Drug excretion and interaction

Question 1

Drug excretion:

• the _____ common pathway for the ________ of drugs
• _______ are the most significant of ________ sites
• extra-_____ sites are what?

Answer 1

last, elimination
kidneys, excretory
renal, biliary, pulmonary, sweat, salivary, mammary glands

Question 2

What are the two components of elimination?

Answer 2

Excretion and metabolism

Question 3

The human kidneys receive __% of the cardiac output, and produce ~____L of glomerular filtration.
Tubules reabsorbing all but ___L of water and ________ substances.
____ mw (less than _____) compounds are allowed to pass during ________.

Answer 3

20%, 180L, 1.5L, dissolved, low MW (<500Da), filtration

Question 4

Blood flow through kidneys is _________.

Answer 4

unidirectional

Question 5

What are the three parts of the nephron important for excretion?

Answer 5

Bowman’s capsule
PCT
DCT

Question 6

What is the relevance of low MW drugs and kidneys?

Answer 6

If a drug has a MW less than 500 Da, it will pass through all the barriers in the filtration apparatus
This is especially true if the drug is water soluble

Question 7

Renal processes _____ the blood level of a drug at different sites.
These are?

Answer 7

modify
Glomerular filtration
Tubular secretion
Tubular reabsorption

Question 8

Tubular secretion:

• occurs in _______ tubular cells
• ______ secretory process
• • these are ______ systems that take place to excrete certain ______ and ______

Answer 8

proximal
active
carrier
acids and bases

Question 9

Describe the limitations of tubular secretion of drugs.

Answer 9

Because of being a carrier system, the secretion at proximal tubule is limited and concentration dependent

Question 10

Describe how tubular secretion can be troublesome when taking multiple drugs.

Answer 10

If two drugs are excreted by the same mechanism/carrier, one could cause the other to have a higher plasma concentration when they are co-administered (penicillin G and probenecid)

Question 11

What is the GFR of kidneys?

Answer 11

125 mL/min

Question 12

Tubular reabsorption:

• occurs at the _____ portion of the tubules
• occurs as a ________ process, it is influenced by a drugs _____, ____ and the ____ of the urine
• __________ drugs that are poorly absorbed in the GI tract are poorly _________ in the kidney, and are readily _______
• when _____ _______ increases, the ____ time the drug is exposed to reabsorption

Answer 12

distal
passive - p-value, pKa, pH
hydrophilic - reasborbed - excreted
urine flow - less

Question 13

What are the Toxicological implications of tubular reabsorption?

Answer 13

Altering the pH of urine could increase drug excretion

Altering the urine flow could accelerate drug clearance

Question 14

What process does tubular reabsorption occur by?

Answer 14

passive diffusion

Question 15

The filtrate of tubular reabsorption goes where?

Answer 15

Collecting duct, then bladder

Question 16

If you want to get rid of a drug faster, what can you do? (related to urine)

Answer 16

Drink more water

Take diuretics

Question 17

How much bile is made by the liver?

Answer 17

0.5-1.0 L daily

Question 18

When is biliary excretion important?

Answer 18

For compounds with a MW > 500 Da

Question 19

How can bacteria play a role in reasborption?

Answer 19

Bacteria in the GI can facilitate the reasborption of some drugs through their hydrolytic enzymes (i.e. remove polar group added by liver enzymes)

Question 20

How does the liver participate in excretion?

Answer 20

Drugs can be secreted with the bile, into the GI tract.

Question 21

There is a __ fold increased risk of having an adverse drug reaction when __ or more drugs are taken simultaneously
Why?

Answer 21

9
4

Drug interactions

Question 22

What is a drug interaction?

Answer 22

A situation in which a substance affects the activity of a drug when they are administered together.

Drug-food or drug-drug interaction

Question 23

When can drug interactions occur?

Answer 23

Interactions could happen during drug absorption, distribution, metabolism and excretion

Question 24

Drug interactions during asborption:
- occur in the ___ ____:
What could a drug change here?

Answer 24

GI tract
Drug could change:
- local pH
- intestinal motility
- formation of complexes

Question 25

What are examples of drugs interactions during absorption?

Answer 25

Tetracylcline (binds to calcium) and milk

Question 26

Regarding absorption and drug interactions, what supplements should not be taken with drugs?
What interval should be used?

Answer 26

Mineral and vitamin supplements should not be taken with other drugs (at least 5 hours difference)

Question 27

Why should tetracycline not be taken with milk?

Answer 27

Complexes with calcium of milk, no longer a free drug, decreased absorption

Question 28

Interactions could happen during drug distribution:

• many drugs are ______ bound to ____ and ______ proteins
• a drug with a _______ ______ could _______ another drug with a ______ affinity and cause the change in the concentration of the _______ drug
• because bound drugs cannot ______, cannot be ______, and cannot be ______, the displacement of plasma-bound drug could affect drug _______, _______ and ________

Answer 28

reversibly, RBCs, plasma proteins

higher affinity, displace, lower, free
diffuse, metabolized, excreted
distribution, metabolism, excretion

Question 29

Interactions could happen during drug metabolism:

• many drugs are ____ ________ or ________
• co-administration of these drugs could change the _______ concentration of the drugs

Answer 29

CYP inducers or inhibitors

plasma

Question 30

Interactions could happen during drug elimination. Explain.

Answer 30

A drug could change the pH of the urine or the volume of urine flow

Question 31

Describe how CYP inhibitors/inducers can affect drug concentrations.

Answer 31

CYP inhibitors can increase the Cp of certain drugs since they are no longer metabolized.

CYP inducers can drastically reduce Cp of drugs by increasing their activity.