Allergy Flashcards
What are the three phases of the triple response to an allergen?
initial redness (vasodilation)
Flare @15sec (depolarization of sensory nerve ending-> itch)
Wheal @few min (vascular permeability ->swelling)
What are the clinically important components of anaphylaxis?
decreased blood pressure, edema (swelling lips, tongue, uvula), bronchconstriction
What is the main mediator of allergic responses
histamine
What are the effects of histamine at skin?
local response-> triple resopnse
What are the effects of histamine at bronchioles?
bronchoconstriction at high doses
What are the effects of histamine at brain?
sedation, appetite (satiety)
What are the effects of histamine at sensory nerve endings
depolarization-> pain and itch
What are the effects of histamine at vascular endothelium
contract endothelial cells-> extravasation of fluid->edema
What are the effects of histamine at arterioles (smooth muscle)
vasodilation (decrease BP)
What are the effects of histamine at heart?
increase heart rate-> direct and reflex
What are the effects of histamine at stomach?
acid secretion
What are the main sources of histamine (synthesis + metabolism)
mast cells + basophils
enterochromaffin cells in stomach
neurons in brain
What are things that trigger mast cells to release their stuffs
allergen, IgE, specific molecules (opioids, contract media, vancomycin)
What are some of the things that mast cells release?
histamine, tryptase, PAF, Lipid, proteases, chemokine, NO, endothelin
these all lead to inflammation
What are the function of histamine pathways of the brain?
sleep-wake cycle
appetite (satiety)
nociception?!?!
What is the process of histamine release into the stomach
vagus nerve -> enterochromaffin cells -> hist to parietal cells -> AC, cAMP, PKA -> Ca2+ release -> TV exocytosis into gastric acid
How many histamine receptors are there? what type of receptor are they?
4
GPCR
What does H1 receptor do? where is it located? what type of GPCR signaling?
vasodilation, edema, bhroncoconstriction, appetite, arousal.
Smooth muscle, endothelial, CNS
Gq IP3, DAG up
What does H2 receptor do? where is it located? what type of GPCR signaling?
release stomach acid, VD, HR up
gastric parietal, cardiac, mast cells, CNS
G2, cAMP up
What does H3 receptor do? where is it located? what type of GPCR signaling?
Inhibitory autoreceptor + heteroreceptors (appetite), arousal
CNS, myenteric plexus
Gi, cAMP down
What does H4 receptor do? where is it located? what type of GPCR signaling?
chemotaxis, cytokine production
CNS, eosinophils, neutrophils, CD4 tcells
Gi, cAMP down
Which are the two histamine targets that are used clinically?
H1 and H2
What are the actions of drugs at H1?
Allergy- block edema, vasodilation, bronchoconstiction
what are the actions of drugs at H2 (antagonists)
block stomach acid, some immune response
What are some 1st generation histamine agonists? 2nd gen?
1st: Chlorpheniramine, diphenhydramine (Benadryl)
2nd: cetirizine (zyrtec), fexofenadine (allegra), loratidine (claritin), olopatidine (patanase), azelastine (astepro)
What at some off target effects of H1 1st generation antagonists?
muscarinic antagonist, penetration of blood brain barrier, sedation
(drugs like diphenhydramine, chlorpheniramine, etc)
Promethazine is used medically for
anti nausea, motion sickness
D3 antagonist properties
What are glucocorticoids used for with allergies? What is MOA? what are some 1st and 2nd gen?
chronic inflammation, back migration and action of incoming immune cells, block cytokines
1st: beclomethasone, budesonide, flunisolide, triamcinonlone
2nd: fluticasone, ciclesonide, mometasone
What is the mechanism of ipratropium and what is it used for?
Muscarinic antagonist (M3) -> block glandular secretion
runny nose
(this is an anticholinergic)
What is montelukast used for? What is mechanism?
chronic allergy
leukotriene antagonist -> counter inflammation and VD produced by leukotriene release from mast cells
What is the mechanism of nasal decongestants? what are examples?
α1 receptor agonist/NE releasers by heteroexchange
oxymetazoline, phenylephrine, pseudoephedrine
Dimenhydrinate and cyclizine can be used for
motion sickness
What do NE α1 do to arterioles?
constrict arterioles.
If taking while having HTN, raise BP. But it will dry up the runny nose so that’s good
What is the advantage of nasal administration for decongestants?
nasal spray more effective and it avoids the systemic effects (BP up)
Why do you use epinephrine for anaphylaxis?
bronchodilator, increase force and rate of heart, increase total peripheral resistance
Why don’t you treat anaphylaxis with antihistamines?
slow onset of reversal, multiple mediators contribute to symptoms
