Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pharm > Exam 1 > Flashcards

Exam 1 Flashcards

1
Q

What is the purpose of biotransformation?

A

To promote drug elimination from the body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How is a drug with a MW<350 excreted?

A

By the kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

How is a drug with a MW>350 excreted?

A

By the liver

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Codeine starts as a what and becomes what? (regarding biotransformation)

A

Codeine (prodrug) > Morphine (active metabolite**)

*Metabolized to become active

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Diazepam starts as what and becomes what? (regarding biotransformation)

A

Diazepam (active drug) > Nordiazepam (active metabolite) and Ozazepam (active metabolite)
*Metabolites are more active than parent drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Acetaminophen starts as what and becomes what? (regarding biotransformation)

A

Acetaminophen (active drug) > N-acetyl-p-benzo-quinone imine (toxic metabolite**)
*Metabolized to toxic metabolites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Describe the process of acetaminophen becoming a toxic metabolite

A
  1. Acetaminophen metabolized (can be induced by ethanol)
  2. Conjugated with glutathione (GSH)
  3. GSH supply gets saturated
  4. Increased production of oxidative metabolites (oxidative stress) leads to hepatotoxicity
  5. Some GSH conjugates are toxic
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

How does ethanol induce acetaminophen metabolism?

A

Through CYP2E1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What is the purpose of a phase I reaction?

A

Modification of molecule:
To convert lipid soluble, non-ionized compounds to more ionized, hydrophilic metabolites
(some metabolites are readily excreted after phase I, others must go to phase II)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the purpose of a phase II reaction?

A

Conjugation:

Adds an ionized, charged particle to a phase I metabolite to form a more polar and hydrophilic conjugate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the most common Phase I reaction?

A

Oxidation reaction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Are phase I reactions specific or nonspecific to compounds?

A

Compound NON-specific (meaning no specific enzymes are metabolizing a particular drug)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How do enzymes work in a phase I reaction?

A
  • They are nonspecific to specific drugs

- Work by attacking specific FUNCTIONAL GROUPS which affects multiple drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which functional groups do enzymes “unmask” in a phase I reaction?

A

OH (major)
SH
NH2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the major enzyme of Phase I Oxidation? Describe this enzyme

A

CYP450

  • Family of enzymes found in the LIVER
  • Are MICROSOMAL enzymes (meaning they are inducible/can be stimulated)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is the primary function of CYP450

A
  • Oxidation (formation of OH) of multiple drugs and foreign molecules during Phase I rxns
  • Acts as a “handle” for phase II rxns
17
Q

What are the 3 subtypes of P450?

A

3A4
2D6
2E1
*All have different affinities for different substrates

18
Q

What is the purpose of the 3A4 enzyme?

A

Metabolizes >50% of drugs

*3A4 part of P450 family

19
Q

What is the purpose of the 2D6 enzyme?

A

Polymorphism impairs codeine metabolism (codeine > morphine)

*2D6 part of P450 family

20
Q

What is the purpose of the 2E1 enzyme?

A

Metabolizes and is induced by alcohol
(Ethanol induces metabolism of acetaminophen AND itself)
*2E1 part of P450 family

21
Q

What is the only Phase II enzyme that is microsomal and inducible?

A

Glucuronyl transferase

22
Q

What are the inducers of the 1A2 enzyme?

A

Smoking, chargrilled foods

23
Q

What are the inducers of the 2A6, 2B6, 2C8, 2C9, 2C18, 3A4 enzymes?

A

Barbituates/phenobarbital, St John’s warts

24
Q

What is the inducer of 2E1?

A

Ethanol

25
Q

What is the inhibitor of 3A4? Is the similar to competitive or non-competitive antagonists?

A 
Grapefruit juice
Competitive antagonist (competes for same active site but not actually a substrate)
26
Q

What is the inhibitor of 2D6? Is the similar to competitive or non-competitive antagonists?

A

Fluoxetine (Prozac)

Non-competitive antagonist (forms tight complex at allosteric site causing reversible inhibition)

27
Q

Name the Phase I CYP450-independent (non-microsomal) oxidative rxns:

A
  • Alcohol dehydrogenase

- Monoamine oxidase

28
Q

Name the Phase I CYP450-independent (non-microsomal) NON-oxidative rxns:

A
  • Reductive rxns (add H+ to compound): warfarin inactivated by CYP2A6
  • Hydrolytic rxns (Occur in plasma and in many tissues): esterases and amidases
29
Q

Where do the majority of conjugation (phase II) rxns occur? What are the mediated by?

A
  • Occur in the liver

- Mediated by glucuronidation and UGTs

30
Q

What is the end product of Phase II rxns?

A
  • Decreased lipid solubility
  • Polar and inactive
  • Have a larger molecular weight
  • Readily eliminated
31
Q

Which functional groups are most commonly conjugated with glucuronic acid?

A

OH, SH, NH2

32
Q

Provide an example in which the phase II rxn occurs before the phase I rxn. Describe the process.

A

Example: Isoniazid

  1. Acetylation by NAC (phase II)
  2. Hydrolysis (phase I)
33
Q

What does acetylation/hydrolysis of isoniazid result in

A

Toxic metabolites

34
Q

Name and describe the 2 examples of Phase I polymorphisms

A
  1. CYD2D6: involves metabolism of codeine to morphine (decreased 2D6 = codeine won’t work)
  2. Alcohol flush rxn: deficiency in aldehyde dehydrogenase leads to accumulation of acetaldehyde (cannot tolerate alcohol)
35
Q

Name and describe the 2 examples of Phase II polymorphisms

A
  1. Butyrylcholinesterase: succinylcholine, local anesthetics (high degree of polymorphisms)
  2. Fast and slow acetylators: seen with isoniazid (give small dose to slow metabolizers)
36
Q

Describe the process of “freeing of drugs”

A

finish later

37
Q

Describe the half lives of drugs that enter enterohepatic circulation. Name an example.

A

Usually have long half lives

Ex: birth control

Pharm (3 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions