Antihistaminics

H1 receptor antihistaminic agents can be classified either clinically or chemically

Clinical classification:
  • Potent and sedative
  1. Diphenhydramine
  2. Promethazine
  3. Dimenhydrinate
  • Potent and less sedative
  1. Chlorpheniramine maleate
  2. Tropolidine
  3. Cyclizine
  4. Meclizine
  • Less potent and less sedative
  1. Mepyramine maleate
  2. Antazoline HCL
  • Non sedative (second generation)
  1. Fexofanadine
  2. Loratadine
  3. Desloratadine
  4. Cetirizine

Pharmacological actions:

Antihistaminic actions:
  • The antihistaminics competitively block the histamine actions at many sites.
  • Thus they antagonise the stimulant action of histamine on the smooth muscle of GI tract ,the bronchi, the uterus and blood vessels and inhibit histamine augmented salivary secretion.
  • They also reduce histamine-induced triple response and itching, but fail to produce resorption of the oedema fluid.
Antiallergic and anti-inflammatory actions:
  • Here it involves
  • Inhibition of the release of mediators from mast cells and basophils and
  • Downregulation of H1 receptors.
  • However bronchospasm and hypotension during anaphylaxis is not adequately reversed by them.
  • This is probably because of other mediators released during the reaction.
  • These agents do not antagonise the cardiovascular actions of histamine.

Other actions of these are related to their blocking of muscarinic ,5-HT as well as alpha 1 adrenergic receptors. They are

Sedation and hypnosis:
  • CNS depression is the common side effect with the classical ( 1st generation) anti-histaminics)
  • Sedation is often accompanied by inability to concentrate, dizziness and disturbances in co-ordination ,thus may interfere with daily work
  • Sedation is negligible with second generation antihistaminics such as fexofenadine and desloratadine
CNS stimulation:
  • Stimulation is less commonly encountered than depression.
Autonomic nervous system:
  • Majority of first generation antihistaminics exhibit muscarinic blocking activity.
  • Dryness of mouth is common.
  • Some other first generation drugs have alpha adrenergic blocking activity.
  • The second generation antihistaminics usually do not have these actions
Antiemetic and antimotion sickness effects:
  • These drugs block the histaminergic signals from vestibular nucleus to vomiting centre
  • Vomiting due to other labyrinthine disturbances, such as labyrinthitis and fenestration operation also responds to antihistaminics.
Cardiovascular system:
  • In therapeutic doses of antihistaminics fail to affect the cardiovascular system
  • Rapid i.v. administration of diphenhydramine , antazoline and tripelennamine may cause dose-related prolongation of QT interval due to their membrane stabilising action.

Absorption ,fate and excretion:

  • They are absorbed orally and parentally
  • The antihistaminic effect start within 15-30min,peaks by 1hour and lasts for 3-6 hours .
  • All first generation compounds are mainly metabolised in the liver by CYP3A4, and the products are eliminated in urine.
  • H1 receptor antagonists can induce hepatic microsomal enzymes, facilitating their own metabolism.

Adverse reactions:

  • CNS : first-generation antihistaminics cause sedation, hypnosis and fatigue.

Individuals taking such antihistaminics should not drive vehicles because of drowsiness and impaired motor coordination

  • Antimuscarinic effects:the commonest effects are
  • Dry mouth
  • Blurring of vision
  • Bladder disturbances and rarely impotence with 1st generation antihistaminics
  • GI : nausea, vomiting, epigastric distress.

Therapeutic uses:

Allergic disorders:the antihistaminics are used to treat

  • Polinosis
  • Urticaria
  • Extremely effective in the treatment of seasonal hay fever where it reduces sneezing, rhinorrhea and other manifestations.
  • They effectively counter the pruritus and urticaria in atopic dermatitis and that induced by various drugs, chemicals and plants.
  • Combination of phenothiazine such as chlorpromazine with an antihistaminic may give better results in severe pruritus than antihistaminic alone.
  • Their topical use is not recommended owing to the risk of sensitisation and tendency to cause eczema.
  • These are used in reaginic allergy
  • Antihistaminics are of some value in controlling mild blood transfusion reactions but not pyrexia or haemolysis
  • H1 receptor antagonists,mast cell stabilisers and drugs having both actions can give symptomatic relief in allergic conjunctivitis
  • Used in urticaria and angioedema
  • The treatment of choice for severe acute urticaria is an s.c. injection of adrenaline in the dose of 0.3ml(1:1000 aqueous solution)
  • Oral antihistaminics are the drugs of choice in chronic urticarias

Drug interactions:

  • Sedation is enhanced when used with alcohol, barbiturates, benzodiazepines or tricyclic antidepressants.

Nonsedative H1 antihistaminics:

  • A second-generation competitive H1 receptor blockers, which poorly cross the BBB .

They are

  • Highly specific H1 receptor antagonists
  • Nonsedating in therapeutic doses
  • Devoid of antimuscarinic,antiserotonergic and antibradykinin action
  • More expensive
  • Less prone to drug interactions

Note:

Cetirizine is largely excreted in urine

Fexofenadine is primarily excreted in the faeces

Therapeutic uses:

  • Allergic rhinitis but not in vasomotor rhinitis
  • Urticaria
  • Dermographia

H2 receptor antagonists:

  • H2 receptors are responsible for histamine induced gastric acid secretion and their antagonists are useful in the treatment of peptic ulcer.

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