CPTP 3.14 - Drugs in Inflammation, Allergy and Pain 1

Question 1

Name 5 Non-opiod analgesic drugs?

Answer 1

Ibuprofen
Paracetamol
Diclofenac
Naproxen
Aspirin

Question 2

Name the four eicosanoids?

Answer 2

Prostaglandins (PGE2 and PGF2)
Prostacyclin (PGI2)
Thromboaxane (TXA2)
Leukotriene

Question 3

Which tissues synthesise eicosanoids?

Answer 3

Virtually all

Question 4

Eicosanoids are synthesised by which molecule and via which pathways?

Answer 4

Arachadonic acid

1. cycooxygenase
2. lipoxygenase

Question 5

Describe eicosanoid synthesis?

Answer 5

Phospholipids converted to arachadonic acid (via phospholipase A2)
Arachadonic acid converted to PGH2 (via cyclooxygenase I/II) OR converted to leukotriene (via lipoxygenase)

Question 6

How is PGH2 converted to its five derivative eicosanoid molecules?

Answer 6

Prostacylin synthase = PGI2
Thromboaxane sythase = TXA2
PGE2 isomerase = PGE2
PGD2 synthase = PGD2
PGF2-a reductase (uterine and vascular walls) = PGF2-a

Question 7

Which two chemicals stimulate pain endings in the skin?

Answer 7

Serotonin 5HT

Kinins (bradykinin)

Question 8

Describe the relationship between prostanoids and pain?

Answer 8

Prostanoids ENHANCE the pain producing effects of other agents - they DO NOT themselves cause pain
Prostanoids released in inflammation sensitise c-fibres

Question 9

Describe prostanoid function?

Answer 9

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

Question 10

What are the general functions of NSAIDs?

Answer 10

Inhibit cyclooxygenase enzyme (inhibiting prostanoid function) therefore prevent vasodilation/Increased vascular permeability/Pain

Question 11

Describe the expression of COX1 and COX2?

Answer 11

COX1 - constitutive (always on)

COX2 - inducible (only on with inflammation)

Question 12

Describe the tissue expression of COX1 and COX2?

Answer 12

COX1 - ubiquitous (high in G.I)

COX2 - Inflamed and activated tissues only

Question 13

How is fever initiated?

Answer 13

IL-1 releases prostaglandins (PGE2 and PGF2) into CNS where they elevate the hypothalamic set point for temperature control

Question 14

Why don’t anti-inflammatory drugs have any effect on chronic inflammation?

Answer 14

Although prostaglandin and prostacyclin levels are reduced = decreased vasodilation and oedema - the drugs can’t prevent the recruitment of more inflammatory mediators

Question 15

Name four side effects associated with NSAIDs?

Answer 15

G.I disturbances (inhibition of COX1 = PGE2 inhibition = increased acid secretion)
Toxic epidermal necrosis
Renal insufficiency
Allergy

Question 16

In order of increasing COX1 selectivity name 4 NSAIDs?

Answer 16

Celecoxib (COX2)
Naproxen
Ibuprofen
Aspirin

Question 17

Describe the basic pharmacology of aspirin (four)?

Answer 17

Irreversibly acetylates (antagonises) COX1
Inhibits NFkB expression (pro-inflammatory cytokine)
Mostly absorbed in the ileum
Rapidly hydrolysed into salicylate

Question 18

Describe the basic pharmacology of Ibuprofen and naproxen?

Answer 18

Competitive inhibitors of COX1 and COX2
Naproxen directly inhibits leukocyte function
Extensively plasma protein bound

Question 19

Describe the basic pharmacology of celecoxib?

Answer 19

Only blocks COX2
Competitive inhibitor
Lipophilic and thus accumulates within the fat compartments

Question 20

What is the metabolite of serotonin (5HT)?

Answer 20

5H1AA

Question 21

How do headaches occur?

Answer 21

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

Question 22

What is pizotifen?

Answer 22

5HT2 Antagonist for migraine PROPHYLAXIS

Question 23

What is Sumatriptan?

Answer 23

5HT1B/D/F AGONIST for migraine ATTACK