Drug excretion

Question 1

Drug Excretion:

Answer 1

• The physical processes that lead to the irreversible removal of a drug and its metabolites from the body.
• Routes: Urine (kidneys), feces (bile), breast milk, expired air (lungs), hair, skin/sweat.

Question 2

Drug Elimination:

Answer 2

• The removal of a drug from the body through metabolic and/or excretory processes.
• Components: Drug metabolism (~75%) and drug excretion.

Question 3

Factors Affecting Drug Excretion:

Answer 3

• Molecular Size and Weight: Most drugs can pass into the filtrate.
• Drug Concentration in Plasma: Transporters are saturable.
• Urine pH: Affects drug ionization and reabsorption.
• Plasma Protein Binding: Affects glomerular filtration but not active secretion.
• Renal Blood Flow: Influences glomerular filtration rate (GFR).
• Impaired Renal Function: Due to aging, disease, or use of drugs (e.g., NSAIDs).
• Transporters: Involved in active secretion and reabsorption.

Question 4

Fraction Unbound (fu):

Answer 4

The fraction of drug unbound in plasma, affecting renal clearance.

Question 5

Routes of Drug Excretion:

Answer 5

• Urine (Kidneys): Main route for hydrophilic drugs and metabolites.
• Feces (Bile): Hepatobiliary excretion.
• Other Routes: Breast milk, expired air, hair, skin/sweat.

Question 6

three processes involved in renal drug excretion

Answer 6

Glomerular Filtration:
Passive Reabsorption:
Active Tubular Secretion:

Question 7

Glomerular Filtration:

Answer 7

• Small and free drugs pass through glomerular capillaries into the filtrate.
• Clinical Application: Measurement of blood creatinine levels to estimate GFR.
• Example: Impaired renal function leads to increased blood creatinine levels.

Question 8

Passive Reabsorption:

Answer 8

• Most filtrate returns to circulation; small, lipophilic, and unionized drugs undergo passive diffusion back into the blood.
• Clinical Application: Alkalinizing urine with sodium bicarbonate to increase ionization and decrease reabsorption of salicylates in overdose cases.
• Example: Aspirin or methyl salicylate overdose.

Question 9

Active Tubular Secretion:

Answer 9

• Transporters in the proximal tubules mediate drug secretion from peritubular capillaries to the tubular lumen.
• Clinical Application: Probenecid inhibits OAT1/3 to increase the concentration of co-administered drugs.
• Example: Cephalexin excreted via glomerular filtration and active tubular secretion; probenecid increases cephalexin concentration.

Question 10

define Enterohepatic Recirculation:

Answer 10

Involves the circulation of drugs between the liver and intestines.

Question 11

Enterohepatic Recirculation Process:

Answer 11

• Lipophilic drugs undergo hepatic metabolism.
• Conjugated metabolites are excreted into bile and stored in the gallbladder.
• Bile is released into the duodenum; conjugates are hydrolyzed by GI bacteria, generating unconjugated drugs.
• Unconjugated drugs are reabsorbed into the bloodstream.

Question 12

Enterohepatic Recirculation drug example

Answer 12

Morphine: Undergoes hepatic metabolism and conjugation, excreted into bile, hydrolyzed by β-glucuronidase in the GI tract, and reabsorbed.

Question 13

Describe individual variation in drug response

Answer 13

Differences in response to the same dose of a drug due to intrinsic and extrinsic factors. With Intrinsic Factors and Extrinsic Factors

Question 14

Intrinsic Factors:

Answer 14

Genetics, age, sex, disease status, physiological conditions (e.g., pregnancy).

Question 15

Extrinsic Factors:

Answer 15

Concomitant medications, diet, exposure to chemicals and environmental causes.

Question 16

individual variation in drug response Impact on Treatment:

Answer 16

Variations can lead to treatment failures or toxicity, requiring dose adjustment or substitution with another drug.

Question 17

CYP Single Nucleotide Polymorphism (SNP): Define

Answer 17

Genetic variations in CYP450 enzymes affect drug metabolism.

Question 18

CYP Single Nucleotide Polymorphism (SNP): Phenotypes:

Answer 18

• Ultrarapid Metabolizer (UM): Increased enzyme activity.
• Extensive Metabolizer (EM): Normal enzyme activity.
• Intermediate Metabolizer (IM): Reduced enzyme activity.
• Poor Metabolizer (PM): Minimal or no enzyme activity.

Question 19

Ultrarapid Metabolizer (UM):

Answer 19

Increased enzyme activity.

Question 20

Extensive Metabolizer (EM):

Answer 20

Normal enzyme activity.

Question 21

Intermediate Metabolizer (IM)

Answer 21

Reduced enzyme activity.

Question 22

Poor Metabolizer (PM):

Answer 22

Minimal or no enzyme activity.

Question 23

Impact on Drug Metabolism and Response: Pharmacologically Active Parent Drug:

Answer 23

UMs may require higher doses; PMs may require lower doses due to prolonged drug effects.

Question 24

Impact on Drug Metabolism and Response:
Prodrug:

Answer 24

UMs convert prodrugs rapidly to active forms; PMs may have reduced therapeutic effects due to inadequate conversion.

Question 25

Drug Clearance:

Answer 25

The efficiency of drug elimination, defined as the volume of plasma cleared of drug per unit time (e.g., L/hr).

Question 26

Total Body Clearance:

Answer 26

Sum of hepatic clearance, renal clearance, and clearance by other routes.

Question 27

Fraction Excreted (fe):

Answer 27

• The fraction of administered drug excreted unchanged in the urine.

Question 28

Fraction Excreted (fe):
Hepatically Cleared Drugs:

Answer 28

Low fe, primarily metabolized in the liver.

Question 29

Fraction Excreted (fe):
Renally Cleared Drugs:

Answer 29

High fe, excreted unchanged in the urine.

Question 30

Determining Total Body Clearance (Non-Compartmental Analysis):

Answer 30

• Administer a single dose of drug (i.v. bolus or oral).
• Collect blood samples and measure drug plasma concentration at defined time points.
• Plot a plasma concentration-time curve and calculate the area under the curve (AUC).

Question 31

Drug Bioavailability (F):

Answer 31

The fraction of administered dose of the parent drug that reaches the systemic circulation.

Question 31

Drug Bioavailability (F):
For Intravenous Administration:

Answer 31

F = 1 (100% bioavailability).

Question 32

Drug Bioavailability (F):
For Other Routes:

Answer 32

F is between 0 and 1.

Question 32

Determining Bioavailability for Orally Administered Drug:

Answer 32

• Obtain plasma concentration-time curves for the drug administered via i.v. and oral routes.
• Calculate the respective AUCs.