Antihistamines bind to histamine H1 receptors and block the effects of histamine. Typically, they are used for the following indications:
- Allergic rhinitis,
- Vasomotor rhinitis,
- Allergic conjunctivitis,
- Urticaria,
- Angioedema,
- Insect bites and stings,
- Nausea and vomiting,
- Motion sickness,
- Insomnia associated with urticaria and pruritus, and
- Adjuvant therapy in the treatment of anaphylaxis.
Generally, antihistamines are administered orally (e.g. in the form of tablets or liquid). Some antihistamines can be administered via the intravenous route, intramuscular route or topically (e.g. in the form of nasal sprays or eye drops).
Antihistamines are classified into two groups – the first-generation (“sedating”) and second-generation (“non-sedating”). Sedating antihistamines cause sedation as they are highly lipid soluble and readily cross the blood-brain barrier. This sedating activity is sometimes used in managing conditions such as eczema where sleep may be disturbed due to pruritus. Sedating antihistamines also have significant anticholinergic activity (sedating antihistamines also act on the muscarinic receptors as antagonists) and should be used with caution in patients with prostatic hypertrophy, urinary retention and angle-closure glaucoma. This anticholinergic activity may result in anticholinergic side effects such as dry mouth, blurred vision, dizziness, constipation, tachycardia/palpitations, sedation and urinary retention. When prescribing antihistamines for older people, it is advisable to steer clear of sedating antihistamines due to their anticholinergic side effects. This is because older people tend to be more sensitive to the effects of medications with anticholinergic activity. Such medications have been linked to a higher risk of falls/fractures and cognitive impairment in older people.
Examples of sedating antihistamines:
- Alimemazine
- Chlorphenamine
- Cyproheptadine
- Hydroxyzine
- Ketotifen
- Promethazine hydrochloride
- Promethazine teoclate
- Cinnarizine
Examples of non-sedating antihistamines:
- Acrivastine
- Bilastine
- Cetirizine
- Desloratadine
- Fexofenadine
- Levocetirizine
- Loratadine
- Mizolastine
- Rupatadine
Sedation is rare with non-sedating antihistamines, however, patients should be made aware that a sedative effect may occur and the performance of skilled tasks such as operating machinery or driving may be affected.
Choice of antihistamine
Due to the higher risk of adverse effects associated with sedating antihistamines, it is preferred to choose a non-sedating antihistamine over a sedating antihistamine.
Comparison of first-generation antihistamines and second-generation antihistamines
This table compares first-generation antihistamines and second-generation antihistamines including the advantages and disadvantages.
|
First-generation antihistamines |
Second generation antihistamines |
|
|
Duration of action |
Shorter duration |
Longer duration |
|
Selectivity for histamine H1 receptor |
Acts on both the peripheral histamine H1 receptors and central histamine H1 receptors (located in the central nervous system). Acting on the central histamine H1 receptors gives rise to central nervous side effects such as sedation, cognitive impairment and fatigue. |
High affinity and selectivity for peripheral histamine H1 receptors. Having selectivity for the peripheral histamine H1 receptors results in the least possible central nervous system side effects. |
|
Binding affinity for muscarinic and alpha-adrenergic receptors |
Higher binding affinity |
Lower binding affinity |
|
Side effects |
Cause more side effects Common side effects: drowsiness, fatigue, cognitive impairment, dizziness, dry mouth |
Cause fewer side effects Does not or is less likely to cross the blood-brain barrier and in effect causes minimal drowsiness/no sedation |
|
Clinically relevant drug interactions |
Possible |
Unlikely |
|
Abuse potential |
Possible |
Likely to be abused less frequently |
|
Older people |
Elimination half-life and duration of action are prolonged and sensitivity to sedative (drowsiness, confusion, agitation) and anticholinergic effects is amplified in older people. Not recommended |
Recommended over first-generation antihistamines |
Source: References 1-5
Patient Counselling/Monitoring
- Monitor patient for anticholinergic side effects and other adverse effects
- Give advice on how to manage the following anticholinergic side effects:
– Dry mouth: suck on a sugar-free lozenge or sweet or take sips of water and monitor
– Constipation: increase fibre and water intake and monitor - Antihistamines are most effective when taken before exposure to the allergen
- Assess whether the antihistamine is providing relief from symptoms associated with the allergy or do they need to be switched to another antihistamine
- Provide advice on how to reduce exposure to allergens
References
1. Church DS, Church MK. Pharmacology of antihistamines. Indian J Dermatol. 2013;58:219-224. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667286/ (Accessed 03/11/23).
2. Coggins MD. Antihistamine Risks. Today’s Geriatric Medicine. 2013; 6(2):6. Available at: https://www.todaysgeriatricmedicine.com/archive/0313p6.shtml (Accessed 03/11/23).
3. Fein MN, Fischer DA, O’Keefe AW, Sussman GL. CSACI position statement: Newer generation H1-antihistamines are safer than first-generation H1-antihistamines and should be the first-line antihistamines for the treatment of allergic rhinitis and urticaria. Allergy Asthma Clin Immunol 2019;15:61. Available at: https://aacijournal.biomedcentral.com/articles/10.1186/s13223-019-0375-9 (Accessed 03/11/23).
4. Han S. Clinical Pharmacology Review for Primary Health Care Providers: I. Antihistamines. Transl Clin Pharmacol. 2014;22(1):13-18. Available at: https://tcpharm.org/DOIx.php?id=10.12793/tcp.2014.22.1.13 (Accessed 03/11/23).
5. Pien LC. Appropriate use of second-generation antihistamines. Cleve Clin J Med. 2000;67(5):372-80. Available at: https://www.ccjm.org/content/67/5/372.long (Accessed 03/11/23).