Antihistamines are among the most commonly prescribed and self-medicated drugs in clinical practice. From seasonal allergies and urticaria to motion sickness and sleep disorders, these drugs span respiratory medicine, dermatology, psychiatry, and emergency care.
For students, antihistamines are a high-yield pharmacology topic because they beautifully illustrate:
- Receptor-based drug action
- Blood–brain barrier penetration
- Differences between first- and second-generation drugs
This article provides a clear, comparative, exam-oriented explanation of four commonly tested antihistamines:
1. FexofenadineWhat Are Antihistamines?
Antihistamines are drugs that block the effects of histamine, a chemical mediator released from mast cells during allergic reactions.
Role of Histamine in Allergy
Histamine causes:
- Sneezing
- Nasal congestion
- Itching
- Urticaria (hives)
- Bronchoconstriction
- Increased capillary permeability
These effects are mediated mainly through H₁ receptors.
Antihistamines = H₁ receptor blockers
Classification of Antihistamines (Very High Yield)
Antihistamines are broadly classified based on generation and CNS penetration.
1. First-Generation H₁ Antihistamines
- Cross the blood–brain barrier
- Cause sedation and anticholinergic effects
Examples:
- Diphenhydramine
- Hydroxyzine
2. Second-Generation H₁ Antihistamines
- Minimal CNS penetration
- Non-sedating or minimally sedating
Examples:
- Loratadine
- Fexofenadine
Mechanism of Action (Core Concept)
Antihistamines:
- Competitively block H₁ receptors
- Prevent histamine-mediated allergic symptoms
- Do not prevent histamine release (important exam point)
Individual Drug Profiles (Exam-Focused)
Fexofenadine
Drug Class
Second-generation H₁ antihistamineKey Features
- Non-sedating
- Poor CNS penetration
- Active metabolite of terfenadine
Indications
- Allergic rhinitis
- Chronic urticaria
Adverse Effects
- Headache
- Mild dizziness (rare)
Clinical Pearl
Safest antihistamine for daytime use
Loratadine
Drug Class
Second-generation H₁ antihistamineKey Features
- Long-acting (24-hour relief)
- Minimal sedation
Indications
- Seasonal allergic rhinitis
- Chronic idiopathic urticaria
Adverse Effects
- Dry mouth
- Headache
Clinical Pearl
Preferred for once-daily allergy control
Hydroxyzine
Drug Class
First-generation H₁ antihistamineKey Features
- Sedating
- Anxiolytic properties
Indications
- Pruritus
- Anxiety
- Preoperative sedation
- Motion sickness
Adverse Effects
- Drowsiness
- Dry mouth
- Urinary retention
Clinical Pearl
Useful when sedation is desirable
Diphenhydramine
Drug Class
First-generation H₁ antihistamineKey Features
- Strong sedative effect
- Significant anticholinergic action
Indications
- Acute allergic reactions
- Motion sickness
- Short-term insomnia
- Drug-induced dystonia
Adverse Effects
- Marked drowsiness
- Confusion (elderly)
- Dry mouth, blurred vision
Clinical Pearl
Commonly used as a night-time allergy or sleep aid
Comparison Table
| Feature | Fexofenadine | Loratadine | Hydroxyzine | Diphenhydramine |
|---|---|---|---|---|
| Generation | Second | Second | First | First |
| Sedation | No | Minimal | Yes | Yes |
| Anticholinergic | No | Minimal | Moderate | Strong |
| BBB penetration | Poor | Low | High | High |
| Daytime use | ✔️ | ✔️ | ❌ | ❌ |
Adverse Effects (Grouped for Easy Recall)
CNS
- Sedation (first-generation)
- Dizziness
Anticholinergic (First-Generation)
- Dry mouth
- Urinary retention
- Constipation
- Blurred vision
Special Risk Groups
- Elderly → confusion, falls
- Glaucoma → worsens condition
- BPH → urinary retention
Contraindications & Precautions
Avoid first-generation antihistamines in:
- Elderly patients
- Glaucoma
- Prostatic hypertrophy
Nursing & Patient Education Points
- Second-generation drugs preferred for daytime allergy
- Warn patients about drowsiness with first-generation drugs
- Avoid driving or operating machinery if sedated
- Do not combine with alcohol unnecessarily
Clinical & Exam Pearls (Must-Remember)
- First-generation antihistamines = sedating
- Second-generation antihistamines = non-sedating
- Antihistamines block effects, not release, of histamine
- Diphenhydramine has antiemetic and anticholinergic uses
- Fexofenadine is safest for working professionals and students
FAQs
1. Why do first-generation antihistamines cause sedation?
They cross the blood–brain barrier and block central H₁ receptors.
2. Which antihistamine is best for daytime allergies?
Fexofenadine or loratadine.
3. Can antihistamines be used as sleep aids?
Yes, first-generation drugs like diphenhydramine are commonly used.
4. Do antihistamines prevent allergic reactions?
No, they only block histamine effects after release.
5. Which antihistamine has anxiolytic effects?
Hydroxyzine.
6. Are second-generation antihistamines completely non-sedating?
They are minimally sedating, but individual sensitivity varies.
7. Which antihistamine is preferred in elderly patients?
Second-generation antihistamines.
8. Can antihistamines worsen glaucoma?
Yes, especially first-generation drugs due to anticholinergic effects.
9. Are these drugs used in anaphylaxis?
They are adjuncts, not first-line treatment (epinephrine is first-line).
10. What is the most tested antihistamine distinction?
Sedating vs non-sedating (generation-based classification)
