Summary Unlocking Pharmacology - Antihistamines

Antihistam
ines
Introduction
 Hay fever and anaphylaxis
 IgE antibody attaches to a mast cell
 Re-exposure to an antigen (Ag) degranulation
 Production and release of mediators
 Mediator are localized-hay fever
 Massive general release of histamine-
anaphylaxis (LIFE THREATNING)
 Antigens-allergens
Mast Cells
 Mast cells occur in almost all tissues
 Contain Histamine
 Release of Histamine involves the influx of
Ca2+ ions
 ↑Permeability of the cell membrane when
↑adenosine monosphosphate (cAMP)
Actions on the receptor
H1 receptor
- Pain and itching
- Bronchoconstriction

, - Vasodilation caused by release of nitric oxide
- Capillary endothelial cells-vasodilation-
↑permeability →local oedema
- Effects occur in allergic reactions
- Inhibit appetite and increases wakefulness
viaH1 receptors in the CNS
- H1 receptors-allergies, urticaria, anaphylactic
reactions
Histamine release by drugs, peptides,
venoms, and other agents
- Mechanical injury
- Many compounds stimulate histamine release
from mast cells directly, without prior
sensitization
- E.g. Tubocurine, succinylcholine, morphine,
some antibiotics, radiocontrast media, and
certain carbohydrate plasma expanders
- May account for unexpected anaphylactoid
reactions
- Some venoms e.g. wasp
Histamine H1 Antagonists
 Oral, IV, topically
 First generation agents
- E.g. Diphenhydramine, promethazine
- Highly sedating
- Significant automatic receptor-blocking
effects
- A newer subgroup of first-generation
agents