Anti-Inflammatory Drugs Flashcards

1
Q

What are examples of immune mediators?

A
Cytokines (interleukins, interferon, TNF-alpha)
Chemokines (IL-8, MCP-1)
Colony-stimulating factors (GM-CSF)
Adhesion molecules (ICAM-1, integrins)
Eicosinoids (Prostaglandins)
Endocrine (steroids, catecholamines)
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2
Q

How do steroids act?

A

Via intracellular receptors to regulate gene transcription.

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3
Q

What is a glucocorticoid?

A

An adrenal steroid that have immuno-suppressive effects.

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4
Q

How is the glucocorticoid receptor activated?

A

By cortisol and aldosterone.

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5
Q

The glucocorticoid receptor also interferes with what major inflammation-associated transcription factor?

A

NF-kB

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6
Q

List the pro-inflammatory genes that are down regulated by glucocorticoids.

A
  • pro-inflam cytokines
  • COX-2
  • Phospholipase A2 (PLA2)
  • Cell adhesion molecules
  • Endothelins
  • Inducible nitric oxide synthase (iNOS)
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7
Q

What are genes that are up regulated by glucocorticoids?

A
  • IL-10/IL-4 (anti-inflam cytokines)

- Lipocortins/annexins (PLA2 inhibitor)

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8
Q

What are different routes for glucocorticoids?

A

Oral: Prednisone, dexamethasone
Inhalable: Fluticasone (Flixanase)
Topical: Prednisone, dexamethasone (deep heat)

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9
Q

In summary, what are steroidal drugs good for?

A

General anti-inflam drugs, BUT can have serious side effects.

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10
Q

What do NSAIDs do?

A

They inhibit prostaglandin (PFH2) biosynthesis via COX enzymes, thus they bock the enzymatic activity of COX.

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11
Q

Name 4 common NSAIDs.

A
  1. Aspirin
  2. Ibuprofen
  3. Diclofenac
  4. Naproxen
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12
Q

What does COX convert arachidonic acid into?

A

Prostaglandin H2

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13
Q

What does Aspirin do?

A

It irreversibly inhibits COX-1, so is an effective inhibitor of PG-mediated pain.

It also inhibits TXA2 release by platelets (anti-thrombotic)

Usually for migraine

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14
Q

What does Paracetamol do?

A

Good for fever and pain relief.

It reduces PG synthesis but is a pretty weak inhibitor of COX-1 and COX-2.

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15
Q

Where is Paracetamol metabolised?

A

Liver, into a toxic intermediate which can cause damage.

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16
Q

What is the therapeutic index?

A

Very low. 10x the adult dose can be fatal.

17
Q

What are some adverse effects of NSAIDs?

A

Gastric ulcers
Renal complications
Early pregnancy loss

18
Q

What is the concept behind COX-2 selective inhibitors?

A

To selectively inhibit COX-2 (pain and inflamm) while leaving COX-1 (maintenance/protective) uninhibited.

SO design drug with high affinity to COX-2 only.

19
Q

What are 2nd generation NSAIDs?

A

COX-2 selective inhibitors.

e.g. Celecoxib, Rofecoxib

20
Q

What are the advantages of 2nd generation NSAIDs?

A

Reduced GI irritation and ulcer rate (similar efficacy to non-selective NSAIDs)

can use long term for chronic conditions

short term pain relief for some

21
Q

What are some unexpected adverse effects of COX-2 selective inhibitors?

A
  • CV events
  • Rofecoxib: increased risk of thrombotic events
  • increased BP
  • renal impairment