Pharmacokinetics 3

Question 1

Active secretion of drugs (even protein bound ones) occurs in which part of the nephron?

(a) Glomerulus
(b) Proximal convoluted tubule
(c) Distal convoluted tubule

Answer 1

b) Proximal convoluted tubule.

Question 2

List the groups that Phase II reactions can conjugate a drug with:

1. G________ _______
2. A_______ a______
3. G________
4. S________
5. M______
6. A______

Answer 2

1. Glucoronic Acid
2. Amino acids
3. Glutathione
4. Sulphate
5. Methyl
6. Acetyl

Question 3

A molecule can be excreted after Phase I, true or false?

Answer 3

True.

Question 4

Passive reabsorption of lipid soluble drugs occurs where in the nephron?

(a) Glomerulus
(b) Proximal convoluted tubule
(c) Distal convoluted tubule

Answer 4

(c) Distal convoluted tubule.

Question 5

What is the catalytic centre of the CYP450 group of enzymes? Why is it the catalytic centre?

Answer 5

The heme-iron complex. It donates and accepts electrons.

Question 6

Which phase of metabolism involved anabolic reactions?

Answer 6

Phase II.

Question 7

The OAT carrier system in the nephron secretes which kinds of drugs:

(a) Weak acids
(b) Weak bases
(c) Lipid soluble

Answer 7

(a) Weak acids

Question 8

Phase II reactions can occur by themselves (i.e. without Phase I), true or false?

Answer 8

True.

Question 9

Hydrolysis occurs in which phase of metabolism?

Answer 9

Phase I

Question 10

The OCT carrier system in the nephron secretes which kinds of drugs:

(a) Weak acids
(b) Weak bases
(c) Lipid soluble

Answer 10

(b) Weak bases

Question 11

Microsomal enzymatic reactions mostly occur in which part of the hepatic cell?

Answer 11

Smooth endoplasmic reticulum.

Question 12

Which of the following is true:

(a) Lipophillic drugs are made more ionic, in order to be excreted.
(b) Ionic drugs are made lipophillic, in order to be excreted.

Answer 12

(a)

This is because it is much easier to secrete ionic/metabolites across the distal convoluted tubule. Lipophillic drugs however can simply diffuse through the lipid membrane, returning to the bloodstream, after being secreted.

Question 13

Give an example of co-adminsitration of drugs to reduce excretion.

Answer 13

Penicillin and probenicid. They compete for the same secretion transporter in the nephron and hence it slows the loss of penicillin from the blood.

Probenicid = Increases in Rx of Gout. Increase uric acid excretion.

Question 14

Conjugation of a drug with hydrophilic groups usually occurs in which phase of metabolism?

Answer 14

Phase II.

Question 15

Oxidation occurs in which phase of the metabolism?

Answer 15

Phase I

Question 16

Protein bound drugs are only eliminaed by?

Answer 16

Tubular secretion.

Question 17

Re: drugs in the blood stream, what factors will stop them being filtered?

Answer 17

Being protein bound or too big to be filtered, e.g. heparin.

Question 18

Catabolic reactions occur in which phase of metabolism?

Answer 18

Phase I

Question 19

Is it low or high molecular-weight drugs that are poorly excreted in bile?

Answer 19

Low. Anything <500-700 daltons is not easily secreted in bile.

Question 20

True or false, all drugs get changed before excretion.
If true, explain why.
If false, give examples.

Answer 20

False.

Digoxin
Gentamicin
Methotrexate

Question 21

Non-microsomal enzymatic reactions mostly occur in which part of the hepatic cell?

Answer 21

Mitochondria.

Question 22

The transfer from plasma to bile occurs via:

(a) Passive diffusion
(b) Active transport

Answer 22

(b) Active transport

Question 23

Reduction occurs in which phase of metabolism?

Answer 23

Phase I

Question 24

Phase I reactions cannot create active metabolites, true or false?

Answer 24

False.

Prodrugs are metabolised in Phase I reactions and turned into an active metabolite. E.g. codeine > morphine.

Question 25

Briefly explain enterohepatic recirculation.

Answer 25

Bile (containing a bile-excreted drug) goes into the stomach.
This then moves through into the duodenum.
The bile and drug then get absorbed into the portal vein, which goes to hepatocytes.
Hepatocytes conjugate the drug with glucuronic acid.
Drug is then hydrophillic and moved back to the small intestine.
Drug then moves to the ileum.
Ileum contains Beta-glucuronidase, which breaks off the bond between drug and glucuronic acid.
Drug is now lipophillic and moves back through the membrane of gut wall and off to the portal vein. (See line 3).

Question 26

Which phase of metabolism involves the CYP450 mixed function oxidase system?

Answer 26

Phase I

Question 27

Which phase of metabolism is more likely to produce reactive or toxic metabolites/compounds?

Answer 27

Phase I.

Question 28

A molecule can only be excreted after going through Phase I reactions, true or false?

Answer 28

False. Phase I reactions can allow for Phase II reactions to occur.

Question 29

Phase I usually introduces reactive groups (four) to the molecule, what are they?

Answer 29

1. -OH (Hydroxyl)
2. -SH (Sulfide)
3. -NH2 (Amide)
4. -COOH (Carboxyl)