Week 3 (Quiz 3) (Antihistimine) Flashcards
Histamine is a neurotransmitter implicated in: (3 things)
1) immediate hypersensitivity rxns
2) bronchospasm
3) gastric acid secretion
Histamine is in ____ tissues
all (esp. GI, lungs, skin)
Histamine is complexed to ___ inside _____ in inactive form
heparin, mast cell/basophil granules
Histidine –> histamine (enzyme)
histidine decarboxylase
Mast cell degranulation is triggered by:
- Binding of allergens
- bacterial toxins/insect stings
- trauma/cold
Autocids
biologically active substances; short half-life; act near site of synthesis
Two types of autocids
- vasoactive amines
2. eicosanoids
Vasoactive amines, What and released by?
Histamine, 5-HT
Released by mast cells and basophils; platelets
Eicosanoids, What and released by?
Prostaglandins, leukotrienes
Released by all leukocytes, platelets
H1 receptor G protein
Gq
H1 impact on IP3 and DAG
increased
Peripheral effects of H1 activation
- increased naso/broncho mucous production
- bronchoconstriction
- pruritis (itching/pain)
- inflammation (rubor, tumor, dolor)
CNS effects of H1 activation
- Increased BP
- Increased HR
- Super increased neurotransmission/cognitive and psychomotor performance
- Super decreased sedation
H2 G protein
Gs
H2 activation impact on cAMP
increased cAMP
H2 activation effect in peripheral and CNS
- increased gastric acid secretion
- decreased BP
- increased HR
- Inflammation (rubor, tumor, dolor)
H3 G protein
Gi
H3 activation impact on cAMP
decreased cAMP
H3 peripheral and CNS activation impact
presynaptic inhibition of CNS neurotransmitter release
H4 G protein
Gi
H4 activation impact on cAMP
decreased cAMP
H4 impact
mast cell chemotaxis
Diphenhydramine; chorpheniramine; dimenhydrinate; doxylamine
What type of antagonist? What generation
1st Generation H1 Antagonist
Mechanism of G1 H1 antagonists?
competitive, reversible inhibition of H1 receptors in PNS and CNS –> ↓ DAG/IP3
Effects of G1 and G2 H1 antagonists on:
mucous production
bronchoconstriction
itching
Decreased
Effects of G1 H1 antagonists on:
Sedation
NT release
Increased, decreased
SE of G1 H1 antagonists
strong SEDATION; low selectivity - also blocks muscarinics, α- adrenergics, 5-HT (sympathetic effects; hypotension/dizziness; tachycardia; increased appetite)
Use of G1 H1 antagonists
- allergic conditions
- motion sickness/nausea
- sleep aid
cetirizine; loratidine; fexofenadine
What type of antagonist? What generation?
2nd Generation H1 antagonist
Mechanism of G2 H1 antagonist?
competitive, reversible inhibition of H1 receptors in PERIPHERY only (do not cross BBB)
SE of G2 H1 antagonists?
less than 1st gen due to greater specificity and no CNS effects
Use for G2 H1 antagonists?
allergic conditions (hay fever, urticaria, contact dermatitis, angioedema, itching)
Cimetidine; ranitidine; famotidine; nizatidine
What type of antagonist? What generation?
H2 antagonist
Mechanism for H2 antagonist
competitive, reversible inhibition of H2 receptors –> ↓ cAMP
Effects of H2 antagonist
↓ gastric acid secretion
SE of H2 antagonist
anti-androgenic effects (prolactin release, impotence, gynecomastia in males);
Use of H2 antagonists
peptic ulcer disease; gastric esophageal reflux; gastritis
Steroids block:
phospholipase A2 and Cox-2
NSAIDS block
Cyclooxygenases (COX-1 and COX-2)
What do prostaglandins do in general at physiologic levels?
- maintenance of gastric mucous secretion
- control renal blood flow
- platelet aggregation
What do prostaglandins do in general at inflammatory levels?
- increased pain sensation
- increased body temp
- vasodilation
Leukotrienes in general:
increase bronchoconstriction
Which enzyme creates leukotrienes from arachidonic acid?
5-lipoxygenase
Which enzymes create prostaglandins from arachidonic acid?
COX-1 and COX-2
What enzyme creates arachidonic acid from membrane phospholipids?
Phospholipase A2
