Excretion Flashcards
What is the most important route of drug elimination of both parent drugs (esp. water soluble) and their metabolites?
renal excretion
Why is the kidney the most widely studied excretory organ?
accessibility of urine and collection for urinalysis
What 3 host factors determine renal excretion? How is renal excretion calculated?
- renal blood flow (glomerular filtration)
- active tubular secretion
- tubular (passive) reabsorption
rate of filtration + secretion - reabsorption
How do drugs enter the glomerulus from the blood? How is this affect filtration?
bulk flow
too large drug and those bound by plasma proteins will not pass if the glomerulus is healthy
How are drugs transported in the proximal tubule? In what 2 ways does it differ from the glomerulus?
active transport using 2 pairs of transport proteins on the brush border and basolateral membrane
- not limited by protein binding
- susceptible to competition between drugs
What are the 2 distinct secretory pathways in the later sections of the proximal renal tubule?
- OAT - organic anion transporter (acidic compounds)
- OCT - organic cation transporter (basic compounds)
What does drug competition in the proximal tubule lead to? What is s good example of this?
drug interactions, especially at OAT
weak acids, like probenecid and phenylbutazone, inhibit the secretion of the weak acid penicillin, thereby prolonging the blood concentration of penicillin
What tends to slow down renal excretion?
reabsorption of drugs from renal tubules into peritubular capillaries
What 2 things is drug reabsorption form the proximal tubule depend on? How does pH affect reabsorption?
- lipid solubility
- ionization
WEAK ACIDS are more likely to be reabsorbed in acidic urine, but are traped and excreted in alkaline urine
WEAK BASES are more likely to be reabsorbed in alkaline urine, but are traped and excreted in acidic urine
How does species differences in urine pH affect drug excretion?
weakly acidic drugs have higher excretion in herbivores because their urine is more alkaline
weakly basic drugs have higher excretion in carnivores because their urine is more acidic
In healthy animals, small changes in urinary pH or urinary flow rate do not…..
significantly contribute to altered drug clearance
Can urinary pH be therapeutically altered to renal excretion rate of a drug can be modified? when is this used?
YES
in cases of toxicity or overdose
What happens to drugs excreted in the urine that don’t undergo passive reabsorption? What can this lead to?
they will be progressively concentrated in the renal tubule
tubular cells are exposed to higher concentrations of drugs, which can increase the risk of nephrotoxicity
can be therapeutic in cases of bacterial cystitis
How do low urine flow rates affect drug diffusion in the distal tubule? What facilitates this process? Slows it down?
greater opportunity for diffusion of a drug from the distal tubule back into the blood
high concentration of the drug in the tubular fluid
polar compounds have low lipid solubility, so they are cannot pass the lipid membrane and are not reabsorbed
In what two situations will active reabsorption occur? What drug is commonly absorbed this way?
- acts on drugs already present in the filtered load
- recovers essential nutrients
furosemide is first secreted by the tubule into tubular fluid and then is actively reabsorbed back into tubular cells to gain access to its receptors for activity
What affects glomerular filtration, active tubular secretion, and passive reabsorption?
GLOMERULAR FILTRATION: molecular weight, protein binding, renal blood flow
ACTIVE TUBULAR SECRETION: renal blood flow, drug pKa
PASSIVE REABSORPTION: drug concentration, molecular weight, lipid solubility, drug pKa, urine pH
Most of Phase I and II enzymatic systems present in the liver also exist in the kidneys. Where do the oxidative processes generally occur?
proximal tubule cells
What are the 2 possible scenarios during renal biostransformation? What 2 drugs are metabolized in the kidneys?
- a drug is solely metabolized in the kidney and not the liver
- kidney metabolizes a drug already biotransformed by the liver via relay metabolism
- morphine
- acetaminophen
What are some other ways drugs are excreted?
bile, milk, saliva, expired air, feces, sweat, tears
(most therapeutic drugs excreted these ways are not generally quantitatively important for reducing total body burden of a drug
What 3 features affect biliary excretion of a drug? Why are drugs excreted this way more likely to cause adverse reactions in the GI tract?
- chemical structure
- polarity
- molecular weight
drugs excreted this way have a lot of contact with the intestine and its flora
What are 2 possible adverse effects of biliary excretion?
- conjugated Phase II drugs may undergo enterohepatic circulation
- intestinal bacteria unconjugate the drug or metabolite, allowing for intestinal absorption to occur
What 2 things happen during enterophepaticvcirculation? What does this do to the drug?
- after oral or parenteral administration, the drug in conjugated in the liver and eliminated in the bile
- degradation results in deconjugation of the drug, allowing it to be reabsorbed
prolongs the elimination half-life
How do drugs enter the saliva for excretion? In what animals is this type of excretion most important? How can this be dangerous for cattle?
passive diffusion from the blood
herbivores receiving parenteral antimicrobials
copious salivation and swallowing of antimicrobial-laden saliva may upset the digestive process in the rumen
In which drugs is expired air an important type of excretion?
volatile drugs, like gas anesthetics
When are we most concerned about drug excretion in milk? What drugs are more likely to distribute into milk?
if the milk is being used for human consumption; requiring a withdrawal period
weakly acidic (penicillin); weakly basic drugs (erythromycin) are more likely to excrete this way
When are drugs excreted in feces?
drugs not absorbed after oral administration or those secreted directly into the intestine or into the bile
The combined effects of hepatic metabolism and renal/biliary excretion, as well as other routes of elimination…..
irreversibly clear the drug from the body
What life stage does neonatal, infant, and pediatric refer to?
NEONATAL = 0-2 weeks
INFANT = >2-6 weeks
PEDIATRIC = >6-12 weeks
In what 3 ways does neonatal physiology affect drug excretion?
- decreased hepatic metabolic capability (Phase I and II metabolism is decreased)
- immature biliary function
- decreased GFR and renal clearance
(longer drug half-life)
When will glomerular filtration and renal tubular filtration reach adult values? When is tubular reabsorption in puppies similar to that in adults?
2.5 months
when body fluids and electrolytes and maintained
In what 2 ways does the increased gastric pH decrease drug absorption in puppies?
- drugs may require to be disintegrated and dissolved first
- drugs ionized in less acidic environments cannot be absorbed
What is an additional way to administer drugs, especially in pediatric patients? What are 5 reasons this way is used?
rectally
- absorption is quick
- can be used on patients where catheterization is difficult
- reduces complications with IV administration (sedation, anesthetics)
- can be used when oral administration is undesirable (antiemetics)
- has efficient systemic effects
How is IM administration different in pediatric patients?
slower, muscle mass and blood flow is decreased
Since muscle mass is so small in pediatric patients, which route of administration is preferred? What part of the environment affects absorption after this kind of administration?
SC
cold environments are likely to reduce absorption if the neonate is not kept warm
(same is true in hypothermic patients)
When is intraperitoneal administration used in pediatric patients? What fluids can be given this way?
when a central veins are inaccessible, which is common in newborns
isotonic fluids, which are readily absorbed
Why is the absorption of volatile anesthetics so high in pediatric patients?
minute ventilation and respiratory rate are higher in younger animals than in adults
(makes puppies more sensitive to the effects of gas anesthetics
True or false: By passive reabsorption, it does not matter how lipid soluble a drug is.
FALSE
True or false: Protein-bound drugs can be filtered by glomerulus.
FALSE
All of the following are routes of excretion except?
a. kidney
b. lung
c. bile
d. fat
e. milk
D
