Topic 8 - Mechanisms of Elimination

Question 1

Methods of Renal Drug Elimination

Answer 1

Filtration: Allows only small molecules to pass
Secretion: Transporters pimp out acidic/basic drugs into tubules

Question 2

Methods that counteract Renal Drug Elimination

Answer 2

Reabsorption: Lipid soluble drugs are just reabsorbed back into blood stream

Charged, water-soluble drugs remain and are concentrated in urine

Question 3

Phase I Metabolism

Answer 3

Functionalism Step

Primes drug for Phase II by adding functional groups to make the drug more water soluble

Question 4

Phase II Metabolism

Answer 4

Conjugation Step

Attaches a large water soluble group, now drug is less lipophilic and is thus less likely to be reabsorbed

Question 5

Fate of Water Soluble Drugs (Elimination)

Answer 5

Excreted in Urine
(Renal Clearance > Hepatic Clearance)

Question 6

Fate of Lipid Soluble Drugs (Elimination-Phase 1 Metabolite)

Answer 6

Enters liver by crossing lipid bilayer –> In ER undergoes Phase I metabolism –> Now water soluble enough to be transported back into bloodstream –> Excreted as urine

Question 7

Fate of Lipid Soluble Drugs (Elimination-Phase 1+2 Metabolite Conjugate)

Answer 7

If Phase I metabolite is still not water soluble enough then it will undergo Phase II metabolism

Can then either
Diffuse into cytosol in hepatocytes where it is then turned into bile and eliminated as feces
Transported into bloodstream and excreted as urine

Question 8

Fate of Lipid Soluble Drugs (Elimination-Phase 2 drug conjugate)

Answer 8

Same as Phase 1+2 Metabolite Conjugate

Can be excreted either as feces or urine

Question 9

Water Soluble (Renal vs Hepatic Clearance)

Answer 9

Renal Clearance > Hepatic Clearance

Question 10

Lipid Soluble (Renal vs Hepatic Clearance)

Answer 10

Hepatic Clearance > Renal Clearance

Question 11

Common Phase I Reactions

Answer 11

CYP carries out:
Ring Hydroxylation Reaction (Attaches OH to ring)
Dealkylation (Gets rid of a methyl from an amine)

Question 12

Phase II Reactions

Answer 12

Glucuronidation
Sulfation
Acetylation
Glutathionylation

Question 13

Glucuronidation (Enzyme and Group Added)

Answer 13

UDP Glucuronyl Transferase (UGT)

Glucuronic Acid (Sugar)

Question 14

Sulfation (Enzyme and Group Added)

Answer 14

Sulfotransferase (SULTs)

Sulfate (SO4)2-

Question 15

Acetylation (Enzyme and Group Added)

Answer 15

N-Acetyl Transferase

Acetyl (-COCH3)

Question 16

Glutathionylation (Enzyme and Group Added)

Answer 16

Glutathione S-transferase

Glutathione (Tripeptide)

Question 17

Glucuronidation (When does it dominate, where it found)

Answer 17

Found in liver and smooth ER

Dominates at high drug concentrations

Question 18

Sulfation

Answer 18

Found in cytosol of hepatocytes
Also found in Kidneys and Intestines

Dominates at low drug concentrations