CPTP 3.14 Drugs used in Inflammation Allergy and Pain 2 Flashcards Preview

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Flashcards in CPTP 3.14 Drugs used in Inflammation Allergy and Pain 2 Deck (55)
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1

Name the analgesic drugs (non-opioid)

NSAIDs (mnemonic = NCAIDs)
• Naproxen
• Celecoxib
• Aspirin
• Ibuprofen
• Diclofenac

Paracetamol

2

What are compound analgesics?

Analgesics made from a combination of two drugs, usually:
• Paracetamol
• Aspirin
• Codeine

3

Recall the eicosanoids. Which of these are prostanoids?

Prostanoids:
• Prostaglandins
• Prostacyclin
• Thromboxanes
Others:
• Leukotrienes

4

What are the main prostaglandins?

• PGE2
• PGD2
• PGF2a

5

What is prostacyclin also called?

PGI2

6

What is the main thromboxane?

TXA2

7

What are the main leukotrienes?

• LTB4
• LTC4
• LTD4

8

When are local hormones such as the eicosanoids made?

They're not pre-formed but generated in response to stimuli in all tissues

9

What are eicosanoids made from? Through which two pathways?

(IMG 8)

Arachidonic acid
• Cyclooxygenase (1 or 2) pathway
• Lipoxygenase pathway

10

How is arachidonic acid made?

From phospholipids in the plasma membrane by Phospholipase A2

11

What do the cyclooxygenase and lipoxygenase enzymes produce from arachidonic acid?

(IMG 8)
Cyclooxygenase:
• PGH2 (prostaglandin H2 is an INTERMEDIATE)

Lipoxygenase
• Leukotrienes

12

What happens to PGH2?

(IMG 8)
It is immediately acted on by various enzymes

• Prostaglandins
• Prostacyclin (from prostacyclin synthase)
• Thromboxane (from thromboxane synthase)

13

What effects does prostacyclin have?

• Potent vasodilator
• Inhibits platelet aggregation
• Hyperalgesic

14

What effects does thromboxane have?

• Vasoconstrictor
• PROMOTES platelet aggregation

15

How do thromboxane and prostacyclin usually operate?

They are antagonists, and are in a homeostatic balance, controlling local blood tone and platelet aggregation

16

Which enzymes produce the prostaglandins? Which tissues are these produced in?

PGE2 (E=everywhere)
• PGE2 isomerase
• All tissues

PGD2 (D=decisions)
• PGD2 synthase
• Mast cells
• Neurones

PGF2a (F=flow and fucking)
• PGF2a reductase
• Vascular smooth muscle
• Uterine smooth muscle

17

Which product of phospholipids are the targets of analgesic drugs?

PGE2 because it potentiates responses to pain.

18

Recall the local hormone substances which stimulate pain

• Serotonin
• Bradykinin (and other kinins)
• Prostaglandin E2

19

What do sensitising local hormones do to pain sensation?

They sensitise the pain response to stimuli, but do not alone cause it:
allodynia and hyperalgesia

20

What are the prostanoid functions on:

1) Vasodilation?
2) Vascular permeability?
3) Pain?

1) Vasodilators, have synergy with:
• Histamine
• Bradykinin

2) Potentiate the following substances: (no effect on their own)
• Histamine
• Bradykinin

3) Potentiate the sensitising effects of bradykinin on C-fibres (except PGE2 which directly sensitises it)

21

How do prostanoids potentiate the effects of histamines and bradykinin in increasing vascular permeability?

The vasodilation caused by prostaglandins facilitates these mediators to increase the permeability

22

What is the mechanism of action of NSAIDs?

They inhibit the cyclooxygenase enzymes thus preventing the production of prostanoids (IMG 8)

23

Compare COX-1 and COX-2:
• Expression
• Role

COX-1:
• Ubiquitously expressed (all tissues) and constitutive (always present and with some basal activity)
• Protection and maintenance

COX-2
• Inducible, not normally present, seen in inflamed and activated tissues
• Pro-inflammatory functions and sensitisation

24

What induces COX-2?

Cytokines:
• LPS
• TNFa
• IL-1 and IL-2
• IFNy

25

Which drugs act on COX-1 and COX-2?

COX-1
• Classic NSAIDS

COX-2
• Classic NSAIDS
• COX-2 inhibitors

26

What three main effects do COX-inhibitors such as NSAIDs have?

Anti-inflammatory
• The decrease in PGE2 decreases vasodilation and permeability

Analgesic
• There is less PGE2 to sensitise neurones

Antipyretic
• Prevents prostaglandins increasing the set point for temperature control

27

What are the shortcomings of NSAIDs when used to treat chronic inflammatory diseases such as rheumatoid arthritis? Which drugs would be needed for this?

They have no effect on processes that contribute to the tissue damage in chronic inflammatory diseases as they cannot prevent the recruitment of inflammatory cells (they're still used for pain relief though)

Corticosteroids would be needed for this

28

What are NSAIDs best used for?

Acute inflammation to reduce the sensitising effects, in those conditions associated with increased prostanoid synthesis:
• Toothache
• Postpartum pain
• Dysmenorrhoea
• Muscular or vascular pain

29

What can NSAIDs be used with?

Opioids or paracetamol

30

What is the purpose of using opioids with NSAIDs together

The process of 'opioid sparing'. Opioids are very potent pain-relievers, however they have many adverse side effects, especially at higher doses:
• Constipation
• Drowsiness
• Withdrawal/addiction

Therefore, to reduce the likelihood of these in post-OP or severe pain, a combination can be given, which strikes a balance between pain relief and loss of side-effects