Lecture 25/26 Flashcards
Antihistamines
histamine synthesis
histidine loses CO2 via L-histidine decarboxylase
in mast cells and basophils
histamine metabolism
oxidation via diamine oxidase reaction
methylation via histamine-N-methyltransferase reaction
into inactive forms imidazole acetic acid riboside and N-methylimidazole acetic acid
histamine storage
in granules as complexes –> sulfated polysaccharides, heparin sulfate, chondroitin sulfate, and proteases
non-mast cells –> in nerve terminals (as NT) and fundus of stomach (for acid secretion stimulation)
Antigen mediated release mechanism
binding of IgE antibodies to FceR
binding of antigen to IgE antibodies
clustering of FceR receptors
influx of Ca2+ via CRAC
H1 receptors
cause contraction of smooth muscles (increased Ca2+) and vasodilation (decreased Ca2+)
via phosphoinositol pathway
distributed throughout cardiovascular system, respiratory system, and GI smooth muscle
H2 receptors
distributed in cardiovascular system, GI smooth muscle, and the stomach
increases cAMP
H1 in vascular endothelium
increase in nitric oxide and increase contraction of endothelial cells
H2 in vascular muscle
relaxation (vasodilation)
histamine in the heart
moderate increase in rate and force of contraction
H2 increase in SA node contraction
reflex tachycardia
histamine involvement in vasodilation
H1 in endothelium
H2 in smooth muscle
histamine in respiratory system
H1 mediated constriction of bronchial smooth muscle
1st generation antihistamines
brompheniramine
cyproheptadine
diphenydramine
promethazine
hydroxyzine
pyrilamine
brompheniramine
dimetapp
class - alkylamine
cyproheptadine
periactin
class - piperidine
property - anti-serotonin
USE - headaches
diphenhydramine
benadryl
class - ethanolamines
property - sedation
USE - sleep aid
promethazine
phenergan
class - phenothiazine
property - extrapyramidal, a adrenergic antagonism, sedation
USES - sleep aid, local anesthetic
SIDE EFFECTS - dystonia, akathisia, hypotension
hydroxyzine
atarax
class - piperazines
pyrilamine
class - ethylenediamine
USE - local anesthetic
anti-cholinergic effects of 1st gen antihistamines
anti-motion sickness
anti-emetic (nausa/vomiting)
CNS access prominent
contraindications of 1st gen antihistamines
urinary retention and narrow angle glaucoma
caused by decreased urination and dry mouth
sedation mechanism
blockade of H1/H2 receptors in wakefullness-promoting circuits
interacts with alcohol, anxiolytics, and antipsychotics
2nd gen antihistamines
loratidine (claritin)
desloratadine (clarinex)
fexofenadine (allegra)
cetrizine (zyrtec)
levocetrizine (xyzal)
terfenidine (seldane)
cetrizine specific
may also block LTC4, neutrophil migration, and eosinophil infiltration
2nd gen antihistamine side effect profile
decreased lipid solubility so little to no CNS affects
thus no sedation, anti-muscarinic acts, anti-emetic acts, and no anti-motionsickness acts
rhinorrhea allergic
histamine indirectly stimulates mucus discharge via H1 receptors on nerve endings
rhinorrhea common cold
virus stimulates reflex independent of peripheral H2 receptors
1st gen common cold treatment
inhibits rhinorrhea and sneezing effects
(second gen is not as effective)
common drugs to treat rhinorrhea
olopatadine (patanol) - eye drop or nasal spray
azelastine (astelin) - eye drop or nasal spray
ketotifen (zaditor) - eye drop
side effect of drugs to treat rhinorrhea
drowsiness if oral or nasal spray dosage form
clinical uses of antihistamines
rhinorrhea
chronic urticaria
motion sickness
adjunct with epinephrine to treat anaphylaxis
motion sickness drugs
dimehydrinate (dramamine) - combination product of diphenhydramine and chlorotheophylline salt
meclizine (antivert)
promethazine (phenergan)
adjunct drugs to treat anaphylaxis
epinephrine is the psychological antagonist with diphenhydramine delivered parenterally
early phase response with T cells
nerves lead to sneeze
glands lead to runny nose
vessels lead to congestion
late phase response with T cells
release of chemoattractant factors –> inflammation –> congestion
fluticasone
flonase
very low systemic absorption from intranasal dose
slow onset so may take a couple of days to develop max benefit
may suppress HPA axis with prolonged high dose
budesonide
rhinocort
1/3 of the dose is absorbed within an hour
may suppress HPA axis with prolonged high dose
slow onset may take a couple of days to develop max benefit
action of glucocorticosteroids in allergic rhinitis
decrease cytokine production in TH2 cells
decrease mucin secretion in glands and goblet cells
