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Flashcards in 6 drug metabolism Deck (17)
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1
Q

What does drug metabolism do?

A
  1. inactivation
  2. activation
  3. maintenance of activity
2
Q

What is the major source of first pass metabolism?

A

liver

3
Q

What happens in phase 1 reactions? Where are the enzymes for phase 2?

A

adding of functional group

  • equal, lower or higher activity
  • makes drugs more hydrophilic and provides functional group used to complete phase 2 reactions

-found in ER (liver and intestine)

4
Q

What happens in phase 2? Where are the enzymes for phase 2?

A

conjugation reaction

  • follows phase 1
  • some already have functional groups and go directly to phase 2
  • example functional groups: glucuronic acid, glutathione, sulfate group, and acetyl group
  • found in cytoplasm
5
Q

Are the drugs more lipophilic or hydrophilic after metabolism?

A

hydrophilic

-net effect is that a lipophilic drug is converted to more hydrophilic metabolite that is easily eliminated in urine

6
Q

What are the three types of phase 1 reactions?

A
  1. microsomal oxidations
    - hydroxylation reactions
  2. non microsomal oxidations
    - alcohol oxidation
  3. hydrolysis reactions (require water)
    - esterases
    - amidases
7
Q

Microsomal oxidation reactions use what type of enzymes?

A

cytochrome P450 enzymes

  • 57 isoforms
  • mixed-function oxidase system (MFO)
  • promiscuity
8
Q

How are microsomes isolated?

A

tissue homogenization and differential centrifugation

-vesicles formed from ER membrane

9
Q

What does a microsomal drug OXIDATION with cytochrome P450 enzymes need? What happens?

A

NADPH, P450, O2

  • one oxygen atom incorporated into durg substrate and one oxygen into water
  • ends with hydroxylated drug metabolite
10
Q

What happens in a non-microsomal oxidation reaction such as in alcohol OXIDATION?

A

ethanol–>acetaldehyde
-alcohol dehydrogenase (most important liver enzyme to metabolize alcohol, some alcohol is met by catalase and CYP2E1)

acetaldehyde–>acetate
acetaldehyde dehydrogenase

11
Q

What happens in phase 1 HYDROLYSIS reactions?

A

when esterases and amidases are hydrolyzed they have a PABA metabolite which competes with sulfonamide for drug site of action and leads to reduced therapeutic effectiveness

12
Q

How does liver disease affect drug metabolism?

A

impact on microsomal oxidases

13
Q

HOw does cardiac disease affect drug metabolism?

A

impact on hepatic blood flow

14
Q

DO neonates and geriatric patients have differnet expression of enzymes?

A

yes

15
Q

What factors increase metabolism?

A
  • environmental pollutants
  • tabacco smoke
  • charcoal-broiled meats
16
Q

What inhibits metabolism?

A
  1. competitive inhibition
    - one drug can compete for enzyme with co-administered drug-reversible
  2. non-competitive inhibition
    - permanent inhibition of enzyme
    - covalent modification
    - irreversible
17
Q

Active drug vs inactive drug

A

Active: very lipid soluble
Inactive: less lipid soluble

Active: less polar
Inactive: more polar

Active: less ionized
Inactive: more ionized

Active: weak electrolyte
Inactive: strong electrolyte

Active: more able to penetrate cell membrane
Inactive: less able to penetrate cell membrane