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
