Lecture 7.5

Question 1

What drug, bound or free, enters glomerular filtrate and filtered at the glomerulus?

Answer 1

free drug

bound drugs do not enter the glomerular filtrate

Question 2

Which part of the kidney does active secretion enters the kidney?

Answer 2

proximal tubule

Question 3

Which part of the kidney does passive reabsorption of lipid-soluble unionized drug into the body take place in?

Answer 3

distal tubule

Question 4

What happens to ionized, lipid-insoluble drug after it enters kidney?

Answer 4

excreted through urine

Question 5

Water soluble drugs and metabolites of lipid soluble drugs are largely eliminated by ___________ and _________________.

Answer 5

renal glomerular
tubular mechanisms

Question 6

Can the efficiency of transport system for individual drugs vary widely?

Answer 6

Yes

Question 7

Can competition occur between drugs using the same transport system?

Answer 7

Yes

Question 8

Besides renal elimination, how else could drugs and their metabolites be eliminated?

Answer 8

in bile, breast milk, and sweat, and by the lungs.

Question 9

What does the excretion of drugs from the kidneys depend on?

Answer 9

• absorption of drugs from the GI tract
• lipid solubility of drug
• the degree of ionization of drugs
• pH of the urine

Question 10

What drugs are reabsorbed and not eliminated by kidneys?

Answer 10

Nonionized lipid-soluble drugs

Question 11

Generally drugs that are bases are excreted when the urine is _________ .

Answer 11

acidic

Question 12

Acidic compounds are excreted in greater quantities if the urine is _________.

Answer 12

alkaline

Question 13

State the influcne of renal tubular fluid pH on the excretion of salicylic acid (a metabolite of aspirin).

Answer 13

if fluid alkanine: acid ionized into salicylate ion and excreted thru urine

If fluid acidic: salicylic acid exist in acid form and pass into blood thru renal tubular cells

Question 14

State the influcne of renal tubular fluid pH on the excretion of amphetamine (a weak base).

Answer 14

if fluid alkanine: exist as lipid soluble free base, passed into blood

if fluid acidic: exist as salt –> excreted thru urine

Question 15

What is an approach to eliminate amphetamine from the body during amphetamine toxicity?

Answer 15

acidification of the urine with ammonium chloride

*if fluid acidic: exists as salt –> excreted thru urine

Question 16

What is an approach to eliminate phenobarbital (a weak acid) from the body during phenobarbital poisoning?

Answer 16

alkalinization of the urine with sodium bicarbonate

if fluid alkanine: the weak acid is ionized into salicylate ion and excreted thru urine

Question 17

What are the 2 parameters to measure drug clearance?

Answer 17

1. rate of extraction of drug from blood
2. rate of clearance by the kidney

both depend on blood flow and the ability of the kidney to extract the drug (the extraction ratio)

Question 18

What is the extraction ratio if all the drug is removed from the blood as it passes through the kidneys?

Answer 18

1

Question 19

how to calculate renal extraction rate?

Answer 19

ER= (A−V)/A

where,
A = Arterial concentration of the substance
V = Renal venous concentration of the substance

Question 20

What is the range of extraction ratio?

Answer 20

0<ER<1

ER=1 when all of the drug is removed from the blood as it passes through the kidneys

Question 21

What is the outcome if the renal extraction ratio of a substance is low?

Answer 21

toxicity is likely to occur in renal failure.

e.g. digoxin

Question 22

What is the outcome if the hepatic extraction ratio of a substance is low?

Answer 22

toxicity is likely to occur in hepatic failure

e.g. digitoxin

Question 23

Name drugs that should be avoided in patients suffering from liver and renal failure

Answer 23

digitoxin and digoxin

because of low hepatic extraction and low renal extraction respectively

Question 24

What is Vd?

Answer 24

pharmacokinetic parameter that describes the theoretical volume in which a drug would need to be uniformly distributed to account for its observed concentration in the blood or plasma. It provides insight into how a drug is distributed in the body relative to the blood plasma.

Question 25

What are the possible values of Vd and what does it indicate?

Answer 25

Low Vd (<10 L) --> Drug is largely restricted to the plasma. Intermediate Vd (10–30 L): --> drug is distributed in extracellular fluid (plasma + interstitial fluid). High Vd (>40 L) --> Drug is distributed extensively into tissues (beyond total body water)

Question 26

How to calculate Vd?

Answer 26

Amount of drug in the body/ Plasma drug conc (per L) ​

Question 27

For drugs that are eliminated by first-order kinetics, the drug half-life is calculated by:

Answer 27

0.693 × Vd / Clearance clearance is the volume of the drug cleared of the drug per unit time

Question 28

What is meant by half-life?

Answer 28

the time required for its concentration in the blood to be reduced by one-half

Question 29

Do both the intravenously and orally administered identical drugs have the same half-lives once they reach the general circulation?

Answer 29

Yes

Question 30

Drugs that undergo both glomerular filtration and active tubular secretion have a very short half-life.

Answer 30

True or false

Question 31

State how the half-life of penicillin is porlonged.

Answer 31

coadministered with probenecid (a uricosuric drug) that inhibits the tubular secretion of penicillin

Question 32

Explain why penicillin has a very short half-life

Answer 32

it undergoes both glomerular filtration and active tubular secretion

Question 33

Why do most drugs have relatively longer half-lives than that of penicillin?

Answer 33

they undergo glomerular filtration, partial tubular resorption, and no active tubular secretion