CPTP 3.13 - Drugs in Inflammation

Question 1

How would Epinephrine be administered to a patient in the event of anaphylaxis?

Answer 1

Intra-muscular injection

Question 2

Name five autocoids (local hormones)?

Answer 2

Histamine
Eicosanoids
Serotonin (5HT)
Nitric Oxide (NO)
Kinins

Question 3

Name the eicosanoids?

Answer 3

Prostaglandin
Prostacyclin
Thromboaxane
Leukotrienes

Question 4

Describe four features of histamine?

Answer 4

Chemical messenger involved in the initiation of an inflammatory response
Stored within granules inside mast cells and basophils
Synthesised by ECL cells in mucosa
synthesised by tuberomamillary nucleus in the brain

Question 5

What actions are elicited by histamine binding to its receptors?

Answer 5

H1 - mediates inflammation and allergic reactions
H2 - mediates gastric acid secretion
H3 - In CNS pre-synaptic auto-regulators

Question 6

What are the actions of histamine on the lungs and which receptor is activated?

Answer 6

Bronchoconstriction
Asthma like symptoms
H1

Question 7

What are the actions of histamine on the vascular smooth muscle and which receptor is activated?

Answer 7

Vasodilator
Erythema
H1

Question 8

What are the actions of histamine on the vascular endothelium and which receptor is activated?

Answer 8

Contraction and separation of endothelial cells
Oedema
H1

Question 9

What are the actions of histamine on the PNS and which receptor is activated?

Answer 9

Sensation of afferent nerve terminals
Itch/pain
H1

Question 10

What are the actions of histamine on the heart and which receptor is activated?

Answer 10

MINOR increase in heart rate

H2

Question 11

What are the actions of histamine on the G.I system and which receptor is activated?

Answer 11

Increased gastric acid secretion
Peptic ulcers and heartburn
H2

Question 12

What are the actions of histamine on the CNS and which receptor is activated?

Answer 12

Acts as neurotransmitter
Epilepsy/wakefulness
H3

Question 13

H1 receptor stimulation leads to the release of which four molecules?

Answer 13

Inflammatory cytokines
Eicosanoids
Endothelial adhesion molecules
NfKB - (activation of Innate/acquired immune system)

Question 14

Define type 1 hypersensitivity reactions?

Answer 14

Allergic reactions due to the production of IgE against innocuous environmental Ag

Question 15

In type 1 hypersensitivity reactions - how do individuals become sensitised?

Answer 15

Initial exposure to Ag = B-cell produce specific IgE antibodies
These allergen Ag specific antibodies bind to mast cells and basophils (FcER.1 receptors)
Subsequent exposure = cross-linking of IgE on mast cells causing de-granulation and release of mediators

Question 16

Name the anti-histamine listed within the student formulary?

Answer 16

Cyclizine

Question 17

Describe the four steps within the management of anaphylaxis?

Answer 17

1. Stop/Remove Ag
2. Intramuscular Epi = vasoconstriction//bronchodilation
3. Parenteral H1 receptor antagonists = Cyclazine//chlorphenamine
4. Glucocorticoid = hydrocortisone - decrease the production of inflammatory mediators

Question 18

What type of receptor is H1?

Answer 18

Gq coupled protein receptor

Exists in 2 states - active (activates phospholipase C)//inactive

Question 19

With no receptor bound to H1 (basal state) what is the conformation of the H1 receptor?

Answer 19

Receptor tends towards activation - constitutive activity
Histamine (agonist) binds preferentially to the activated conformation of H1 receptor and shift equilibrium further towards ACTIVE receptor state

Question 20

How do H1 antagonists work?

Answer 20

Act as INVERSE agonist = bind preferentially to INACTIVE conformation of H1 receptor and shift equilibrium to inactive state

Question 21

What are the major side effects of H1 antagonists?

Answer 21

Severe sedation