Antihistamines (Maize)

Question 1

Antigen-Mediated Release or Degranulation

Answer 1

• tissue mast cells and blood basophils are the primary cells involvedin the immediate hypersensitivity reaction
• antigen causes the generation of IgE
• IgE binding to the surface of mast cells or basophils
• antigen bridges the IgE and increases calcium levels in the cell
• exocytosis of contents (degranulation)

Question 2

Nonantigen-mediated Release of Histamine

Answer 2

• Mechanism: receptor mediated and increase in intracellular calcium
• Compounds and agents that release histamine: any thermal or mechanical stress of sufficient intensity, basic drugs and chemicals (morphine, codeine, d-turbocurarine, guanethidine, succinylcholine & vancomycin), venoms from stinging insects

Question 3

Mechanisms of Action of the H1 Antihistamines

Answer 3

• All antihistamines are H1 inverse agonist
• inverse agonist at the H1 receptor
• Bind and stabilize the inactive state of the receptor
• -> there is less histamine being released when we have an inverse agonist

Question 4

Side Effects of 1st gen Antihistamines

Answer 4

• Sedation: the sedative effect may be a result of inverse agonism at the central H1 receptors, readily cross the BBB and occupy 50-90% of the H1 receptors in the brain
• Paradoxical excitement in children: restlessness, tremors, euphoria, delirium, palpitations and seizures
• Nervous system effects: disturbed coordination & decreased cognition
• Increased appetite
• Abuse potential: diphenhydramine & dimenhydrinate, euphoria, hallucinations & “getting high”
• Peripheral sodium channel blockade-local anesthetic

Question 5

Side effects of 1st gen continued

Answer 5

• Anticholinergic effects: anti-SLUDGE–> everything dries up!
• Cardiovascular effects: tachycardia, palpitations, prolonged QT interval, hypotension or orthostatic hypotension
• Sensitivity reactions: occurs most commonly w/topical antihistamines, ethylenediamine derivates are the most common chemical type to cause the reaction (Benedryl)
• Order of ability to cross BBB= sedation (diphenhydramine= promethazine)
• Anticholinergic effects: (diphenhydramine= promethazine)

Question 6

Side Effects of 2nd gen Antihistamines

Answer 6

• No or low sedation: doesn’t cross the BBB
• Cardiovascular effects: astemizole and terfenadine (off market)
• Food drug interations: 5 oz of orange, apple or grapefruit juice of fexofenadine (Allegra). Separate by 2 hours.
• -> cetirize (Zyrtec): can cause some sedation, but minimal

Question 7

Uses of 1st & 2nd gen Antihistamines

Answer 7

Anti-allergy (1st & 2nd): relieves nasal itching, sneezing, rhinorrhea, congestion, conjunctival itching, red & watery eyes, itching of palate, throat & ears
Uticaria (2nd > 1st): reduced number, size, duration and itching of hives (Zyrtec)
Parkinson’s Disease: not used anymore

Question 8

Uses of 1st gen Antihistamines

Answer 8

Motion sickness/antiemetic action: acts on the vestibular apparatus, integrative vomiting center and the medullary chemoreceptive trigger zone of the midbrain, depresses labyrinth excitability and conduction in the vestibular-cerebella pathway, efficacy= scopolamine> promethazine> meclizine= cyclizine= dimenhydrinate

Question 9

Uses of 1st gen continued

Answer 9

Dermal itching & pain: combo of antihistamine and local anesthetic effects, diphenhydramine & promethazine are more potent than the local anesthetic procaine
Insomnia: exploit the antihistamine and anticholinergic effects