CPTP 3.14 - Drugs in Inflammation, Allergy and Pain 1 Flashcards
Name 5 Non-opiod analgesic drugs?
Ibuprofen Paracetamol Diclofenac Naproxen Aspirin
Name the four eicosanoids?
Prostaglandins (PGE2 and PGF2)
Prostacyclin (PGI2)
Thromboaxane (TXA2)
Leukotriene
Which tissues synthesise eicosanoids?
Virtually all
Eicosanoids are synthesised by which molecule and via which pathways?
Arachadonic acid
- cycooxygenase
- lipoxygenase
Describe eicosanoid synthesis?
Phospholipids converted to arachadonic acid (via phospholipase A2)
Arachadonic acid converted to PGH2 (via cyclooxygenase I/II) OR converted to leukotriene (via lipoxygenase)
How is PGH2 converted to its five derivative eicosanoid molecules?
Prostacylin synthase = PGI2 Thromboaxane sythase = TXA2 PGE2 isomerase = PGE2 PGD2 synthase = PGD2 PGF2-a reductase (uterine and vascular walls) = PGF2-a
Which two chemicals stimulate pain endings in the skin?
Serotonin 5HT
Kinins (bradykinin)
Describe the relationship between prostanoids and pain?
Prostanoids ENHANCE the pain producing effects of other agents - they DO NOT themselves cause pain
Prostanoids released in inflammation sensitise c-fibres
Describe prostanoid function?
Vasodilation = redness and increased blood flow
Vascular permeability = potentiates permeability effect of histamine and bradykinin - oedema
Pain = no affect alone - potentiates effect of bradykinin by sensitising C-fibres
What are the general functions of NSAIDs?
Inhibit cyclooxygenase enzyme (inhibiting prostanoid function) therefore prevent vasodilation/Increased vascular permeability/Pain
Describe the expression of COX1 and COX2?
COX1 - constitutive (always on)
COX2 - inducible (only on with inflammation)
Describe the tissue expression of COX1 and COX2?
COX1 - ubiquitous (high in G.I)
COX2 - Inflamed and activated tissues only
How is fever initiated?
IL-1 releases prostaglandins (PGE2 and PGF2) into CNS where they elevate the hypothalamic set point for temperature control
Why don’t anti-inflammatory drugs have any effect on chronic inflammation?
Although prostaglandin and prostacyclin levels are reduced = decreased vasodilation and oedema - the drugs can’t prevent the recruitment of more inflammatory mediators
Name four side effects associated with NSAIDs?
G.I disturbances (inhibition of COX1 = PGE2 inhibition = increased acid secretion)
Toxic epidermal necrosis
Renal insufficiency
Allergy
In order of increasing COX1 selectivity name 4 NSAIDs?
Celecoxib (COX2)
Naproxen
Ibuprofen
Aspirin
Describe the basic pharmacology of aspirin (four)?
Irreversibly acetylates (antagonises) COX1
Inhibits NFkB expression (pro-inflammatory cytokine)
Mostly absorbed in the ileum
Rapidly hydrolysed into salicylate
Describe the basic pharmacology of Ibuprofen and naproxen?
Competitive inhibitors of COX1 and COX2
Naproxen directly inhibits leukocyte function
Extensively plasma protein bound
Describe the basic pharmacology of celecoxib?
Only blocks COX2
Competitive inhibitor
Lipophilic and thus accumulates within the fat compartments
What is the metabolite of serotonin (5HT)?
5H1AA
How do headaches occur?
Large arteries and veins are usually vasoconstricted - activation of 5HT1A receptors causes dilation of the intracranial arteries and veins = headache
5HT can also lead to direct vasodilation
What is pizotifen?
5HT2 Antagonist for migraine PROPHYLAXIS
What is Sumatriptan?
5HT1B/D/F AGONIST for migraine ATTACK
