PED2001 Elimination

Question 1

What is biliary excretion?

Answer 1

The process by which liver cells transfer substances, including drugs, from plasma to bile using transport systems like OCTs and OATs

Biliary excretion is crucial for the elimination of hydrophilic drug conjugates, particularly glucuronides.

Question 2

What is enterohepatic circulation?

Answer 2

A process where glucuronides in the intestine are hydrolyzed, regenerating active drug that can be reabsorbed, prolonging drug action

Enterohepatic circulation accounts for about 20% of total drug in the body.

Question 3

What types of drugs are significantly excreted in bile?

Answer 3

Drugs like vecuronium and rifampicin

Vecuronium is mainly excreted unchanged, while rifampicin is deacetylated before being secreted.

Question 4

What does renal clearance quantify?

Answer 4

The elimination of drugs by the kidneys

Renal clearance is defined as the volume of plasma containing the amount of drug removed from the body by the kidneys in a unit of time.

Question 5

How is renal clearance (CLren) calculated?

Answer 5

CLren = (Cu x Vu) / Cp

Where Cu is urinary concentration, Vu is the rate of urine flow, and Cp is plasma concentration.

Question 6

What are the three fundamental processes accounting for renal drug excretion?

Answer 6

1. Glomerular filtration
2. Active tubular secretion
3. Passive reabsorption

Question 7

What is the molecular weight limit for drug molecules to pass into glomerular filtrate?

Answer 7

About 20 kDa

Plasma albumin, with a molecular weight of 68 kDa, is almost completely impermeable to the glomerular barrier.

Question 8

What happens to drug molecules that bind to plasma albumin?

Answer 8

Only the free drug is filtered into the glomerular filtrate

Drugs like warfarin, which is approximately 98% bound to albumin, have reduced clearance by filtration.

Question 9

What is the role of OATs and OCTs in tubular secretion?

Answer 9

They transport drugs to the tubular lumen in a non-selective manner

OAT handles acidic drugs, while OCT handles organic bases.

Question 10

What is the effect of tubular secretion on drug elimination?

Answer 10

It can achieve maximal drug clearance even when most of the drug is bound to plasma protein

This is particularly effective for drugs like penicillin.

Question 11

What is the significance of diffusion across the renal tubular epithelium?

Answer 11

Approximately 99% of filtered drug will be reabsorbed passively if the tubule is permeable

Lipid soluble drugs are excreted poorly while polar drugs remain concentrated in the lumen.

Question 12

What factor significantly affects the renal excretion of weak acids or bases?

Answer 12

The degree of ionization, which is pH dependent

Question 13

Fill in the blank: Probenecid was initially developed to inhibit the secretion of _______.

Answer 13

penicillin

Question 14

What are some mechanisms through which drug-drug interactions can affect drug excretion?

Answer 14

1. Altering protein binding
2. Inhibiting tubular secretion
3. Altering urine flow and/or urine pH

Question 15

True or False: Diuretics typically decrease the urinary excretion of other drugs.

Answer 15

False

Diuretics usually increase the excretion of other drugs and their metabolites.

Question 16

What can lithium carbonate toxicity be exacerbated by?

Answer 16

Loop and thiazide-like diuretics

These diuretics reduce body sodium content, prompting increased proximal tubular reabsorption of sodium and lithium.

Question 17

What is the purpose of altering urinary pH in treating salicylate poisoning?

Answer 17

To enhance the excretion of weak acids or bases