Excretion

Question 1

What is the most important route of drug elimination of both parent drugs (esp. water soluble) and their metabolites?

Answer 1

renal excretion

Question 2

Why is the kidney the most widely studied excretory organ?

Answer 2

accessibility of urine and collection for urinalysis

Question 3

What 3 host factors determine renal excretion? How is renal excretion calculated?

Answer 3

1. renal blood flow (glomerular filtration)
2. active tubular secretion
3. tubular (passive) reabsorption

rate of filtration + secretion - reabsorption

Question 4

How do drugs enter the glomerulus from the blood? How is this affect filtration?

Answer 4

bulk flow

too large drug and those bound by plasma proteins will not pass if the glomerulus is healthy

Question 5

How are drugs transported in the proximal tubule? In what 2 ways does it differ from the glomerulus?

Answer 5

active transport using 2 pairs of transport proteins on the brush border and basolateral membrane

1. not limited by protein binding
2. susceptible to competition between drugs

Question 6

What are the 2 distinct secretory pathways in the later sections of the proximal renal tubule?

Answer 6

1. OAT - organic anion transporter (acidic compounds)
2. OCT - organic cation transporter (basic compounds)

Question 7

What does drug competition in the proximal tubule lead to? What is s good example of this?

Answer 7

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

Question 8

What tends to slow down renal excretion?

Answer 8

reabsorption of drugs from renal tubules into peritubular capillaries

Question 9

What 2 things is drug reabsorption form the proximal tubule depend on? How does pH affect reabsorption?

Answer 9

1. lipid solubility
2. 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

Question 10

How does species differences in urine pH affect drug excretion?

Answer 10

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

Question 11

In healthy animals, small changes in urinary pH or urinary flow rate do not…..

Answer 11

significantly contribute to altered drug clearance

Question 12

Can urinary pH be therapeutically altered to renal excretion rate of a drug can be modified? when is this used?

Answer 12

YES

in cases of toxicity or overdose

Question 13

What happens to drugs excreted in the urine that don’t undergo passive reabsorption? What can this lead to?

Answer 13

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

Question 14

How do low urine flow rates affect drug diffusion in the distal tubule? What facilitates this process? Slows it down?

Answer 14

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

Question 15

In what two situations will active reabsorption occur? What drug is commonly absorbed this way?

Answer 15

1. acts on drugs already present in the filtered load
2. 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

Question 16

What affects glomerular filtration, active tubular secretion, and passive reabsorption?

Answer 16

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

Question 17

Most of Phase I and II enzymatic systems present in the liver also exist in the kidneys. Where do the oxidative processes generally occur?

Answer 17

proximal tubule cells

Question 18

What are the 2 possible scenarios during renal biostransformation? What 2 drugs are metabolized in the kidneys?

Answer 18

1. a drug is solely metabolized in the kidney and not the liver
2. kidney metabolizes a drug already biotransformed by the liver via relay metabolism
3. morphine
4. acetaminophen

Question 19

What are some other ways drugs are excreted?

Answer 19

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

Question 20

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?

Answer 20

1. chemical structure
2. polarity
3. molecular weight

drugs excreted this way have a lot of contact with the intestine and its flora

Question 21

What are 2 possible adverse effects of biliary excretion?

Answer 21

1. conjugated Phase II drugs may undergo enterohepatic circulation
2. intestinal bacteria unconjugate the drug or metabolite, allowing for intestinal absorption to occur

Question 22

What 2 things happen during enterophepaticvcirculation? What does this do to the drug?

Answer 22

1. after oral or parenteral administration, the drug in conjugated in the liver and eliminated in the bile
2. degradation results in deconjugation of the drug, allowing it to be reabsorbed

prolongs the elimination half-life

Question 23

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?

Answer 23

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

Question 24

In which drugs is expired air an important type of excretion?

Answer 24

volatile drugs, like gas anesthetics

Question 25

When are we most concerned about drug excretion in milk? What drugs are more likely to distribute into milk?

Answer 25

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

Question 26

When are drugs excreted in feces?

Answer 26

drugs not absorbed after oral administration or those secreted directly into the intestine or into the bile

Question 27

The combined effects of hepatic metabolism and renal/biliary excretion, as well as other routes of elimination.....

Answer 27

irreversibly clear the drug from the body

Question 28

What life stage does neonatal, infant, and pediatric refer to?

Answer 28

NEONATAL = 0-2 weeks INFANT = >2-6 weeks PEDIATRIC = >6-12 weeks

Question 29

In what 3 ways does neonatal physiology affect drug excretion?

Answer 29

1. decreased hepatic metabolic capability (Phase I and II metabolism is decreased) 2. immature biliary function 3. decreased GFR and renal clearance (longer drug half-life)

Question 30

When will glomerular filtration and renal tubular filtration reach adult values? When is tubular reabsorption in puppies similar to that in adults?

Answer 30

2.5 months when body fluids and electrolytes and maintained

Question 31

In what 2 ways does the increased gastric pH decrease drug absorption in puppies?

Answer 31

1. drugs may require to be disintegrated and dissolved first 2. drugs ionized in less acidic environments cannot be absorbed

Question 32

What is an additional way to administer drugs, especially in pediatric patients? What are 5 reasons this way is used?

Answer 32

rectally 1. absorption is quick 2. can be used on patients where catheterization is difficult 3. reduces complications with IV administration (sedation, anesthetics) 4. can be used when oral administration is undesirable (antiemetics) 5. has efficient systemic effects

Question 33

How is IM administration different in pediatric patients?

Answer 33

slower, muscle mass and blood flow is decreased

Question 34

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?

Answer 34

SC cold environments are likely to reduce absorption if the neonate is not kept warm (same is true in hypothermic patients)

Question 35

When is intraperitoneal administration used in pediatric patients? What fluids can be given this way?

Answer 35

when a central veins are inaccessible, which is common in newborns isotonic fluids, which are readily absorbed

Question 36

Why is the absorption of volatile anesthetics so high in pediatric patients?

Answer 36

minute ventilation and respiratory rate are higher in younger animals than in adults (makes puppies more sensitive to the effects of gas anesthetics

Question 37

True or false: By passive reabsorption, it does not matter how lipid soluble a drug is.

Answer 37

FALSE

Question 38

True or false: Protein-bound drugs can be filtered by glomerulus.

Answer 38

FALSE

Question 39

All of the following are routes of excretion except? a. kidney b. lung c. bile d. fat e. milk

Answer 39

D