Brainscape's Knowledge GenomeTM

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


See full index

PT3001: Introduction to Pharmacology > Pharmacokinetics II: Metabolism & Elimination > Flashcards

Pharmacokinetics II: Metabolism & Elimination Flashcards

1
Q

What is Drug Metabolism?

A

A biologically protective mechanism that has evolved to rid the body of exogenous substances (e.g. toxins)

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

What is Biotransformation?

A

Chemical modification made by an organism on a chemical compound

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

What compounds do metabolic enzymes transform drugs into?

A

Polar, water-soluble compounds

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

How are metabolised drugs eliminated?

A

In urine and/or bile

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

TRUE OR FALSE:
Drug metabolites are generally MORE pharmacologically active?

A

False.
They are LESS pharmacologically active

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

What TWO key reactions can drug metabolism be classified into?

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

What is involved in Functionalism?

A
  • Addition of a function group
  • Drug is made MORE chemically reactive
  • Prepares drug for Phase II reactions
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is involved in Conjugation?

A

Drug is coupled to a second, relatively large water-soluble molecule that increases the drugs water solubility

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

What are the FOUR Phase 1 reactions?

A
  1. Oxidation
  2. Reduction
  3. Hydrolysis
  4. Hydration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What are the FOUR Phase 2 reactions?

A
  1. Glucuronidation
  2. Sulfation
  3. Acetylation
  4. Glutathione Conjugation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Which organ has a HIGH biotransformation capacity?

A

Liver

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

Which organ(s) has a MEDIUM biotransformation capacity?

A
  • Lung
  • Kidney
  • Intestine
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Which organ(s) has a LOW biotransformation capacity?

A
  • Skin
  • Testes
  • Placenta
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which enzyme catalyses Oxidation reactions, and where does it occur?

A
  • Cytochrome P450
  • Smooth ER
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which reaction is the main Phase 1 reaction?

A

Oxidation

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

Which enzymes are involved in Reduction reactions?

A

Reductases

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

Which enzymes are involved in Hydrolysis reactions?

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

Give TWO examples of drugs that undergo Reduction reactions?

A
  1. Warfarin
  2. Chloral hydrate
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Give TWO examples of drugs that undergo Hydrolysis reactions by Esterases?

A
  1. Aspirin -> Salicylic Acid
  2. Procaine -> 4-aminobenzoic acid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Give an example of a drug that undergoes Hydrolysis reaction by Amidases?

A

Procainamides -> p-aminobenzoic acid

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

What enzyme is Cytochrome P450 closely associated with in membrane?

A

NADPH P450 Reductase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

How many gene families of CYP450 do humans have?

A

> 74 different families

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Which THREE families of CYP450 are mainly involved in drug metabolism?

A

1, 2 & 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which TWO CYP450 isoforms metabolise paracetamol?

A
  1. CYP1A2
  2. CYP2E1
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the major Phase 2 reaction?

A

Glucuronidation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What substance is added during Glucuronidation?

A

UDP-glucuronic acid (UDPGA)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What enzyme is involved in Glucuronidation?

A

Glucuronyl Transferases

28
Q

What is the cell location of Glucuronidation?

A

Endoplasmic Reticulum

29
Q

What are FOUR examples of drugs that undergo Glucuronidation?

A
  1. Paracetamol
  2. Morphine
  3. 4-hydroxyphenytoin
  4. Salicylic acid
30
Q

What enzyme is involved in Sulfation reactions?

A

Sulfotransferases

31
Q

What is the cell location of Sulfation reactions?

A

Cytosol

32
Q

What are TWO examples of drugs that undergo Sulfation?

A
  1. Paracetamol
  2. Tamoxifen
33
Q

What enzyme is involved in Glutathione Conjugation reactions?

A

Glutathione - S - Transferases

34
Q

What are the cell locations of Glutathione Conjugation reactions?

A
  • Cytosol
  • Microsomes (ER)
  • Mitochondria
35
Q

Which toxic metabolite of paracetamol is eliminated by conjugation to Glutathione in the liver?

A

NAPQI

36
Q

What is First Pass Metabolism, and where does it take place?

