Brainscape's Knowledge GenomeTM

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


See full index

PHARM2060 > Module 4 > Flashcards

Module 4 Flashcards

1
Q

Define kinetics

A

the branch of chemistry or biochemistry concerned with measuring and studying the rates of reactions

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

What is drug metabolism and the purpose of drug metabolism?

A

Metabolism is the enzyme mediated alteration of a drug’s structure.

Drug metabolism is the term used to describe the biotransformation of pharmaceutical substances in the body so that they can be eliminated more easily.

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

Sites of drug metabolism include what?

A

Liver, intestine, stomach, kidney, intestinal bacteria

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

Where is the primary site of drug metabolism?

A

Liver

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

What in the intestine are able to metabolize drugs?

A

Enterocytes that line the gut

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

Why do we need drug metabolism?

A

Drug metabolism is important in humans to protect us from a number of environmental toxins as well as synthesize essential endogenous molecules.

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

What are some examples of endogenous molecules synthesized by drug metabolizing enzymes?

A
  • Vit D synthesis
  • Bile Acid synthesis
  • Cholesterol metabolism
  • Steroid hormones
  • Bilirubin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What happens to a drug after it has been metabolized (therapeutic consequences of drug metabolism)?

A

Varies between drugs.
Therapeutic consequences of drug metabolism are summarized below:
1) Increase water solubility of drugs to promote their excretion
Lipophilic to Hydrophilic
2) Inactivate drugs
Active to Inactive
3) Increase drug effectiveness
Active to More active
4) Activate prodrugs (prodrugs are inactive until metabolized)
Prodrug (inactive) to Active drug
5) Increase drug toxicity
Non-toxic to Toxic

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

Most drugs in clinical use exhibit what (in regards to kinetics of drug metabolism)?

A

First order kinetics

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

Describe first order kinetics

A
  • In most clinical situations the concentration of a drug is much lower than the metabolic capacity of the body. In these situations drug metabolism displays 1st order kinetics.
  • In 1st order kinetics drug metabolism is directly proportional to the concentration of free drug.
  • This means a constant fraction of drug is metabolized per unit time.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe zero order kinetics

A
  • In zero order kinetics, the plasma drug concentration is much higher than the metabolic capacity of the body.
  • One of the best examples of zero order kinetics is ethanol.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

In which kinetics is drug metabolism constant over time?

A

Zero order kinetics.

This means a constant amount of drug is metabolized per unit time.

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

Metabolism is also referred to as what?

A

biotransformation

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

What are prodrugs?

A

prodrugs are inactive until metabolized

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

Define metabolite

A

a substance formed in or necessary for metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is one of the less favourable consequences of drug metabolism?

A

It could in some cases increase drug toxicity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

PO drugs may undergo significant metabolism prior to entering the systemic circulation, this is called what?

A

first pass metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Where can first pass metabolism occur?

A
  1. Hepatocytes in the liver
  2. Intestinal enterocytes
  3. Stomach
  4. Intestinal bacteria
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What is the result of first pass metabolism?

A

decreased amount of parent drug that enters systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe extraction ration (ER)

A

Drugs are characterized as having high or low extraction ratio (ER) depending on how much metabolism occurs on the first pass through the liver.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What are the characteristics of high ER drugs?

A
  • Have low oral bioavailability ( 1- 20%)
  • PO doses are usually much higher than
    IV doses (to compensate for high first
    pass metabolism).
  • Small changes in hepatic enzyme
    activity produce large changes in
    bioavailability.
  • Very susceptible to drug-drug
    interactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the characteristics of low ER drugs?

A
  • Have high oral bioavailability ( > 80%)
    PO doses are usually similar to IV doses.
  • Small changes in hepatic enzyme
    activity have little effect on bioavailability.
  • Not very susceptible to drug-drug
    interactions.
  • Take many passes through the liver via the systemic circulation before they are completely metabolized.
23
Q

True or False: In low ER drugs, PO doses are usually similar to IV doses?

