Flashcards in CPTP 3.14 Drugs used in Inflammation Allergy and Pain 2 Deck (55)
Name the analgesic drugs (non-opioid)
NSAIDs (mnemonic = NCAIDs)
What are compound analgesics?
Analgesics made from a combination of two drugs, usually:
Recall the eicosanoids. Which of these are prostanoids?
What are the main prostaglandins?
What is prostacyclin also called?
What is the main thromboxane?
What are the main leukotrienes?
When are local hormones such as the eicosanoids made?
They're not pre-formed but generated in response to stimuli in all tissues
What are eicosanoids made from? Through which two pathways?
• Cyclooxygenase (1 or 2) pathway
• Lipoxygenase pathway
How is arachidonic acid made?
From phospholipids in the plasma membrane by Phospholipase A2
What do the cyclooxygenase and lipoxygenase enzymes produce from arachidonic acid?
• PGH2 (prostaglandin H2 is an INTERMEDIATE)
What happens to PGH2?
It is immediately acted on by various enzymes
• Prostacyclin (from prostacyclin synthase)
• Thromboxane (from thromboxane synthase)
What effects does prostacyclin have?
• Potent vasodilator
• Inhibits platelet aggregation
What effects does thromboxane have?
• PROMOTES platelet aggregation
How do thromboxane and prostacyclin usually operate?
They are antagonists, and are in a homeostatic balance, controlling local blood tone and platelet aggregation
Which enzymes produce the prostaglandins? Which tissues are these produced in?
• PGE2 isomerase
• All tissues
• PGD2 synthase
• Mast cells
PGF2a (F=flow and fucking)
• PGF2a reductase
• Vascular smooth muscle
• Uterine smooth muscle
Which product of phospholipids are the targets of analgesic drugs?
PGE2 because it potentiates responses to pain.
Recall the local hormone substances which stimulate pain
• Bradykinin (and other kinins)
• Prostaglandin E2
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
What are the prostanoid functions on:
2) Vascular permeability?
1) Vasodilators, have synergy with:
2) Potentiate the following substances: (no effect on their own)
3) Potentiate the sensitising effects of bradykinin on C-fibres (except PGE2 which directly sensitises it)
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
What is the mechanism of action of NSAIDs?
They inhibit the cyclooxygenase enzymes thus preventing the production of prostanoids (IMG 8)
Compare COX-1 and COX-2:
• Ubiquitously expressed (all tissues) and constitutive (always present and with some basal activity)
• Protection and maintenance
• Inducible, not normally present, seen in inflamed and activated tissues
• Pro-inflammatory functions and sensitisation
What induces COX-2?
• IL-1 and IL-2
Which drugs act on COX-1 and COX-2?
• Classic NSAIDS
• Classic NSAIDS
• COX-2 inhibitors
What three main effects do COX-inhibitors such as NSAIDs have?
• The decrease in PGE2 decreases vasodilation and permeability
• There is less PGE2 to sensitise neurones
• Prevents prostaglandins increasing the set point for temperature control
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
What are NSAIDs best used for?
Acute inflammation to reduce the sensitising effects, in those conditions associated with increased prostanoid synthesis:
• Postpartum pain
• Muscular or vascular pain
What can NSAIDs be used with?
Opioids or paracetamol