Antihistamines Flashcards
Distribution of mast cells
high numbers in the skin, nose, mouth, lungs, and intestinal mucosa
Histamine is complexed with
sulfated-polysaccharides, heparin sulfate, chondroitin sulfate, and proteases
Where is the non-mast cell histamine located?
nerve terminals in some areas of the brain (NT) and in the fundus of the stomach (specialized cells store histamine for stimulation of acid secretion)
Causes of histamine release from mast cells and basophils
- Antigen mediated binding of antigen to antibodies bound to IgE on the cell surface
- Non-antigen mediated thermal or mechanical stress, cytotoxic agents (venoms/drugs)
What kind of receptors are histamine receptors?
G-protein coupled
Where are H1 receptors distributed?
distributed throughout CV, respiratory system, and G.I. smooth muscle
The H1 receptor is linked to what pathway?
linked to the phosphoinositol pathway, activation causes contraction of smooth muscle
What is the H1 receptor also linked to?
also linked to vasodilation and stimulation of sensory nerves
Where is the H2 receptor distributed?
distributed in the CV system, GI smooth muscle and stomach
What is the H2 receptor linked to?
linked to relaxation of vascular smooth muscle and gastric secretion
Where are H1 and H2 receptors colocalized?
vascular smooth muscle and endothelium
Where are H3 receptors located?
mainly in the CNS; autoreceptor in neurons that use histamine as a neurotransmitter
What are H3 receptors linked to?
linked to inhibition of neurotransmitter releases
Where are H4 receptors located?
located on mast cells, basophils and eosinophils
What are H4 receptors linked to?
linked to histamine-induced chemotaxis; promising target for future antiinflammatory drugs
What does histamine do to the cardiovascular system?
Causes a moderate increase in rate and force of contraction of the heart; H2 receptors causes an increased in SA conduction; reflex tachycardia
What does histamine do to the respiratory system?
H1 mediated constriction of bronchial smooth muscle
What does histamine do to acid release in the stomach?
H2 mediated release from parietal cells in the stomach
What happens with histamine and anaphylaxis?
hypotension and loss of fluid to the interstitial space; lowers effective blood volume; swelling
Triple response that occurs when you inject histamine into the skin
- red spot at the point of injection (immediate)
- red flare radiating ~ 1 cm from injection site (~10s)
- wheal (raised welt) at site of injection (1-2 min)
Skin pathologies caused by histamine
- Urticaria (hives, rash, edematous welts
- Dermatographia (redness or welt with mechanical stimulation
- Flushing (erythema, redness in skin due to vasodilation)
H1 receptor antagonists are referred to as
antihistamines
H2 receptor antagonists are referred to as
acid blockers
First generation antihistamines
Brompheniramine, cyproheptadine, diphenhydramine, promethazine, hydroxyzine, pyrilamine
What can happen when children take H1 receptor antagonists?
paradoxical excitation in children at normal doses
What happens with antihistamines at high doses?
CNS stimulation at high doses
The most sedative antihistamines
ethanolamines and phenothiazies
ex. diphenhydramine and promethazine
OTC sleep aids
diphenhydramine: Sominex and Nytol
Second generation H1 antagonists
Loratadine, desloratadine, fexofenadine, citirizine, levocetirizine
How are second generation H1 antagonists different from first generation H1 antagonists?
decreased lipid solubility, little or no sedation, no anti-muscarinic activity, no anti-emetic activity, no anti-motion sickness activity
Topical H1 receptor antagonists (eye drops and nasal sprays)
Olopatadine, azelastine, ketotifen
What are topical H1 receptor antagonists indicated for?
indicated for treatment of seasonal allergic rhinitis and/or conjunctivitis; approved for prevention of asthma symptoms in Europe
Clinical use of H1 antagonists
- Seasonal and perennial allergic rhinoconjuctivitis
- Chronic urticaria
- Motion sickness
- Adjunct with epinephrine to treat anaphylaxis
H1 antagonists for motion sickness
demenhydrinate, meclizine, promethazine
Adverse effects and drug interactions for H1 receptor antagonists
sedation; 1st gen drugs tend to enhance CNS depression; antimuscarinic effects
What are 1st generation antihistamines contraindicated in
urinary retention and narrow angle glaucoma
Specific effects of phenothiazine
extrapyramidal effects: dystonia, akathisia, and Parkinsonian rigidity
Mechanism of CNS depression by H1 antagonists
- Drug must gain entry to the CNS
- H1 receptors in the thalamic relay cells maintain a relatively depolarized membrane potential, low frequency action potentials and wakefullness
- H1 antagonists block these receptors, leading to hyperpolarization, bursts of action potentials and sleep
