Histamine and Antihistamines

Question 1

List the first and second geenration of AntiHistamins

Answer 1

first : Chlorpheniramine
Diphenhydramine
Promethazine

second : Cetirizine
Fexofenadine
Loratadine

Question 2

Actions of Histamine

Answer 2

 Smooth muscle contraction (e.g. bronchial)
 Vasodilation (endothelium-derived NO-mediated)
 Increased vascular permeability (contraction of endothelial barrier and increase gap junctions) –
extravasation and edema
 Immediate symptoms of wheal-and-flare reaction in skin
 Sensory neuron to mediate pain and itch
 Increase release of histamine and other mediators from mast cells and basophils
 Stimulation of gastric acid secretion
 Modulation of histaminergic neurotransmissions, sleep/wake cycle, arousal, alertness, attention,
cognition, learning, memory
 Immunomodulation

Question 3

role of antihistamines

Answer 3

 H1-Histamine receptors are constitutively
active
 Inactive and Active receptors in equilibrium
 Histamine stabilizes H1-receptors in Active
form
 Antihistamines stabilize H1-receptors in
Inactive form
 In principle, H1-Antihistamines are Inverse
Agonists, NOT competitive antagonists

Question 4

clinical use of antihistamine first-generation

Answer 4

Non-Allergic conditions: 1st Generation Antihistamines are commonly used
Motion sickness and vertigo (e.g. promethazine, hydroxyzine, diphenhydramine)
Nausea and vomiting as anti-emetic (e.g. hydroxyzine, diphenhydramine)
Insomnia and perioperation (e.g. promethazine, diphenhydramine)

Question 5

clinical use of antihistamine second-generation

Answer 5

Allergic disorders:
2nd Generation Antihistamines are the Preferred Choice for mild-moderate allergy
Allergic rhinitis: relieve nasal itching, sneezing, rhinorrhea
Allergic conjunctivitis: relieve itching, erythema, tearing, edema
Allergic urticaria: decrease itching, and the number, size and duration of wheals and flares
Food allergy
Mastocytosis: relieve itching and flushing

Question 6

mechanism of actions of H1 antiHistamine

Answer 6

Blocks H1 rreceptor, blockk vascular permeability, decrese vasodialtion, decrease sesonry nerve simulation(itch), reduce Ca2+ levels inside cel, increase antigen presentation,
increase expression of pro inflammatory cytokines cell adhesions

Question 7

1st Gen AntiHistamines

Answer 7

 Sedating antihistamines
 Low H1-receptor selectivity
 Anti-muscarinic cholinergic
Anti-adrenergic
Anti-hydroxytryptaminergic (5-HT)
 Highly lipophilic
 Lower molecular weight
 Readily pass BBB
 Lack interaction with P-glycoprotein efflux pump
 High CNS H1 receptor occupancy
 Onset of action: 2-3 h
 Duration: ~12 h

Question 8

2nd Gen Anti Histamines

Answer 8

 Non-sedating or Less-sedating antihistamines
 High H1-receptor specificity
no interaction with muscranic
no interaction with adrenergic
no interaction with hydroxytryptaminergic
 Less lipophilic
 Higher molecular weight
 Less ready to pass BBB
 High affinity with P-glycoprotein efflux pump
 Low CNS H1 receptor occupancy (0 for
fexofenadine and 30% for cetirizine)
 Onset of action: 1-2 h
 Duration: 24 h (once daily)

Question 9

strong coorelation for treatment using second gen

Answer 9

allergic rhinitis
allergic conjunctivitis
urticaria

Question 10

weak coorealtion with H1

Answer 10

upper respiratory tract infections

sinusitis
non specific cough

Question 11

weak coorealtion with first gen H1

Answer 11

insomnia
perioperative sedation
motion sickness
vertigo

Question 12

side effects of first gen

Answer 12

 1st generation antihistamine should be avoided for pilots, drivers and any
machinery operators require psychomotor skills. Fexofenadine is recommended.
 Contraindication for 1st gen antihistamines: patients with glaucoma (esp. narrow-
angle glaucoma) or prostatic hyperplasia
 Drug abuse: euphoria, hallucination (hydroxyzine, diphenhydramine)