Antihistamines Flashcards
Four things other than histamine in a mast cell storage granule?
- Sulfated-polysaccharide
- Heparin Sulfate
- Chondroitin Sulfate
- Proteases
Causes of non-antigen mediated mast cell release
Thermal or Mechanical Stress Cytotoxic Agents (Venoms) Drugs (high dose morphine)
What happens when an H1 receptor is activated (molecularly)
Gq –> PLC –> IP3+DAG –> increased Ca –> Calmodulin binding –> phosp. MLC
What does H1 receptor activation do (in the context of tissues
Contraction of the smooth muscle
Important in the CV, Resp., and GI systems
How does H1 activation trigger vasodilation
In vascular endothelial cells it acts of increase NO release. NO diffuses to vascular smooth muscle and increases cGMP. Higher cGMP will lower the Ca, relaxing the muscles.
What happens when an H2 receptor is activated (molecularly)
Gs –> Inc. adenylate cyclase –> Inc. cAMP
Important roles of H2 activation?
Relaxation of Vascular Smooth muscle (don’t confuse with H1 in the vascuar endothelium)
Triggers Gastric Secretion
Role of H3 receptors?
Autoreceptor in neurons that use His as a transmitter that inhibits NT release
Role of H4 receptors?
Located on mast cells, basophils, and eosinophils
May be in future anti-inflammatories, none out now though
Effects of Histamine on the CV system
Heart – Inc rate and force of contraction
Vasodilation
Effects of Histamine on the Resp system
H1 med. Constriction of the bronchial sm. muscle
Effects of Histamine on the digestive?
H2 mediated acid release from parietal cells
Massive Histamine release can trigger _____. Treat with ______
Anaphylaxis
Ephinephrine
Which Histamine receptor(s) are important for Vasodilation? Endothelial contraction?
Vaso – H1 and H2
Endo – H1
Triple response of histamine
- Red spot at the point of injection (immediate)
- Red flare radiating (1 cm, happens 10 s later)
- Wheal (reised welt) at injection site
Aside from the triple response, what other skin pathologies are Histamine driven
Urticaria
Dermatographia
Flushing (erythema)
Describe urticaria
Hives, Rash, Edematous Welts
Six important examples of first generation antihistamines
DIPHENHYDRAMINE Promethazine Hydroxyzine Brompheniramine Pyrilamine Cyproheptadine
Important molecular structural info on first gen H1 antagonists
Need an amino group
DON’T need an amidazole group
What types of 1st gen H1 blockers have the strongest sedative effcts
Ethanolamines and Phenothiazines
What types of 1st gen H1 blockers have the strongest anti-cholinergic effcts
Diphenhydramine, Promethazine
Why give a shit that 1st gen H1 blockers have anti-cholinergic effects?
anti-motion sickness/vertigo effect
Anti-emetic effect
Not seen in 2nd gen
Which 1st gen H1 blockers have local anesthetic effects? weak alpha adrenergic antagonism?
anesthetic – pyrilamine, promethazine
alpha-adrenergive – phenothiazines
Four main examples of 2nd gen H1 antagonists
Loratadine (Claritin)
Desloratadine (Clarinex)
Citirizine (Zyrtec)
Fexofenadine (Allegra)
