Brainscape's Knowledge GenomeTM

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


See full index

BMS 242 - Core Phys/pharm > Anti- inflammartories I > Flashcards

Anti- inflammartories I Flashcards

1
Q

3 examples of anti-inflammatory and immunosuppressant drugs?

A

1) NSAIDs (inc. coxibs)
2) Antirheumatic drugs
3) Biologicals (biopharmaceuticals)

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

What are NSAIDs?

Examples?

A

Non-steroidal anti-inflammatory drugs

Including:

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

What is special about the bark of the willow tree?

A

Fever lowing (antipyretic) and pain lowering (analgesic)

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

What is the precursor of aspirin and isolated it discovered it and when?

A

Salicylic acid

Isolated by Henry Leroux in 1828

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

What did Felix Hoffmann do?

A

Added an ester group to salicylic acid - making acetyl salicylic acid

  • Gave the drug to his grandfather
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which was more tolerated, salicylic acid or acetyl salicylic acid?

A

Acetyl salicylic acid

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

What do NSAIDs provide? (3)

A
  • Pain relief
  • Lower fever
  • Some reduce swelling
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the action of NSAIDs?

A

They inhibit the production of certain inflammatory meditators by inhibiting the CYLCOOXYGENASE enzymes which lead to the production of PROSTANOIDS

This inhibits the production of PROSTAGLANDINS and THROMBOXANES

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

What are inflammatory mediators an example of?

A

Paracrine mediators

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

What are paracrine mediators?

A

Produced by one cell and interact with other cells
Can interact with:
- The same type of cell
- Different types of cell

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

What are prostanoids?

A

Prostanoids are a subclass of molecules consisting of:

1) Prostaglandins
2) Thromboxanes
3) Prostacyclins

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

What are prostaglandins mediators of?

A

Inflammatory and anaphylatic reactions

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

What are thromboxanes mediators of?

A

Vasoconstriction and clot formation

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

What are prostacyclins and what are they mediators of?

A

They are a PROSTAGLANDIN member

Mediators of:

  • Inhibition of platelet aggregation
  • Vasodilation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the process for formation of inflammatory mediators?

A

1) Phospholipase A2 enzyme in the plasma membrane creates an intermediates from phospholipids - ARACHIDONATE
2) Aracadonate is the substrate of CYCLOOXYGENASE
3) Leads to the production of prostaglandins, prostacyclins and thromboxanes (PROSTANOIDS)

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

What determines what mediators are made?

A

Which ENZYMES are expressed in a particular tissue

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

What is COX?

A

Cyclo-oxygenase

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

What prostaglandins are made as a result of the COX pathway?

What are their functions?

A

PGD2 - Vasodilator and inhibitor of platelet aggregation

PGE2 - Vasodilator and hyperalgesic (increase pain signalling) and HYPERPYRETIC

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

What prostacyclins are made as a result of the COX pathway?

What is its function?

A

PGI2

  • Vasodilator
  • Inhibit platelet aggregation
  • Hyperalgesic (increase pain sensitivity)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What thromboxanes are made as a result of the COX pathway?

What is its function?

A

TXA2

  • Thrombotic (cause clot formation)
  • Vasoconstrictor
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens if cyclo-oxygenase is inhibited by NAIDs?

A

Inhibit the functions of the prostanoids (prostaglandins, prostanoids, thromboxanes):

1) Anti-inflammatory
2) Analgesic
3) Antipyretic

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

What does algesic relate to?

A

Sensitivity of pain

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

What does pyretic relate to?

A

Fever (temperature)

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

How are NSAIDs anti-inflammatory?

A
  • Inhibit prostanoids (PGI2, PGE2)

- Inhibit VASODILATION and ODEMA (swelling an bruising)

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

What are NSAIDs ineffective against?

Why?

A

Mediators that contribute to tissue damage associated with CHRONIC INFLAMMATION

These mediators AREN’T prostanoids (NSAIDs are only affective with prostanoids)

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

How do NSAIDs reduce pain sensitivity?

A

Inhibit prostanoids (PGI2 and PGE2)

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

How does PGI2 (prostacyclin) usually cause pain sensitivity?

A

1) Released in area of tissue damage
2) Feeds onto nerve endings - activating GPCR
3) Sensitises nociceptive receptors to inflamaory mediators such as bradykinins and 5-HT

28
Q

How doe NSAIDs reduce temperature/fever?

A

Prevent production of IL-1 which causes the release of PGE2 which activates the thermostat in the hypothalamus and increases the temperature of the body

29
Q

How are headaches controlled?

Why?

A

Anti-inflammatory mechanisms!!

Caused by vasodilation of the blood vessels of the brain

30
Q

What is the structure of COX (cyclo-oxygenase)?

A
  • 2 identical subunits, each with a catalytic active site

- Forms a CHANNEL where arachidonate goes through

31
Q

What is the substrate of COX?

What happens to this as is passes through the COX enzyme?

A

Arachindonate (precursor of prostanoid)

As passes through enzyme - undergoes 2 catalytic reactions which lead to prostaglandin synthesis

32
Q

Where are COX enzymes situated?

A

In the endoplasmic reticulum membrane (INTRACELLULAR)

33
Q

What are the different isoforms of COX?

