(4) Smooth Muscle: Allergy & Pulm (2.1-2.2) Flashcards
Where is most Histamine found?
Mast cells
What type of G-protein is H1 receptor?
Gq
What type of G-protein is H2 receptor?
Gs
Name 6 effects of H1 receptor stimulation
(1) ↑ Nasal/Bronchial mucus
(2) ↑ Vascular permeability
(3) Bronchoconstriction
(4) ↑ Arousal
(5) Pain
(6) Pruritus
* (CNS Effects: Regulates sleep, arousal, and functions as a neurotransmitter)*
Which Histamine receptor mediates gastric acid secretion?
H2
Name the first-generation H1 receptor blockers
(1) Diphenhydramine
(2) Dimenhydrinate
(3) Chlorpheniramine
(4) “-zine”
Indications (5) : H1 receptor blockers
(1) Type I Allergic Reactions
(2) Motion sickness
(3) Insomnia
(4) Extrapyramidal side effects of antipsychotics
(5) Anorexia
* (Note: Only first-generation H1 blockers treat motion sickness)*
What other receptors do first-generation H1 blockers antagonize (not H1)?
(1) CNS/PNS Muscarinic receptors
(2) CNS 5-HT receptors
(3) α1 receptors
Why do H1-blockers cause cognitive impairment in the elderly?
(1) Central antihistamine effects
(2) Central antimuscarinic effects
What are the second-generation H1 blockers?
(1) Fexofenadine
(2) Cetirizine
(3) Loratidine
How are second-generation H1 blockers different than the first-generation blockers?
(1) Do not cross BBB
(2) ↑ H1 specificity
* (↑ Specificity ⇒ ↓ Affinity for muscarinic receptor, 5-HT receptors, and adrenergic receptors)*
Which class of sympathomimetics are used to treat bronchoconstriction in asthma?
β2 agonists
(“-rol” drugs)
What β2 does not end in “-erol” and is used to treat asthma?
Terbutaline
Treatment (8) : Persistent asthma (not β2 agonist)
(1) Inhaled corticosteroids
(2) Direct lipoxygenase inhibitors
(3) Methylxanthines
(4) Omalizumab
(5) Cromolyn Sulfate
(6) LTD4-receptor antagonists
(7) Ipratropium
(8) Epinephrine
How do corticosteroids help with asthma?
(1) ↓ Inflammation
(2) ↓ Leukocyte infiltration
* (Importantly, they also upregulate β2 receptors)*
Adverse Effect: Inhaled corticosteroids
Oral candidiasis
(Inhaled steroids are not absorbed systemically ∴ they avoid systemic effects)
Which leukotriene is a potent chemoattractant for neutrophils?
LTB4
(IL-8 also a potent neutrophil chemoattractant. IL-8 looks like IL-B)
Which leukotrienes are potent bronchoconstrictors?
LTC4, D4, E4
(Also ↑ Airway vascular permeability and mucus production)
What receptor mediates the most potent bronchoconstricting effects of leukotrienes?
CysLT1
Suffix: LTD4-receptor antagonists
“-kast”
ROA: LTD4-receptor antagonists
Oral
What drug is a direct lipoxygenase inhibitor?
Zileuton
Which asthma drug requires monitoring for hepatotoxicity?
Zileuton
What drug can cause a leukotriene-induced asthma attack?
Aspirin
(NSAIDs in general)
Name two long acting β2 agonists
(1) Salmeterol
(2) Formoterol
* (Salute ∝ Salmeterol)*
* (Formation ∝ Formoterol)*
MOA: Methylxanthines
(1) Non-selective PDE inhibitor
(2) Adenosine receptor antagonist
* (∴ ↑ cAMP)*
ROA: Theophylline
Oral
Adverse Effects (2) : Methylxanthines
(1) CNS effects incl. tremor
(2) Tachycardia
Which asthma drug is metabolized by the CYP-450 system?
Methylxanthines
What monoclonal antibody is used to treat allergic asthma?
Omalizumab
MOA: Omalizumab
Binds Fc portion of IgE
MOA: Cromolyn Sulfate
Inhibits mast cell degranulation
(And ∴ histamine release)
Treatment (4) : Acute severe asthma attack
(1) IV corticosteroid
(2) β2 agonist
(3) Ipratropium
(4) Epinephrine
