Antihistamines Flashcards
Histamine
Biogenic amine
Mast cell pool: circulating basophils and tissue mast cells
Non-mast cell pool: GI, lungs, skin, brain
Mast cell granule content
Histamine, serotonin, heparin-protein complex, proteolytic enzymes, autocoids
Pre-capillary arteriole
Targets H1 receptor → dilation → hypotension
Post-capillary venule
With H1 receptor → increased permeability → edema
Cardiac
With H2 receptor → positive ionotrope and chronotrope → tachycardia
Smooth muscle
With H1 receptor → contraction in bronchi and GI tract → bronchoconstriction/ spasm/ contraction
Lung
Tissue mast cell (systemic anaphylaxis) shock organ for:
Cat, sheep, cows, pig and human
GI tract
Tissue mast cell (systemic anaphylaxis) shock organ for:
Horse, pig, dog (hepatic/ GI)
H1 receptor
Inflammation
Anaphylaxis, allergies, drug rxs (resp., arteriol, venous)
Other histamine receptors
H2: gastric acid secretion
H3: NT release
H4 cells types associated with inflamm.
Histamine in the GI tract
Gastric acid secretion
Histamine continually secreted by gastric mucosa
H2 receptor: HCl secreted by parietal cell
H1 Antihistamine effects on vasculature
Stabilizes → antagonize arterial vasodilation and venous leaking
H1 Antihistamine effects on smooth muscle (resp. system)
Relaxation → ↓ bronchoconstriction
H1 Antihistamine effects on extracellular fluid
Decrease → minimize local and systemic
H1 Antihistamine effects on inflammatory mediators
Decrease release → ↓inflammatory response
Alternate antihistamine approaches
Physiologic antagonists
Opposite response as histamine: don’t block release or compete
Clinical situations to use alternate antihistamine approaches
Acute anaphylaxis: sympathomimetics (EP, ephedrine, isoproterenol)
Bronchoconstriction: anaphylaxis, asthma (EP)
↓ histamine associated inflamm response (glucocorticoids - prednisone and dexamethasone, prevent degranualation)
Clinical uses for Antihistamines
H1 blockers: allergies, motion sickness, resp. disorders
H2 blockers: gastric ulcers
H1 receptor antihistamine classes
Ethylenediamines, ethanolamines, alkylamines, piperazines, phenothiazines (1st gen)
Piperidines (2nd gen)
H1 antagonists, 1st gen
Older, more familiar drugs
Cross BBB
Diphenhydramine (Benadryl), hydroxyzine, chlorpheniramine
Ethylenediamines
CNS depression or sedation
Gastric upset
Tripelennamine, pyrilamine
Ethanolamines
Atropine effects (anti-motion effect, low gastric upset, sedation)
Diphenhydramine
Alkylamines
Greatest antihistamine activity
Seldom produce drowsiness (stimulates CNS)
In cold meds
Piperazines
Prolonged action
Used for anti-motion
Slight drowsiness
Meclizine, hydroxyzine
Phenothiazines
Long acting, good sedative
Good antihistamine activity
Trimeprazine
H1 antagonists, 2nd gen
For acute inflamm. and allergic rxs
Doesn’t cross BBB (lack CNS effects- no sedation)
Loratadine (claritin), fexofenadine (allegra), cetirizine (zyrtec)
Piperidines
Newest/ second gen
Minimal to no sedation
Loratadine (claritin)
Side effects of antihistamines
Sedation (ataxia)
CNS excitement (high doses, irritability, convulsions, hyperexia, death)
GI disturbances (anorexia, V/D, consitpation)
Cyproheptadine MOA
Antiserotonergic antihistamine
Serotonin receptor antagonist (inhibit receptors in hypothalamus controlling statiety)
Histamine receptor antagonist
Cyproheptadine uses
Cats for appetite stimulant and acute phase of asthma
