Allergy

Question 1

What are the three phases of the triple response to an allergen?

Answer 1

initial redness (vasodilation)
Flare @15sec (depolarization of sensory nerve ending-> itch)
Wheal @few min (vascular permeability ->swelling)

Question 2

What are the clinically important components of anaphylaxis?

Answer 2

decreased blood pressure, edema (swelling lips, tongue, uvula), bronchconstriction

Question 3

What is the main mediator of allergic responses

Answer 3

histamine

Question 4

What are the effects of histamine at skin?

Answer 4

local response-> triple resopnse

Question 5

What are the effects of histamine at bronchioles?

Answer 5

bronchoconstriction at high doses

Question 6

What are the effects of histamine at brain?

Answer 6

sedation, appetite (satiety)

Question 7

What are the effects of histamine at sensory nerve endings

Answer 7

depolarization-> pain and itch

Question 8

What are the effects of histamine at vascular endothelium

Answer 8

contract endothelial cells-> extravasation of fluid->edema

Question 9

What are the effects of histamine at arterioles (smooth muscle)

Answer 9

vasodilation (decrease BP)

Question 10

What are the effects of histamine at heart?

Answer 10

increase heart rate-> direct and reflex

Question 11

What are the effects of histamine at stomach?

Answer 11

acid secretion

Question 12

What are the main sources of histamine (synthesis + metabolism)

Answer 12

mast cells + basophils
enterochromaffin cells in stomach
neurons in brain

Question 13

What are things that trigger mast cells to release their stuffs

Answer 13

allergen, IgE, specific molecules (opioids, contract media, vancomycin)

Question 14

What are some of the things that mast cells release?

Answer 14

histamine, tryptase, PAF, Lipid, proteases, chemokine, NO, endothelin
these all lead to inflammation

Question 15

What are the function of histamine pathways of the brain?

Answer 15

sleep-wake cycle
appetite (satiety)
nociception?!?!

Question 16

What is the process of histamine release into the stomach

Answer 16

vagus nerve -> enterochromaffin cells -> hist to parietal cells -> AC, cAMP, PKA -> Ca2+ release -> TV exocytosis into gastric acid

Question 17

How many histamine receptors are there? what type of receptor are they?

Answer 17

4

GPCR

Question 18

What does H1 receptor do? where is it located? what type of GPCR signaling?

Answer 18

vasodilation, edema, bhroncoconstriction, appetite, arousal.
Smooth muscle, endothelial, CNS
Gq IP3, DAG up

Question 19

What does H2 receptor do? where is it located? what type of GPCR signaling?

Answer 19

release stomach acid, VD, HR up
gastric parietal, cardiac, mast cells, CNS
G2, cAMP up

Question 20

What does H3 receptor do? where is it located? what type of GPCR signaling?

Answer 20

Inhibitory autoreceptor + heteroreceptors (appetite), arousal
CNS, myenteric plexus
Gi, cAMP down

Question 21

What does H4 receptor do? where is it located? what type of GPCR signaling?

Answer 21

chemotaxis, cytokine production
CNS, eosinophils, neutrophils, CD4 tcells
Gi, cAMP down

Question 22

Which are the two histamine targets that are used clinically?

Answer 22

H1 and H2

Question 23

What are the actions of drugs at H1?

Answer 23

Allergy- block edema, vasodilation, bronchoconstiction

Question 24

what are the actions of drugs at H2 (antagonists)

Answer 24

block stomach acid, some immune response

Question 25

What are some 1st generation histamine agonists? 2nd gen?

Answer 25

1st: Chlorpheniramine, diphenhydramine (Benadryl) 2nd: cetirizine (zyrtec), fexofenadine (allegra), loratidine (claritin), olopatidine (patanase), azelastine (astepro)

Question 26

What at some off target effects of H1 1st generation antagonists?

Answer 26

muscarinic antagonist, penetration of blood brain barrier, sedation (drugs like diphenhydramine, chlorpheniramine, etc)

Question 27

Promethazine is used medically for

Answer 27

anti nausea, motion sickness | D3 antagonist properties

Question 28

What are glucocorticoids used for with allergies? What is MOA? what are some 1st and 2nd gen?

Answer 28

chronic inflammation, back migration and action of incoming immune cells, block cytokines 1st: beclomethasone, budesonide, flunisolide, triamcinonlone 2nd: fluticasone, ciclesonide, mometasone

Question 29

What is the mechanism of ipratropium and what is it used for?

Answer 29

Muscarinic antagonist (M3) -> block glandular secretion runny nose (this is an anticholinergic)

Question 30

What is montelukast used for? What is mechanism?

Answer 30

chronic allergy | leukotriene antagonist -> counter inflammation and VD produced by leukotriene release from mast cells

Question 31

What is the mechanism of nasal decongestants? what are examples?

Answer 31

α1 receptor agonist/NE releasers by heteroexchange | oxymetazoline, phenylephrine, pseudoephedrine

Question 32

Dimenhydrinate and cyclizine can be used for

Answer 32

motion sickness

Question 33

What do NE α1 do to arterioles?

Answer 33

constrict arterioles. | If taking while having HTN, raise BP. But it will dry up the runny nose so that's good

Question 34

What is the advantage of nasal administration for decongestants?

Answer 34

nasal spray more effective and it avoids the systemic effects (BP up)

Question 35

Why do you use epinephrine for anaphylaxis?

Answer 35

bronchodilator, increase force and rate of heart, increase total peripheral resistance

Question 36

Why don't you treat anaphylaxis with antihistamines?

Answer 36

slow onset of reversal, multiple mediators contribute to symptoms