07 - Drug Metabolusm and Elimination

Question 0

14) Phase 2 of drug metabolism

Answer 0

• Conjugation reaction
• Coupling with relatively large water-soluble molecule to increase water solubility.
• Processes involved: 1. Glucuronidation
  2. Sulfation
  3. Acetylation
  4. Glutathione Conjugation

Question 1

13) Phase 1 of drug metabolism

Answer 1

• To made drugs more chemically reactive.
• Functionalisation: addition of a functional group
• Processes involved: 1. Oxidation
  2. Reduction
  3. Hydrolysis
  4. Hydration

Question 2

15) Enzymes involved in oxidation reaction (phase 1)

Answer 2

1. Cytochrome P450
   
   • in smooth ER
   • phenytoin -> p-hydroxyphenytoin
2. acohol and aldehyde dehydrogenase
   
   • in cytosol
   • ethanol -> acetaldehyde -> acetic acid

Question 3

16) Enzyme involved in reduction reaction (phase 1)

Answer 3

Cytochrome P450

Question 4

17) Enzymes involved in hydrolysis reaction (phase 1)

Answer 4

Mostly cytosolic enzymes

1. Carboxyesterases
   
   • Aspirin -> salicylic acid
   • Procaine -> p-aminobenzoic acid
2. Amidases
   
   • Procainamides -> p-aminobenzoic acid

Question 5

18) Cytochrome P450..

Answer 5

• In smooth ER
• Contains iron protoporphyrin
• Closely associated with NADPH cytochrome reductase

Question 6

19) Cytochrome P450 isoform that reacts with paracetamol

Answer 6

• CYP1A2

- CYP2E1

Question 7

20) Drugs bound to plasma protein are not filtered during..

Answer 7

Glomerular filtration

Question 8

21) Tubular secretion..

Answer 8

• Proximal tubule
• Active transport
• Drugs bound to plasma protein can be excreted
• Competition (penicillin and probenecid)

Question 9

22) Example of acidic drugs

Answer 9

1. Penicillin
2. Methotrexate
3. Probenecid
4. Indometacine
5. Thiazide diuretics
6. Glucuronic acid conjugates
7. Sulphate conjugates

Question 10

23) Examples of basic drugs:

Answer 10

1. Dopamine
2. Histamine
3. Serotonin
4. Mepacrine
5. Morphine
6. Quinine

Question 11

24) Factors affecting urinary excretion

Answer 11

1. Urinary pH
   
   • If filtrate is ionized at pH of tubular fluid, no re-absorption
   • Eg. phenobarbital (weak acid) ionized -> increase exretion
2. Diet
   
   • High protein diet -> decrease urinary pH ->
     - increase excretion of weak bases
     - decrease excretion of weak acid

Question 12

25) The effects of repeated dosing will depend on..

Answer 12

1. Dosing interval

2. Plasma half-life