6. Histamine & Antihistamines Flashcards
Types of H1 antihistamines
1st Gen: chlorpheniramine, triprolidine, ketotifen, diphenydramine, promethazine
2nd Gen: cetirizine, loratadine, fexofenadine
3rd/New Gen: levocetirizine, desloratadine
Histamine is a ……
CNS neurotransmitter
Antihistamines acting at H1 in the CNS lead to:
- antiemetic effect
- sedation
- impaired cognition, memory and psychomotor function
What does histamine triggers?
Triple response
- Flush - capillary dilatation
- Flare - arteriolar dilatation (nerve reflex)
- Wheal - vascular permeability, oedema
How does histamine induces itch?
histamine → H1 and H4 receptors → c-afferent terminal → dorsal root ganglion → spinothalamic projections → hypothalamus (H1) & thalamus (H4) → somatic sensory cortex
positive feedback loop as scratching leads to further mast cell degranulation
Antihistamines are …..
Inverse agonists
They are not COMPETITIVE ANTAGONISTS!
1st gen H1 antihistamines
- selective for H1 over other histamine receptor subtypes
2. low specificity as they also interact with muscarinic cholinergic, alpha-adrenergic and serotonin receptors
Adverse effects of H1 antihistamines
- Inhibition of cholinergic receptors → dry mouth, urinary retention, sinus tachycardia
- Inhibition of alpha adrenergic receptors → hypotension, dizziness, reflex tachycardia
- Inhibition of serotonin → increase appetite
- Inhibition of histamine H1 → increase sedation, increase appetite, decrease cognitive and psychomotor performances
2nd gen H1 antihistamines
- Improved selectivity for H1 histamine receptors
2. Reduced lipophilicity or increased affinity for the P-glycoprotein efflux so reduced CNS effects
Relative drowsiness of 2nd gen H1 antihistamines
(most) cetirizine > fexofenadine > loratadine (least)
Clinical uses of H1 antihistamines
- Allergic disorders (2nd gen preferred)
- Antiemetics (1st gen only)
- Sedation (1st gen only)
Contraindications and caution for use of H1 antihistamines
- Do not combine with other CNS depressants (e.g. alcohol, benzodiazepines, opioids)
- Caution in pregnancy as safety uncertain
- Do not use late in 3rd trimester of pregnancy
- Do not use when breast-feeding
- Elderly patients are susceptible to CNS effects, anticholinergic and postural hypotension
- Do not use 1st gen H1 antihistamines in closed-angle glaucoma due to muscarinic antagonism
Contraindications and cautions for use of promethazine
Can cause fatal respiratory depression in young children
- Contraindicated under 2 years
- Use with caution in children over 2 years
Contraindications and cautions for use of fexofenadine
- Fruit juices inhibit organic anion transporting polypeptides and interfere with absorption
- Do not drink fruit juices from 4 hours before to 1-2 hours after dosing
