Anti-inflammatories

Question 1

What is the precursor to histamine?

Answer 1

Histadine

Question 2

What are the roles of histamine?

Answer 2

Tissue repair
inflammation
vasodilation
allergic/anaphylactic reactions

Question 3

Where is histamine found?

Answer 3

In mast cells

Question 4

Where are mast cells produced?

Answer 4

Bone marrow

Question 5

What is the IgE receptor on mast cells?

Answer 5

FcER1

Question 6

How does mast cell degranulation occur?

Answer 6

Exposure to allergen creates IgE antibodies which bind to mast cells
second exposure to mast cells bind to IgE on mast cell surface and activates mast ecll

Question 7

What can inhibit histamine release?

Answer 7

cAMP

Question 8

What is the main histamine receptor called?

Answer 8

H1

Question 9

What does the H1 receptor cause?

Answer 9

Systemic vasodilation
increased vascular permeability
itching

Question 10

What are used to treat allergies?

Answer 10

H1 receptor antagonists

Question 11

What are the two types of H1 receptor antagonists?

Answer 11

1st gen - shorter generation, cross blood brain barrier

2nd gen - longer, dont cross

Question 12

What do H2 receptors do?

Answer 12

Inhibit gastric acid secretion

treat gastric ulcers

Question 13

What is used to treat anaphylaxis?

Answer 13

Adrenaline

Question 14

What are eicosanoids generated from and when?

Answer 14

Phospholipids, on demand rather than stored

Question 15

What is the intermediate form of eicosanoids?

Answer 15

Arachidonic acid

Question 16

What is the enzyme which changes phospholipids into arachidonic acid/eicosanoids?

Answer 16

Phospholipase A2

Question 17

What are the 3 eicosanoids?

Answer 17

Prostaglandins
Thromboxanes
Leukotrienes

Question 18

What can stimulate phospholipase A2?

Answer 18

Bradykinin
Mast cells
thrombin
complement
cell damage

Question 19

Which prostaglandins are involved in inflammation?

Answer 19

PGE2 and PGI2

Question 20

What converts arachidonic acid to prostaglandins?

Answer 20

Cyclooxygenase

Question 21

What are the two isoforms of cyclooxygenase?

Answer 21

COX1 and COX2

Question 22

What is the difference between COX1 and COX2?

Answer 22

1 is normally expressed in most cells

2 is not normally present, induced by inflammation

Question 23

What is significant about cyclooxygenase?

Answer 23

It is the target of corticosteroids and NSAIDS

Question 24

What effect does PGE2 and PGI2 have on vascular smooth muscle?

Answer 24

Relaxation

Question 25

What effect does PGE2 have on bronchial muscle?

Answer 25

Dilation

Question 26

What other effects do prostaglandins have on the body?

Answer 26

Hyperalgesia - increased pain sensitivity | PGE2 also causes fever

Question 27

What actions do thromboxanes cause?

Answer 27

Vasoconstriction and bronchoconstriction | Induce platelet aggregation

Question 28

How is thromboxane synthesised?

Answer 28

From PGH2 | TXA2 synthase activates it

Question 29

Where is TXA2 synthase found?

Answer 29

in platelets

Question 30

What enzyme converts arachidonic acid to leukotrienes?

Answer 30

Lipoxygenase

Question 31

Where are leukotrienes produced?

Answer 31

Leukocytes, mast cells

Question 32

What do leukotrienes do?

Answer 32

activates leukocytes and cytokines | cause bronchoconstriction and vasodilation - asthma

Question 33

What are the main sources of prostaglandins?

Answer 33

Mast cells, leukocytes

Question 34

Where are glucocorticoids synthesised?

Answer 34

Zona fasciculata in the adrenal gland

Question 35

What is the main glucocorticoid in animals?

Answer 35

Corticosterone (cortisol)

Question 36

What causes glucocorticoid release?

Answer 36

Hypothalamus releases CRF - corticotrophin releasing factor | Anterior pituitary releases ACTH

Question 37

What is the pattern of glucocorticoid release?

Answer 37

Pulsetile

Question 38

What do glucocorticoids cause?

Answer 38

Increased or decreased gene transcription Hyperglycaemia increased protein catabolism - muscle wasting redistribution of fat increased Ca2+ excretion - hypocalcaemia

Question 39

What is the condition called from reduced glucocorticoids?

Answer 39

Addisons disease

Question 40

What is the condition for excess corticosteroids called?

Answer 40

Cushing's syndrome

Question 41

What are the symptoms of cushing's disease?

Answer 41

Hyperglycaemia Muscle wasting Osteoporosis

Question 42

What effects do glucocorticoids have on inflammation?

Answer 42

Glucocorticoids decrease the expression of COX2 so cant produce prostaglandins Inhibits the early inflammatory response - good inhibits late response - bad

Question 43

What are glucocorticoids used to treat?

Answer 43

Asthma, hypersensitivity, inflammatory skin conditions

Question 44

What is bad about glucocorticoids?

Answer 44

Inhibits late inflammatory response | Supresses immune response by preventing Th cell proliferation

Question 45

What are chondroprotective drugs?

Answer 45

Provide the building blocks to make the cartilage matrix

Question 46

What is cartilage made up of?

Answer 46

Collagen Hyaluronic acid Glycosaminoglycan Proteoglycan

Question 47

What do NSAIDs do?

Answer 47

Inhibit cyclooxygenase | reduce prostaglandin and thromboxane synthesis

Question 48

What symptoms do NSAIDs treat?

Answer 48

Inflammation fever pain

Question 49

What is the binding pocket like on COX2?

Answer 49

Wider than COX1

Question 50

What are the side effects of NSIADs?

Answer 50

Gastric ulceration

Question 51

What do NSAIDs cause gastric ulceration

Answer 51

Inhibit PGE2 and PGI2 which usually protect mucosa | also inhibit platelet aggregation

Question 52

Why are NSAIDs particularly dangerous for dogs?

Answer 52

Have enterohepatic recycling from liver out in bile increases time drug is in GI tract

Question 53

What is a problem with COX2?

Answer 53

Increases sodium retention in the kidney | reduce kidney function

Question 54

How are NSAIDs metabolised?

Answer 54

Hepatic metabolism | glucouronidation - cats cant