Histamine and antihistamines

Question 1

Give 3 examples of 2nd generation antihistamins

Answer 1

Loratadine
Fexofenadine
Cetirizine

Question 2

2nd gen antihistamines clinical uses

Answer 2

mild, moderate allergy (rhinitis, conjunctivitis, urticaria, food allergy, mastocytosis)

Question 3

give 3 example of 1st generation antihistamine

Answer 3

Chlorpheniramine
Diphenhydramine
Promethazine

Question 4

1st gen antihistamines clinical uses

Answer 4

non allergic conditions (motion sickness, nausea, vomitting, insomnia, perioperation)

Question 5

what is the side effect of 1st generation antihistamine

Answer 5

sedating (readily pass BBB, lipophilic, low MW, high CNS H1 occupancy), slower onset of action (2-3h), duration (~12h), contraindication (glaucoma/prostatic hyperplasia), drug abuse (hallucination: dipheniramine)

Question 6

Roles of antihistamines in allergic disorders

Answer 6

inverse agonist; stabilise H1 receptors in inactive form

Question 7

Direct mechanisms of action

Answer 7

direct: prevent mast cell degranulation, decrease vascular permeability, decrease vasodilation

Question 8

Hitsamine receptor

Answer 8

H1, GPCR (G alpha q –> PIP2 / PLC pathaway)

Question 9

effects of histamines

Answer 9

smooth muscle contraction, vasodilation, increased vascular permeability, sensory neuron to mediate pain and itch, increase release of histamine + mediators from mast + basophil, stimulate gastric acid secretion, modulate histaminergic neurotransmission, sleep/wake etc

Question 10

NFkB and Ca2+ channel modulated mechanisms of action

Answer 10

decrease antigen presentation. decrease mediator release,/increase mast cell stabilisation,

Question 11

least sedating

Answer 11

fexofenadine (0% CNS H1 receptor occupancy) vs cetirizine (30%)