Lecture 25- Anti-inflammatory drugs Flashcards Preview

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Flashcards in Lecture 25- Anti-inflammatory drugs Deck (15):
1

How do steroidal anti-inflammatory drugs act?

Steroids such as cortisol, progesterone act via intracellular receptors to regulate gene transcription.

2

What is the main steroid, which produces anti-inflammatory effects?

Glucocorticoids

3

How do Glucocorticoids function?

  • The glucocorticoid receptor(GR) is activated by cortisol and aldosterone.
  • Activated receptor moves from cytoplasm to nucleus and alters transcription of genes
  • GR also interferes with a major inflammation-associated transcription factor , NF-kB.

Glucocorticoid receptors are globally expressed in the body so the anti-inflammatory response will be spread throughout all cells in body.

4

Give examples of pro-inflammatory genes that are down-regulated by glucocorticoids?

  • Cytokines
  • COX-2
  • Phospholipase A2(PLA2)
  • Cell-adhesion molecules
  • Endothelins
  • Inducible nitric oxide synthase

 

5

Give examples of genes that are up-regulated by glucocorticoids?

-IL 10/Il-4

-Lipocortins

6

Give some examples of common glucocorticoids?

Oral- Dexamethasone

Inhalable-Flixotide

Topical- Prednisone

7

NSAIDS- Describe the mechanism of action of non-steroidal anti-inflammatory drugs?

NSAIDS block the enzymatic activity of cyclo-oxygenase.(COX) COX converts arachidonic acid to prostaglandin H2. So inhibiting COX inhibits prostaglandin bio-synthesis.

8

What are NSAIDS used to treat?

Pain(analgesic), inflammation and fever( anti-pyretic).

BUT can have significant side-effects. Blocking COX pathways can have serious cardiovascular, renal, gastrointestinal effects.

9

Name some of the common NSAIDS?

1. Asirin

2. Ibuprofen

3. Diclofenac

4. Naproxen

10

What are properties of aspirin as a  NSAID?

- Irreversibly inhibits COX-1

-Used for migraine

-Effective inhibitor og PG mediated pain

- Inhibits TXA2 release by platelets(anti-thrombotic)

Associated with GI problems

11

What are properties of paracetamol as a NSAID?

-Good anti-pyretic and analgesic

-Ineffective anti-inflammatory however

_Reduces prostaglandin synthesis

- Non-selective

- Metabolised in the liver to a toxic metabolite which causes liver damage.

Very low therapeutic index-requires a high dose to be lethal.

12

Why do NSAIDS cause serious adverse effects?

  • Largely due to the fact that they are NON-SELECTIVE. Ibuprofen, Naproxen, Diclofenac are all non-selective. So they can act at other receptors in the body.
  • Another reason is most are associated with COX-1 inhibition.

Side-effects- GI problems(inhibiton of COX-1 derived PGE2), renal complications,  cardiovascular effects, hepatic toxicity and pregnancy loss.

13

What do COX-2 selective inhibitors do?

They selectively inhibit COX-2 while leaving COX-1 uninhibited. It is used in chronic inflammatory diseases where COX-1 inhibiton causes problems.

Advantages

-Reduced GI irritation, ulcer rate with similar efficacy to non-selective NSAIDS.

-Useful for long-term use in treatment of chronic conditions.

-Also for good short-term pain relief

14

What were some of the COX-2 selective inhibitor drugs, that caused unwanted side-effects?

-Celecoxib- cardiovascular effects

-Rofecoxib- increased risk of thrombotic events.

Both cause increased BP and renal impairment.

-Vioxx- increased risk of CVD(heart attack and stroke).

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