H1 receptor antihistaminic agents can be classified either clinically or chemically
- Potent and sedative
- Potent and less sedative
- Chlorpheniramine maleate
- Less potent and less sedative
- Mepyramine maleate
- Antazoline HCL
- Non sedative (second generation)
- 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
- 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.
- 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.
- 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.
Allergic disorders:the antihistaminics are used to treat
- 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
- 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 .
- Highly specific H1 receptor antagonists
- Nonsedating in therapeutic doses
- Devoid of antimuscarinic,antiserotonergic and antibradykinin action
- More expensive
- Less prone to drug interactions
Cetirizine is largely excreted in urine
Fexofenadine is primarily excreted in the faeces
- Allergic rhinitis but not in vasomotor rhinitis
H2 receptor antagonists:
- H2 receptors are responsible for histamine induced gastric acid secretion and their antagonists are useful in the treatment of peptic ulcer.