A

True

24
Q

Phase I metabolism is mediated by what?

A

CYP450 enzymes primarily and also esterases and dehydrogenases

25
Q

What is the primary purpose of Phase I metabolism?

A

Convert lipophilic drugs to more polar molecules by introducing or unmasking polar functional groups such as hydroxyl (-OH) or amine (-NH2).

26
Q

Which reactions does Phase I metabolism involve?

A

Involves oxidation, reduction and hydrolysis reactions

27
Q

What is the primary purpose of Phase II metabolism?

A

Increase the polarity of lipophilic drugs by conjugation reactions (addition of large water soluble molecule to drug; very similar purpose to phase I)

28
Q

Define conjugate

A

a substance formed by the reversible combination of two or more others - the addition of large water soluble molecules to a drug

29
Q

What is the possible outcome for metabolites of Phase I drug metabolism?

A

They can be more active, less active, or equally active as the parent drug

30
Q

What is the outcome for metabolites of Phase II drug metabolism?

A

Metabolites are less active than the parent drug
(with the exception of morphine 6-glucuronide which is a more potent analgesic than morphine)

31
Q

Which reactions does Phase II metabolism involve?

A

conjugation reactions (addition of large water soluble molecule to a drug)

32
Q

Where does Phase I drug metabolism occur?

A

In the smooth endoplasmic reticulum (ER) of the cell

33
Q

Where does Phase II drug metabolism occur?

A

In the cytosol of the cell
(with the exception of glucuronidation which is localized to the smooth ER)

34
Q

What are CYPs?

A
  • a large family of drug metabolizing enzymes
  • CYPs are the predominant Phase I drug metabolizing enzyme system
35
Q

The majority of drug metabolism in the body is performed by which enzymes?

A

hepatic CYP enzymes

36
Q

How do CYPs work?

A

CYPs oxidize drugs by inserting one atom of oxygen into the drug molecule producing water as a byproduct.

37
Q

How many families of CYPs are there?

A

12 families with 3 accounting for the majority of drug metabolism

38
Q

Malnutrition can do what to CYPs?

A

Decrease CYP activity as these enzymes require dietary protein, iron, folic acid and zinc for full activity.

39
Q

Which CYP metabolizes the largest fraction of currently marketed drugs (approx. 50%)?

A

CYP3A4

40
Q

List the Phase II drug metabolizing enzymes

A
  1. UDP-glucuronosyltransferases (UGTs)
  2. Sulfotransferases (SULTs)
  3. Glutathione S Transferases (GSTs)
  4. N-acetyltransferases (NATs)
  5. Thiopurine Methyltransferase (TPMT)
41
Q

Where are UGTs localized and which metabolism are they part of?

A

They are localized in the smooth endoplasmic reticulum and are part of phase II drug metabolism.

42
Q

UGTs catalyze the transfer of what?

A

Catalyze the transfer of a glucuronic acid (sugar) to a drug.

43
Q

How many UGT enzymes are there?

A

19 (human) UGT enzymes

44
Q

SULTS catalyze the transfer of what?

A

Catalyze the transfer of a sulfate group to a hydroxyl group of drugs.

45
Q

SULTs is short form for what?

A

Sulfotransferases

46
Q

UGTs is short form for what?

A

UDP-glucuronosyltransferases

47
Q

What are SULTs?

A

cytosolic phase II drug metabolizing enzymes

48
Q

Glucuronidated drugs are what?

A

more polar and therefore more easily excreted (UGT)

49
Q

Sulfated drugs are what?

A

more polar and therefore more easily excreted (SULTs)

50
Q

How many human SULT enzymes are there?

A

11

51
Q

What is GSTs short form for?

A

Glutathione S Transferases

52
Q

What are GSTs?

A

They are phase II drug metabolizing enzymes that may be cytosolic or microsomal.

53
Q

What do GSTs catalyze the transfer of?

A

catalyze the transfer of a glutathione molecule to a drug

54
Q

How many human GST enzymes are there?

A

20

PHARM2060 (16 decks)

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