Antihistamines

Question 1

Mast cell degranulation: IgE mediated allergy

Answer 1

via mass cell degranulation (IgE mediated responses)
- allergen binding to IgE goes to mast cells and basophils
- mast cells have receptors known as fcepsilonR1 that binds with IgE
- allergen causes cross-linking between IgE results in mast cells to degranulate releasing histamines

Question 2

Histamine: Biological actions

Answer 2

• smooth muscle constriction
• vasodilation (endothelial cells have H1 receptors > binding of histamine to H1 > Nitric oxide increases > stimulates Guanylyl cyclase to catalyse conversion of GMP to cGMP > increase cGMP levels causes muscles to relax)
• increase vascular permeability (endothelial lining contraction due to binding of histamines to H1 receptors > increase gap junction)
• sensory neuron sensing pain and itch
• increase gastric secretion
• wheals and flares allergy skin reactions
• histamines can stimulate more mediator release from mast cells and basophils

Question 3

what are histamine receptors?

Answer 3

G protein couples receptors (GPCR), activated by G alpha q (H1) others are G alpha s and i

Question 4

what type of drug is anti-histamines? explain how it works

Answer 4

inverse agonist.
histamine receptors are constitutively active even without histamines.
- Histamine stabilises active form
- antihistamines stabilises inactive form, they reduce the baseline activities of the receptors

Question 5

clinical uses of gen1 anti histamines

Answer 5

they are used to treat non-allergic disorders like nausea and vomitting

Question 6

clinical uses of gen2 anti histamines

Answer 6

treat allergic disorders like
- allergic rhinitis (relieve sneezing and itchy)
- allergic conjunctivitis (relieves tearing, edema, itchy)
- allergic uticaria (relieves wheals and flares on skin)

Question 7

describe gen 1 H1 antihistamines

Answer 7

• narrow therapeutic index
• sedative antihistamines
• anti muscarinic cholinergic drugs & anti adrenergic drugs
• H1 receptor non selective (means binds to other histamine receptors too)
• highly lipophilic and low molecular weight > able to pass through BBB (blood brain barrier) > enters into CNS affects psycho motor abilities, learning, cognitive, memory
• high occupancy in CNS H1 receptors

Question 8

describe gen 2 H1 antihistamines

Answer 8

• wide therapeutic index
• little to no sedative effects
• selectively occupies H1 receptors more
• high molecular weight & less lipophilic > cannot pass through BBB > only cetirizine can cause slight sedative, fexofenadine does not
• low occupancy of H1 receptors in CNS

Question 9

what are the gen 1 anti histamines

Answer 9

chlorpheniramide
diphenhydramide

Question 10

what are the gen 2 anti histamines

Answer 10

cetirifizine
fexofenadine

Question 11

side effects of 1st gen anti histamines

Answer 11

• CNS: alertness, psychomotor, affects cognitive learning and memory
• glands and muscles: decrease secretions of sweat, lacrimation salivary. Urinary bladder, GI motility decrease
• weight gain and increase appetite
• alpha adrenergic receptors: hypotension (dilation of blood vessels), increase dizziness

Question 12

contraindications of gen 1 anti histamines

Answer 12

glaucoma and prostate hyperplasia

Question 13

adverse side effects due to overdose of gen 1 anti histamines

Answer 13

euphoria and hallucination