Drug elimination

Question 1

efflux transporters

Answer 1

E.g. ABC (ATP binding cassette) transporters help in the removal of drugs
requires ATP

Question 2

Renal elimination

Answer 2

• Glomerular filtration
• Active tubular secretion
• Tubular reabsorption

Question 3

Glomerular filtration

Answer 3

• Removal of free drug at the glomerulus

Question 4

Active tubular secretion

Answer 4

• Energy dependent
• drug secreted into urine
• specialised cation and anion transporters
• E.g. penicillin
  Some drugs such as probenecid spare penicillin to be secreted

Question 5

Tubular reabsorption

Answer 5

• passive process where drugs is reabsorbed into the blood
• favours neutral form
• thus urinary pH can be slightly alkaline as excretion of weak acids (are ionised so will not be reabsorbed.)

Question 6

Ammonium chloride - tubular reabsorption

Answer 6

ammonium chloride enables some toxic bases to be eliminated more rapidly, eg amphetamine overdose treated by decreasing urinary pH and minimising tubular reabsorption

Question 7

Faecal excretion

- two major mechanisms where drugs can appear

Answer 7

• not being absorbed into the systemic circulation
• absorbed and excreted in bile and then deposited into intestines
• transporters efflux drug from hepatocytes

Question 8

Enterohepatic recycling of biliary excreted drugs

Answer 8

after excretion in bile gut, bacteria can cleave glucuronides

• after cleavage, some drugs may be reabsorbed
• drug is lost over several cycles (purpose of the cycle is to prolong the effect of the drug)

Question 9

intracellular drug conc.

Answer 9

a drug must reach its intraceullar target to produce a therapeutic effect - but unable to measure intracellular conc. easily
we measure blood levels –> serum conc. produced and effectiveness of drug

Question 10

Clearance

Answer 10

the volume of plasma cleared of drug per unit time

Question 11

volume distribution

Answer 11

volume of plasma into which the drug equilibrates to give its initial conc

Question 12

elimination rate

Answer 12

is inversely related to half-life

Question 13

First order pharmacokinetic model

Answer 13

• treating the whole body as a single compartment

- as plasma conc. decrease so does time

Question 14

Dose linearity

Answer 14

relationship between dose and systemic drug exposure (AUC)

A change in dose produces a corresponding change in exposure

Question 15

Digoxin

Answer 15

used for heart failure (bind to muscle)
- It has narrow therapeutic index
- long half life (40hr)
- large Vd (400L) 
- normal person plasma volume is 40L
Thus a large Vd indicates that the drug is conc. in tissue outside the plasma area
- take longer to eliminate

Question 16

saturation kinetics

Answer 16

the rate of elimination is independent of the conc. of the drug in plasma, occurs as plasma conc, needed to have therapuetic effect are high compared to the capacity of the system to eliminate the drug
e.g. ethanol elimination by alcohol dehydrogenase is max. at low conc. Increasing ethanol does not increase elimination

Question 17

Steady state pharmacokinetics

Answer 17

• if the next dose is given before the first dose is eliminated, it can build up
• thus the dose must be administered where the rate of intake and elimination are stable (After 5 half-life)
• digoxin 4-5 half-life is several days, thus IV loading doses are administered to achieve steady state faster

Question 18

Therapeutic drug monitoring

Answer 18

to monitor plasma drug conc so dose can be adjusted

• assay can be expensive and inconvenient so only used for low therapeutic index drugs
• Drugs such as digoxin

Question 19

Pharmacogenetic testing

Answer 19

• identifying people before hand
• benefit: can benefit from another drug
• however not used as widely
• PCR –> amplify a particular part of a gene in extracted DNA
• expensive and laborious