A
  • Pre-Systemic Metabolism
  • GI tract and Liver
37
Q

What is an example of a drug that cannot be administered orally due to First Pass Metabolism?

A

Morphine

38
Q

What are TWO issues with First Pass Metabolism?

A
  1. Larger dose needed
  2. Individual variation (unpredictable effects)
39
Q

TRUE OR FALSE:
Drug metabolism frequently results in the formation of pharmacologically active products (metabolites)?

A

True

40
Q

What types of drugs are NOT filtered by Glomerular Filtration?

A

Drugs bound to plasma protein (albumin)
e.g. warfarin - 98% bound to albumin

41
Q

Which transporters in the proximal tubule select for ACIDIC drugs?

A

Organic Anion Transporters (OATs)

42
Q

Which transporters in the proximal tubule select for BASIC drugs?

A

Organic Cation Transporters (OCTs)

43
Q

TRUE OR FALSE:
Drugs bound to plasma proteins can be excreted in the proximal tubule?

A

True

44
Q

Where does Diffusion and Reabsorption occur?

A

Distal tubule

45
Q

What are THREE types of membrane permeable substances?

A
  1. Lipid soluble substances
  2. Unionised drugs
  3. Some ionised drugs
46
Q

How does urinary pH affect drug / metabolite excretion?

A

If compound in filtrate is ionised at pH of tubular fluid, then it is NOT reabsorbed

47
Q

How is Phenobarbital (weak acid) excreted?

A
  • Ionised at alkaline pH
  • Sodium bicarbonate for overdose patients
  • INCREASES urinary pH
  • INCREASES excretion
48
Q

How does a high protein diet affect urinary excretion of a WEAK BASE drug?

A
  • DECREASES urinary pH
    *INCREASES excretion
49
Q

How does a high protein diet affect urinary excretion of a WEAK ACID drug?

A
  • DECREASES urinary pH
  • DECREASES excretion
50
Q

Which types of drug molecules are actively transported across the liver epithelial cells and into the bile duct for excretion?

A

Large drug molecules > 300 Daltons

51
Q

What is an example of a drug that is eliminated via the biliary system?

A

Rifampicin

52
Q
A
53
Q

What are the TWO rate constants in Pharmacokinetics?

A
  1. Rate of Absorption - Kab
  2. Rate of Elimination - Kel
54
Q

What are the characteristics of Intravenous administration?

A

*Absorption is INSTANTANEOUS
* Rapid distribution
* Only elimination (Kel) needs to be considered

55
Q

What are the characteristics of Oral administration?

A
  • Absorption is NOT instantaneous
  • Plasma concentration rises initially, then declines
  • Absorption AND Elimination both occur
56
Q

What is the shape of the curve in plasma conc. vs time plot after I.V. bolus for FIRST ORDER elimination kinetics?

A

Exponential decay

57
Q

What is the shape of the curve in plasma conc. vs time plot after I.V. bolus for ZERO ORDER elimination kinetics?

A

Linear

58
Q

What is the shape of the curve in log plasma conc. vs time plot after I.V. bolus for FIRST ORDER elimination kinetics?

A

Linear

59
Q

What is the shape of the curve in log plasma conc. vs time plot after I.V. bolus for ZERO ORDER elimination kinetics?

A

Non-linear

60
Q

What is the relationship between elimination rate and drug concentration in FIRST ORDER elimination kinetics?

A

Elimination rate is PROPORTIONAL to drug concentration

61
Q

What is the relationship between elimination rate and drug concentration in ZERO ORDER elimination kinetics?

A

Elimination rate SATURATES with higher drug concentration

62
Q

What is the term for FIRST ORDER kinetics in Clinical Pharmacology?

A

Linear Kinetics

63
Q

What is the term for ZERO ORDER kinetics in Clinical Pharmacology?

A

Non-Linear Kinetics

64
Q

What is a concern for FIRST ORDER elimination kinetics?

A

95% of drugs, at therapeutic concentrations

65
Q

What is a concern for ZERO ORDER elimination kinetics?

A

Remaining 5% of drugs, and ethanol

PT3001: Introduction to Pharmacology (18 decks)

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