Brainscape's Knowledge GenomeTM

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


See full index

Metabolism > Drug metabolism > Flashcards

Drug metabolism Flashcards

0
Q

What is pharmacokinetics?

A
  • The time course of drugs and its metabolites in the body, i.e. what the body does to the drug
  • ADME -> absorption, distribution, metabolism, elimination
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
1
Q

What is pharmacodymanics?

A

-How the drug works, i.e. what the drug does to the body

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

What is the overall aim of the body’s drug metabolism?

A

-To deactivate and eliminate

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

Why is elimination a problem in drug metabolism?

A

-Majority of drugs are lipid-soluble so they are not readily excreted in the urine (always reabsorbed in the tubules) so need to be made water-soluble

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

What is the aim of the first phase of drug metabolism?

A

-To expose/add a reactive group on the parent molecule in order to produce a reactive metabolite

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

What are the three main types phase 1 reactions?

A
  • Oxidation
  • Reduction
  • Hydroxylation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is required in phase 1 of drug metabolism?

A
  • Cytochrome P450 enzyme system

- NADPH

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

Give an example of phase I metabolism

A

-Diamorphine-> hydroxylation breaks ester bonds producing morphine

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the main location of phase I drug metabolism?

A

-Hepatocytes in the liver (contain microsomes)

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

What are the other locations of phase I drug metabolism besides the liver?

A
  • GI tract
  • Kidneys
  • Lungs
  • Plasma
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

When giving drugs metabolised in the GI tract, what needs to be altered?

A

-Increase the dosage

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

What metabolic reaction occurs in the plasma for phase 1 drug metabolism?

A

-Hydrolysis of ester bonds through cholinesterases

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

What is the ultimate aim of phase II metabolism?

A

-Elimination of the drug

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

What happens in phase II drug metabolism?

A

-Conjugation: The reactive derivative is conjugated with a polar molecule to form a water-soluble complex which can be excreted in urine

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

What is the most common conjugate used in phase II metabolism and why?

A

-Glucaronic acid because it is a very polar molecule which is freely available due it being a by-product of metabolism

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

What other conjugates, apart from glucaronic acid, can be used in phase II metabolism?

A
  • Suplhate ions

- Glutathione

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

What is conjugation with glucaronic acid in phase II drug metabolism known as?

A

-Glucaronidation

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

What is required in order for conjugation to occur in phase II metabolism?

A
  • Specific enzymes

- High energy co-factor, typically UDP

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

Why is UDP required in phase II drug metabolism?

A

-To provide energy to transfer glucaronic acid onto reactive metabolite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Which cyp enzyme is responsible for 55% of drug metabolism?

A

-CYP3 A4

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

What is meant by the CYP P450 enzymes being inducible?

A

-Certain drugs will increase the synthesis of certain enzymes and certain drugs will inhibit the production of certain enzymes

21
Q

What are gene polymorphisms a problem in drug metabolism?

A
  • Certain people with a certain gene polymorphisms may metabolise a drug more slowly/quickly
  • eg, gene polymorphisms for acetylation may mean that the patient will be slow acetylators and therefore metabolise the drug slower
22
Q

When can gene polymorphisms of drug metabolism become a problem in surgery?

A
  • Patient may have polymorphism which produces low amount of plasma cholinesterases
  • Suxamethonium is a muscle relaxant given in anaesthetic
  • normally lasts 15 mins but can last hours in these patients
23
Q

Why can some drugs enter phase II metabolism immediately?

A

-Already have reactive group

24
Q

What environmental factors can involve with drug metabolism?

A
  • Enzyme levels are not fixed, influenced by lifestyle
  • Some CYP enzymes can be induced through drinking/smoking/barbituates resulting in quicker drug metabolism -> problem for surgery
  • Some CYP enzymes can be inhibited through food and drink -> cranberry/grapefruit juice interferes with metabolism of cimetidine (gastric ulcer treatment)
25
Q

What is enzyme inhibition in drug metabolism?

A

-One drug inhibits the metabolism of another drug

26
Q

What is enzyme induction in drug metabolism?

A

-One drug induces the enzymes needed for metabolism of another drug

27
Q

When can enzyme inhibition/induction be a problem in drug metabolism?

