Chapter 6 - Drug Elimination Flashcards
Differentiate between elimination and excretion
the terms are pretty much interchangeable
the removal of waste products of metabolism from the blood, through the action of the kidneys
is it possible for things to be excreted unchanged
yes - can either be unchanged or as metabolites
around what % of drug is excreted renally? are there any things that can’t be excreted renally?
over 90% of drug is excreted renally
however, only small substances that can undergo passive diffusion are able to be filtered through the kidney
(less than 300 MW, POLAR AND HIGHLY IONIZED WATER SOLUBLE COMPOUNDS)
Name 6 routes of drug excretion that are NOT renal
lungs
perspiration (sweat)
biliary (enterohepatic circulation)
salivary
fecal
milk
what kind of substances are excreted through the lungs?
give a specific example
volatile substances, such as alcohol
is alcohol eliminated through the lungs via 1st or zero order elimination?
as a recap, briefly differentiate between 1st and zero order
zero order
the rate of elimination is CONSTANT and is independent of concentration
first order elimination IS concentration dependent
what kind of drug substances are excreted through perspiration (sweat)
low MW
water soluble electrolytes like NaCl
non-electrolytes like garlic
which is a more GENERAL term - elimination or excretion
excretion
true or false
high molecular weight drug molecules are excreted through perspiration
FALSE - low MW
*biliary excretion is for ____ molecules
LARGE - over 500 MW
*biliary excretion is also known as….
enterohepatic circulation
drugs with a molecular weight exceeding _____ are too large to be eliminated through the kidney
MW of 500
enterohepatic circulation is also known as what kind of excretion
biliary excretion
the pH of the saliva ranges between….
5.5-7.8
the ____/____ ratio is used
to determine if a drug can undergo TDM (therapeutic drug monitoring) through the saliva instead of the plasma (less invasive)
salivary/plasma ratio
“un-recycled biliary secretion”
fecal excretion
fecal excretion is the excretion of drugs through ____
the intestines
the presence of drug in the feces can be due to what 2 things
either the drug was incompletely absorbed OR due to biliary excretion - difficult to tell
pH of breast milk
6.6
do acidic or basic drugs tend to be excreted through the milk? why?
basic drugs
bc they will be ionized in the acidic (6.6pH) environment of the breast milk
again - explain what kind of drugs are eliminated renally and why is this
small MW (less than 300), polar, highly ionized, water soluble compounds
these drugs tend to stay in the plasma, and our kidney is related to the plasma
2 tests that are most commonly used to evaluate kidney function
excretion ratio (ER)
effective renal plasma flow (ERPF)
formula for excretion ratio
ER = Carterial - Crenal / C arterial
the ER (excretion ratio) ranges from ___ to ___
explain what a low vs high value means
0-1
0 means not removed and 1 means 100% removed by the kidney
if a drug is highly protein bound, will it have a low or high excretion ratio
if the drug is highly protein bound – it will be a low ER. the kidney is unable to separate the drug from the plasma protein - can only eliminate free drug
what does an ER of zero mean in terms of arterial/venous drug concentration
when ER is 0, it means that the renal concentration of the drug is equal to the ARTERIAL concentration of the drug – meaning that no drug was excreted through the kidneys
what does an ER of 1 mean
the renal concentration of the drug is zero and all is in the arteries - 100% excreted through the kidneys
the numerator equals the denominator - can only happen when the renal concentration of drug is zero
do arteries or veins carry drug to organs
arteries
true or false
if ER is high, that means a lot of drug is in the veins
true - removed by the kidney
the ER value is 0.35
explain what this means
the renal concentration is 65% of the arterial concentration
most drug is still in the arteries!
what is used as the “measure” of renal plasma flow in the ERPF equation
PAH (p-aminohippuric acid) 650mL/min
what is a normal range of renal plasma flow
590-695mL/min
as mentioned, a normal range of renal plasma flow is 590-695mL/min
of this, what % undergoes FILTRATION by the glomerulus?
around 20% — so like 118-140 or 130mL/min is passive glomerular filtration/minute
average MOVEMENT OF BLOOD/min
1L per minute – but like 40-45% of that is cells – we only care about the plasma flow - 590-695mL/min
inulin GFR
130mL/min
if a drug only undergoes passive filtration, drug clearance = _________
renal clearance (130mL/min)
true or false
glomerular filtration does not follow Fick’s first law
false - it does
3 factors that influence glomerular filtration
the surface area available for filtration
the permeability of the filtration membrane
the net filtration pressure
what is the net filtration pressure in the kidney? what is this pressure created by?
10mmHg
created by membrane/glomerular tissue
true or false
the glomerular capillaries have a huge surface area available for filtration
TRUE
name 2 things that can be used to determine glomerular filtration rate and why
manitol and inulin
they are only removed by filtration and do not undergo metabolism and do not affect the filtration rate
true or false
drug clearance usually only depends on GFR
true
2 mechanisms in which a drug goes from the blood to the glomerular filtrate
glomerular filtration (passive)
tubular secretion (active)
is the kidney ever able to dissociate the drug-protein complex
yes - in the case of tubular secretion
tubular secretion is sometimes done to eliminate undesirable substances that have been reabsorbed by passive diffusion
name 2 of these substances
urea and uric acid
true or false
tubular secretion does not control blood pH
false - it does
how is tubular secretion related to potassium ions
tubular secretion is done to remove excess potassium ions from the body
bc potassium ions in the filtrate are automatically reabsorbed in the PCT – the active tubular secretion mechanism removes these potassium ions out from the body
true or false
tubular secretion mechanism can be used to dispose substances that are NOT already in the filtrate
true
the active tubular secretion process follows….
michaelis-menten concept
competitive - binding site with carrier
true or false
in tubular secretion, the drug is being carried with its concentration gradient
FALSE - against the concentration gradient
true or false
the active tubular secretion of drugs does not have an upper rate limit of transport
false - it does. the system can be saturated! follows michaelis-menten kinetics. there will be a maximum rate once all of the carriers are saturated
true or false
the active tubular secretion process can be blocked by metabolic inhibitors
true
true or false
the tubular secretion process is a noncompetitive secretory transport mechanism
false - competitive
give 2 general examples of things that undergo active tubular secretion
acids (anions) and bases (cations)
tubular REABSORPTION may be considered a _____ process that begins when?
RECLAMATION process
begins as soon as the filtrate enters the proximal tubules
the reabsorption of ACIDIC DRUGS is enhanced under acidic or basic conditions and why?
acidic conditions - will be unionized and readily reabsorbed across the renal tubule membrane
the reabsorption of BASIC DRUGS is enhanced under acidic or basic conditions and why
basic conditions bc the drug will be unionized and readily reabsorbed across the renal tubule membrane
true or false
weakly basic drugs are more ionized in an acidic environment
true
for acidic drugs, if the ph-pka is ______, the drug will be more than 99% ionized and thus not be reabsorbed
2 or more
true or false
for ACIDIC DRUGS, the higher the difference between pH-pka, the more ionized is the drug
true
explain the rationale of reabsorption for a drug that treats a UTI
we dont want a UTI drug to be reabsorbed back into the body - we want it to stay in the urinary tract to treat the infection
thus, we want it to be ionized so it’s not reabsorbed
