Histamine and H1 antihistamines

mechanism of action – H1 receptors

1. vasodilation
prostacyclin (PGI2) – adenylyl cyclase - cAMP
NO – guanylyl cyclase – cGMP
smooth muscle relaxation
2. Phospholipase C-coupled H1 receptor –
Formation of inositol triphosphate (IP3) and
diacylglycerol – release of intracellular calcium –
contraction of smooth muscle in bronchi
 Histamine and H1 antihistamines

H2 receptors – parietal cells of the stomach

Activation of proton pump – release of HCl acid
H3 receptors – CNS – inhibition of the release
neurotransmitters
effects of histamine
In the skin - capilary dilatation – urticaria
Heart – increased heart rate and inceased strenght
of contraction
Increase exocrine secretion (H1 - nasal and
bronchial mucus); gastric secretion (H2)
 Histamine and H1 antihistamines

Release of adrenaline
Stimulation of sensory nerve endings – itch and
pain
Migraine (vascular) headache
Classification (first and second generation)
A major difference in the two groups is that first
generation are distributed to the CNS –
sedation, whereas the second generation
antihistamines do not cross the blood-brain
barrier
 Histamine and H1 antihistamines
Pharmacological effects and indications
The H1 antihistamines are all equally effective
in treating allergies, but they differ markedly
in ther sedative, antiemetic and
anticholinergic properties
Second gen. – little or no sedation – preferred
for the treatment of allergies BUT NOT
EMERGENCY TREATMENT OF
ANAPHYLACTIC REACTIONS
More effective when administered before
exposure to an allergen than afterward
 Histamine and H1 antihistamines

Causions and contraindications

Sedating antihistamines have significant
antimuscarinic activity
Causion:
Prostatic hypertrophy
Urinary retention
Glaucoma (angle-closure)
Epilepsy
Children and elderly are more susceptible to
side-effects!
 Histamine and H1 antihistamines

First generation
Sedative effects
Nausea and vomiting
To prevent motion sickness
Vertigo
Diphenhydramine - high sedative and
anticholinergic ; medium antiemetic effect –
urticaria, itching (topically)
Due to anticholinergic effect – releave of acute
dystonia (Parkinson᾿s disease)
 Histamine and H1 antihistamines

promethazine - high sedative, antiemetic and

anticholinergic effect – emergency treatment
of anaphylaxis and angioedema
Promethazine suppositories – releave nausea
and vomiting
Additional effect – block of alpha 1 adrenergic
receptors – orthostatic hypotension!
 Histamine and H1 antihistamines

Chorpheniramine - hloropiramin (medium

sedative and anticholinergic, none entiemetic
effect) – anaphylaxis and angioedema
Motion sickness – dimenhydrinate,
diphenhydramine
Meclizine, diphenhydramine, hydroxyzine and
promethazine – higher antiemetic activity
than other
Meclizine is less sedating – vertigo, motion
sickness
 Histamine and H1 antihistamines
Second generation antihistamines
Lack antiemetic activity – their use is limited to the
treatment of allergies
Loratadine - allergic rhinitis and chronic idiopathic
urticaria
Desloratadine
Fexofenadine (twice a day)
Cetirizine – some sedation
Ketotifen – allergic rhinitis and conjunctivitis
Astemozole and terfenadine are withdrawn from
the marked due to cardiotoxicity!
 Histamine and H1 antihistamines

Intranazal antihistamines
Azelastine – allergic rhinitis
Two sprays per nostril twice daily
Can cause drowsiness
(all H1 antihistamines should be used
cautiosly/or should not be used when patients
are driving or operating machinery!)
 Histamine and H1 antihistamines

Opthalmic antihistamines
Eye drops
Olopatadine, epinastine
Adverse effects ant interactions – (few serious side
effects)
First gen – sedation
Paradoxically – excitement in infants and children
(caution in these patients)
Diphenhydramine and promethazine – the highest
anticholinergic activity (but the other also!) – dry
mouth, constipation, urinary retention, tachycardia)
 Other H1 antihistamines

Cyclizine is a histamine H1 receptor antagonist

low incidence of drowsiness
It possesses anticholinergic and antiemetic
properties.
Motion sickness.
Nausea and vomiting caused by narcotic
analgesics and by general anaesthetics in the
post-operative period.
 Other H1 antihistamines

Vomiting associated with radiotherapy,

especially for breast cancer since cyclizine
does not elevate prolactin levels.
cyclizine may be of value in relieving vomiting
and attacks of vertigo associated with
Meniere's disease and other forms of
vestibular disturbance.
 Other H1 antihistamines

Cinnarizine

Vestibular disorders – vertigo, tinnitus, nausea

and vomiting in Meniere᾽s disease

Betahistine – reduce endolymphatic pressure

by improving microcirculation
Vertigo, tinnitus, Meniere᾽s disease
 Histamine and H1 antihistamines

Overdose – physostigmine treats

anticholinergic effect in CNS
Second generation
Astemizole and terfenadine are withdrawn
because prolong Q-T interval and cause
cardiac arrhythmia
Fexofenadine (an active metabolite of
terfenadine) – does not produce cardiac
arrhythmias!
Loratadine – lack cardiac effects!
 Histamine and H1 antihistamines
Vomiting during pregnancy
Short – term treatment with promethazine
second-line – prochlorperazine,
metoclopramide
Postoperative nausea and vomiting
5HT3 antagonists
Droperidol
Dexamethazone
Phenothiazines
antihistamines
 Anaphylaxis

Adrenaline (0,5 mg)

High-flow oxigen
Chlorpheniramine (slow i.v. injection or i.m. 10
mg)
Hydrocortisone sodium succinate (200 mg)
Bronchodilators
Inhaled or i.v. salbutamol
Inhaled ipratroium
i.v. aminophylline