A

-Polytherapy

28
Q

Where does phase II drug metabolism occur?

A

-Liver

29
Q

Describe paracetamol metabolism at therapeutic levels

A
  • Metabolised by phase II

- Conjugation with glucaronic acid/sulphate

30
Q

Describe paracetamol metabolism at toxic levels

A
  • Glucaronidation/sulphation becomes saturated
  • Paracetamol enters phase I metabolism
  • Metabolised to NAPQI which is toxic to hepatocytes
  • Undergoes conjugation with glutathione
31
Q

Why is paracetamol conjugation with glutathione a problem?

A
  • Depletes glutathione stores
  • Cells become vulnerable to ROS
  • Leads to destruction of liver cells
  • Leads to liver failure (can take 1 week)
32
Q

What is the treatment for paracetamol overdose?

A
  • N-acetyl-cysteine to provide protection against ROS
  • Must be injected intravenously within a time window before the liver becomes too necrosed
  • If too necrosed transplant is only option
33
Q

How can alcohol be excreted other than metabolised?

A

-Breathed out

34
Q

What is phase I of alcohol metabolism?

A

-Alcohol is oxidised to acetoaldehyde by alcohol dehydrogenase and CYP2 E1

35
Q

What is phase II of alcohol metabolism?

A

-Acetoaldehyde oxidised to acetate by aldehyde dehydrogenase

36
Q

What happens to acetate produced from alcohol metabolism?

A

-Converted to acetyl CoA

37
Q

Why is alcohol metabolised quicker the more a person drinks?

A

-CYP2 E1 is inducible

38
Q

Where is alcohol metabolised?

A

-Liver

39
Q

Why is acetoaldehyde removed so quickly?

A

-Aldehyde dehydrogenase has very high affinity

40
Q

What are the product results of prolonged drinking?

A
  • Increased AcetylCoA
  • Increased acetoaldehyde
  • Decreased NAD+/NADH ratio
41
Q

Why is NAD+ dercreased from long term drinking?

A

-Used as a cofactor in alcohol metabolism

42
Q

What effects does decreased NAD+ have on the body, in releation to the liver?

A
  • Inadequate levels for b-oxidation
  • inadequate levels for lactate conversion to pyruvate
  • Inadequate levels for glycerol metabolism
43
Q

How does increased drinking lead to fatty liver?

A

-Increased acetyl coA produced which are converted to TAGs and not transported due to insufficient lipoprotein synthesis so are stored in the liver

44
Q

How does gout occur in alcoholics?

A
  • Increased lactate due to decreased conversion to pyruvate due to lack of NAD+
  • Reduces kidneys ability to excrete uric acid
  • Crystal deposition in the kidneys leads to gout
45
Q

Why can lactic acidosis occur in alcoholics?

A
  • Decreased NAD+ due to use in alcohol metabolism

- Lactic acid builds up leading to acidosis

46
Q

Why can fasting hypoglycaemia occur in alcoholics?

A
  • Decreased gluconeogenesis from glycerol due to insuffcient NAD+
  • Poor diet so low glycogen store
47
Q

What are the toxic effects of acetoaldehyde?

A
  • Damaged hepatocytes-> leaky pm-> loss of enzymes (transaminases and gamma glutamyl transpeptidases)-> defective N metabolism resulting in hyperammonia
  • Hyperbilirubinaemia/jaudice-> decreased ability to conjugate and clear bilirubin
  • Low serum albumin potentially causing oedema
  • Reduced clotting factor production increasing clotting time
48
Q

What is the rate of alcohol metabolism?

A

-7g/hr (8g pure ethanol in one unit)

49
Q

What are the direct effects of acetaldehyde on the GI tract?

A
  • loss of appetite
  • Diarrhoea
  • Impaired absorption of nutrients
50
Q

What nutrient deficiences are associated with alcoholics?

A
  • Wernickle-Korsakoffe syndrome-> malabsorption of thiamine

- Anaemia-> malabsorption of folic acid

51
Q

What are the treatments for alcoholism?

A
  • Mental heath councilling and support

- Disulfram -> aldehyde dehydrogenase inhibitor-> build up produces a direct toxic effects on GI that last for a week

Metabolism (14 decks)

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