Clearance and Excretion

Question 1

What are the two types of drug elimination?

Answer 1

1. excretion: physical removal of a drug from the body (kidney). Parent drug must be UNCHANGED!
2. metabolism: conversion of parent drug to metabolite (liver)

Question 2

What are the major and minor routes of excretion?

Answer 2

• Major: urine and feces (kidney principal organ)
• minor: fecal excretion (passive or active, passive is determined by pH, pKa, protein binding, etc), respiratory excretion (volatile drugs such as inhalated anesthetics), excretion via sweat or milk, biliary excretion (must be larger than 300 kDal and some polar characteristics)

Question 3

What is enterohepatic recycling?

Answer 3

• When conjugates and aa conjugates are excrted into bile and go into GI tract, they are exposed to bacteria. bacteria can recover parent drug.
• prolongs action of ethinyl estradiol and digoxin

Question 4

What are the three major processes involved in urinary excretion of drugs?

Answer 4

1. GFR
2. proximal tubular secretion
3. distal tubule reabsorption

Question 5

T/F drugs can alter GFR

Answer 5

False. Only disease

Question 6

How does the tubular secretion system work ? What is a problem that occurs with and how is it fixed?

Answer 6

• both areas for anion (organic acid) and cation (organic base) secretion (acid secretion system is the issue)
• some diuretics compete w/ active secretion of uric acid leading to hyperuricemia. Treat w/ Probenecid, which prevents the reabsorption of uric acid from the tubule

Question 7

What affects whether a drug get reabsorbed in the kidney or not?

Answer 7

• ionization

- polar drugs do not passively reabsorb

Question 8

What is the equation for urinary excretion? Is reabsorption passive or active?

Answer 8

excretion= filtration+ secreted- reabsorption

-can be both

Question 9

What is an example of ion trapping?

Answer 9

• overdosing on aspirin (acidic)

- pee will become basic trap aspirin in the filtrate and thus decrease reabsorption

Question 10

What is the extraction ratio equation?

Answer 10

• fraction of drug presented to an organ that is eliminated

- Ca-Cv/Ca (rate of presentation-rate of leaving/Rate of presentation)

Question 11

What is clearance? What are key points about it? Equation general? Specific to the kidney?

Answer 11

• clearance is the theoretical volume of blood that is cleared of drug per unit time. Volume/time
• clearance is proportional to extraction ratio, is additive, blood flow to an organ can be reduced by disease or age
• clearance= volumerric flow rateX extraction ratio
• cl= (GFR)alpha + (active secretion rate) - (reabsorption rate