Lecture 26: antihistamines Flashcards
H1 antagonists referred to as
antihistamines
H2 antagonists referred to as
acid blockers
H1 antagonists
-competitive
-inverse agonists
1st gen antihistamines
-alkylamines
-ethanolamines
-ethylenediamines
-phenothiazines
-piperadines
-piperazines
structures
slide 26
H1 Antagonist effects
-sedation
-anticholinergic effects (piss less, dry mouth)
-local anesthetic
-anti-serotonin
-extrapyramidal
Sedation (H1 antagonist)
-CNS effect
-block H1/H2 receptors in wakefullness-promoting circuits
-dif from sedatives/hypnotics
H1 Antagonist interactions
-alcohol
-anxiolytics
-antipsychotics
-drowsiness
most sedating H1 antagonists
-ethanolamines (diphenhydramine)
-phenothiazines (promethazine)
Anti-cholinergic mech of H1 antagonists
-anti-muscarinic (atropine-like)
-more lipid soluble = inc CNS access
H1 antagonist anticholinergic effects
-anti-motion sickness
-anti-emetic
-dec urination
-dry mouth
best H1 antagonist for motion sickeness/nausea
-promethazine
-dyphenhydramine
-only 1st generation drugs
Local anesthetic H1 Antagonists
-pyrilamine
-promethazine
anti-serotonin H1 antagonists
-cyproheptadine
-azatidine
-for headaches
a-adrenergic antagonism H1 antagonists
-phenothiazines
-hypOtension
extrapyramidal H1 antagonists
-phenothiazine
-promethazine
-dystonia,akathisia
1st generation antihistamines (H1 antagonists)
-brompheniramine
-cyproheptadine
-diphenhydramine
-promethazine
-hydroxyzine
-pyrilamine
2nd gen antihistamines (H1 antagonists)
-loratidine
-desloratadine
-fexofenadine (metabolized to terfenidine)
-cetrizine (metabolized to hydroxyzine)
-levocetirizine
2nd gen antihistamines (H1 antagonists) traits
-dec lipid solubility
-efflux from CNS by P-glycoprotein transporter
-structures slide 31
2nd gen antihistamine differences from 1st gen
-no sedation
-no antimuscarinic act
-no motion sickness/anti-emetic effect
2nd gen antihistamine mech
-block H1
-may block LTC4, neutrophil migration, eosinophil infiltration
Allergic rhinorrhea
-histamine indirectly stimulates mucus discharge via H1 on nerve endings
common cold rhinorrhea
-virus stimulates reflex independent of peripheral H1 receptors
-use 1st gen
-2nd prob not as effective
1st gen drug effect on common cold rhinorrhea
-act in brain to inhibit rhinorrhea and sneeze
-dont use 2nd gen they prob wont b effective
Topical H1 antagonists
-olopatadine (eye drops/nasal spray)
-azelastine*
-ketotifen*
*approved for systemic use in europe
Topical H1 antagonist effects
-indicated for treatment of seasonal allergic rhinitis and conjunctivitis
-all cause drowsiness if taken orally or as nasal spray
clinical use of H1 antagonists
-seasonal and perennial allergic rhinoconjunctivitis
-chronic urticaria
-motion sickeness (diphenhydramine, meclizine, promethazine)
-w epinephrine for anaphylaxis (diphenhydramine give parenterally)
Adverse effects of H1 receptor ANTAgonists
-sedation and interactions w other sedatives (1st gen only)
-anti-cholinergic effects
1st gen drugs contraindicted in: (bc of anticholinergic effects)
-urinary retention
-narrow angle glaucoma
how do sedative effects of antihistamines differ from sedatives/hypnotics?
-CNS stimulation at high dose
-paradoxical excitation in kids
most sedative antihistamines
-ethanolamines and phenothiazines
-ex: diphenhydramine and promethazine
Effect of 2nd gen antihistamines on CNS
-no sedation
-none to limited CNS affects
OTC sleep aids
-sominex and nytol
-contain diphenhydramine
Antihistamine patient information
-report history of glaucoma, urinary retention, pregnancy
-drowsiness/dizziness
-avoid alcohol and other CNS depressants
-report any involuntary movements w phenothiazines
H2 antagonists
-famotidine
-cimetidine
-nizatidine
-ranitidine
H2 antagonist use
-reduce gastric acid secretion
-peptic ulcer
-gerd
H2 antagonist side effects
-CNS dysfunction
-antiandrogen (gynecomastia, galactorrhea)
-impotence
-blood dyscrasias
-hepatotoxicity
GCs used in allergic rhinitis
-fluticasone
-budesonide
-mometasone
GCs for allergic rhinitis characteristics
-nasal sprays
-slow onset (may take days)
-may suppress HPA axis w high doses
Fluticasone absorption
-low absorption
budesonide absorption
1/3 dose absorbed in less than hour
Role of T cells in allergic rhinitis
-chemoattractant
-eosinophils/neutrophils/basophils
-inflammation
GC effect on TH2 cells
-decrease cytokine expression
