Anti-Histamines Flashcards
2 Broad mechanisms of histamine release from mast cells
cytolytic - membrane damage, high levels of drugs, mechanical damage
non-cytolytic - immune response, non-immunological response, substances can displace it from granules
H1 receptor
Smooth muscle cells (vascular, respiratory, GI)
Vascular endothelial cells
CNS neurons
Peripheral sensory nerves
Gq protein
H2 receptor
Gastric parietal cells
Cardiac muscle
CNS neurons
Gs protein
H3 receptor
CNS neurons
Peripheral sensory nerves
Gi/o protein
H4 receptor
Neutrophils
Eosinophils
Monocytes
Other immune cells
Gi/o protein
Both peripheral and CNS histamine receptors mediate _____
itch
Histamine in the CNS released in _____
circadian pattern
controls release of pituitary hormones, wakefullness, appetite, satiety
Histamine physiologic effects
vasodilation - decreased TPR
increased vascular permeability - edema
epidermis - itch
dermis - pain
lungs - increased fluid and electrolyte secretion, bronchoconstriction
Cardiac (H2) - increase calcium (increase contracitility), increase SA node
Diseases that increase histamine levels
myelogenous leukemia
gastric carcinoid tumors
systemic mast cell diseases - mast cell leukemia
Classes of Anti-histamines
Physiological antagonists
Release inhibitors
Receptor Antagonists
Important characteristic of 2nd generation H1-anti-histamines
Non-sedating - don’t penetrate BBB
H1-antihistamines MOA
reversibly bind receptor and stabilize INACTIVE FORM
Potential adverse effects of 1st generation H1-antihistamines
CNS H1 receptors - sedation, decreased alertness
Muscarinic receptors - dry mouth, urinary retention, sinus tachycardia
Serotonin receptors - increase appetite and wt gain
Alpha- receptors - dizziness and postural hypotension
1st generation H1-antihistamines
Chlorpheniramine Diphenhydramine Pyrilamine Hydroxyzine Meclizine Promethazine Cyproheptadine
Chlorpheniramine primary uses
allergic rhinitis and other allergic conditions
Diphenhydramine characteristics
sedative
anti-muscarinic
anti-motion sickness
Pyrilamine characteristics
low to moderate sedative actions
Hydroxyzine important characteristics
marked sedation and anti-muscarinic
Meclizine important characteristics
less sedating than hydroxyzine
minimal anti-muscarinic
primarily for motion sickness and vertigo
Promethazine important characteristics
strong anti-motion sickness and anti-emetic activities
local anesthetic
alpha-1 and muscarinic inhibition
Phenothiazines (promethazine and chlorpromazine) can also
BLOCK D2 RECEPTORS
anti-psychotic
Cyproheptadine important characteristics
Low to moderate sedative and antimuscarinic actions
Anti-serotonin activity
H1 Antihistamines with strongest anti-emetic effects (4)
Diphenhydramine
Promethazine
Hydroxyzine
Meclazine
H1 Antihistamines with strongest sedative effects (3)
Diphenhydramine
Hydroxyzine
Promethazine
Strongest cholinergic anti-histamines
diphenhydramine
promethazine
Strongest alpha-1 antagonist anti-histamine
promethazine
strongest serotonin antagonist anti-histamine
cyproheptadine
Drug-interactions with 1st generation H1 antihistamines
MAOI’s
Opioids, alcohol, sedatives
Anti-cholinergics
2nd Generation H1 Anti-histamines characteristics
bind non-competitively to H1
reduced lipophilicity
higher selectivity toward H1
2nd Generation H1 Anti-histamines
Fexofenadine Loratadine Desloratadine Levocetirizine Cetirizine Azelastine
Azelastine characteristics
ALSO INHIBITS MAST CELL HISTAMINE RELEASE
INTRANASAL AND OPTHALMIC
Cromolyn and Nedocromil MOA
stabilize mast cells
inhibition of chloride channels in cell membranes
nasal spray, eye drops, aerosols
Omalizumab MOA
clinical
recombinant humanized IgE ANTIBODY - binds and sequesters IgE
urticaria, asthma
Other drugs with anti-histaminic activity
Doxepin - TCA
Ketotifen - H1 antihistamine with mast cell and basophil stabilizing properties
