metabolism Flashcards
What type of reactions are carried out during phase 1 metabolism?
Oxidation
Reduction
Hydrolysis
What is phase 1 metabolism?
Chemically diverse small molecules are converted (transformed) generally to more polar compounds
Give some examples of oxidation reactions carried out in phase 1 metabolism?
Oxidation Dehalogenation Deamination Dealkylation Epoxide formation Hydroxylation
Which enzymes are responsible for aromatic hydroxylation reactions in phase 1 metabolism?
CYP450
How can aromatic hydroxylation be slowed down or blocked?
Substitute the phenyl ring with a para-fluorine or para-chlorine
- deactivates the ring
How does the half life change for drugs that have had halogens substituted on to their phenyl ring?
Diclofenac - half life = 1 hour
Fenclofenac - half life = > 20 hours ( has para chlorine)
Which enzymes are responsible for aliphatic hydroxylation reactions in phase 1 metabolism?
CYP450
How is diazepam metabolised to temazepam?
Aliphatic hydroxylation
How is carbemazepine metabolised to carbamazepine 10,11-epoxide?
Epoxide formation
How is diazepam metabolised to nor-diazepam?
Oxidative N-dealkylation
How is codeine metabolised to morphine?
Oxidative O-dealkylation
How is amphetamine metabolised to phenylacetone?
Deamination
Which enzymes are responsible for deamination reactions in phase 1 metabolism?
CYP450
Amine oxidases
How is imipramine metabolised to imipramine N-oxide?
N-oxidation
Which enzymes are responsible for N-oxidation reactions in phase 1 metabolism?
Microsomal amine oxidase
Which enzymes are responsible for S-oxidation reactions in phase 1 metabolism?
CYP450
Flavoprotein oxidase
How is omeprazole metabolised to omeprazole sulphone?
S-oxidation
What proportion of ingested ethanol is metabolised by alcohol dehydrogenase?
Two thirds
What proportion of ingested ethanol is metabolised by CYP2E1?
One third
How is ethanol metabolised to acetaldehyde?
Alcohol oxidation
What causes hepatotoxicity after excessive alcohol consumption?
Excessive amounts of acetaldehyde generated from ethanol metabolism
How is chloramphenicol metabolised?
Aliphatic dehalogenation
Give some examples of reduction reactions that take place in phase 1 metabolism
Azo reduction
N-oxide reduction
NO2 reduction
Ketone reduction
Which enzymes are responsible for NO2 reduction reactions in phase 1 metabolism?
Gut microflora
- anaerobic
- NOT OXIDATIVE!!
How is nitrazepam converted to 7-amino-nitrazepam in phase 1 metabolism?
NO2 reduction
Which enzymes are responsible for azo reduction reactions in phase 1 metabolism?
Gut microflora
- anaerobic
- NOT OXIDATIVE!!
why are aliphatic halides not often used in drugs ?
they are too reactive
