificity, drugs can compete for carriers
incompletely developed in infants and neonates can cause toxicity due to inability to eliminate |
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|
Term
| explain how DCT reabsorption works |
|
Definition
drug concentration now increases that of the perivascular space
if uncharged the drug back diffuse back into circulation
you can manipulate pH of urine do decrease reabsorption and increase elimination. increase percent of drug ionizationed form |
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|
Term
|
Definition
| acidify urine traps protonated weak bases increasing their clearance |
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|
Term
| how is clearance calculated |
|
Definition
| rate of elimination of te drug / plasma drug concentration |
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|
Term
| how is rate of elimination calculated |
|
Definition
|
|
Term
|
Definition
|
|
Term
| what is excreted in the GI |
|
Definition
poo
drugs orally administered and not absorbed
MW > 300 |
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|
Term
| what is excreted in the pulmonary |
|
Definition
|
|
Term
|
Definition
| highly lipid soluble drugs |
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|
Term
| give 5 examples of drugs secreted in milk |
|
Definition
| barbituates, salicylates, morphine, steroids, radioactive substances |
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|
Term
| what is half life not affected by |
|
Definition
| constant infusion, injection, or oral if the drug is eliminated by 1st order kinetics |
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|
Term
| what is half life affected by |
|
Definition
| clearance which is easily changed too |
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|
Term
| how os half live calculated |
|
Definition
|
|
Term
|
Definition
diminished renal plasma flow
renal disease
decreased metabolism |
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|
Term
| what causes deminished plasma renal flow |
|
Definition
| cardiogenic shock, heart failure, hemorrhage |
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|
Term
| what causes decreased metabolism |
|
Definition
cytochrome p45o inhibitor
hepatic insufficiency
cirrhosis |
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