Drug excretion

Question 1

drug excretion

Answer 1

Drug excretion refers solely to the physical processes
that lead to the irreversible removal of a drug and its
metabolites from the body

Question 2

drug elimination

Answer 2

Drug elimination is the removal of
drug from the body through metabolic
and/or excretory processes

Question 3

factors that affect drug excretion (renal)

Answer 3

(a) molecular size and weight
* most drugs can pass into the filtrate
(b) drug concentration in plasma
* transporters are saturable
(c) urine pH
* affect drug ionisation and reabsorption
(d) plasma protein binding
* affects glomerular filtration but not active secretion
(e) renal blood flow
* influence GFR
(f) impaired renal function
* ageing and/or disease
* use of drugs, e.g., NSAIDs (non-steroidal anti-inflammatory drugs)
(g) transporters

Question 4

describe fu

Answer 4

the fraction of drug unbound in plasma

Question 5

describe routes of drug excretion

Answer 5

1. renal excretion
2. faeces
3. breast milk

Question 6

three processes involved in renal drug excretion

Answer 6

glomular filtration
reabsorption
active tubular secretion

Question 7

clinical application of renal drug excretion with example

Answer 7

aspirin or methyl salicylic acid (e.g., infant teething gels)
intravenously administered sodium bicarbonate (an alkalinising agent)
o ↑ urine pH
o ↑ salicylic acid ionisation
o ↓ reabsorption

Question 8

describe enterohepatic recirculation with a drug example

Answer 8

lipophilic drugs –> hepatic metabolism –> conjugates excreted into bile –> glucuronides in the GI tract –> generate unconjugated drug

Question 9

describe individual variation in drug response

Answer 9

Individual variation in drug response refers to differences in response between individuals to the same dose of a drug
- intrinsic fctr
- extrensic fctrs

Question 10

glomerular filtration

Answer 10

• kidneys receive 25% of cardiac output

small and free drugs pass glomerular capillaries into the filtrate
- altered plasma protein binding can influence filtration

Question 11

passive reabsorption

Answer 11

water reabsorption → drug concentration ↑ in the filtrate
- passive diffusion - small, lipophilic and unionised drugs

urine pH affects drug ionisation and reabsorption

Question 12

active tubular secretion

Answer 12

peritubular capillaries → the tubular lumen
* occurs predominantly in proximal tubules
* mediated by transporters

Question 13

Hepatobiliary excretion

Answer 13

hepatocytes produce and secrete bile
* stored in the gallbladder
* drained into bile duct then duodenum
drug excreted into bile
* glucuronides are concentrated in bile

Question 14

breast milk

Answer 14

Most drugs enter breast milk via passive diffusion
* can be important for lipophilic and basic drugs (breast milk is slightly acidic)

Question 15

CYP single nucleotide polymorhpism

Answer 15

Ultrarapid metaboliser (UM) - three CYP2D6 metabolisers - metabolises quickly

Extensive metaboliser (EM)

Intermediate metaboliser (IM)

Poor metaboliser (PM)
- two defective CYP2D6 transporters - high plasma conc., exaggreated response, toxicity

Question 16

why is understanding phenotype important

Answer 16

helps to understand drug dose and prescription dosage depending on the metabolising capabilties of each individuals body

Question 17

describe drug clearance

Answer 17

Drug clearance refers to the efficiency of drug elimination, defined as the ratio of the elimination rate
(e.g., mg∙h-1) to the concentration of drug in plasma (e.g., mg∙L-1)

• total body clearance
• specific organ clearance

Question 18

fe

Answer 18

the fraction of administered drug excreted unchanged in the urine

Question 19

a simple approach to determine total body clearance in noncompartmental analysis

Answer 19

• 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 AUC

Question 20

describe drug bioavailability

Answer 20

Drug bioavailability (F) is the fraction of administered dose of the parent drug that reaches the systemic
circulation

Question 21

describe the determination for an orally administered drug based on drug bioavailibility

Answer 21

bioavailability of an orally administered drug
* obtain plasma concentration-time curve of the drug via i.v. and oral routes
* calculate respective AUC
F=AUC(other routes)/AUC(i.v.)

Question 22

Hepatically cleared drugs

Answer 22

undergos hepatic metabolism and metabolites are excreted
- low fe excreted

Question 23

Renally cleared drugs

Answer 23

undergoes little hepatic metabolism and primarily parent drug is excreted
- high fe