Antihistaminics

Dr. Pramod Bhalerao

• Histamine is categorised as autacoids or local hormones. (autos=self; akos=remedy).

Histamine Biosynthesis

Histamine storage

• Mast cells• Basophil• Histaminocytes in stomach• Histaminergic neurons in brain.

Histamine receptors

• H1• H2• H3• H4

Pharmacological actions of Histamine

H1 receptor mediated actions

• Stimulant of sensory nerve endings• Pain, itch.• Urticaria response to insect bites and stings.

H1 receptor mediated actions

• Smooth muscle • Bronchoconstriction• Contraction of intestinal smooth muscles

H1 receptor mediated actions

• Increased secretions of exocrine glands in bronchioles, pancreas, salivary, and lacrimal glands.

H1 receptor mediated actions

• Effect in CNS• wakefulness

H1 receptor mediated actions

• Dilatation of arterioles • Dilatation of post-capillary venules• Fall in BP.• Headache

vasodilatation

H1 receptor mediated actions

• Positive chronotropic• Positive ionotropic• These effects may occur reflexly due to fall in

BP.

H1 receptor mediated actions

• When histamine is injected intradermally• Triple response• Flush-reddening of skin• Wheal- formation of oedematous patch• Flare- red irregular halo surrounding wheal.

H1 receptor mediated actions

• Severe hypersensitivity reactions may also occur following injection of histamine.

• Anaphylaxis.

H2 receptor mediated actions

• Gastric acid secretion by activation of H2 receptors on gastric parietal cells.

H1- Receptor antagonists

Clinical classification

• First generation drugs- short duration of action, more sedating, antimuscarinic(anticholinergic) side effects.

• Second generation drugs- long duration of action, least sedating, devoid of antimuscarinic side effects.

First generation antihistaminics• Highly sedative• Diphenhydramine• Dimenhydrinate• Promethazine• Hydroxyzine

• Moderately sedative• Pheniramine• Meclizine• Buclizine• Cinnarizine

• Mild sedative• Chlorpheniramine• Dexchlorpheniramine• Cyclizine• Clemastine

Second generation antihistaminics

• Fexofenadine• Loratadine • Desloratadine• Cetirizine • Levocetirizine• Azelastine • Second generation drugs- long duration of action,

least sedating, devoid of antimuscarinic side effects.

Side effects of antihistaminics

• Sedation (Patients should be cautioned not to operate motor vehicles or machinery requiring constant attention).

• Dryness of mouth, constipation, urinary retention can be ascribed to anticholinergic property.

Uses of H1 antihistaminics

Allergic disorders

Urticaria

Angioedema of lips

Allergic conjunctivitis

Itching

Other conditions involving histamine

ivy poisoning insect bite

blood/saline infusion induced rigor.

Common cold

• Symptomatic relief by anticholinergic (reduce rhinorrhoea) and sedative actions.

Motion sickness

• Promethazine, diphenhydramine, dimenhydrinate and meclozine.

• Should be taken one hour before starting journey.

• Other uses• morning sickness,• drug induced vomitting• postoperative vomitting, • radiation sickness.

Vertigo

• Vertigo is a sensation of spinning while stationary.

• Cinnarizine

Preanaesthetic medication

• Promethazine has been used for its anticholinergic and sedative properties.

Cough

• They have no selective cough suppressant action.

• may afford symptomatic relief by • sedative and • anticholinergic property.

Parkinsonism

• Promethazine and some others afford mild symptomatic relief in early cases based on

• anticholinergic • sedative property.

Acute muscle dystonia• Caused by antipsychotic drugs is promptly

relieved by parenteral promethazine, diphenhydramine or hydroxyzine.

• Based on central anticholinergic action of the drugs.

H2 antagonist

• Cimetidine• Ranitidine, • Famotidine,• Roxatidine

• Used in peptic ulcer disease.

Thank You