A

COX1

COX2

COX3 (a spliced variant of COX1)

34
Q

What is the differences between COX1 and COX2?

A

COX1:

  • Expressed all the time in a vast majority of cells (constitutive expression)
  • ISOLEUCINE amino acid

COX2:

  • Inducible - expression is tightly regulated by certain triggers
  • VALINE amino acid (has a smaller side chain than isoleucine)
  • Therefore pore in COX2 is larger than in COX1
  • Quick acting and switched off quickly too
35
Q

Which COX isoform is expressed in the kidney and colon?

A

COX1

36
Q

What is the function of COX1?

A

House-keeping:

  • Involved in homeostasis
  • Produces prostaglandins involved in platelet aggregation and mucus secretion (to protect the stomach and GI tract)
37
Q

What can taking chronic aspirin cause and why?

How can this be overcome?

A

Ulceration of the stomach and GI tract as it prevents COX1 from functioning (which makes prostaglandins involved in making mucus)

Can be overcome by developing drugs which are selective to COX2

38
Q

What is COX2 expression triggered by?

A

Inflammation, cytokines and growth factors

39
Q

What do NSAIDs inhibit?

A

BOTH COX1 and COX2

40
Q

What are examples of where COX2 is expressed?

A

Kidney and CNS

41
Q

What is COX3 and where is it expressed?

What exerts its action here

A

A spliced variant of COX1

Expressed largely in the brain

Where PARACETAMOL exerts its action

42
Q

Which drugs are more selective to COX2?

Examples?

A

COXIBS:

Celecoxib
Etoricoxib
Rofecoxib

43
Q

What is more selective to COX1, aspirin or ibuprofen?

A

Aspirin

44
Q

What type of drugs are coxibs?

A

Non-steroidal anti-inflmmatories

COX2 selective inhbitors

45
Q

How can drugs be more selective to COX2 than COX1?

A
  • Pore in COX2 is larger due to the isoleucine –> valine amino acid switch
  • Therefore drugs can be too big to fit in COX1 but small enough to fit in COX2
46
Q

What are the side effects of NSAIDs in the gut?

Why?

A
  • Dyspepsia (indegestion)
  • Diarrhoea
  • Nausea
  • Vomiting
  • Gastric bleeding
  • Ulceration

Due to preventing prostanoids which protect the gut with mucus and PREVENT ACID SECRETION

47
Q

What is normally prescribed with high doses of NSAIDs to prevent ulceration?

A

Analogue of prostaglandins (misoprostol)

48
Q

What are some side effect of NSAIDs?

A

1) Renal faliure
2) Problems in the gut
3) Bronchospasms
4) Skin rashes
5) Liver damage
6) Bleeding disorder

49
Q

Why can NSAIDs cause renal faliure?

A

Prostanoids are involved in maintaining renal blood flow

50
Q

Which NSAID can cause liver damage and how?

A

High doses of paracetamol

  • Forms a toxic intermediate after phase 1 reaction, which normally undergoes glucuronidation to prevent it
  • However, in large doses - GLUCAONIDASE enzyme is overloaded, so the phase 2 reaction cannot occur
  • High conc of toxic intermediate
51
Q

Why can NSAIDs cause a bleeding disorder?

When is this prevalent?

A

NSAIDs prevent thromboxaines, which usually work at the level of platelets to cause clots

Prevalent in patients taking Warfarin (already reduces blood clotting)

52
Q

What are the advantages of COX1 selective NSAIDs?

A

Favoured because of its actions on platelets - good for people at risk of thrombosis

53
Q

What are the advantages of COX2 selective NSAIDs?

A
  • Less side effects

- Reduces pain associated with inflammation

54
Q

What are the limitations of using COX1 selective NSAIDs?

A

Have to asses the overall health of the patients (ulcers etc)

55
Q

What are the limitations of using COX2 selective NSAIDs?

A

COX2 is important in the kidneys

56
Q

In some people, what can COX2 inhibition cause?

A

Cardiac complictations

57
Q

Why is aspirin a ‘suicide inhibitor’? (process of inhibition)

A

1) Converts back to salicylic acid in the body
2) Interacts with SERINE residues in the COX enzymes to form a COVALENT bond
3) COX enzyme becomes PERMANENTLY inactive
4) Have to synthesise a NEW enzyme to overcome the effects of the aspirin

58
Q

What is the time taken for aspirin to wear off proportional to?

A

The time taken for the body to re-synthesise new COX enzymes, which have been permanently inactivated by salicylic acid interacting with the serine residues in the enzyme

59
Q

What does paracetamol target?

A

COX3 enzymes in the brain

60
Q

Describe the absorption of aspirin

A

Rapid and efficient in the ileum

61
Q

What does the use of aspirin reduce?

A

Colonic and rectal cancer

Alzhemier’s

Thrombosis (has anti-platelet action)

62
Q

What are the actions of paracetamol? Why?

A

Analegesic and antipyretic

Due to its actions in the CNS

63
Q

What is paracetamol not good at?

A

Reducing inflammation

64
Q

With long term use, which has fewer side-effects; aspirin or paracetamal?

A

Paracetamol

65
Q

How is aspirin made?

A

Bark of willow tree –> salycilic acid –> add ester group –> acetyl salycilic acid (aspirin)

BMS 242 - Core Phys/pharm (13 decks)

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